Alzheimer's & other dementias

Alzheimer's Prevention - Mental & Social Stimulation

See separate page for

Alzheimer's Prevention (chiefly diet & exercise)

Older news items (pre-2010) brought over from the old website

Mental & Social Stimulation

Cognitive activities may delay memory decline in dementia

A 5-year study involving 488 people age 75 to 85 found that, for the 101 people who developed dementia, the more stimulating activities they engaged in, the longer rapid memory loss was delayed. Participants reported at the beginning of the study how often they participated in six activities: reading, writing, doing crossword puzzles, playing board or card games, having group discussions, and playing music. For each activity, daily participation was rated at seven points, several days a week was rated at four points, and weekly participation was rated at one point. The average was seven points total for those who later developed dementia, meaning they took part in one of the six activities each day, on average. Ten people reported no activities, and 11 reported only one activity per week. Accelerated decline was delayed by more than two months for each activity, so for example a person participating in 11 activities per week put off rapid decline by 1.29 years compared to a person participating in only four activities per week.

Hall, C.B. et al. 2009. Cognitive activities delay onset of memory decline in persons who develop dementia. Neurology, 73, 356-361.

Some activities associated with less memory loss

A study involving 1321 randomly selected people aged 70 to 89, of whom 197 had mild cognitive impairment, has found that reading books, playing games, participating in computer activities or doing craft activities such as pottery or quilting was associated with a 30 to 50% decrease in the risk of developing memory loss compared to people who did not do those activities. Also, those who watched television for less than seven hours a day were 50% less likely to develop memory loss than people who watched for more than that. Other activities in later age were not significantly associated with a reduced chance of having MCI. Only two activities during middle age (50-65) were significantly associated with a reduced chance of later memory loss: participation in social activities and reading magazines.

Geda, Y.E. et al. 2009. Cognitive Activities Are Associated with Decreased Risk of Mild Cognitive Impairment: The Mayo Clinic Population-Based Study of Aging. Presented April 28 at the American Academy of Neurology's 61st Annual Meeting in Seattle.

No support for 'brain exercise' software for healthy elderly

A review of research on the impact of cognitive training on the healthy elderly (not those with mild cognitive impairment or Alzheimer's disease), has found no evidence that structured cognitive intervention programs affects the progression of dementia in the healthy elderly population. This is not to say that it doesn’t; the fault lies in the quality of the research. The researchers found only a very small number of studies that met their criteria. Those that did meet the criteria were mostly found to be limited in their methodologies or lacking in follow-up. They concluded that more random clinical trials in cognitive training need to be conducted with sufficient follow-up time that can actually measure changes in daily functioning.

Papp, K.V., Walsh, S.J. & Snyder, P.J. 2009. Immediate and delayed effects of cognitive interventions in healthy elderly: A review of current literature and future directions. Alzheimer's & Dementia, 5 (1), 50-60.

Mental and physical exercise delays dementia

A study using genetically engineered mice has found providing the mice with an enriched environment that enhanced their mental and physical stimulation improved performance on memory tests at an early stage of Huntington's disease, when memory impairment has begun. Specific molecular changes were also observed at the synapses in the hippocampus. Those without increased mental and physical activity showed decreased levels of specific proteins that are expressed at the synapse, but those exposed to stimulation didn’t. The finding offers hope for slowing the progression of the disease, as well as other dementias.

Nithianantharajah, J., Barkus, C., Murphy, M. & Hannan, A.J.  Gene–environment interactions modulating cognitive function and molecular correlates of synaptic plasticity in Huntington’s disease transgenic mice. Neurobiology of Disease, Published online ahead of print 24 November 2007

Mental stimulation in old age reduces Alzheimer's risk

Post-mortem analysis of participants in a large, long-running study has provided more support for the idea that mental stimulation protects against Alzheimer’s. The study found a cognitively active person in old age was 2.6 times less likely to develop dementia and Alzheimer’s disease than a cognitively inactive person in old age. This association remained after controlling for past cognitive activity, lifetime socioeconomic status, and current social and physical activity. Frequent cognitive activity during old age was also associated with reduced risk of mild cognitive impairment.

Wilson, R.S., Scherr, P.A., Schneider, J.A., Tang, Y. & Bennett, D.A. 2007. The relation of cognitive activity to risk of developing Alzheimer’s disease. Neurology, published online ahead of print June 27

Enhanced environment restores memory in mice with neurodegeneration

Research involving genetically engineered mice has found that mice whose brains had lost a large number of neurons due to neurodegeneration regained long-term memories and the ability to learn after their surroundings were enriched with toys and other sensory stimuli. The same effect was also achieved through the use of a drug that encourages neuronal growth. The findings suggest not only new approaches to treatment for those with Alzheimer's or other neurodegenerative diseases, but also supports recent suggestions that "memory loss" may be an inaccurate description of the kinds of mental deficits associated with neurodegenerative diseases. The memories are still there; they are simply inaccessible.

Fischer, A., Sananbenesi, F., Wang, X., Dobbin, M. & Tsai, L-H. 2007. Recovery of learning and memory is associated with chromatin remodelling. Nature, 447, 178-182.

Learning slows physical progression of Alzheimer's disease

A mouse study has found that short but repeated learning sessions can slow the development of two brain lesions that are the hallmarks of Alzheimer's disease —beta amyloid plaques, and tau tangles. The researchers are now investigating whether more frequent and vigorous learning will have bigger and longer benefits.

Billings, L.M., Green, K.N., McGaugh, J.L. & LaFerla, F.M. 2007. Learning Decreases Aß*56 and Tau Pathology and Ameliorates Behavioral Decline in 3xTg-AD Mice. Journal of Neuroscience, 27, 751-761.

How mental and physical stimulation slows Alzheimer's

A new study reveals how mental and physical activity slows the cognitive decline seen in Alzheimer’s. In the study, genetically engineered mice were housed in either standard cages or ones with access to an enriched environment. After five months, the mice housed in the enriched environment had fewer Ab plaques, smaller plaque size, and reduced amyloid angiopathy compared to mice housed in standard cages. However there were no differences in the levels of soluble Ab peptide or the expression levels of its precursor protein (APP). Further investigation revealed differences suggesting that an enriched environment elicits protection via pathways that prevent Ab accumulation and enhance its clearance. The data confirm that an environment rich in mental and physical stimulation slows the progression of Alzheimer-like brain pathology.

Ambrée, O. et al. 2006. Reduction of amyloid angiopathy and A² plaque burden after enriched housing in TgCRND8 mice: involvement of multiple pathways. American Journal of Pathology, 169, 544-552.

Social networks protect against Alzheimer's

Previous studies have found that older people with more extensive social networks are less likely to suffer cognitive impairment. Now a new study provides evidence that social networks, like education, offers a 'protective reserve' capacity that spares them the clinical manifestations of Alzheimer's disease. 89 elderly people without known dementia participating in the Rush Memory and Aging Project underwent annual clinical evaluation and cognitive tests. To determine social network, participants were asked about the number of children they have and see monthly; about the number of relatives, excluding spouse and children, and friends to whom they feel close and with whom they felt at ease and could talk to about private matters and could call upon for help, and how many of these people they see monthly. Their social network was the number of these individuals seen at least once per month. Brain autopsy was done at the time of death. It was found that, as the size of the social network increased, the same amount of Alzheimer’s pathology in the brain (i.e., extent of plaques and tangles) had less effect on cognitive test scores. In other words, for persons without much pathology, social network size had little effect on cognition. However, as the amount of pathology increased, the apparent protective effect on cognition also increased.

Bennett, D.A., Schneider,J.A., Tang,Y., Arnold,S.E. & Wilson,R.S. 2006. The effect of social networks on the relation between Alzheimer's disease pathology and level of cognitive function in old people: a longitudinal cohort study. Lancet Neurology,5, 406-412.

Use your brain, halve your risk of dementia

In the first comprehensive review of the research into 'cognitive reserve', which looks at the role of education, occupational complexity and mentally stimulating activities in preventing cognitive decline, researchers concluded that complex mental activity across people’s lives almost halves the risk of dementia. All the studies also agreed that it was never too late to build cognitive reserve. The review covered 29,000 individuals across 22 studies.

Valenzuela, M.J. & Sachdev, P. 2006. Brain reserve and dementia: a systematic review. Psychological Medicine, In press

Enriched environment delays onset of Alzheimer's in mice

A study of genetically engineered mice has found that an enriched environment, with more opportunities to exercise, explore and interact with others, can dramatically reduce levels of beta-amyloid peptides, hallmarks of Alzheimer's disease. The mice also showed greater activity for several genes involved in memory and learning, the growth of new nerve cells, cell survival, and the growth of new blood vessels within the brain. As with humans, mice in the enriched environment showed varying levels of activity. The most active were found to have the least beta-amyloid. Researchers suggested the reason may simply be a matter of blood flow; physical and mental activity can stimulate growth of new blood vessels and keep existing vessels open and functional.

Lazarov, al. 2005. Environmental Enrichment Reduces Aβ Levels and Amyloid Deposition in Transgenic Mice. Cell, 120(5), 701-713.

More evidence that mental exercise helps prevent or postpone dementia

Another study provides support for the idea that mentally demanding activities can help stave off dementia. The study involved 469 people aged 75 and older. Over the course of the study, dementia developed in 124 of the participants (Alzheimer's disease in 61, vascular dementia in 30, mixed dementia in 25, and other types of dementia in 8). Those who participated at least twice weekly in reading, playing games (chess, checkers, backgammon or cards), playing musical instruments, and dancing were significantly less likely to develop dementia. Although the evidence on crossword puzzles was not quite statistically significant, those who did crossword puzzles four days a week had a much lower risk of dementia than those who did one puzzle a week. Most physical activities, like group exercise or team games, had no significant impact. The only exception - ballroom dancing - possibly occurred because of the mental demands of remembering dance steps, responding to music and coordinating with a partner. Although the study was careful to include only those who showed no signs of dementia at the start, it cannot be ruled out that people in very early, pre-clinical stages of dementia may be less likely to participate in mentally demanding activities.

Verghese, J., Lipton, R.B., Hall, C.B., Kuslansky, G. & Katz, M.J. 2003. Low blood pressure and the risk of dementia in very old individuals. Neurology, 61, 1667-1672.

Mentally stimulating activities may reduce Alzheimer's risk

A study of 700 seniors over several years found that more frequent participation in cognitively stimulating activities, such as reading books, newspapers or magazines, engaging in crosswords or card games, was significantly associated with a reduced risk of Alzheimer’s disease (AD). Over the period, 111 participants developed AD. In comparing levels of cognitive activity with the risk of developing AD, it was found that a one-point increase in cognitive activity (on a 5-point scale) corresponded with a 33% reduction in the risk of AD. On average, compared with someone with the lowest activity level, the risk of disease was 47% lower for those whose frequency of activity was highest. General cognitive decline was also less among people who did more cognitively stimulating activities.

Wilson, R.S., de Leon, C.F.M., Barnes, L.L., Schneider, J.S., Bienias, J.L., Evans, D.A. & Bennett, D.A. 2002. Participation in Cognitively Stimulating Activities and Risk of Incident Alzheimer Disease. JAMA, 287,742-748.

Education & IQ

Language skills in your 20s may predict risk of dementia decades later

Confirming earlier indications, autopsies of the brains of 38 Catholic nuns in the Nun Study has found that those who had no memory problems, whether or not their brains showed Alzheimer’s disease hallmarks, had higher early language scores compared to those who showed symptoms of Alzheimer’s or mild cognitive impairment. Early language was assessed in terms of the number of ideas produced every 10 words in the essays they wrote in their late teens or early 20s when they entered the Order. There was no effect in terms of grammatical complexity. Those with Alzheimer's disease hallmarks and no memory problems also had enlarged neurons in the CA1 region of the hippocampus.

Iacono, D. et al. 2009. The Nun Study. Clinically silent AD, neuronal hypertrophy, and linguistic skills in early life. Neurology, first published on July 8, 2009 as doi: doi:10.1212/WNL.0b013e3181b01077

Education may not affect how fast you will lose your memory

A study involving some 6,500 older Chicago residents being interviewed 3-yearly for up to 14 years (average 6.5 years), has found that while at the beginning of the study, those with more education had better memory and thinking skills than those with less education, education was not related to how rapidly these skills declined during the course of the study. The result suggests that the benefit of more education in reducing dementia risk results simply from the difference in level of cognitive function.

Wilson, R.S., Hebert, L.E., Scherr, P.A., Barnes, L.L., de Leon, C.F.M. & Evans, D.A. 2009. Educational attainment and cognitive decline in old age. Neurology, 72, 460-465.

Education protects against pre-Alzheimer's memory loss

Another study has come out supporting the view that people with more education and more mentally demanding occupations may have protection against the memory loss that precedes Alzheimer's disease, providing more evidence for the idea of cognitive reserve. The 14-month study followed 242 people with Alzheimer's disease, 72 people with mild cognitive impairment, and 144 people with no memory problems. During the study period, 21 of the people with MCI developed Alzheimer's. The metabolic changes in those with MCI who developed Alzheimer’s indicate the cognitive reserve is already in play in the pre-dementia stage.

Garibotto, V. et al. 2008. Education and occupation as proxies for reserve in aMCI converters and AD: FDG-PET evidence. Neurology, 71, 1342-1349.

Connection between Alzheimer's, education & head size

Earlier findings from the Nun Study have found associations with smaller head size and Alzheimer’s disease, and lower educational achievement and Alzheimer’s disease. The latest analysis clarifies these associations. It appears that a smaller head size is associated with lower educational achievement only in those who carry the “Alzheimer’s” APOE-4 gene, and those who later developed Alzheimer’s or Alzheimer’s pathology.

Mortimer, J,A., Snowdon, D.A.  & Markesbery, W.R. 2008. Small Head Circumference is Associated With Less Education in Persons at Risk for Alzheimer Disease in Later Life. Alzheimer Disease & Associated Disorders, 22(3), 249-254.

Low childhood IQ linked to vascular dementia

A study of 173 people from the Scottish Mental Survey of 1932 who have developed dementia has found that, compared to matched controls, those with vascular dementia were 40% more likely to have low IQ scores when they were children than the people who did not develop dementia. This difference was not true for those with Alzheimer's disease. The findings suggest that low childhood IQ may act as a risk factor for vascular dementia through vascular risks rather than the "cognitive reserve" theory.

McGurn, B., Deary, I.J. & Starr, J.M. 2008. Childhood cognitive ability and risk of late-onset Alzheimer and vascular dementia. Neurology, first published on June 25, 2008 as doi: doi:10.1212/01.wnl.0000319692.20283.10

Effect of cognitive reserve on dementia confirmed

Another study has come out confirming that people with more years of education begin to lose their memory later than those with less education, but decline faster once it begins. Researchers note that since the participants were born between 1894 and 1908, their life experiences and education may not represent that of people entering the study age range today.

Hall, C.B., Derby, C., LeValley, A., Katz, M.J., Verghese, J. & Lipton, R.B. 2007. Education delays accelerated decline on a memory test in persons who develop dementia. Neurology, 69, 1657-1664.

Not finishing high school may lead to memory problems

A long-running Finnish study has found that compared with people with five or less years of education, those with six to eight years had a 40% lower risk of developing dementia and those with nine or more years had an 80% lower risk. Generally speaking, people with low education levels seemed to lead unhealthier lifestyles, but the association remained after lifestyle choices and characteristics such as income, occupation, physical activity and smoking had been taken into account.

Ngandu, T. et al. 2007. Education and dementia: What lies behind the association? Neurology, 69, 1442-1450.

Brain network associated with cognitive reserve identified

An imaging study involving young (18-30) and older (65-80) adults has identified a brain network within the frontal lobe that is associated with cognitive reserve, the process that allows individuals to resist cognitive decline due to aging or Alzheimer’s disease. Those with higher levels of cognitive reserve were able to activate this network in the brain while working on more difficult tasks, while participants with lower levels of reserve were not able to tap into this particular network. The network was found more often in younger participants, suggesting the network may degrade during aging.

Stern, Y. et al. 2007. A Common Neural Network for Cognitive Reserve in Verbal and Object Working Memory in Young but not Old. Cerebral Cortex, Advance Access published on August 3, 2007

Bilingualism has protective effect in delaying onset of dementia

An analysis of 184 people with dementia (132 were diagnosed with Alzheimer’s; the remaining 52 with other dementias) found that the mean age of onset of dementia symptoms in the 91 monolingual patients was 71.4 years, while for the 93 bilingual patients it was 75.5 years — a very significant difference. This difference remained even after considering the possible effect of cultural differences, immigration, formal education, employment and even gender as influencers in the results.

Bialystok, E., Craik, F.I.M. & Freedman, M. 2007. Bilingualism as a protection against the onset of symptoms of dementia. Neuropsychologia, 45 (2), 459-464.

Alzheimer's progresses more rapidly in highly educated people

A study of 312 New Yorkers aged 65 and older, who were diagnosed with Alzheimer's disease and monitored for over 5 years, found that overall mental agility declined faster for each additional year of education, particularly in the speed of thought processes and memory, and was independent of age, mental ability at diagnosis, or other factors likely to affect brain function, such as depression and vascular disease. It’s suggested this may reflect the greater ability of brains with a higher cognitive reserve to tolerate damage, meaning the damage is greater by the time it becomes observable in behavior. The finding confirms earlier findings from some epidemiological studies.

Scarmeas, N., Albert, S.M., Manly, J.J. & Stern, Y. 2006. Education and rates of cognitive decline in incident Alzheimer’s disease. Journal of Neurology Neurosurgery and Psychiatry, 77, 308-316.

Study links adolescent IQ/activity levels with risk of dementia

An analysis of high school records and yearbooks from the mid-1940s, and interviews with some 400 of these graduates, now in their 70s, and their family members, has found that those who were more active in high school and who had higher IQ scores, were less likely to have mild memory and thinking problems and dementia as older adults.

Fritsch, T., Smyth, K.A., McClendon, M.J., Ogrocki, P.K., Santillan, C., Larsen, J.D. & Strauss, M.E. 2005. Associations Between Dementia/Mild Cognitive Impairment and Cognitive Performance and Activity Levels in Youth. Journal of the American Geriatrics Society, 53(7), 1191.

Higher education or larger brain size may protect against dementia

More findings from the Nun Study, a longitudinal study of aging and Alzheimer's disease. It was found that nuns who completed 16 or more years of formal education or whose head circumference was in the upper two-thirds were four times less likely to be demented than those with both smaller head circumferences and lower education. (Head circumference is a good indicator of the volume or size of the brain.) It was not that these nuns were less likely to have the brain abnormalities characteristic of Alzheimer's disease, but that the larger brain size and more education provided extra reserve, allowing them to function normally in the presence of such brain abnormalities.

Mortimer, J.A., Snowdon, D.A. & Markesbery, W.R. 2003. Head Circumference, Education and Risk of Dementia: Findings from the Nun Study. Journal of Clinical and Experimental Neuropsychology, 25 (5), 671-679.

Effects of Alzheimer's disease may be influenced by education

New findings from the Religious Orders Study (ROS), a long-running prospective study of aging and cognitive function in Catholic clergy, provides evidence that formal education may provide a cognitive reserve or a "neuroplasticity" that can reduce the effect of AD brain abnormalities on cognitive function in later life. A post-mortem study of the brains of 130 participants who had all undergone cognitive testing some months before death, found that the relationship between cognitive performance and the number of amyloid plaques in the brain (characteristic of Alzheimer’s) changed with level of formal education. The more years education you had, the less effect the same number of plaques had on actual cognitive performance. For example, an 84-year-old woman in the most highly educated group (postgraduate work after college) might score 98.1 (on a scale where the average participant scores 100) in the absence of any plaques. The same age woman with the least education (some college attendance) would score 96.8. In the presence of about 18 plaques (more than the number required for a diagnosis of Alzheimer’s), the more highly educated woman's score would drop about two points, to 96.2, while the score of the woman with less formal education would drop more than 14 points, to 82. It’s worth noting that this considerable difference was observed in a population where even the least educated had some college attendance; presumably the difference would be even more marked in the general population.

Bennett, D.A., Wilson, R.S., Schneider, J.A., Evans, D.A., de Leon, M.C.F., Arnold, S.E., Barnes, L.L. & Bienias, J.L. 2003. Education modifies the relation of AD pathology to level of cognitive function in older persons. Neurology, 60, 1909-1915.

Early language ability may be linked to lower risk of Alzheimer's

The " Nun Study" has followed 678 Catholic nuns from 7 convents of the School Sisters of Notre Dame for 15 years. The stability and similarity of their lives makes them wonderful subjects, and the duration of the project means that it began when many were too young to manifest Alzheimer's or other diseases related to aging. Particularly helpful in this regard is that the sisters were required to write autobiographical essays when they took their vows in their 20's.
The research has shown that folic acid may help stave off Alzheimer's disease; that small, barely perceptible strokes may trigger some dementia; and, in an especially striking finding, that early language ability may be linked to lower risk of Alzheimer's because nuns who packed more ideas into the sentences of their early autobiographies were less likely to get Alzheimer's disease six decades later.
The latest report says nuns who expressed more positive emotions in their autobiographies lived significantly longer — in some cases 10 years longer — than those expressing fewer positive emotions.

The report was published in the Journal of Personality and Social Psychology.

Alzheimer's & Hypertension

See also


Older news items (pre-2010) brought over from the old website

Why sufferers from Alzheimer's disease might have lower blood pressure

A review of studies relating to dementia and blood pressure suggests that rather than low blood pressure being a causative factor for cognitive impairment, it is the failing memory that reduces blood pressure — by allowing the patient to forget the anxieties that cause stress. If confirmed, the finding also suggests that heart disease could be substantially reduced in old people simply by making them happier about themselves and their lives.

Sven, K. et al. 2008. Is sympathetic activation by stressful memories linked to the occurrence of hypertension and metabolic syndrome? Bioscience Hypotheses, 1 (4), 179-184.
Full text available at

High blood pressure or irregular heartbeat linked to Alzheimer's disease progression

A study of 135 men and women newly diagnosed with Alzheimer’s found that those with high blood pressure at the time of diagnosis showed a rate of memory loss roughly 100% faster than those with normal blood pressure, and those with atrial fibrillation (an irregular heartbeat) showed a rate of memory decline that was 75% faster than those with normal heartbeats. The findings suggest that treating these conditions may also slow memory loss in Alzheimer’s sufferers.

Mielke, M.M. et al. 2007. Vascular factors predict rate of progression in Alzheimer disease. Neurology, 69, 1850-1858

Low blood pressure risk factor for Alzheimer's

A long-term study of 488 adults over 75 (the Bronx Aging Study) found that 122 participants developed dementia (65 Alzheimer’s, 28 vascular dementia, 29 other), and that the relative risk of dementia increased as a function of decreases in blood pressure (diastolic and mean arterial). Low diastolic BP significantly increased the risk of developing Alzheimer’s, but not vascular dementia. Those with mildly to moderately raised systolic BP had a reduced risk of developing Alzheimer’s. The risk of developing dementia was higher in those who had persistently low BP over 2 years.

Verghese, J., Lipton, R.B., Hall, C.B., Kuslansky, G. & Katz, M.J. 2003. Low blood pressure and the risk of dementia in very old individuals. Neurology, 61, 1667-1672.

High blood pressure and cholesterol are risk factors for Alzheimer's disease

A large-scale Finnish study following 1449 men and women over 21 years found that raised systolic blood pressure and high serum cholesterol concentration, particularly in combination, in midlife, increase the risk of Alzheimer's disease in later life. Raised diastolic blood pressure had no significant effect.

The study was reported in the British Medical Journal.

Alzheimer's & Depression

Depression, stress, & distress as risk factors for Alzheimer's

See also

Depression (as a factor in general cognitive & memory problems)

Older news items (pre-2010) brought over from the old website

Apathy common in dementia patients with white matter changes

A study involving 176 patients with Alzheimer's, vascular dementia or mixed dementia, or mild cognitive impairment, has found that 82% of the patients with changes in their white matter were apathetic, compared to an overall rate of 58%. This discovery suggests that there is a common biological reason behind this apathy, irrespective of which type of dementia a patient has. White matter changes were also associated with age, gender, blood pressure, hypertension, ischaemic heart disease, mental slowness, disinhibition, gait disturbance and focal neurologic symptoms. Apathy, mental slowness and age were the most consistent predicting factors for WMCs.

Jonsson, M., Edman, Å., Lind, K., Rolstad, S., Sjögren, M., & Wallin, A. (2009). Apathy is a prominent neuropsychiatric feature of radiological white-matter changes in patients with dementia. International Journal of Geriatric Psychiatry, 9999(9999), n/a. doi: 10.1002/gps.2379.

Depression may increase risk of Alzheimer's disease in people with memory problems

A three-year study involving 756 people with mild cognitive impairment found increases in depressive symptoms was positively associated with increased risk in developing Alzheimer’s. The study also found that, for those who were depressed, taking the Alzheimer’s drug donepezil significantly reduced the risk of developing Alzheimer’s, compared to those taking vitamin E or placebo. Donepezil had little effect on those who were not depressed.

Lu, P.H. et al. 2009. Donepezil delays progression to AD in MCI subjects with depressive symptoms. Neurology, 72, 2115-2121.

Being social and not easily stressed reduces dementia risk

A six-year Swedish study involving 506 older people who did not have dementia when first examined has found that those who scored high in extraversion and low in neuroticism (meaning easily distressed) had the lowest dementia risk. Those people who were not socially active but calm and relaxed had a 50% lower risk of developing dementia compared with people who were isolated and prone to distress. The dementia risk was also 50% lower for people who were outgoing and calm compared to those who were outgoing and prone to distress. However, neither high neuroticism nor low extraversion alone was related to a significantly higher risk of dementia.

Wang, H. -X. et al. 2009. Personality and lifestyle in relation to dementia incidence. Neurology, 72, 253-259.

Depression a risk factor for Alzheimer's disease

Previous studies have found higher levels of depressive symptoms among patients with Alzheimer’s disease or mild cognitive impairment. Now the Religious Orders Study reveals that although those with more symptoms of depression at the beginning of the study (in 1994) were more likely to develop Alzheimer’s disease, those who developed Alzheimer’s disease showed no increase in depressive symptoms in the years before the diagnosis was made. This suggests that depression is a risk factor for dementia rather than a consequence.

Wilson, R.S., Arnold, S.E., Beck, T.L., Bienias, J.L. & Bennett, D.A. 2008. Change in Depressive Symptoms During the Prodromal Phase of Alzheimer Disease. Archives of General Psychiatry, 65(4), 439-445.

High stress and genetic risk factor lead to increased memory decline

A study involving 91 older, healthy subjects (mean age 78.8 years) has found that those low on stress (low levels in cortisol) or without the APOE-ε4 gene performed better on memory measures than those with high stress or those with the APOE-ε4 gene. Those who had the gene and had high stress levels showed the greatest memory impairment.

Peavy, G.M. et al. 2007. The Effects of Prolonged Stress and APOE Genotype on Memory and Cortisol in Older Adults. Biological Psychiatry, 62 (5), 472-478.

Distress-prone people more likely to develop memory problems

Data from two large, long-running studies, the Religious Orders Study and the Memory and Aging Project, has revealed that those who most often experience negative emotions such as depression and anxiety (according to self report) were 40% more likely to develop mild cognitive impairment than those who were least prone to negative emotions. This follows on from an earlier study showing that people who are easily distressed are more likely to develop Alzheimer’s disease than more easygoing people.

Wilson, R.S., Schneider, J.A., Boyle, P.A., Arnold, S.E., Tang, Y. & Bennett, D.A. 2007. Chronic distress and incidence of mild cognitive impairment. Neurology, 68, 2085-2092.

Loneliness increases risk of Alzheimer's disease

Social isolation has been linked with an increased risk of dementia and cognitive decline, but perceived isolation — feeling alone rather than being alone — hasn’t been investigated. A new four-year study of 823 older adults provides evidence that loneliness is a risk factor for Alzheimer’s. 76 individuals developed Alzheimer’s over the course of the study, and the risk of developing it increased around 51% for each point on the 5-point loneliness score. The findings did not change significantly when the researchers factored in markers of social isolations, such as a small network and infrequent social activities. Autopsies performed on 90 individuals who died during the study show that loneliness is a risk factor rather than an early sign of the disease.

Wilson, R.S., Krueger, K.R., Arnold, S.E., Schneider, J.A., Kelly, J.F., Barnes, L.L., Tang, Y. & Bennett, D.A. 2007. Loneliness and Risk of Alzheimer Disease. Archives of General Psychiatry, 64, 234-240.

Depression associated with changes in the brain in Alzheimer's

A lifetime history of depression is associated with increased plaques and tangles in the brains of those with Alzheimer's disease and more rapid cognitive decline, confirming previous indications that depression may be a risk factor for Alzheimer’s.

Rapp, M.A. et al. 2006. Increased Hippocampal Plaques and Tangles in Patients With Alzheimer Disease With a Lifetime History of Major Depression. Archives of General Psychiatry, 63,161-167.

Distress-prone people more likely to develop Alzheimer's disease

The Religious Orders Study has found that those who most often experience negative emotions like depression and anxiety were twice as likely to develop Alzheimer's disease as those who were least prone to experience negative emotions. A person’s tendency to experience psychological distress has been shown to be a stable personality trait throughout adulthood. Proneness to stress was specifically associated with a decline in episodic memory (measured by asking participants to recall a list of words or a story) — an area particularly problematic for those with Alzheimer's. Episodic memory ability declined 10 times faster in those high in proneness to distress than in those low in this response. This result was not altered when participants’ engagement in cognitively stimulating activities. Examination of the brains of those who have died during the long-term study appears to rule out the possibility that proneness to distress is an early sign of Alzheimer's disease rather than a risk factor, although more research is needed to confirm this.

Wilson, R.S., Evans, D.A., Bienias, J.L., Mendes de Leon, C.F., Schneider, J.A. & Bennett, D.A. 2003. Proneness to psychological distress is associated with risk of Alzheimer’s disease. Neurology, 61, 1479-1485.

Study points to depression as a risk for developing Alzheimer's disease

More than 650 elderly people took part in a seven-year study which has revealed that those with the greatest number of depressive symptoms at the start of the study were more likely to develop Alzheimer's disease and also showed more rapid cognitive decline.

Wilson, R.S., Barnes, L.L., de Leon, C.F.M., Aggarwal, N.T., Schneider, J.S., Bach, J., Pilat, J., Beckett, L.A., Arnold, S.E., Evans, D.A. & Bennett, D.A. 2002. Depressive symptoms, cognitive decline, and risk of AD in older persons. Neurology, 59, 364-370.

Risk Factors

Older news items (pre-2010) brought over from the old website

High protein diet shrinks brain in Alzheimer’s mice

A study using genetically engineered mice has tested the effects of four diets for their effects on Alzheimer’s pathology: a regular diet, a high fat/low carbohydrate custom diet, a high protein/low carb version, or a high carbohydrate/low fat option. Unexpectedly, mice fed the high protein/low carbohydrate diet had brains 5% lighter that all the others, and regions of their hippocampus were less developed. Mice on the high fat diet had higher levels of amyloid-beta protein, although no effect on plaque burden was detected.

Franciosi, S., Gama Sosa, M., English, D., Oler, E., Oung, T., Janssen, W., et al. (2009). Novel cerebrovascular pathology in mice fed a high cholesterol diet. Molecular Neurodegeneration, 4(1), 42. doi: 10.1186/1750-1326-4-42. Full text available at

Infections may lead to faster memory loss in Alzheimer's disease

A 6-month study involving 222 people with Alzheimer's disease (average age 83) has found that people who had infections or even bumps and bruises from a fall were more likely to have high blood levels of tumor necrosis factor-α, a protein involved in the inflammatory process, and were also more likely to experience memory loss or cognitive decline than people who did not have infections and who had low levels of the protein. Nearly half the participants experienced an infection or injury that led to inflammation during the study, and they experienced memory loss that was at twice the rate of those who did not have infections or injuries. Those with high levels of the protein in their blood at the beginning of the study had memory loss at four times the rate of those with low levels of the protein at the start of the study, and those with high levels who also experienced acute infections during the study had memory loss at 10 times the rate of those who started with low levels and had no infections over the six-month period.

Holmes, C. et al. 2009. Systemic inflammation and disease progression in Alzheimer disease. Neurology, 73, 768-774.

Poor sleep linked to later development of Alzheimer's

A mouse study has found that amyloid-beta significantly increases during periods of sleep deprivation. The discovery follows observation that peptide levels in both mice and humans increase significantly during the day and drop at night. When mice were only allowed to sleep four hours a day for 21 days, they had higher amyloid-beta plaque build-up in their brain than similar-aged mice with regular sleeping habits. The circadian fluctuation was found to reflect the activity of orexin, a hormone that regulates wakefulness. The findings suggest insomnia, late-night habits, and irregular sleep schedules during mid-life may be linked to the later development of Alzheimer's disease.

Kang, J-E. et al. 2009. Amyloid- Dynamics Are Regulated by Orexin and the Sleep-Wake Cycle. Science, Published Online September 24 
Alzheimers linked to lack of Zzzzs

Greater dementia risk in former N.F.L. players

A study commissioned by the National Football League reports that Alzheimer’s disease or similar memory-related diseases appear to have been diagnosed in the league’s former players vastly more often than in the national population: five times the national average among those 50 and older (6.1%)and 19 times for those aged 30 through 49. The findings are consistent with several recent studies regarding N.F.L. players and the effects of their occupational head injuries. The study involved a phone survey of 1,063 retired players (from an original random list of 1,625), who were asked questions derived from the standard National Health Interview Survey. Some health issues were reported at higher than the population rate (sleep apnea and elevated cholesterol — both risk factors for cognitive problems).

Oxygen treatment hastens memory loss in Alzheimer's mice

A study using genetically engineered mice has found that young adult Alzheimer's mice exposed to 100% oxygen during several 3-hour sessions demonstrated substantial memory loss, while those exposed to normal air had no measurable memory loss, and neither did normal mice without any genetic predisposition for Alzheimer's disease. The results suggest that people genetically predisposed to Alzheimer's disease or with excessive amounts of beta amyloid in their brains are at increased risk of developing the disease earlier if they receive high concentrations of oxygen, for example during or after surgery. The findings may help explain why some elderly patients develop memory loss after major surgery.

Arendash, G.W. et al. 2009. Oxygen treatment triggers cognitive impairment in Alzheimer's transgenic mice. NeuroReport, 20 (12), 1087-1092.

Delirium rapidly accelerates memory decline in Alzheimer's patients

A new analysis of data spanning 15 years and involving 408 Alzheimer’s patients, has revealed that among those 72 patients who developed delirium at some point, the average decline on cognitive tests was 2.5 points per year before the episode of delirium, and 4.9 points per year after. Across groups, the rate of decline was about three times faster in those who had delirium compared to those who did not. Delirium often develops in elderly patients following a medical disturbance, surgery or infection, but it is preventable in up to 40% of cases.

Fong, T.G. et al. 2009. Delirium accelerates cognitive decline in Alzheimer disease. Neurology, 72, 1570-1575.

Connection between heart disorder and Alzheimer's

A very large study, involving over 37,000 patients, has found that those with atrial fibrillation, regardless of age, were 44% more likely to develop dementia, and those younger than 70 were 130% more likely to develop Alzheimer's. Previous studies have shown a connection between atrial fibrillation and vascular dementia. Atrial fibrillation is the most common heart rhythm problem, and has a strong genetic link. It is also a risk factor for stroke.

The findings were presented Friday, May 15, at "Heart Rhythm 2009," the annual scientific sessions of the Heart Rhythm Society in Boston.

Inflammatory response to infection and injury may worsen dementia

Systemic inflammation – inflammation in the body as a whole – is known to have direct effects on brain function, but there has been little research into the impact of systemic inflammation on the progress of dementia and neurodegenerative diseases. Now, in a study to mimic the effect of bacterial infection in people with dementia, a mouse study has revealed that that the inflammatory response to infection in mice with prior neurodegenerative disease leads to exaggerated symptoms of the infection, causes changes in memory and learning and leads to accelerated progression of dementia.

Cunningham, C. et al. In press. Systemic Inflammation Induces Acute Behavioral and Cognitive Changes and Accelerates Neurodegenerative Disease. Biological Psychiatry

Physical frailty may be linked to Alzheimer's disease

Autopsies of the brains of 165 people who had been participants in a larger community study of chronic diseases of aging has revealed that Alzheimer's disease pathology (plaques and tangles) was associated with physical frailty in older persons regardless of whether they had dementia. The level of frailty was approximately twice as high in a person with a high level of Alzheimer’s pathology, and this was true regardless of medical history or level of physical activity. These findings raise the possibility that Alzheimer's disease may contribute to frailty or that frailty and Alzheimer's disease share a common cause. Studies show that about 7% of people over age 65 are considered frail; 45% after age 85.

Buchman, A.S., Schneider, J.A., Leurgans, S. & Bennett, D.A. 2008. Physical frailty in older persons is associated with Alzheimer disease pathology. Neurology, 71, 499-504.

Thyrotropin levels associated with Alzheimer's risk in women

A clinically detectable over- or under-active thyroid has long been recognized as a potentially reversible cause of cognitive impairment. Now a large long-running study of thyrotropin (a hormone secreted by the pituitary gland that helps regulate thyroid gland function) levels has found that women with the lowest and highest levels of thyrotropin had more than double the risk of developing Alzheimer's disease. No relationship was observed between thyrotropin levels and Alzheimer's disease risk in men.

Tan, Z.S. et al. 2008. Thyroid Function and the Risk of Alzheimer Disease: The Framingham Study. Archives of Internal Medicine, 168(14), 1514-1520.

Short arms and legs linked to risk of dementia

Several studies have shown that early life environment plays an important role in susceptibility to chronic disease later in life. Data from the Cardiovascular Health Cognition Study (involving 2,798 people for an average of five years) has now found that women with the shortest arm spans were 1.5 times more likely to develop dementia and Alzheimer’s disease than women with longer arm spans. For every inch longer a woman’s leg, the risk of dementia and Alzheimer’s disease was reduced by 16%. In men, only arm span was associated with a lower risk of dementia. With every increased inch in arm span, men had a 6% decrease in risk of dementia. The association between short limbs and dementia risk may be due to poor nutrition in early life, which can affect limb growth (which implies that there should be no such connection if your short limbs are due to genetics).

Szekely, C.A. et al. 2008. No advantage of Aβ42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies. Neurology, 70, 2291-2298.

Inhaled anesthetics might increase the risk of Alzheimer's

A study using a new imaging technique has been able to see why anesthetics might cause amyloid β peptides to clump together, and whether one method of anesthesia was better than another. Previous studies have found that the inhaled anesthetics halothane and isoflurane and the intravenous anesthetic propofol encouraged the growth and clumping of Aβ in a test tube experiment. The new study found that the inhaled anesthetics caused the highest levels of Aβ aggregation, while the injected anesthetic propofol only interacted and caused aggregation at high concentrations, and thiopental did not cause the clustering of Aβ peptides even at high concentrations.

Mandal, P.K., Williams, J.P. & Mandal, R. 2007. Molecular Understanding of Aβ Peptide Interaction with Isoflurane, Propofol, and Thiopental: NMR Spectroscopic Study. Biochemistry, 46 (3), 762 –771.

Anesthetics a risk factor for Alzheimer’s?

The link between surgery and cognitive problems has long been noted, but it’s never been clear whether postoperative cognitive dysfunction was the result of the surgery itself or the anaesthetics. Now animal studies and test tube experiments are beginning to show that certain anaesthetics reduce the rate at which brain cells are born and develop. The latest study reveals that the inhaled anaesthetics halothane and isoflurane encourage clumping of beta amyloid protein, as does the commonly used intravenous anaesthetic propofol, at least at higher concentrations — suggesting that giving elderly patients certain general anaesthetics could increase their risk of developing Alzheimer's disease. The intravenous anaesthetic thiopental appears to have no effect on the proteins.

The study was presented at the annual Society for Neuroscience Meeting held in Atlanta, Georgia, October 14-18.

Brain activity, drugs could affect Alzheimer's progression

Mouse studies have revealed that the activity of connections among brain cells significantly affects levels of the toxic protein beta-amyloid, suggesting that the kind of mental activity people practice or drugs they might take fo affect their risk of Alzheimer’s or the disease progression. The researchers suggest that enriched environments may increase overall synaptic activity in some brain regions and decrease it in others. Increased activity in some brain regions might result in increased susceptibility to beta-amyloid deposition if the activated neural circuits contain high levels of human APP expression. Drugs used to treat neuropsychiatric disorders directly influence neurotransmitters, and their receptors, thereby altering synaptic activity.

Cirrito, J.R. et al. 2005. Synaptic Activity Regulates Interstitial Fluid Amyloid-b Levels In Vivo. Neuron, 48, 913–922.

New research suggests heart bypass surgery increases risk of Alzheimer's disease

Patients who have either coronary artery bypass graft surgery or coronary angioplasty are at an increased risk of developing Alzheimer's disease, according to a study involving 5,216 people who underwent coronary artery bypass graft surgery (CABG) and 3,954 people who had a percutaneous transluminal coronary angioplasty (PTCA) in 1996 and 1997. The researchers suggest the trauma to the brain during surgery is the principle cause.

Lee, T.A., Wolozin, B., Weiss, K.B. & Bednar, M.M. 2005. Assessment of the Emergence of Alzheimer's Disease Following Coronary Artery Bypass Graft Surgery or Percutaneous Transluminal Coronary Angioplasty. Journal of Alzheimer's Disease, 7 (4), 319-324.

Testosterone loss may lead to Alzheimer's

A new study suggests that, like estrogen loss in older women, decreased levels of testosterone may put aging men at risk for Alzheimer's disease. The research suggests that testosterone both protects neurons from injury, and reduces levels of beta-amyloid.

Rosario, E.R., Chang, L., Stanczyk, F.Z. & Pike, C.J. 2004. Age-Related Testosterone Depletion and the Development of Alzheimer Disease. JAMA, 292, 1431-1432.

Coronary artery bypass surgery not a risk factor for dementia

A comparison of dementia patients with controls has found that dementia patients are no more likely than those without dementia to have had coronary artery bypass surgery.

Minorities hardest hit by Alzheimer's disease

A study of 119 Latinos and 55 non-Latino white Alzheimer patients suggests that Latinos in the U.S. develop Alzheimer's symptoms much earlier than their white, non-Latino peers. There are several known factors which may be responsible for this apparent vulnerability in Latinos: high rates of vascular disease, leave school earlier, and less likely to use medical services or have health insurance than other Americans.

South Carolina, as the only U.S. state that keeps a comprehensive database of people with a diagnosis of Alzheimer's disease, has found that African Americans aged 55 to 64 years were more than three times as likely to have Alzheimer's as their European American counterparts. At ages 65 to 84, African Americans were more than twice as likely to have Alzheimer's. South Carolina has greater rates of obesity, diabetes, and related health problems than the rest of the country, especially amongst African Americans.

Another study has found that, in order to avoid overestimating the number of African Americans who may have early signs of Alzheimer's disease, screening tests must be adapted to cultural differences. The study involved 635 people over the age of 60. Researchers found that, using current scoring methods, African Americans scored lower on various neuropsychological tests. Even when education was taken into account, 35% of African Americans scored low enough to warrant a diagnosis of MCI, compared to only 15% of European Americans. However, when the researchers applied new, racially sensitive scoring methods they've developed, the difference in MCI rates disappeared.

Reported at The 9th International Conference on Alzheimer's Disease and Related Disorders (ICAD), July 17-22, at the Pennsylvania Convention Center in Philadelphia, Pennsylvania:

Christopher Clark – Latino Patients with AD Have An Earlier Age of Symptoms Onset Compared to Anglos (P1-041)

James Laditka – Epidemiology of Alzheimer's Disease: Race Effects, Area Variation, and Clustering (P3-132)

Marjorie Marenberg – Racial Differences in Screening of MCI in a Primary Care Population (O4-01-02)

Alzheimer's Association offers information about providing culturally sensitive care at

Low free testosterone levels linked to Alzheimer's disease in older men

A study evaluating the testosterone levels of 574 men, ages 32 to 87, who participated in the Baltimore Longitudinal Study of Aging (BLSA), found that older men with lower levels of free, or unbound, testosterone circulating in their bloodstreams were apparently at higher risk of developing Alzheimer's than their peers. This is believed to be the first study to associate low circulating blood levels of free testosterone with Alzheimer’s years before diagnosis. Previously, the same researchers had found that older men with high levels of circulating free testosterone have better visual and verbal memory and perform spatial tasks more adeptly than their peers.

Moffat, S.D., Zonderman, A.B., Metter, E.J., Kawas, C., Blackman, M.R., Harman, S.M. & Resnick, S.M. 2004. Free testosterone and risk for Alzheimer disease in older men. Neurology, 62, 188-193.

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Alzheimer's & Diabetes

See also



Older news items (pre-2010) brought over from the old website

Does diabetes speed up memory loss in Alzheimer's disease?

A four-year study involving 608 people with mild to moderate Alzheimer's disease, of whom just over 10% (63) had diabetes, has unexpectedly found that memory loss in those without diabetes declined faster than those with diabetes. The researchers speculate that elderly people with diabetes may be more likely to be taking cardiovascular medications (although having vascular factors was controlled for), or there may be some differences in the brain pathology of Alzheimer’s with diabetes compared to Alzheimer’s without diabetes.

Sanz, C., Andrieu, S., Sinclair, A., Hanaire, H., Vellas, B., & For the REAL.FR Study Group. (2009). Diabetes is associated with a slower rate of cognitive decline in Alzheimer disease. Neurology, 73(17), 1359-1366. doi: 10.1212/WNL.0b013e3181bd80e9.

Diabetes, high blood pressure may cause Alzheimer's sufferers to die sooner

A study involving 323 people who had no memory problems when first tested but later developed dementia has found that, after an Alzheimer’s diagnosis, people with diabetes were twice as likely to die sooner than those without diabetes, while those with high blood pressure were two-and-a-half times more like to die sooner than those with normal blood pressure. The average lifespan of a person diagnosed with Alzheimer's is three to nine years.

Helzner, E.P. et al. 2008. Survival in Alzheimer disease: A multiethnic, population-based study of incident cases. Neurology, 71, 1489-1495.

Diabetes in mid-life linked to increased risk of Alzheimer's disease

A large Swedish study involved over 2000 men has found that those with low insulin secretion capacity at age 50 were nearly one-and-a-half times more likely to develop Alzheimer’s disease than people without insulin problems. The risk remained significant regardless of blood pressure, cholesterol, body mass index and education, and was strongest in people who did not have the APOE4 gene.

Rönnemaa, E. et al. 2008. Impaired insulin secretion increases the risk of Alzheimer disease. Neurology, first published on April 9 as doi: doi:10.1212/01.wnl.0000310646.32212.3a

Significant dementia risk attributable to small blood vessel damage

Autopsy data of 221 men and women found that the brains of one-third of individuals who had dementia before death showed evidence of small, cumulative blood vessel damage that can arise from hypertension or diabetes.

The findings were reported at the annual meeting of the American Society for Biochemistry and Molecular Biology, April 5-9, San Diego.

Link between diabetes and Alzheimer's disease

A mouse study has shed light on the connection between diabetes and Alzheimer’s. It appears that the elevated blood glucose levels characteristic of diabetes interacts with beta amyloid in a way damaging to blood vessels in the brain.

Burdo, J.R. et al. 2008. The pathological interaction between diabetes and presymptomatic Alzheimer's disease. Neurobiology of Aging, Available online 26 March 2008

Support for view of Alzheimer's as form of diabetes

Research in the last few years has raised the possibility that Alzheimer’s memory loss could be due to a third form of diabetes. A new study clarifies the connection between insulin and Alzheimer’s. It seems that the toxic protein ADDL, found in the brains of individuals with Alzheimer’s, removes insulin receptors from nerve cells, rendering those neurons insulin resistant. The findings suggest that some existing drugs now used to treat diabetic patients may be useful for Alzheimer’s treatment.

Zhao,W-Q. et al. 2007. Amyloid beta oligomers induce impairment of neuronal insulin receptors. FASEB Journal, published online ahead of print August 24.

Diabetes associated with increased risk of mild cognitive impairment

A study involving 918 individuals older than 65 years (average age 75.9) who did not have mild cognitive disorder or dementia when they enrolled has found that, over some 6 years, diabetes was related to a significantly higher risk of developing amnestic mild cognitive impairment, after controlling for other risk factors. The results support other findings that type 2 diabetes mellitus increases the risk of Alzheimer's.

Luchsinger, J.A. et al. 2007. Relation of Diabetes to Mild Cognitive Impairment. Archives of Neurology, 64, 570-575.

High blood sugar linked to MCI and dementia

The first study to investigate the association over time between blood sugar and the risk of cognitive difficulties involved 1,983 post-menopausal women (mean age 67 years) and found that each 1% increase in their glycosylated hemoglobin level at the start of the four-year study period was associated with a 40% increased risk of developing MCI or dementia four years later. The glycosylated hemoglobin test gives a more stable measure of blood sugar level than the standard test, which measures blood sugar it the time of testing. A result of 7% or less indicates good long-term blood sugar control. Those with a level of 7% or more were four times more likely to develop MCI or dementia than women who tested at less than 7%.

Yaffe, K. et al. 2006. Glycosylated Hemoglobin Level and Development of Mild Cognitive Impairment or Dementia in Older Women. Journal of Nutrition, Health, and Aging, 10 (4)

Reduced insulin in the brain triggers Alzheimer's degeneration

By depleting insulin and its related proteins in the brain, researchers have replicated the progression of Alzheimer's disease – including plaque deposits, neurofibrillary tangles, impaired cognitive functioning, cell loss and overall brain deterioration – in an experimental animal model. Brain deterioration was not related to the pancreas, raising the possibility that Alzheimer's is a neuroendocrine disorder, or a Type 3 diabetes.

Lester-Coll, N. et al. 2006. Intracerebral streptozotocin model of type 3 diabetes: relevance to sporadic Alzheimer’s disease. Journal of Alzheimer’s Disease, 9(1)

Link between insulin and Alzheimer's

A new study has found that insulin and its related proteins are produced in the brain as well as the pancreas, and that reduced levels of these contribute to the degeneration of brain cells, an early symptom of Alzheimer's disease. The finding raises the possibility of a Type 3 diabetes.

de la Monte, S.M. & Wands, J.R. 2005. Review of insulin and insulin-like growth factor expression, signaling, and malfunction in the central nervous system: Relevance to Alzheimer's disease Journal of Alzheimer's Disease, 7(1), 45-61.

Diabetics at significantly higher risk for Alzheimer's disease

New findings from the Religious Orders Study add to research suggesting a link between diabetes mellitus and an increased risk of developing Alzheimer's disease. Some aspects of cognitive function appear to be affected differently than others, in particular perceptual speed declined significantly faster in those with diabetes.

[1296] Arvanitakis, Z., Wilson R. S., Bienias J. L., Evans D. A., & Bennett D. A.
(2004).  Diabetes Mellitus and Risk of Alzheimer Disease and Decline in Cognitive Function.
Arch Neurol. 61(5), 661 - 666.

Insulin-degrading enzyme may affect risk of Alzheimer’s disease

A new mouse study suggests that low levels of insulysin, an enzyme that degrades insulin, could increase the risk for Alzheimer's, and points to a new mechanism linking diseases like diabetes and Alzheimer's — the competition of multiple substrates, such as insulin and amyloid-beta, for a limiting amount of the insulysin enzyme. The insulysin enzyme, it seems, also degrades amyloid-beta peptides, and even a partial decrease in insulysin activity was found to raise amyloid-beta peptide levels in the brain.

[2406] Miller, B. C., Eckman E. A., Sambamurti K., Dobbs N., Chow M. K., Eckman C. B., et al.
(2003).  Amyloid-β peptide levels in brain are inversely correlated with insulysin activity levels in vivo.
Proceedings of the National Academy of Sciences. 100(10), 6221 - 6226.

Poorly controlled diabetes could lead to dementia in the elderly

It now appears that the reason why diabetic people age 60 and older tend to perform more poorly on cognitive tests is because of improper management of their disease. A recent study evaluated the association between diabetes mellitus status and cognitive function in 2,583 adults aged 60 and older, grouping participants according to their diabetic status (poorly controlled diabetes; adequately controlled diabetes; those with impaired glucose tolerance; and a non-diabetic control group). Cognitive ability was measured by a series of simple memory questions. Only those with poorly controlled diabetes performed poorly on the cognitive test.

The researchers presented their findings in April at the American Academy of Neurology conference in Honolulu.


Alzheimer's Prevention

Older news items (pre-2010) brought over from the old website


Olive oil compound may help against Alzheimer's

Oleocanthal, a naturally-occurring compound found in extra-virgin olive oil, has been found to change the size of ADDLs, impeding their ability to bind to synapses — thought to be a crucial first step in Alzheimer’s development. The compound also protected synapses from structural damage caused by ADDLs.

Pitt, J. et al. 2009. Alzheimer's-associated Aβ oligomers show altered structure, immunoreactivity and synaptotoxicity with low doses of oleocanthal. Toxicology and Applied Pharmacology, 240 (2), 189-197.

Alzheimer's-fighting compounds need regular consumption

A rat study has found that the amount of polyphenols from grapeseed extract that can reach the brain is as much as 200% higher on the 10th consecutive day of feeding as compared to the first. The finding points to the value of regular consumption. Polyphenols are thought to prevent the formation of beta-amyloid protein.

Ferruzzi, M.G. et al. 2009. Bioavailability of Gallic Acid and Catechins from Grape Seed Polyphenol Extract is Improved by Repeated Dosing in Rats: Implications for Treatment in Alzheimer’s Disease. Journal of Alzheimer's Disease, 18 (1), 113-124.

Exercise and Mediterranean-type diet associated with lower risk for Alzheimer's

A New York study involving 1880 elderly (average age 77) is the first to investigate both exercise and diet in connection with the later development of Alzheimer’s (within a five and a half year period). Participants were asked about their activity in the two weeks prior to the interview, about the regularity and duration, as well as the quality (vigorous, moderate, light). They were also asked about their food consumption over the previous year, and their responses grouped into nine food categories, the sum of which represented a Mediterranean-type diet score. Those who were very physically active had a 33% risk reduction of Alzheimer's; those who adhered more strongly to a Mediterranean-type diet had a 40% risk reduction. Those who did both had a 60% reduction. A Mediterranean-type diet is typically characterized by high intake of fish, vegetables, legumes, fruits, cereals and monounsaturated fatty acids; relatively low intake of dairy products, meats and saturated fats; and moderate alcohol consumption.

Scarmeas, N. et al. 2009. Physical Activity, Diet, and Risk of Alzheimer Disease. Journal of the American Medical Association, 302(6), 627-637.
Full text available at

Mediterranean diet associated with lower risk of cognitive impairment

A study of 1,393 individuals with no cognitive problems and 482 patients with mild cognitive impairment has found that eating a Mediterranean diet was associated with less risk of developing mild cognitive impairment or of transitioning from MCI to Alzheimer's disease. Over an average of 4.5 years of follow-up, 275 of the 1,393 developed MCI. The third with the highest scores for Mediterranean diet adherence had a 28% lower risk of developing MCI compared to the third with the lowest scores, while the middle third had 17% less risk. Among the 482 with MCI, 106 developed Alzheimer's disease over an average 4.3 years of follow-up. The third with the highest scores for Mediterranean diet adherence had 48% less chance of developing Alzheimer’s and those in the middle third had 45% less chance. A number of the components of the Mediterranean diet have been associated with reduced risk of developing MCI or Alzheimer’s.

Scarmeas, N. et al. 2009. Mediterranean Diet and Mild Cognitive Impairment. Archives of Neurology, 66(2), 216-225.

Moderate drinking can reduce risks of Alzheimer's dementia and cognitive decline

A review of 44 studies has concluded that moderate drinkers often have lower risks of Alzheimer's disease and other cognitive loss. Moderate alcohol consumption generally is defined as 1 drink or less per day for women and 1-2 drinks or less per day for men.

Collins, M.A. et al. 2008. Alcohol in Moderation, Cardioprotection, and Neuroprotection: Epidemiological Considerations and Mechanistic Studies. Alcoholism: Clinical and Experimental Research, Published Online 20 November

Midlife coffee drinking reduces risk of dementia

A large, long-running Finnish study has found that those who were coffee drinkers at midlife had lower risk for dementia and Alzheimer’s later in life compared to those drinking no or only little coffee midlife. The lowest risk was found among moderate coffee drinkers (drinking 3-5 cups of coffee/day). Tea drinking was relatively uncommon and was not associated with dementia.

Eskelinen, M.H. et al. 2009. Midlife Coffee and Tea Drinking and the Risk of Late-Life Dementia: A Population-based CAIDE Study. Journal of Alzheimer's Disease, 16(1).

Gingko biloba does not prevent dementia

A six-year study involving over 3000 older adults has found no reduction in the rate of dementia for those taking twice-daily 120 mg doses of Ginkgo biloba.

DeKosky, S.T. et al. Ginkgo biloba for prevention of dementia: A randomized controlled trial. JAMA, 300, 2253.

Red grape seeds may help prevent Alzheimer's disease

Research into the nearly 5000 compounds contained in red wine to reveal the source of the health benefits seen from red wine has revealed that polyphenols derived from red grape seeds may be useful agents to prevent or treat Alzheimer's disease. Red grape seeds currently being developed with the name of Meganatural AZ were found to significantly reduce cognitive deterioration in genetically engineered mice, by preventing the formation of amyloid beta. The mice were given the extract before the age at which they normally develop signs of disease, suggesting the extract may help prevent or postpone the development of Alzheimer’s. The major polyphenol components in the grape seed extract product are catechin and epicatechin, which are also abundant in tea and cocoa. Unlike the polyphenol resveratrol, which has been shown to have similar effects, but requires extremely high doses, the catechins appear to be effective at much lower doses. Further research will of course be needed before human recommendations can be made.

Wang, J. et al. 2008. Grape-Derived Polyphenolics Prevent Aβ Oligomerization and Attenuate Cognitive Deterioration in a Mouse Model of Alzheimer's Disease. Journal of Neuroscience, 28, 6388-6392.

Vitamin E or C does not reduce risk of dementia or Alzheimer's

A five-year study involving nearly 3000 people has found that use of Vitamin C or E or both was not associated with a reduced risk of developing dementia or Alzheimer’s.

Gray, S.L. et al. 2008. Antioxidant Vitamin Supplement Use and Risk of Dementia or Alzheimer's Disease in Older Adults. Journal of the American Geriatrics Society, 56 (2), 291–295.

Why fish oil is good for you

Confirming previous research indicating that fish oil helps delay or prevent Alzheimer’s, a new study shows why. The study reveals that the omega-3 fatty acid DHA found in fish oil increases the production of LR11, a protein that is found at reduced levels in Alzheimer's patients and which is known to destroy the protein that forms the "plaques" associated with the disease. The study looked at both rodent brains and human brain cells. Still to be determined is what the optimal dose should be.

Ma, Q-L. et al. 2007. Omega-3 Fatty Acid Docosahexaenoic Acid Increases SorLA/LR11, a Sorting Protein with Reduced Expression in Sporadic Alzheimer's Disease (AD): Relevance to AD Prevention. Journal of Neuroscience, 27 (52), 14299 - 14307.

Healthy diet lowers risk of dementia

A very large study of older adults has found that those who regularly consumed omega-3 rich oils, such as canola oil, flaxseed oil and walnut oil, reduced their risk of dementia by 60% compared to people who did not regularly consume such oils. People who ate fruits and vegetables daily also reduced their risk of dementia by 30% compared to those who didn’t regularly eat fruits and vegetables. Additionally, those who ate fish at least once a week had a 35% lower risk of Alzheimer’s and a 40% lower risk of dementia, but only if they did not carry ApoE4 gene. And finally, the study found those who didn’t have the gene but consumed an unbalanced diet characterized by regular use of omega-6 rich oils, but not omega-3 rich oils or fish, were twice as likely to develop dementia compared to those who didn’t eat omega-6 rich oils, which include sunflower or grape seed oil. The study did not find any association between consuming corn oil, peanut oil, lard, meat or wine and lowering risk of dementia.

Barberger-Gateau, P. et al. 2007. Dietary patterns and risk of dementia: The Three-City cohort study. Neurology, 69, 1921-1930.

Higher level of certain fatty acid associated with lower dementia risk

A nine year study of 899 participants in the Framingham Heart Study (average age 76 years) has found that those with the highest levels of an omega-3 polyunsaturated fatty acid known as docosahexaenoic acid (DHA) had a 47% lower risk of developing dementia and 39% lower risk of developing Alzheimer's. Among the participants who completed the dietary questionnaire, those in this top quartile of blood DHA levels reported that they ate an average of .18 grams of DHA a day and an average of three fish servings a week. Those in the other quartiles ate substantially less fish.

Schaefer, E.J. et al. 2006. Plasma Phosphatidylcholine Docosahexaenoic Acid Content and Risk of Dementia and Alzheimer Disease. Archives of Neurology, 63, 1545-1550.

Omega-3 fatty acids may slow cognitive decline in some patients with very mild Alzheimer's disease

Several studies have shown that eating fish, which is high in omega-3 fatty acids, may protect against Alzheimer's disease. A Swedish study has now tested whether supplements could have similar effects. Patients with mild-to-moderate Alzheimer’s who took 1.7 grams of DHA and .6g of EPA showed the same rate of cognitive decline as those taking a placebo, however, among a subgroup of 32 patients with very mild cognitive impairment, those who took the fatty acids experienced less decline in six months compared with those who took placebo. It may be that anti-inflammatory effects are an important reason for the benefit, potentially explaining why effects were seen only in those with very early-stage disease, when levels of inflammation seem to be higher.

Freund-Levi;, Y. et al. 2006. w-3 Fatty Acid Treatment in 174 Patients With Mild to Moderate Alzheimer Disease: OmegAD Study: A Randomized Double-blind Trial. Archives of Neurology, 63, 1402-1408.

Cabernet sauvignon red wine reduces the risk of Alzheimer's disease

A mouse study has found moderate consumption of the red wine Cabernet Sauvignon significantly reduced Alzheimer’s-type deterioration of spatial memory function. The Cabernet Sauvignon used contained a very low content of resveratrol, 10-fold lower than the minimal effective concentration shown to promote Aß clearance in vitro. It is suggested that, instead, the benefit occurred through promoting non-amyloidogenic processing of amyloid precursor protein. The finding supports epidemiological evidence indicating that moderate wine consumption (one drink per day for women and two for men) may help reduce the relative risk for Alzheimer’s.

Wang, J. et al. 2006. Moderate consumption of Cabernet Sauvignon attenuates Aß neuropathology in a mouse model of Alzheimer’s disease. FASEB Journal, 20, 2313-2320.

Juices may reduce Alzheimer's disease risk

In a large epidemiological study, that followed 1836 Seattle residents for up to 10 years, it was found that those who drank three or more servings of fruit and vegetable juices per week had a 76% lower risk of developing Alzheimer’s disease than those who drank juice less than once a week. The benefit seemed greatest for those who carried the so-called “Alzheimer’s gene”. Previously, researchers suspected that antioxidant vitamins (vitamins C, E and -carotene) might help protect against Alzheimer's disease, but this has not been supported in recent clinical studies. Another class of antioxidant chemicals, polyphenols, are now suspected. Polyphenols generally exist primarily in the skins of fruits and vegetables and are particularly abundant in teas, juices and wines.

Dai, Q. et al. 2006. Fruit and Vegetable Juices and Alzheimer's Disease: The Kame Project. The American Journal of Medicine, 119 (9), 751-759.

Calorie restriction may help prevent Alzheimer's

A mouse study has found that beta-amyloid peptides can be reduced by restricting calorie intake, primarily through a low carbohydrate diet. Conversely, a high caloric intake based on saturated fat was shown to increase levels of beta-amyloid peptides. This is the first study to suggest that caloric restriction might inhibit the generation of beta-amyloid peptides, but there have been a number of studies providing evidence that high cholesterol, obesity, and other cardiovascular risk factors increase the likelihood of Alzheimer’s.

Qin, W. et al. 2006. Neuronal SIRT1 Activation as a Novel Mechanism Underlying the Prevention of Alzheimer Disease Amyloid Neuropathology by Calorie Restriction. Journal of Biological Chemistry, 281 (31), 21745 – 21754.

Apples fight memory loss

The study involved adult and old mice (some engineered to develop Alzheimer's-like symptoms) being fed either a standard diet, a nutrient-deficient diet, or a nutrient-deficient diet supplemented with apple juice concentrate. The mice on the apple juice-supplemented diet showed an increased production of acetylcholine in their brains and performed significantly better on maze tests. The amount of consumption was comparable to humans drinking approximately two 8 oz. glasses of apple juice or eating 2-3 apples a day. The findings also suggest that the apple-supplemented diet was most helpful in the framework of an overall healthy diet. Acetylcholine levels declined in both adult and old mice on the nutrient-deficient diet.

Chan, A., Graves, V. & Shea, T.B. 2006. Apple juice concentrate maintains acetylcholine levels following dietary compromise. Journal of Alzheimer's Disease, 9(3), 287-291.

Dietary supplements offer new hope for Alzheimer's patients

A "cocktail" of dietary supplements (omega-3 fatty acids, uridine and choline) has been found to dramatically increase the amount of membranes that form brain cell synapses in gerbils. The treatment is now in human clinical trials. It is hoped that such treatment may significantly delay Alzheimer's disease. The treatment offers a different approach from the traditional tactic of targeting amyloid plaques and tangles. Choline can be found in meats, nuts and eggs, and omega-3 fatty acids are found in a variety of sources, including fish, eggs, flaxseed and meat from grass-fed animals. Uridine, which is found in RNA and produced by the liver and kidney, is not obtained from the diet, although it is found in human breast milk.

Wurtman, R.J., Ulus, I.H., Cansev, M., Watkins, C.J., Wang L. & Marzloff, G. 2006. Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally. Brain Research, Available online ahead of print 21 April 2006.

Blackcurrants may protect against Alzheimer's

A cultured cell study has found that compounds in blackcurrants strongly protect neuronal cells against the types of stress caused by dopamine and amyloid-b, a peptide associated with Alzheimer's disease. Blackcurrants and boysenberries also contain anthocyanins and polyphenolics. Those that are darker (like British blackcurrants) have more anthocyanins and are likely to be more potent. Compounds from these berries are already known to act as antioxidants, but a role in neuroprotection has not been demonstrated previously.

Ghosh, D., McGhie, T.K., Zhang, J., Adaim, A. & Skinner, M. 2006. Effects of anthocyanins and other phenolics of boysenberry and blackcurrant as inhibitors of oxidative stress and damage to cellular DNA in SH-SY5Y and HL-60 cells. Journal of the Science of Food and Agriculture, in press

Folates more effective in limiting Alzheimer's disease risk than antioxidants, other nutrients

Analysis of data from the Baltimore Longitudinal Study of Aging has revealed that those with higher intake of folates, vitamin E and vitamin B6 had a lower risk of developing Alzheimer’s. When the three vitamins were analyzed together, only folates were associated with a significantly decreased risk. Those who had at least 400mcg of folates a day (the recommended daily allowance) had a 55% reduction in risk of developing Alzheimer’s. Unfortunately, most people who reached that level did so by taking supplements, suggesting the difficulty of doing so through diet alone. Folates are abundant in foods such as liver, kidneys, yeast, fruits (like bananas and oranges), leafy vegetables, whole-wheat bread, lima beans, eggs and milk; however, they are often destroyed by cooking or processing. No association was found between vitamin C, carotenoids (such as beta-carotene) or vitamin B-12 intake and decreased Alzheimer's risk.

Corrada, M.M., Kawas,C.H., Hallfrisch,J., Muller,D. & Brookmeyer,R. Reduced risk of Alzheimer’s disease with high folate intake: The Baltimore Longitudinal Study of Aging. Alzheimer’s & Dementia, 1 (1), 11-18.

Fish oil may help prevent Alzheimer's

A study involving genetically engineered mice has found that a diet high in docosahexenoic acid, or DHA — an omega-3 fatty acid found in relatively high concentrations in cold-water fish — dramatically slowed the progression of Alzheimer's, by cutting the harmful brain plaques that mark the disease. An earlier study showed that DHA protected against damage to the "synaptic" areas where brain cells communicate and enabled mice to perform better on memory tests. Food sources of omega-3 fatty acids include fish such as salmon, halibut, mackerel and sardines, as well as almonds, walnuts, soy, and DHA-enriched eggs.

Lim, G.P., Calon, F., Morihara, T., Yang, F., Teter, B., Ubeda, O., Salem, N.Jr, Frautschy, S.A. & Cole, G.M. 2005. A Diet Enriched with the Omega-3 Fatty Acid Docosahexaenoic Acid Reduces Amyloid Burden in an Aged Alzheimer Mouse Model. Journal of Neuroscience, 25(12), 3032-3040.

Fewer calories may slow Alzheimer's

Restricting the diets of genetically engineered mice by 40% over 4 weeks reduced the build-up of plaques in the brain that are linked to Alzheimer's disease by 50%. It remains to be seen whether such dietary changes would similarly affect humans. Researchers are now looking to isolate the specific factors of the diet restriction which are important.

Patel, N.V., Gordon, M.N., Connor, K.E., Good, R.A., Engelman, R.W., Mason, J., Morgan, D.G., Morgan, T.E. & Finch, C.E. (in press). Caloric restriction attenuates Aβ-deposition in Alzheimer transgenic models. Neurobiology of Aging, In Press, Corrected Proof, Available online 25 November 2004.

Compound in apples may help fight Alzheimer's disease

Researchers are recommending that apples may be a particularly beneficial food to protect against Alzheimer’s. A study that exposed groups of isolated rat brain cells to varying concentrations of either quercetin or vitamin C supports the theory that quercetin protects against cellular damage. A particularly good source of quercetin is apples — mainly in the skin. In general, red apples tend to have more of the antioxidant than green or yellow ones. Other foods containing high levels of quercetin include onions, which have some of the highest levels of quercetin among vegetables, as well as berries, particularly blueberries and cranberries.

The study appeared in the December 1 issue of the Journal of Agricultural and Food Chemistry.

Tea may protect against Alzheimer’s

A study investigating the properties of coffee and green and black tea has found that both green and black tea inhibited the activity of enzymes associated with the development of Alzheimer's Disease (acetylcholinesterase and butyrylcholinesterase), but coffee had no significant effect. Green tea also obstructed the activity of beta-secretase, which plays a role in the production of protein deposits in the brain which are associated with Alzheimer's disease, and continued to have its inhibitive effect for a week, whereas black tea's enzyme-inhibiting properties lasted for only one day.

Okello, E.J., Savelev, S.U. & Perry, E.K. 2004. In vitro Anti-beta-secretase and dual anti-cholinesterase activities of Camellia sinensis L. (tea) relevant to treatment of dementia. Phytotherapy Research, 18 (8), 624-627.

Omega-3 fatty acid may prevent Alzheimer's disease and slow its progression

A study using genetically engineered mice has shown that a diet high in the omega-3 fatty acid DHA helps protect the brain against the memory loss and cell damage caused by Alzheimer's disease. Cheap sources of DHA include coldwater fish, like salmon, halibut, mackerel, sardines and herring. These fish consume algae, which is high in DHA. Because these fishes' oiliness makes them absorb more mercury, dioxin, PCP and other metals, however, a less risky yet more costly strategy is to consume fish oil or purified DHA supplements made from algae. Other options include DHA-rich eggs laid by chickens that eat DHA-supplemented feed.

The paper appeared in the September 2 issue of Neuron.

Why diet, hormones, exercise might delay Alzheimer’s

A theory that changes in fat metabolism in the membranes of nerve cells play a role in Alzheimer's has been supported in a recent study. The study found significantly higher levels of ceramide and cholesterol in the middle frontal gyrus of Alzheimer's patients. The researchers suggest that alterations in fats (especially cholesterol and ceramide) may contribute to a "neurodegenerative cascade" that destroys neurons in Alzheimer's, and that the accumulation of ceramide and cholesterol is triggered by the oxidative stress brought on by the presence of the toxic beta amyloid peptide. The study also suggests a reason for why antioxidants such as vitamin E might delay the onset of Alzheimer's: treatment with Vitamin E reduced the levels of ceramide and cholesterol, resulting in "a significant decrease in the number of neurons killed by the beta amyloid and oxidative stress.

Cutler, R.G., Kelly, J., Storie, K., Pedersen, W.A., Tammara, A., Hatanpaa, K., Troncoso, J.C. & Mattson, M.P. 2004. Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease. PNAS, 101, 2070-5.

Using vitamin E and C supplements together may reduce risk of Alzheimer's

A study involving 4,740 elderly (65 years or older) found the greatest reduction in both prevalence and incidence of Alzheimer's in those who used individual vitamin E and C supplements in combination, with or without an additional multivitamin. There was no significant benefit in using vitamin C alone, vitamin E alone, or vitamin C and multivitamins in combination.

Zandi, P.P., Anthony, J.C., Khachaturian, A.S., Stone, S.V., Gustafson, D., Tschanz, J.T., Norton, M.C., Welsh-Bohmer, K.A. & Breitner, J.C.S. 2004. Reduced Risk of Alzheimer Disease in Users of Antioxidant Vitamin Supplements: The Cache County Study. Archives of Neurology, 61, 82-88.

High-dose vitamin regime may help slow Alzheimer's

A preliminary study suggests that a regime of high doses of folic acid, B12 and B6 reduces levels of homocysteine in people with mild to moderate Alzheimer’s. A larger study, recruiting 400 participants from all over the U.S., is to be undertaken to assess whether such a vitamin regime can slow the progression of Alzheimer's disease. In the meantime, it is not advised that people take high doses of these vitamins, as there are possible side-effects, including peripheral nerve damage.

Aisen, P.S. et al. 2003. Effects of Rofecoxib or Naproxen vs Placebo on Alzheimer Disease Progression: A Randomized Controlled Trial. JAMA, 289, 2819-2826.

Drinking wine may lower risk of dementia

Researchers in Copenhagen have followed up an analysis of drinking patterns for wine, beer and liquor of 1,709 people in the 1970s with an assessment of dementia in the 1990s, when participants were age 65 or older. 83 of the participants had developed dementia. Their alcohol intake was compared to that of those who did not develop dementia. It was found that those who drank wine occasionally had a lower risk of developing dementia, including Alzheimer's disease. Those who drank wine every day were no more or less likely to develop dementia than those who drank it less often. The study also found that occasional beer drinking was associated with an increased risk of developing dementia. It is important to note that eating habits were not investigated, and research suggests that wine drinkers may have better dietary habits than beer and liquor drinkers.

Truelsen, T., Thudium, D. & Grønbæk, M. 2002. Amount and type of alcohol and risk of dementia: The Copenhagen City Heart Study. Neurology, 59, 1313-1319.

Eating fish cuts risk of dementia

Using data from a French epidemiological study of cognitive and functional aging, researchers found that those who ate fish or seafood at least once a week had a significantly lower risk of being diagnosed as having dementia (including Alzheimer’s) over the seven years follow-up. This confirms earlier findings from the Rotterdam Study, which had a much shorter follow-up (a mean of 2.1 years). There was an association between level of education and diet which partly, but not completely, explains this. It does appear that this is a benefit from eating fish / seafood, possibly from the fatty acids found in fish oils. There was no significant association between meat consumption and risk of dementia.

Barberger-Gateau, P., Letenneur, L., Deschamps, V., Pérès, K., Dartigues, J. & Renaud, S. 2002. Fish, meat, and risk of dementia: cohort study. BMJ, 325, 932-933.

Diet rich in foods with Vitamin E may reduce Alzheimer’s disease risk

Two studies have come out in favor of a diet rich in foods containing vitamin E to help protect against Alzheimer's disease. One study involved 815 Chicago residents age 65 and older with no initial symptoms of mental decline, who were questioned about their eating habits and followed for an average of about four years. When factors like age and education were taken into account, those eating the most vitamin E-rich foods had a lower risk of developing Alzheimer’s, provided they did not have the ApoE e4 allele. This was not true when vitamin E was taken as a supplement. Intake of vitamin C and beta carotene appeared protective, but not at a statistically significant level. The other study involved 5,395 people in the Netherlands age 55 and older who were followed for an average of six years. Those with high intakes of vitamins E and C were less likely to become afflicted with Alzheimer's, regardless of whether they had the gene variation. This association was most pronounced for current smokers, for whom beta carotene also seemed to be protective. A number of clinical trials are underway to further investigate these links.

Engelhart, M.J., Geerlings, M.I., Ruitenberg, A., van Swieten, J.C., Hofman, A., Witteman, J.C.M. & Breteler, M.M.B. 2002. Dietary Intake of Antioxidants and Risk of Alzheimer Disease. JAMA, 287, 3223-3229. Morris, M.C., Evans, D.A., Bienias, J.L., Tangney, C.C., Bennett, D.A., Aggarwal, N., Wilson, R.S. & Scherr, P.A. 2002. Dietary Intake of Antioxidant Nutrients and the Risk of Incident Alzheimer Disease in a Biracial Community Study. JAMA, 287, 3230-3237.

Folic acid possibly a key factor in preventing Alzheimer's disease

Experiments with mice bred with mutant genes that cause Alzheimer's disease found that those mice fed on a diet deficient in folate had fewer neurons in the hippocampus ( a brain region critical for learning and memory that is destroyed as plaques accumulate during Alzheimer’s disease), and elevated levels of homocysteine. Researchers suspect that increased levels of homocysteine in the brain caused damage to the DNA of nerve cells in the hippocampus. In the mice fed an adequate amount of folate, nerve cells in this brain region were able to repair the damage. But in those mice fed a folate-deficient diet, nerve cells were unable to repair this damage. A human study is being planned.
Green leafy vegetables, citrus fruits and juices, whole wheat bread and dry beans are good sources of folate. In the U.S., since 1998, the Food and Drug Administration has required the addition of folic acid to enriched breads, cereals, flours, corn meals, pastas, rice, and other grain products.

Kruman, I.I., Kumaravel, T.S., Lohani, A., Pedersen, W.A., Cutler, R.G., Kruman, Y., Haughey, N., Lee, J., Evans, M. & Mattson, M.P. 2002. Folic Acid Deficiency and Homocysteine Impair DNA Repair in Hippocampal Neurons and Sensitize Them to Amyloid Toxicity in Experimental Models of Alzheimer's Disease. Journal of Neuroscience, 22, 1752-1762.

Physical exercise & fitness

Reduced muscle strength associated with Alzheimer's risk

A study involving 970 older adults (average age 80.3) has found that over the average 3.6 years follow-up period, those with weaker muscles had a higher risk of developing Alzheimer’s. For each one-unit increase at the beginning of the study, older adults had about a 43% decrease in the risk of developing Alzheimer's disease during follow-up (strength scores ranged from -1.6 to 3.3 units). Those in the top 10% had about a 61% reduced risk of developing Alzheimer's compared with those in the bottom 10%. The association remained even after factors such as body mass index and physical activity level were accounted for. The association also was found with mild cognitive impairment.

Boyle, P. A., Buchman, A. S., Wilson, R. S., Leurgans, S. E., & Bennett, D. A. (2009). Association of Muscle Strength With the Risk of Alzheimer Disease and the Rate of Cognitive Decline in Community-Dwelling Older Persons. Arch Neurol, 66(11), 1339-1344.

Physical fitness improves memory in seniors

A study of 165 older adults (59-81) has found a significant association between physical fitness and performance on certain spatial memory tests. Fitness was also strongly correlated with hippocampus size. Although rodent studies have shown that exercise increases hippocampus size and spatial memory, this is the first study to show that in humans. The findings provide more evidence for the benefits of physical exercise in preventing memory loss in older adults.

Erickson, K.I. et al.  2009. Aerobic fitness is associated with hippocampal volume in elderly humans. Hippocampus, Published online 2 January

Moderate exercise helps mild cognitive impairment

An Australian study involving 138 older adults (50 years and over) with mild cognitive impairment, has found that those who undertook to achieve 2 ½ hours of physical activity each week (three 50 minute sessions), ranging from walking, ballroom dancing to swimming, for a six month period, continually out-scored the control group on cognitive tests during the 18 month testing period — showing that memory improvement was still evident a year after the supervised exercise period.

Lautenschlager, N.T. et al. 2008. Effect of Physical Activity on Cognitive Function in Older Adults at Risk for Alzheimer Disease: A Randomized Trial. Journal of the American Medical Association, 300(9), 1027-1037.

Exercise may slow brain shrinkage in early Alzheimer's

A study of 121 people age 60 and older, of whom 57 were in the early stages of Alzheimer's disease, has found that those with early Alzheimer's disease who were less physically fit (measured by cardiorespiratory fitness) had four times more brain shrinkage when compared to normal older adults than those who were more physically fit. The findings suggest the value of physical fitness in slowing down the progression of Alzheimer's disease. The association existed even after age, gender, severity of dementia, physical activity and frailty were accounted for. There was no relationship between higher fitness levels and brain changes in the group of people without dementia.

Burns, J.M. et al. 2008. Cardiorespiratory fitness and brain atrophy in early Alzheimer disease. Neurology, 71, 210-216.

Walking and moderate exercise help prevent dementia

A four-year study involving 749 older adults has found that the top one-third of participants who exerted the most energy in moderate activities such as walking were significantly less likely to develop vascular dementia than those people in the bottom one-third of the group. Contrary to some reports, no such association was found with Alzheimer’s disease.

Ravaglia, G. et al. 2007. Physical activity and dementia risk in the elderly. Findings from a prospective Italian study. Neurology, published online ahead of print December 19

Good physical function linked to Alzheimer's delay

A study following 2,288 older adults for six years found that those whose physical function was higher at the start of the study were three times less likely to develop dementia than were those whose physical function was lower.

Wang, L., Larson, E.B., Bowen, J.D. & van Belle, G. 2006. Performance-Based Physical Function and Future Dementia in Older People. Archives of Internal Medicine, 166, 1115-1120.

Exercise protects against Alzheimer's

A study following 1,740 seniors (aged 65 and older) over a six-year period, found that those who exercised three or more times a week had a 30 — 40% lower risk for developing dementia compared with those who exercised fewer than three times per week. Even modest amounts, such as walking 15 minutes a day, appear beneficial, and the more frail the person was, the more they benefited from regular exercise.

Larson, E.B., Wang, L., Bowen, J.D., McCormick, W.C., Teri, L., Crane, P., & Kukull, W. 2006. Exercise Is Associated with Reduced Risk for Incident Dementia among Persons 65 Years of Age and Older. Annals of Internal Medicine, 144 (2), 73-81.

Exercise slows development of Alzheimer's-like brain changes in mice

Population-based studies have provided evidence that various lifestyle interventions might help slow the onset and progression of Alzheimer’s. A mouse study now provides a clue how that might work. Physical activity enhanced the learning ability of mice genetically engineered to develop amyloid plaques and decreased the level of plaque-forming beta-amyloid protein fragments in their brains. The mice were divided into mice with access to running wheels or no access. The findings are supported by another recent study that found that beta-amyloid levels decreased in the brains of another kind of transgenic mice when they were housed in groups and in environments that were enriched with running wheels, colored tunnels, and toys.

Adlard, P.A., Perreau, V.M., Pop, V. & Cotman, C.W. 2005. Voluntary Exercise Decreases Amyloid Load in a Transgenic Model of Alzheimer's Disease. Journal of Neuroscience, 25, 4217-4221.



Estrogen use before 65 linked to reduced risk of Alzheimer's disease

Data from the Women’s Health Initiative Memory Study looked at prior hormone use in 7,153 healthy women ages 65-79 before they enrolled in the WHI Memory Study, and followed their cognitive health over an average of five years. In that time, 106 of the women developed Alzheimer’s disease or dementia. The study found women who used any form of estrogen hormone therapy before the age of 65 were nearly 50% less likely to develop Alzheimer’s disease or dementia than women who did not use hormone therapy before age 65, but women who began estrogen-only therapy after the age of 65 had roughly a 50% increased risk of developing dementia. The risk jumped to nearly double for women using estrogen-plus-progestin hormone therapy.

The findings were presented at the American Academy of Neurology’s 59th Annual Meeting in Boston, April 28 – May 5, 2007.

Low dose aspirin does not protect women against cognitive decline

Evidence that aspirin and other anti-inflammatory drugs may protect against dementia has been inconclusive. Now a large, long-running study involving 6,377 women aged 65 years or more, over ten years, has found that those who took low dose aspirin (100 mg on alternate days) performed at similar levels to a placebo group on cognitive tests. However, there was evidence of benefit in one very specific area of cognition: category fluency.

Kang, J-E., Cirrito, J.R., Dong, H., Csernansky, J.G. & Holtzman, D.M. 2007. Acute stress increases interstitial fluid amyloid-beta via corticotropin-releasing factor and neuronal activity. Proceedings of the National Academy of Science, 104 (25), 10673-10678.

Common painkillers may help protect against Alzheimer’s disease

Observations that people who take anti-inflammatory medications over several years have a lower risk of later developing Alzheimer's disease have received support from an exciting new study which has revealed that common over-the-counter pain medications (such as ibuprofen and naproxen) bind to amyloid plaques, and may help dissolve existing plaques and prevent the formation of new ones. Amyloid plaques are one of the definitive hallmarks of Alzheimer's disease.

Agdeppa, E.D., Kepe, V., Petri, A., Satyamurthy, N., Liu, J., Huang, S.-C., Small, G.W., Cole, G.M. & Barrio, J.R. 2003. In vitro detection of (S)-naproxen and ibuprofen binding to plaques in the Alzheimer's brain using the positron emission tomography molecular imaging probe 2-(1-{6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile, Neuroscience, 117(3), 723-730.

Regular long-term use of aspirin may reduce the risk of Alzheimer’s

A large-scale study of 5,092 older adults has found that regular use of aspirin and other non-steroidal anti-inflammatory drugs may reduce the incidence of dementia in elderly people, but only when taken for more than two years, and provided the use occurred well before the onset of dementia.

Zandi, P.P., Anthony, J.C., Hayden, K.M., Mehta, K., Mayer, L. & Breitner, J.C.S. 2002. Reduced incidence of AD with NSAID but not H2 receptor antagonists: The Cache County Study. Neurology, 59, 880-886.

Alzheimer's Knowledge

Older news items (pre-2010) brought over from the old website

Poor Understanding of Alzheimer's Link to Heart Health Risk Factors

An online survey of 690 adults (average age 50; well-educated, with 87% having had some college) found that 64% did not realize there was an association between Alzheimer's and obesity or high blood pressure; 66% didn’t know that high stress is a risk factor for dementia; 34% didn’t know that physical exercise is a protective factor.

Jackson, C.E. et al. 2009. Dementia literacy: Public understanding of known risk factors. Presented at the Alzheimer's Association International Conference on Alzheimer's Disease July 11-16 in Vienna.

Misconceptions about Alzheimer's common

A recent survey of nearly 1200 people has found a high degree of misconceptions about Alzheimer’s in America. Half the respondents were unaware that anything could be done to maintain cognitive functioning and reduce Alzheimer's risk. Although there were no significant differences among races in the level of concern about getting Alzheimer's, many more blacks and Hispanics than whites responded that they believe that Alzheimer's is a normal part of aging. However, blacks and Hispanics were also more likely than whites to report changing their diet or lifestyle to avoid developing Alzheimer's.

Connell, C.M., Scott Roberts, J. & McLaughlin, S.J. 2007. Public Opinion About Alzheimer Disease Among Blacks, Hispanics, and Whites: Results From a National Survey. Alzheimer Disease & Associated Disorders, 21(3), 232-240.

Survey reveals ethnic differences in knowledge about Alzheimer's

The Alzheimer's Foundation of America's (AFA) second Investigating Caregivers' Attitudes and Needs survey has revealed that African-American and Hispanic caregivers of people with Alzheimer's disease are significantly more likely (37% and 33%, respectively) than caregivers of other races (23%) to consider the disease a normal part of the aging process and also more likely (70% and 67%, vs 53%) to dismiss its symptoms as part of getting older, thus delaying diagnosis. They were also more likely (67% and 63%, vs 49%) to report that they did not know enough about the disease to recognize the symptoms.

Fears of stigma also play a part in delaying diagnosis, with around one-third (33%) of respondents reporting that their loved one's concern about stigma delayed diagnosis, and about a quarter (26%) indicating that their own concern about stigma contributed to the delay. African-American caregivers were significantly more concerned about stigma (36%) than Hispanic (22%) and other race (18%) caregivers.

Races other than African-American and Hispanic were far more likely to consider placing their loved one in a facility: 32% compared to African-American (19%) and Hispanic (21%) caregivers. African-American and Hispanic caregivers were more likely to use a support groups than other races (47% and 50%, vs 29%). Yet only around half of African-American respondents and a little more than one-third of Hispanic respondents said that they felt the support groups they were able to access were appropriate to their specific religious or ethnic background. At diagnosis, caregivers overall wished they had received more information about Alzheimer's disease (75%) and treatment options (75%), with African-American caregivers (83%) significantly more likely than Hispanic (73%) and other (68%) caregivers to wish they had received more information.

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Cognitive Tests

Older news items (pre-2010) brought over from the old website

Effective new cognitive screening test for detection of Alzheimer's

A new cognitive test for detecting Alzheimer's has been developed, and designed to be suitable for non-specialist use. The TYM ("test your memory") involves 10 tasks including ability to copy a sentence, semantic knowledge, calculation, verbal fluency and recall ability. It has been tested on 540 healthy individuals and 139 patients with diagnosed Alzheimer's or mild cognitive impairment. Healthy controls completed the test in an average time of five minutes and gained an average score of 47 out of 50, compared to 45 for those with mild cognitive impairment, 39 for those with non-Alzheimer dementias and 33 for those with Alzheimer’s. Among controls, the average score was not affected by age until after 70, when it showed a small decline. There were no gender or geographical background differences in performance. The TYM detected 93% of patients with Alzheimer's, compared to only 52% by the widely used mini-mental state examination.

Brown, J. et al. 2009. Self administered cognitive screening test (TYM) for detection of Alzheimer’s disease: cross sectional study. BMJ, 338:b2030, doi: 10.1136/bmj.b2030
Full text available here.

Early identification of dementia increasingly difficult

A study comparing nondemented 70-year-olds examined in the early 1970s with nondemented 70-year-olds examined in the year 2000 has revealed that those who were examined in 2000 scored much higher on non-memory cognitive tests than those examined 30 years earlier — indicating that such tests can no longer be used to predict future dementia. Moreover, although memory loss was a predictor for later development of dementia, it wasn’t conclusive —not everybody with poor memory developed dementia. This was particularly true of the very old (85 year olds).

Sacuiu, S.F. 2009. Prodromal Cognitive Signs of Dementia. Doctoral thesis from Sahlgrenska Academy, University of Gothenburg.

Degree of test variability improves dementia diagnosis

A study of nearly 900 older adults has found that the degree of variability in performance across neuropsychological tests, measured within a person, improved the prediction of dementia above and beyond one's level of performance on each test alone.

Holtzer, R. et al. 2008. Within-Person Across-Neuropsychological Test Variability and Incident Dementia. JAMA, 300(7), 823-830.

New criterion may improve identification of dementia risk in highly educated older adults

A shift in the cutoff point on the widely used cognitive screening tool, the mini-mental state examination (MMSE), is suggested for highly educated older adults, in order to more effectively assess the risk of dementia.

Bryant, S.E. et al. 2008. Detecting Dementia With the Mini-Mental State Examination in Highly Educated Individuals. Archives of Neurology, 65 (7), 963-967.

New 'everyday cognition' scale tracks how older adults function in daily life

A new, carefully validated questionnaire called Everyday Cognition (ECog) has been developed by seven psychologists. The 39-question screening tool is designed to enable mild functional problems in older adults to be quickly and easily identified. The questionnaire needs to be filled out by someone who knows an older adult well, such as a spouse, adult child, or close friend. It looks at everyday function in seven key cognitive domains: memory, language, semantic (factual) knowledge, visuospatial abilities, planning, organization and divided attention. The test has been shown to be sensitive to early changes present in Mild Cognitive Impairment, and unlike other cognitive tests, does not appear to be strongly influenced by education level. The test even differentiated between people diagnosed with mild impairment in memory only and those mildly impaired in several areas.

Farias, S.T. et al. 2008. The Measurement of Everyday Cognition (ECog): Scale Development and Psychometric Properties. Neuropsychology, 22 ( 4), 531-544.

Simple test predicts 6-year risk of dementia

A 14-point index combining medical history, cognitive testing, and physical examination — a simple test that can be given by any physician — has been found to predict a person’s risk for developing dementia within six years with 87% accuracy. As measured by the index, the risk factors for developing dementia are an age of 70 or older, poor scores on two simple cognitive tests, slow physical functioning on everyday tasks such as buttoning a shirt or walking 15 feet, a history of coronary artery bypass surgery, a body mass index of less than 18, and current non-consumption of alcohol. The results do need to be validated in other populations — for example, they have not yet been tested on Hispanics or Asian-Americans.

The tests were described in a presentation at the 2007 International Conference on Prevention of Dementia, in Washington, DC.

Personality changes may help detect Lewy bodies dementia

Dementia with Lewy bodies is the second most common neurodegenerative cause of dementia. It shares characteristics with both Alzheimer's and Parkinson's disease, but some medications used to treat Alzheimer's patients are potentially dangerous for people with dementia with Lewy bodies. Early diagnosis is therefore important. A new study has found that people with dementia with Lewy bodies often display passive personality changes some time before cognitive deficits are evident, offering hope that a simple personality test might help diagnosis.

Galvin, J.E., Malcom, H., Johnson, D. & Morris, J.C. 2007. Personality traits distinguishing dementia with Lewy bodies from Alzheimer disease. Neurology, 68, 1895-1901.

New dementia screening tool detects early cognitive problems

A new screening tool for dementia — the Saint Louis University Mental Status Examination (SLUMS) — appears to work better in identifying mild cognitive problems in the elderly than the commonly used Mini Mental Status Examination — particularly for the more educated patients. It takes a clinician about seven minutes to administer the SLUMS, which supplements the Mini Mental Status Examination by asking patients to perform tasks such as doing simple math computations, naming animals, recalling facts and drawing the hands on a clock. The SLUMS is available at this link

Tariq, S.H. et al. 2006. Comparison of the Saint Louis University Mental Status Examination and the Mini-Mental State Examination for Detecting Dementia and Mild Neurocognitive Disorder—A Pilot Study. American Journal of Geriatric Psychiatry, 14, 900-910.

More sensitive tests for predicting Alzheimer's

The first study used data from 119 participants in the Longitudinal Aging Study Amsterdam. The memory test scores of those who two years later developed Alzheimer's were compared with the scores of those who stayed healthy. Three tests were very good at predicting who would later develop Alzheimer's: a Paired-Associate Learning Test, which cued participants to recall five semantically related and five semantically unrelated pairs of words; a Perceptual Identification Task, which measured how fast participants read aloud words briefly presented on a computer screen; a Visual Association Test, which cued participants to recall six line drawings of common objects that had been presented earlier in an illogical interaction with another object or cue. On the word-pair memory test, people destined to develop Alzheimer's disease didn't do any better when words were related than when they weren't, suggesting they’d already lost deep semantic knowledge. On the word-reading test, word repetition didn't help high-risk participants to perform better, a sign that implicit learning was impaired. The popular Mini Mental Status Exam (MMSE), a test mainly sensitive to episodic memory, was not as good a predictor.
In the second study, a dichotic listening task, which measures how well people process information when they hear one thing in the left ear and another in the right ear, was found to also be predictive of Alzheimer’s, confirming that people have problems with selective attention very early in the disease.

Spaan, P.E.J., Raaijmakers, J.G.W. & Jonker, C. 2005. Early Assessment of Dementia: The Contribution of Different Memory Components. Neuropsychology, 19 (5).

Duchek, J.M. & Balota, D.A. 2005. Failure to Control Prepotent Pathways in Early Stage Dementia of the Alzheimer's Type: Evidence from Dichotic Listening. Neuropsychology, 19 (5).

Early warning signs of Alzheimer's show up years before official diagnosis

A meta-analysis of 47 studies of Alzheimer's disease has revealed that people can show early warning signs across several cognitive domains years before they are officially diagnosed, confirming that Alzheimer's causes general deterioration and tends to follow a stable preclinical stage with a sharp drop in function. People at the preclinical stage showed marked preclinical deficits in global cognitive ability, episodic memory, perceptual speed, and executive functioning; along with somewhat smaller deficits in verbal ability, visuospatial skill, and attention. There was no preclinical impairment in primary memory. There is no clear qualitative difference between the normal 75-year old and a preclinical Alzheimer’s sufferer; instead it seems that the normal elderly person, the preclinical Alzheimer’s person, and the early clinical Alzheimer’s patient represent three instances on a continuum of cognitive capabilities.

Bäckman, L., Jones, S., Berger, A-K. & Laukka, E.J. 2005. Cognitive impairment in preclinical Alzheimer's disease: A meta-analysis. Neuropsychology, 19 (4).

More sensitive test norms better predict who might develop Alzheimer's disease

Early diagnosis of Alzheimer's is becoming more important with new medical and psychological interventions that can slow (but not stop) the course of the disease. Given this, it is suggested that more sensitive testing may be necessary for highly intelligent people, who, on average, show clinical signs of Alzheimer's later than the general population. Once they show such signs, they decline much faster. A study of 42 older people with IQ's of 120 or more, used two different test norms to forecast problems: the standard norm, derived from a large cross-section of the population, or an adjusted high-IQ norm that measured changes against the individual's higher ability level. The raised cutoffs predicted that 11 of the 42 individuals were at risk for future decline – compared with standard cutoffs, which indicated they were normal. True to the former prediction, three and a half years later, nine of those 11 people had declined. Six of those went on to develop mild cognitive impairment (MCI), a transitional illness from normal aging to a dementia (of which one type is Alzheimer's). Five of these individuals have since received a diagnosis of Alzheimer's disease, two years after this study was submitted. It is also suggested that, at the other end of the scale, those with below-average intelligence have the potential for being misdiagnosed as 'demented' when they are not, and the norms should be adjusted downwards accordingly.

Rentz, D.M., Huh, T.J., Faust, R.R., Budson, A.E., Scinto, L.F.M., Sperling, R.A. & Daffner, K.R. 2004. Use of IQ-Adjusted Norms to Predict Progressive Cognitive Decline in Highly Intelligent Older Individuals. Neuropsychology, 18 (1).

New method of distinguishing Alzheimer's from Lewy body dementia

Looking at specific changes in alertness and cognition may provide a reliable method for distinguishing Alzheimer's from dementia with Lewy bodies (DLB) and normal aging. Four characteristics significantly distinguished patients with DLB from persons with Alzheimer’s and normal elderly controls: daytime drowsiness and lethargy despite getting enough sleep the night before; falling asleep two or more hours during the day; staring into space for long periods and episodes of disorganized speech. "For the normal elderly control group, one or two of these behaviors was found in only 11 percent of the group. For the patients with AD, one or two of these behaviors were not uncommon, but over 63% of the patients with DLB had three or four of these behaviors.” DLB accounts for as much as 20 to 35% of the dementia seen in the United States.

Ferman, T.J., Smith, G.E., Boeve, B.F., Ivnik, R.J., Petersen, R.C., Knopman, D., Graff-Radford, N., Parisi, J. & Dickson, D.W. 2004. DLB fluctuations: Specific features that reliably differentiate DLB from AD and normal aging. Neurology, 62,181-187.

Brief telephone questionnaire screens for early signs of dementia

Researchers have developed a brief telephonic questionnaire that helps distinguish between persons with early signs of dementia and persons with normal cognitive function. The questionnaire provides a way to reach out to persons with dementia whose impairment otherwise may go undetected until substantial cognitive deterioration has occurred. The questionnaire consists of a test of delayed recall and 2 questions that ask whether the person needs help with remembering to take medications or with planning a trip for errands. It is estimated that of 100 people who score positive on this test, 42 will actually have cognitive impairment. In other words, this does not provide a diagnosis of Alzheimer’s, but provides evidence that further evaluation is required. The rate of false positives compares favorably to other types of screening tests. A further study is underway to confirm the validity and reliability of the test.

Fillit, H. et al. 2003. A Brief Telephonic Instrument to Screen for Cognitive Impairment in a Managed Care Population. Journal of Clinical Outcomes Management, , 419-429.

Verbal memory tests predict dementia

The Longitudinal Aging Study Amsterdam tested the memories of a large group of elderly people on two occasions, two years apart. Performance on the memory tests was then compared between those who developed dementia during those two years and those who did not. It was found that those who later were found to have dementia were scarcely better at remembering word pairs clearly linked in meaning (for example, pipe - cigar) than word pairs without such a link (for example nail - butter), on the first test. (those who not have dementia two years later did, as is usual, benefit from such a link in meaning). In addition, those in the early stage of dementia did not benefit from the repeated presentation of words. The results suggest a means by which elderly people in the early stages of dementia can be identified, which is important because the drugs used to inhibit dementia only work in the earliest stages of the disease.

This was revealed in doctoral research by the neuropsychologist Pauline Spaan from the University of Amsterdam.

Verbal memory test best indicator of who will have Alzheimer's disease

A meta-analysis of 31 studies involving a total of 1,144 Alzheimer's patients and 6,046 healthy controls, supports the use of the California Verbal Learning Test in predicting future Alzheimer’s type dementia. Long delay recall and percent recall were the best predictors, with executive function type measures also being predictive but less so than both the long and short delay memory tests. Changes in the hippocampus were the best volumetric or neuroimaging measure but in general volumetric measures were less sensitive to preclinical stages of the dementia than were the neuropsychological tests. It should be noted that a decline in various types of memory, especially verbal episodic memory, is also observable in normal elderly; the crucial factor in determining a pre-dementia state lies in the size of the memory deficit.

Zakzanis, K.K. & Boulos, M.I. 2002. A Meta-Analysis of ApoE Genotype and Neuropsychologic and Neuroanatomic Changes in Preclinical Alzheimer's Disease. Presentation at the 110th Annual Convention of the American Psychological Association (APA) on August 25.

Early diagnosis of Alzheimer's

An analysis of data from 40 participants enrolled in a long-term study at the UCSD Alzheimer’s Disease Research Center (ADRC) found that "paper-and-pencil" cognitive skills tests administered to normal subjects averaging 75 years of age contained early signs of cognitive decline in those subjects who later developed Alzheimer’s disease. All participants were symptom-free when they took the test. The differences were quite subtle - only some performance measures were affected.

Jacobson MW, Delis DC, Bondi MW, Salmon DP. Do neuropsychological tests detect preclinical Alzheimer's disease: Individual-test versus cognitive-discrepancy score analyses. Neuropsychology. 2002;16(2):132–139.

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Early Markers

Older news items (pre-2010) brought over from the old website

Measuring brain atrophy in patients with mild cognitive impairment

A study involving 269 patients with mild cognitive impairment provides evidence that a fully automated procedure called Volumetric MRI (that can be done in a clinical setting) can accurately and quickly measure parts of the medial temporal lobe and compare them to expected size. It also found that not only atrophy in the hippocampus but also the amygdala is associated with a greater risk of conversion to Alzheimer’s.

Kovacevic, S. et al. 2009. High-throughput, Fully Automated Volumetry for Prediction of MMSE and CDR Decline in Mild Cognitive Impairment. Alzheimer Disease & Associated Disorders, 23 (2), 139-145.

Cerebrospinal fluid shows Alzheimer's disease deterioration much earlier

A study involving 60 patients with subjective cognitive impairment, 37 patients with non-amnestic mild cognitive impairment, and 71 with amnestic mild cognitive impairment, has found that 52% of those with SCI, 68% of those with naMCI, and 79% of those with aMCI showed decreased concentrations of Aβ42 and increased concentrations of tau protein in the cerebrospinal fluid. The findings confirm the use of biomarkers in the CSF for very early diagnosis

Visser, P.J. et al. 2009. Prevalence and prognostic value of CSF markers of Alzheimer's disease pathology in patients with subjective cognitive impairment and mild cognitive impairment in the DESCRIPA study: a prospective, case-control study. The Lancet Neurology, 8 (7), 619–627.

Weight loss in old age may signal dementia

An 8-year study involving over 1,800 older Japanese Americans has found that those with lower body mass index (BMI) scores at the beginning of the study were 79% more likely to develop dementia than those with higher scores. In addition, those who lost weight over the study period at a faster rate were nearly three times more likely to develop dementia than those who lost weight more slowly, and this association was stronger in those who were overweight or obese to start.

Hughes, T.F. et al. 2009. Association between late-life body mass index and dementia: The Kame Project. Neurology, 72, 1741-1746.

New tool can help predict Alzheimer's risks

A new 15-point scale of risk factors for Alzheimer's has been developed and correctly classified 88% of the 3,375 older adults in the study. 56% of those with scores of 8 or higher developed dementia within six years, compared to 23% with moderate scores and just 4% with low scores. The risk factors include poor cognitive test performance (2–4 points), body mass index below 18.5 (2 points), older age (1–2 points), history of bypass surgery (1 point), slow physical performance (1 point), and lack of alcohol consumption (1 point), presence of the ApoE4 gene (1 point), MRI findings of white matter disease (1 point) or ventricular enlargement (1 point), internal carotid artery thickening on ultrasound (1 point).

Barnes, D.E. et al. 2009. Predicting risk of dementia in older adults. The late-life dementia risk index. Neurology, published May 13, 2009.

Eye tracking test detects mild cognitive impairment

A test first developed for use with nonhuman primates is now being used to detect mild cognitive impairment (MCI) in humans. The infrared eye-tracking test involves showing one image and then another after a 2-second delay, and then repeating the test 2 minutes later. Those without cognitive impairment spend most of their time looking at the new image, but it was found that those with MCI spent less time looking at the new picture, presumably because they have less memory of seeing the original image before. Those with Alzheimer's disease look at both images equally. It’s hoped that this test may allow dementia to be spotted much earlier.

Crutcher, M.D. et al. 2009. Eye Tracking During a Visual Paired Comparison Task as a Predictor of Early Dementia. American Journal of Alzheimer's Disease and Other Dementias, Published online February 26 2009.

Shrinking in hippocampus precedes Alzheimer's

An imaging study of 64 Alzheimer's patients, 44 people with mild cognitive impairment, and 34 people with no memory or thinking problems, has found that those with smaller hippocampal volumes and higher rates of shrinkage were two to four times as likely to develop dementia over the study period (average 18 months) as those with larger volumes and a slower rate of atrophy. During that time, 23 of the people with MCI developed Alzheimer's, and three of the healthy participants.

Henneman, W.J.P. et al. 2009. Hippocampal atrophy rates in Alzheimer disease: Added value over whole brain volume measures. Neurology, 72, 999-1007.

Brain atrophy pattern in some MCI patients predicts Alzheimer's

A study of 84 patients with mild Alzheimer's, 175 patients with MCI and 139 healthy controls has revealed a pattern of regional brain atrophy in patients with MCI that indicates a greater likelihood of progression to Alzheimer's. Brain scans results showed widespread cortical atrophy in some patients with MCI, most importantly, atrophy in parts of the medial and lateral temporal lobes and in the frontal lobes — a pattern also present in the patients with mild Alzheimer's disease. Those exhibiting such atrophy declined significantly over a year and were more likely to progress to a probable diagnosis of Alzheimer's. MCI patients without that pattern of atrophy remained stable after a year. It should be noted that such atrophy affects not only memory, but also planning, organization, problem solving and language.

McEvoy, L.K. et al. 2009. Alzheimer Disease: Quantitative Structural Neuroimaging for Detection and Prediction of Clinical and Structural Changes in Mild Cognitive Impairment. Radiology, Published online February 6.

Blood test could give early warning of Alzheimer’s risk

A simple blood test may enable us to predict whether someone will soon develop Alzheimer’s, allowing them to take action that might delay its development. In the study of 1,125 elderly persons without dementia, 104 (9.2%) of the participants developed Alzheimer’s over 4.6 years of follow-up. Higher blood levels of amyloid-beta 42 peptide at the onset of the study were associated with a threefold increased risk of Alzheimer’s, with the levels significantly declining at the onset of Alzheimer’s (perhaps because it has started accumulating in the brain).

Schupf, N. et al. 2008. Peripheral Aβ subspecies as risk biomarkers of Alzheimer's disease. PNAS, 105 (37), 14052-14057.

Women lose weight at least a decade before developing dementia

Another study has come out associating weight loss with later dementia. The study found that women who later developed dementia started losing weight up to 20 years before the disease was diagnosed. On average, those with dementia weighed 12 pounds less than those without the disease the year the disease was diagnosed. The association may be related to a loss in the sense of smell, and increasing apathy. The association was not found with men, probably because older men were less likely to be preparing their own food. The findings do of course conflict with others suggesting that obesity in middle-age may be a risk factor for dementia. More research is needed to clarify the situation.

Knopman, D.S. et al. 2007. Incident dementia in women is preceded by weight loss by at least a decade. Neurology, 69, 739-746.

Simple test predicts 6-year risk of dementia

A 14-point index combining medical history, cognitive testing, and physical examination — a simple test that can be given by any physician — has been found to predict a person’s risk for developing dementia within six years with 87% accuracy. As measured by the index, the risk factors for developing dementia are an age of 70 or older, poor scores on two simple cognitive tests, slow physical functioning on everyday tasks such as buttoning a shirt or walking 15 feet, a history of coronary artery bypass surgery, a body mass index of less than 18, and current non-consumption of alcohol. The results do need to be validated in other populations — for example, they have not yet been tested on Hispanics or Asian-Americans.

The tests were described in a presentation at the 2007 International Conference on Prevention of Dementia, in Washington, DC.

Brain structure changes years before memory loss begins

Another study provides evidence that people who develop dementia or Alzheimer's disease experience brain structure changes years before any signs of memory loss begin. The study involved 136 people over the age of 65 who were considered cognitively normal at the beginning of the five-year study. By the end of the study, 23 people had developed MCI, and nine of the 23 went on to be diagnosed with Alzheimer's disease. Compared to the group that didn't develop memory problems, the 23 who developed MCI or Alzheimer's disease had less gray matter in key memory processing areas (specifically, anteromedial temporal lobes and left angular gyrus) even at the beginning of the study when they were cognitively normal. They also had lower cognitive test scores, though these scores were still within normal range.

Smith, C.D. et al. 2007. Brain structural alterations before mild cognitive impairment. Neurology, 68, 1268-1273.

Memory complaints early warning for Alzheimer's

A post-mortem study of 90 older adults from the Rush Memory and Aging Project found that those who had yet to have any clinical symptoms of Alzheimer's disease still showed a strong link between their self-reported memory complaints and brain pathology associated with Alzheimer's disease.

Barnes, L.L., Schneider, J.A., Boyle, P.A., Bienias, J.L. & Bennett, D.A. 2006. Memory complaints are related to Alzheimer disease pathology in older persons. Neurology, 67, 1581-1585.

New early diagnostic test trialed

A mouse study has used a laser scan of the eyes to accurately diagnose Alzheimer's well before the disease was evident in the brain. The study follows on from earlier research revealing that beta-amyloid protein is evident in the eyes of Alzheimer’s patients. The test, which is a very quick and simple procedure, is now in the first stage of experimental trials in people.

The findings were announced at the annual meeting of the Optical Society of America.

Link between increased weight-loss rate and dementia

Confirming earlier indications, a long-term study of the elderly has revealed that their average rate of weight loss doubles (from 0.6 pounds per year to 1.2 pounds per year) in the year before symptoms of Alzheimer's-type dementia first become detectable. The finding may be useful as one of several early biomarkers. The study analyzed data on 449 seniors, of whom 125 were eventually diagnosed with mild dementia. Interestingly, at the beginning of the study, this group weighed about 8lb less on average than the other participants, although the two groups lost weight at the same rate for four to five years, before weight loss increased in the group that would eventually be diagnosed with mild dementia. It is not yet known why there should be this connection between weight loss and dementia.

Johnson, D.K., Wilkins, C.H. & Morris, J.C. 2006. Accelerated weight loss in Alzheimer's disease precedes diagnosis. Archives of Neurology, 63, 1312-1317.

Weight Loss Precedes Dementia Diagnosis In Women

A study has come out finding that, in women, declining weight precedes dementia by many years.
The retrospective study analyzed the medical records of 560 patients diagnosed with the onset of dementia between 1990 and 1994. The patients were matched with 560 controls. Among the women, average weight increased slightly over the preceding 30 years for the control group, but drifted downwards over the 30 years for those who developed dementia. The researchers suggest that changes in the brain interfered somehow with maintenance of body weight. The trend was not observed in men.

Findings were presented July 16 at the Alzheimer's Association International Conference on Alzheimer's Disease and Related Disorders in Madrid, Spain.

Link between size of hippocampus and progression to Alzheimer's

A study of 20 older adults with mild cognitive impairment has found that the hippocampus was smaller in those who developed into Alzheimer's during the 3 year period.

Apostolova, L.G. et al. 2006. Conversion of Mild Cognitive Impairment to Alzheimer Disease Predicted by Hippocampal Atrophy Maps. Archives of Neurology, 63, 693-699.

Alzheimer's disease onset tied to lapses in attention

A new finding may lead to another tool to detect Alzheimer’s early, and also offers support for the idea that breakdowns in attention may be at the heart of many of the memory problems experienced by Alzheimer’s sufferers. The study, involving 94 older adults (average age mid-70s) who were either healthy controls or in the early stages of Alzheimer’s, found those in the early stages of Alzheimer's disease had greater difficulty shifting attention back and forth between competing sources of information in a dichotic listening task. The finding may also explain why early-stage patients start to struggle with everyday tasks that call for processing a lot of information, such as driving. Prior research has found that performance on dichotic listening predicts accident rates in commercial bus drivers.
[note: this study was briefly reported on in September, but only mentioning its use as an early test]

Duchek, J.M. & Balota, D.A. 2005. Failure to Control Prepotent Pathways in Early Stage Dementia of the Alzheimer's Type: Evidence from Dichotic Listening. Neuropsychology, 19 (5).

A new analysis of a standard brain test may help predict dementia

A new study gives promise of early diagnosis of Alzheimer’s. A computer analysis of an EEG (electroencephalograph) test was almost 95% accurate in predicting those people in their 60s and 70s who would develop dementia over the next 7 to 10 years. There were several distinctive features in the brain waves of those who would later show cognitive impairment. The study now needs to be replicated with a larger sample.

Prichep, L.S., John, E.R., Ferris, S.H., Rausch, L., Fang, Z., Cancro, R., Torossian, C. & Reisberg, B. 2005. Prediction of longitudinal cognitive decline in normal elderly with subjective complaints using electrophysiological imaging. Neurobiology of Aging, In Press, Corrected Proof, Available online 6 October 2005.

Biosensor reveals new information about ADDLs

A new method using nanoscale optical biosensors allows researchers to detect and estimate the size and structure of ADDLs in cerebrospinal fluid. It’s believed that only ADDLs of a certain size cause problems for neurons in the early stages of Alzheimer’s disease. It is hoped that eventually this technology will help us diagnose Alzheimer’s accurately in living people, and aid our understanding of how ADDLs are involved in Alzheimer’s.

Haes, A.J., van Duyne, R.P., Klein, W.L. & Chang, L. 2005. The paper, ANYL 396, was presented at 9:00 a.m., Wednesday, Aug. 31, during the "New Frontiers in Ultrasensitive Analysis: Nanobiotech, Single Molecule Detection, and Single Cell Analysis" symposium.

Protein studies may lead to new Alzheimer's test

A new technique has identified more than 400 proteins in human spinal fluid — 40 times more than previously known. On average, one of every five proteins identified was substantially changed in patients with Alzheimer's disease compared to older people without neurological disease. The finding may lead to a new test for diagnosing Alzheimer’s.

Zhang, J., Goodlett, D.R., Quinn, J.F., Peskind, E., Kaye, J.A., Zhou, Y., Pan, C., Yi, E., Eng, J., Wang, Q., Aebersold, R.H. & Montine, T.J. 2005. Quantitative proteomics of cerebrospinal fluid from patients with Alzheimer disease Journal of Alzheimer's Disease, 7(2), 125-133.

New test is first step in early detection of Alzheimer's disease

A new technique called bio-bar-code amplification (BCA) technology has been found to be able to detect miniscule amounts of ADDL in human cerebrospinal fluid, bringing promise of an early diagnostic test for Alzheimer’s. The researchers hope to develop the technology so that the test could be done using a blood or urine sample instead of cerebrospinal fluid, which is more difficult to obtain.

Georganopoulou, D.G., Chang, L., Nam, J.M., Thaxton, C.S., Mufson, E.J., Klein, W.L. & Mirkin, C.A. 2005. Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer's disease. Proceedings of the National Academy of Sciences, 102, 2273-2276.

Smell test to help early diagnosis

One of the first types of memory affected by Alzheimer’s is olfactory memory – our database of smells. Researchers have now developed a simple scratch-and-sniff test that may enable Alzheimer’s to be detected in its very early stages. On the basis of a five-year study tracking 150 people with mild memory loss and Alzheimer's disease and 63 healthy adults, 10 specific odors proved to be the best predictors for Alzheimer's Disease: strawberry, smoke, soap, menthol, clove, pineapple, natural gas, lilac, lemon and leather. The test takes only 5 to 8 minutes, and seems to have comparable predictive ability as detailed memory and neuropsychological testing.

The findings were presented at the 2004 meeting of the American College of Neuropsychopharmacology.

Antibody detection in Alzheimer's may improve diagnosis, treatment

A study has found that people with Alzheimer’s disease have three to four times more antibodies to RAGE (receptor for advanced glycation end products) and beta amyloid — both major players in Alzheimer’s — than their healthy counterparts. The ability to measure these specific antibody levels could lead to a method for very early diagnosis. The finding may also point to a new treatment approach. The study supports the theory that autoimmunity and resulting inflammation play a big role in Alzheimer’s.

Mruthinti, S., Buccafusco, J.J., Hill, W.D., Waller, J.L., Jackson, T.W., Zamrini, E.Y. & Schade, R.F. 2004. Autoimmunity in Alzheimer’s disease: increased levels of circulating IgGs binding Ab and RAGE peptides. Neurobiology of Aging, 25 (8), 1023-1032.

Loss of smell linked to key protein in Alzheimer's disease

Loss of smell is one of the first clinical signs of Alzheimer’s and Parkinson’s disease. Now researchers have linked smell loss in genetically altered mice with excessive levels of a key protein associated with these diseases. If smell function declines as the levels of this protein increase in brain regions associated with smelling, the research could validate the use of smell tests for diagnosing Alzheimer's disease.

Macknin, J.B., Higuchi, M., Lee, V.M-Y., Trojanowski, J.Q. & Doty, R.L. 2004. Olfactory dysfunction occurs in transgenic mice overexpressing human t protein. Brain Research, 1000, 174-178.

Diagnosing Alzheimer's disease may soon be possible earlier

Diagnosing Alzheimer's disease is problematic because we have had no definitive tests for the disease (other than after death, by examining the brain). Recent research suggests that two markers in cerebrospinal fluid may indicate the presence of Alzheimers. This is exciting not only because it would make diagnosis easier, but because it might enable us to diagnose it much earlier. However, to be clinically useful, they will need to develop tests that use more readily available fluids (such as urine).

Praticò, D., Clark, C. M., Lee, V. M.-Y., Trojanowski, J. Q., Rokach, J., & FitzGerald, G. A. (2000). Increased 8,12-iso-iPF2α-VI in Alzheimer’s disease: Correlation of a noninvasive index of lipid peroxidation with disease severity. Annals of Neurology, 48(5), 809–812. doi:10.1002/1531-8249(200011)48:5<809::AID-ANA19>3.0.CO;2-9

Gene marker for late-onset Alzheimer's disease nearer discovery

Three independent studies have linked late-onset Alzheimer's disease to a locus on chromosome 10 that affects processing of the amyloid-beta protein, a peptide important in the formation of the characteristic amyloid plaques found in the brains of people with Alzheimer's disease. Researchers are optimistic the precise gene will be found in the next few years.
Before this, a particular form of the apolipoprotein E (APOE) gene on chromosome 19 has been the only widely recognized genetic risk factor in late onset Alzheimer’s disease. There is also some evidence of a risk factor gene on a region of chromosome 12.
So far, three genes have been found that are linked to the rare early-onset Alzheimer's (when symptoms appear before age 60).

Bertram, L., Blacker, D., Mullin, K., Keeney, D., Jones, J., Basu, S., … Tanzi, R. E. (2000). Evidence for Genetic Linkage of Alzheimer’s Disease to Chromosome 10q. Science, 290(5500), 2302–2303. doi:10.1126/science.290.5500.2302

Ertekin-Taner, N., Graff-Radford, N., Younkin, L. H., Eckman, C., Baker, M., Adamson, J., … Younkin, S. G. (2000). Linkage of Plasma Aβ42 to a Quantitative Locus on Chromosome 10 in Late-Onset Alzheimer’s Disease Pedigrees. Science, 290(5500), 2303–2304. doi:10.1126/science.290.5500.2303

Myers, A., Holmans, P., Marshall, H., Kwon, J., Meyer, D., Ramic, D., … Goate, A. M. (2000). Susceptibility Locus for Alzheimer’s Disease on Chromosome 10. Science, 290(5500), 2304–2305. doi:10.1126/science.290.5500.2304

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Alzheimer's Genes

Older news items (pre-2010) brought over from the old website

Impact of Alzheimer's gene on healthy brains

And another new imaging analysis technique has cast light on the impact of the Alzheimer’s gene ApoE4 in healthy brains. Healthy older adults with the gene were found to have reduced cognitive performance, decreased brain volume in the hippocampus and amygdala, and decreased white matter integrity in the left parahippocampal gyrus.

Honea, Robyn A., Eric Vidoni, Amith Harsha and Jeffrey M. Burns. Impact of APOE on the Healthy Aging Brain: A Voxel-Based MRI and DTI Study. J Alzheimers Dis 18:3, 553-564.

Three new genes associated with Alzheimer's found

Only one gene, ApoE4, has been associated with the non-familial (common) form of Alzheimer’s. Now the largest ever Alzheimer's genome-wide association study involving 16,000 individuals, has found three more. CLU or ApoJ (which produces a protective protein called clusterin or apolipoprotein J), PICALM (important at synapses and involved in transporting molecules within and into nerve cells), and CR1. Both CLU and CR1 have previously been implicated in the clearance of amyloid beta peptide. CLU is encoded on chromosome 8, CR1 on chromosome 1, and PICALM on chromosome 11.

Harold, D. et al. 2009. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Nature Genetics, 41, 1088–1093. Lambert, J-C et al. 2009. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease. Nature Genetics, 41, 1094-1099.

Carriers of Alzheimer's gene show different brain activity as young adults

Possession of the ApoE4 gene variant associated with Alzheimer’s risk is found in about a quarter of the population, and has been shown to be associated with differences in the hippocampus in middle-aged and elderly healthy carriers. Now a new study of 36 younger adults (20-35) has revealed that differences in brain activity patterns between carriers and non-carriers are also evident at this stage, not only when performing a memory task, but even when the brain was at rest. Carriers of the gene had more brain activity in the hippocampus during the memory task, and more activity in the default mode network during rest. The findings support a theory that the brain's memory function may gradually wear itself out in those who go on to develop Alzheimer's.

Filippini, N. et al. 2009. Distinct patterns of brain activity in young carriers of the APOE-ε4 allele. Proceedings of the National Academy of Sciences, 106, 7209-7214.

Having a parent with dementia may affect memory in midlife

A study of 715 participants from the second generation of the Framingham Heart Study (average age 59) has found that, among those with the ApoE ε4 gene, those who had parents with dementia scored significantly worse on tests of verbal memory and visual memory than persons who did not have parents with dementia. The impairment was strongest in those whose parents had Alzheimer’s (rather than other forms of dementia), and in them was equivalent to around 15 years of brain aging. The effect of parental dementia was not found in those who didn’t have the ApoE ε4 gene.

Debette, S. et al. 2009. Parental Dementia and Alzheimer Disease Are Associated with Poorer Memory in Middle-Aged Adults: The Framingham Offspring Study. Presented April 29 at the American Academy of Neurology's 61st Annual Meeting in Seattle, Washington.

Memory gene linked to late-onset Alzheimer's

Following the finding that carriers of one variant (the T-allele) of the KIBRA gene performed better on memory tests compared to those carrying the C-allele, researchers have now found that carriers of the T-allele have a 25% lower risk of developing Alzheimer's disease. The conclusion is supported by three studies. A study of 702 deceased persons diagnosed with Alzheimer's, and 1,026 living and deceased persons with and without Alzheimer's, found that non-carriers of the KIBRA T-allele had increased risk of late-onset Alzheimer¹s. A study of brain tissue from 47 deceased individuals found that KIBRA, and a subset of other molecules directly interacting with it, were significantly altered in regions of the brain involved in Alzheimer's disease pathology, but not in a region of the brain typically unaffected -- the primary visual cortex. PET scans of 136 individuals aged 47 to 68, with close relatives diagnosed with Alzheimer's, of whom half carried the T-allele, found that non-carriers exhibited, on average, less metabolic activity in key brain regions known to be altered in the earliest stages of the disease. Similar findings have been found when looking at the epsilon 4 allele of apolipoprotein E (the ‘Alzheimer’s gene’). In the current study, the effects of this allele were controlled for.

Corneveaux, J.J. et al. In press. Evidence for an association between KIBRA and late-onset Alzheimer's disease. Neurobiology of Aging

Healthy children of Alzheimer patients show early brain changes

A study of 28 neurologically-normal subjects, between ages 45 and 65, of whom 12 carried the ‘Alzheimer’s gene’ APOE-4, has found that although there was no significant difference in educational level or neuropsychological performances, those who didn’t carry the gene had significantly better functional connectivity between the hippocampus and the posterior cingulated cortex.

The findings were presented at the Alzheimer's Association International Conference on Alzheimer's disease in Chicago, July 29.

Women more likely to have memory problems in very old age

Dementia risk for both men and women increases from age 65 to 85, but a study of about 900 people age 90 and older has found that women were nearly twice as likely to have dementia in their 90s compared to men. The results also showed that the likelihood of having dementia doubled every five years in women but not in men. Women with a higher education appeared to be as much as 45% less likely to have dementia compared to women with less education.

Corrada, M.M. et al. 2008. Prevalence of dementia after age 90: Results from The 90+ Study. Neurology, 71 (5), 337-343.

Gene variation linked to earlier onset of Alzheimer's symptoms

Another genetic variation has been found for Alzheimer’s disease. Unlike the ‘Alzheimer’s gene’ APOe4, which is linked to the rare early-onset form, this gene variant is linked to early presentation in people afflicted with the more common, late-onset form. Rather than increasing the risk of Alzheimer’s, the gene increases the vulnerability of carriers to the effects of amyloid plaques, so that symptoms become evident earlier. The gene codes for the tau protein found in neurofibrillary tangles. Previous studies have had inconsistent results, but the new study has dealt with previous difficulties.

Kauwe, J.S.K. et al. 2008. Variation in MAPT is associated with cerebrospinal fluid tau levels in the presence of amyloid-beta deposition. Proceedings of the National Academy of Sciences, 105 (23), 8050-8054.

Maternal inheritance more importance than paternal for Alzheimer's risk?

In an intriguing preliminary study comparing brain metabolism among cognitively normal people who have a father, a mother, or no relatives with Alzheimer’s disease, researchers have found that only those with an affected mother have reduced brain metabolism in the same brain regions as Alzheimer’s patients.

Mosconi, L. et al. 2007. Maternal family history of Alzheimer's disease predisposes to reduced brain glucose metabolism. PNAS, 104, 19067-19072.

Familial link between Parkinson's and dementia

A study of relatives of patients with Parkinson’s disease provides evidence that relatives of patients with Parkinson’s disease (primarily younger age at onset Parkinson’s) have an increased risk of cognitive impairment or dementia.

Rocca, W.A. et al. 2007. Risk of Cognitive Impairment or Dementia in Relatives of Patients With Parkinson Disease. Archives of Neurology, 64(10),1458-1464.

High stress and genetic risk factor lead to increased memory decline

A study involving 91 older, healthy subjects (mean age 78.8 years) has found that those low on stress (low levels in cortisol) or without the APOE-ε4 gene performed better on memory measures than those with high stress or those with the APOE-ε4 gene. Those who had the gene and had high stress levels showed the greatest memory impairment.

Peavy, G.M. et al. 2007. The Effects of Prolonged Stress and APOE Genotype on Memory and Cortisol in Older Adults. Biological Psychiatry, 62 (5), 472-478.

New Alzheimer's gene

A study comparing more genetic markers in the DNA of people with and without Alzheimer’s disease than ever before has revealed a new gene that may increase a person’s risk for developing Alzheimer’s disease. The gene — GAB2 — appears to modify an individual’s risk when associated with other genes, including APOE4. It’s suggested that the healthy form of the GAB2 gene protects brain cells from developing tangles. If confirmed, this discovery could provide a target for future therapeutic drugs.

Reiman, E.M. et al. 2007. GAB2 Alleles Modify Alzheimer's Risk in APOE e4 Carriers. Neuron, 54, 713-720.

Study examines genetic risk factors for Alzheimer's disease

A Welsh study that tested more than 17,000 gene variants in 4,000 volunteers has found evidence for several genes contributing to Alzheimer’s disease, the most interesting one being GALP, thought to affect the development of tangles within brain cells.

The findings will be published in a future issue of Human Molecular Genetics.

Two-fold role of Alzheimer’s genes?

The genes responsible for an inherited form of Alzheimer's disease — two genes known as presenilins — are primarily known for their role as an enzyme that cleaves amyloid precursor protein (APP) to form amyloid ß-peptide, which function has a direct connection to Alzheimer’s, and consequently has been the focus of attention. However, new research indicates that these genes also may control the balance of calcium within cells by acting as a calcium channel, and that the mutated forms of these genes lose this ability. Given the role that calcium signaling plays in cognitive function, it may be that this other role of presenilins is also important in the development of Alzheimer’s. If so, drugs that restore normal calcium levels might be useful for treating Alzheimer's disease.

Tu, H. et al. 2006. Presenilin Forms ER Ca2+ Leak Channels, a Function Disrupted by Familial Alzheimer's Disease-Linked Mutations. Cell, 126, 981–993.

New genetic cause of Alzheimer's disease

Amyloid protein originates when it is cut by enzymes from a larger precursor protein. In very rare cases, mutations appear in the amyloid precursor protein (APP), causing it to change shape and be cut differently. The amyloid protein that is formed now has different characteristics, causing it to begin to stick together and precipitate as amyloid plaques. A genetic study of Alzheimer's patients younger than 70 has found genetic variations in the promoter that increases the gene expression and thus the formation of the amyloid precursor protein. The higher the expression (up to 150% as in Down syndrome), the younger the patient (starting between 50 and 60 years of age). Thus, the amount of amyloid precursor protein is a genetic risk factor for Alzheimer's disease.

Theuns, J. et al. 2006. Promoter Mutations That Increase Amyloid Precursor-Protein Expression Are Associated with Alzheimer Disease. American Journal of Human Genetics, 78, 936-946.

Alzheimer's has higher genetic risk than thought

In a study far larger than any undertaken before, results suggest the highest estimates of the genetic risk of developing Alzheimer’s are in fact correct. The study involved all participants in the Swedish Twin Registry aged 65 or older in 1998 (nearly 12,000 of them) and found 392 pairs with evidence of Alzheimer's in at least one twin. In the model that best fit the data, genetic influence accounted for 79% of Alzheimer's risk, with 95% probability of being within the range 67 to 88%. The other 21% of Alzheimer's risk was due to non- shared environmental causes. Risk from shared environments was statistically negligible. Genetic risk for Alzheimer's was the same for men and women after controlling for age. The study raises doubts about the widely held view that Alzheimer's has two forms: the "familial," with genetic roots, and the "sporadic," with environmental causes. This doesn’t mean, however, that environment is unimportant.

Gatz, M. et al. 2006. Role of Genes and Environments for Explaining Alzheimer Disease. Archives of General Psychiatry, 63, 168-174.

Key genetic risk for Alzheimer's linked to myelin breakdown

Myelin, the fatty insulation coating the brain's internal wiring, builds up in childhood, and breaks down as we age. Myelin is critical for speedy communication between neurons. A new study supports a growing body of evidence that myelin breakdown is a key contributor to the onset of Alzheimer disease later in life. Moreover, it has also revealed that the severity and rate of myelin breakdown in healthy older individuals is associated with ApoE status. Thus both age, the most important risk factor for Alzheimer disease, and ApoE status, the second-most important risk factor, seem to act through the process of myelin breakdown.

Bartzokis, G., Lu, P.H., Geschwind, D.H., Edwards, N., Mintz, J. & Cummings, J.L. 2006. Apolipoprotein E Genotype and Age-Related Myelin Breakdown in Healthy Individuals: Implications for Cognitive Decline and Dementia. Archives of General Psychiatry, 63, 63-72.

Inactivation of Alzheimer's genes in mice causes dementia and brain degeneration

Mutations in two related genes known as presenilins are the major cause of early onset, inherited forms of Alzheimer's disease, but how these mutations cause the disease has not been clear. Since presenilins are involved in the production of amyloid peptides (the major components of amyloid plaques), it was thought that such mutations might cause Alzheimer’s by increasing brain levels of amyloid peptides. Accordingly, much effort has gone into identifying compounds that could block presenilin function. Now, however, genetic engineering in mice has revealed that deletion of these genes causes memory loss and gradual death of nerve cells in the mouse brain, demonstrating that the protein products of these genes are essential for normal learning, memory and nerve cell survival.

Saura, C.A., Choi, S-Y., Beglopoulos, V., Malkani, S., Zhang, D., Shankaranarayana Rao, B.S., Chattarji, S., Kelleher, R.J.III, Kandel, E.R., Duff, K., Kirkwood, A. & Shen, J. 2004. Loss of Presenilin Function Causes Impairments of Memory and Synaptic Plasticity Followed by Age-Dependent Neurodegeneration. Neuron, 42 (1), 23-36.

Genes influence memory in families with Alzheimer's disease

A study of 1,036 people from 266 families, most of whom had more than one person living with Alzheimer's in the extended family, found that about half of the variation in memory performance among individuals was due to genetics. The influence of genetics was not as strong in the areas of attention, abstract reasoning, language and visual-spatial ability. The genetic influence seemed to have little to do with the gene apolipoprotein E, known to increase the risk of developing Alzheimer's. It should be noted, however, that participants in the study had an average of only six years of education.

Lee, J.H., Flaquer, A., Stern, Y., Tycko, B. & Mayeux, R. 2004. Genetic influences on memory performance in familial Alzheimer disease. Neurology, 62, 414-421.

Genes identified for age of onset of Alzheimer's

Genes responsible for controlling the age of onset of Alzheimer's or Parkinson's diseases in those individuals genetically predisposed to developing these diseases have been identified. It appears that chromosome 10, already thought to contain a risk gene for Alzheimer's disease, could also contain an age at onset gene that affects both Alzheimer's and Parkinson's diseases.

Li, Y. et al. 2002. Age at Onset in Two Common Neurodegenerative Diseases Is Genetically Controlled. American Journal of Human Genetics, 70, 985-993.

Evidence that Alzheimer's protein switches on genes

Amyloid b-protein precursor (APP) is snipped apart by enzymes to produce three protein fragments. Two fragments remain outside the cell and one stays inside. When APP is produced in excessive quantities, one of the cleaved segments that remains outside the cell, called the amyloid b-peptides, clumps together to form amyloid plaques that kill brain cells and may lead to the development of Alzheimer’s disease. New research indicates that the short "tail" segment of APP that is trapped inside the cell might also contribute to Alzheimer’s disease, through a process called transcriptional activation - switching on genes within the cell. Researchers speculate that creation of amyloid plaque is a byproduct of a misregulation in normal APP processing.

[2866] Cao, X., & Südhof T. C.
(2001).  A Transcriptively Active Complex of APP with Fe65 and Histone Acetyltransferase Tip60.
Science. 293(5527), 115 - 120.

New genetic risk factor for susceptibility to Alzheimer's disease

In a decade-long research study following more than 300 first-degree relatives of 189 Alzheimer's patients, researchers at the University of Pittsburgh have identified a small area of chromosome 10 that, when combined with the previously identified APOE E4 gene, significantly increase a person's risk of developing the disease. This combination of genes produced a 16-fold increase in the risk of AD among first-degree relatives. By comparison, this effect is greater than the increased risk of lung cancer caused by smoking. These new results are supported by independent studies of AD patients and controls from Pittsburgh, Boston, and Bonn, Germany.

The study was reported in Molecular Psychiatry, 6 (4), pages 413-419.

Gene marker for late-onset Alzheimer's disease nearer discovery

Three independent studies have linked late-onset Alzheimer's disease to a locus on chromosome 10 that affects processing of the amyloid-beta protein, a peptide important in the formation of the characteristic amyloid plaques found in the brains of people with Alzheimer's disease. Researchers are optimistic the precise gene will be found in the next few years.
Before this, a particular form of the apolipoprotein E (APOE) gene on chromosome 19 has been the only widely recognized genetic risk factor in late onset Alzheimer’s disease. There is also some evidence of a risk factor gene on a region of chromosome 12.
So far, three genes have been found that are linked to the rare early-onset Alzheimer's (when symptoms appear before age 60).

The findings are reported in the Dec. 22 issue of Science.

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