mild cognitive impairment
Six months of resistance training has improved executive function and associative memory in older women with mild cognitive impairment.
A study involving 86 older women (aged 70-80) with probable MCI has compared the effectiveness of resistance and aerobic training in improving executive function. The women were randomly allocated either to resistance training, aerobic training, or balance and tone training (control group). The programs all ran twice weekly for six months.
The 60-minute classes involved lifting weights (resistance training), outdoor walking (aerobic training), or stretching, balancing, and relaxation exercises (control).
Executive function was primarily assessed by the Stroop Test (measuring selective attention/conflict resolution), and also by Trail Making Tests (set-shifting) and Verbal Digits Tests (working memory). Associative memory (face-scene pairs) and problem-solving ability (Everyday Problems Test) were also assessed.
The study found that resistance training significantly improved performance on the Stroop Test and also the associative memory task. These improvements were associated with changes in some brain regions. In contrast to previous studies in healthy older adults, aerobic training didn’t produce any significant cognitive improvement, although it did produce significantly better balance and mobility, and cardiovascular capacity, compared to the control.
Interestingly, a previous study from these researchers demonstrated that it took a year of resistance training to achieve such results in cognitively healthy women aged 65-75. This suggests that the benefits may be greater for those at greater risk.
It may be that the greater benefits of resistance training over aerobic training are not be solely due to physical differences in the exercise. The researchers point out that resistance training required more cognitive engagement (“If you’re lifting weights you have to monitor your sets, your reps, you use weight machines and you have to adjust the seat, etc.”) compared to walking.
Note that impaired associative memory is one of the earliest cognitive functions affected in Alzheimer’s.
It’s also worth noting that exercise compliance was low (55-60%), suggesting that benefits might have been greater if the participants had been more motivated — or found the programs more enjoyable! The failure of aerobic exercise to improve cognition is somewhat surprising, and perhaps it, too, may be attributed to insufficient engagement — in terms of intensity as well as amount.
The researchers have put up a YouTube video of the resistance training exercises used in the study.
 Nagamatsu, L. S., Handy T. C., Hsu C. L., Voss M., & Liu-Ambrose T.
(2012). Resistance Training Promotes Cognitive and Functional Brain Plasticity in Seniors With Probable Mild Cognitive Impairment.
Archives of Internal Medicine. 172(8), 666 - 668.
Full text available at http://archinte.jamanetwork.com/article.aspx?articleid=1135414
A four-year study involving 716 elderly (average age 82) has revealed that those who were most physically active were significantly less likely to develop Alzheimer’s than those least active. The study is unique in that, in addition to self-reports of physical and social activity, activity was objectively measured (for up to 10 days) through a device worn on the wrist. This device (an actigraph) enabled everyday activity, such as cooking, washing the dishes, playing cards and even moving a wheelchair with a person's arms, to be included in the analysis.
Cognitive performance was assessed annually. Over the study period, 71 participants (10%) developed Alzheimer’s.
The study found that those in the bottom 10% of daily physical activity were more than twice as likely (2.3 times) to develop Alzheimer's disease as those in the top 10%. Those in the bottom 10% of intensity of physical activity were almost three times (2.8 times) as likely to develop Alzheimer's disease as people in the top 10%.
Moreover, the level of activity was associated with the rate of cognitive decline.
The association remained after motor function, depression, chronic health conditions, and APOE gene status were taken into account.
The findings should encourage anyone who feels that physical exercise is beyond them to nevertheless engage in milder forms of daily activity.
Another recent study, involving 331 cognitively healthy elderly, has also found that higher levels of physical activity were associated with better cognitive performance (specifically, a shorter time to complete the Trail-making test, and higher levels of verbal fluency) and less brain atrophy. Activity levels were based on the number of self-reported light and hard activities for at least 30 minutes per week. Participants were assessed in terms of MMSE score, verbal fluency, and visuospatial ability.
 Buchman, A. S., Boyle P. A., Yu L., Shah R. C., Wilson R. S., & Bennett D. A.
(2012). Total Daily Physical Activity and the Risk of AD and Cognitive Decline in Older Adults.
Neurology. 78(17), 1323 - 1329.
 Benedict, C., Brooks S. J., Kullberg J., Nordenskjöld R., Burgos J., Le Grevès M., et al.
(Submitted). Association between physical activity and brain health in older adults.
Neurobiology of Aging.
A study involving nearly 20,000 people age 45 and older, of whom nearly half were taking medication for high blood pressure, has found that those with high diastolic blood pressure (the bottom number of a blood pressure reading) were more likely to have cognitive impairment than those with normal diastolic readings. For every 10 point increase in the reading, the odds of a person having cognitive problems was 7% higher. There was no correlation with systolic blood pressure. The results were adjusted for age, smoking status, exercise level, education, diabetes and high cholesterol. High diastolic blood pressure is known to lead to weakening of small arteries in the brain.
 Tsivgoulis, G., Alexandrov A. V., Wadley V. G., Unverzagt F. W., Go R. C. P., Moy C. S., et al.
(2009). Association of higher diastolic blood pressure levels with cognitive impairment.
Neurology. 73(8), 589 - 595.
The Dietary Approaches to Stop Hypertension (DASH) diet lowers blood pressure and is often recommended by physicians to people with high blood pressure or pre-hypertension. An 11-year study of over 3800 seniors found that those with higher DASH diet adherence scores had higher cognitive scores at the beginning of the study and increasingly so over time. Four of the nine food-group/nutrient components were independently associated with cognitive scores -- vegetables, whole grains, low-fat dairy, nut/legumes. When a score based on just these four components was used, the difference between those in the highest quintile and those in the lowest was even greater, particularly by the end of the study.
Wengreen, H.J. et al. 2009. DASH diet adherence scores and cognitive decline and dementia among aging men and women: Cache County study of Memory Health and Aging. Presented at the Alzheimer's Association International Conference on Alzheimer's Disease July 11-16 in Vienna.
An 8-year study of over 2,500 seniors in their 70s, has found that 53% showed normal age-related decline, 16% showed major cognitive decline, and an encouraging 30% had no change or improved on the tests over the years. The most important factors in determining whether a person maintained their cognitive health was education and literacy: those with a ninth grade literacy level or higher were nearly five times as likely to stay sharp than those with lower literacy levels; those with at least a high school education were nearly three times as likely to stay sharp as those who have less education. Lifestyle factors were also significant: non-smokers were nearly twice as likely to stay sharp as smokers; those who exercised moderately to vigorously at least once a week were 30% more likely to maintain their cognitive function than those who do not exercise that often; people working or volunteering and people who report living with someone were 24% more likely to maintain cognitive function.
 Ayonayon, H. N., Harris T. B., For the Health ABC Study, Yaffe K., Fiocco A. J., Lindquist K., et al.
(2009). Predictors of maintaining cognitive function in older adults: The Health ABC Study.
Neurology. 72(23), 2029 - 2035.
A study of 32 newly diagnosed hypertensive children and adolescents (10 to 18 years old) plus 32 matched children with normal blood pressure has revealed that, according to parental assessment, those with high blood pressure scored significantly lower on executive function — that is, were poorer at planning, at complicated goal-directed tasks, and had more working memory problems. Additionally, more than half the children with both hypertension and obesity demonstrated clinically significant anxiety and depression.
Lande, M.B. et al. 2009. Parental Assessments of Internalizing and Externalizing Behavior and Executive Function in Children with Primary Hypertension. Journal of Pediatrics, 154 (2), 207-212.
A study involving 36 community-dwelling elderly (60-87 years old) whose blood pressure and cognitive functioning was monitored for 60 days has found that those with high blood pressure tended to perform more poorly on one of the three cognitive tasks, and this was particularly so when their blood pressure was higher than normal. The finding suggests that high blood pressure impacts on inductive reasoning, and thus the ability to work flexibly with unfamiliar information and find solutions. It also suggests that, for those with high blood pressure, such reasoning will be particularly difficult when they are stressed.
Gamaldo, A.A., Weatherbee, S.R. & Allaire, J.C. 2008. Exploring the Within-Person Coupling of Blood Pressure and Cognition in Elders. Journal of Gerontology: Psychological Science, 63, 386-389.
A study of nearly 1000 older adults (average age 76.3) without mild cognitive impairment at the start of the study found that over the follow-up period (average: 4.7 years), 334 individuals developed mild cognitive impairment, of which 160 were amnestic (reduced memory) and 174 were non-amnestic. Hypertension (high blood pressure) was associated with an increased risk of non-amnestic mild cognitive impairment; but not with amnestic mild cognitive impairment.
 Reitz, C., Tang M-X., Manly J., Mayeux R., & Luchsinger J. A.
(2007). Hypertension and the Risk of Mild Cognitive Impairment.
Arch Neurol. 64(12), 1734 - 1740.
Previous studies have found an association between high blood pressure and cognitive decline in older adults, but the evidence hasn’t been entirely consistent. Now a new study helps explain why the situation is not entirely straightforward. It appears that people with high blood pressure required more blood flow to the parts of the brain that support memory function than those with normal blood pressure. Moreover, and surprisingly, it turned out that antihypertensive medication actually made it worse, increasing the inefficiency of the brain’s work during memory tasks.
The findings were reported at the American Heart Association’s 61st Annual Fall Conference of the Council for High Blood Pressure Research.
A review of three large-scale studies of patients with hypertension who were treated with either medication or lifestyle strategies found no convincing evidence that lowering blood pressure prevents the development of dementia or cognitive impairment in hypertensive patients without apparent prior cerebrovascular disease. However, there is some evidence that midlife hypertension but not late life hypertension is related to cognitive decline; these studies involved patients aged 60 and older.
McGuiness, B., et al. The effects of blood pressure lowering on development of cognitive impairment and dementia in patients without apparent prior cerebrovascular disease. The Cochrane Database of Systematic Reviews 2006, Issue 2.
A review of 96 papers involving 36 very large, ongoing epidemiological studies in North America and Europe looking at factors involved in maintaining cognitive and emotional health in adults as they age has concluded that controlling cardiovascular risk factors, such as reducing blood pressure, reducing weight, reducing cholesterol, treating (or preferably avoiding) diabetes, and not smoking, is important for maintaining brain health as we age. The link between hypertension and cognitive decline was the most robust across studies. They also found a consistent close correlation between physical activity and brain health. However, they caution that more research is needed before specific recommendations can be made about which types of exercise and how much exercise are beneficial. They also found protective factors most consistently reported for cognitive health included higher education level, higher socio-economic status, emotional support, better initial performance on cognitive tests, better lung capacity, more physical exercise, moderate alcohol use, and use of vitamin supplements. Psychosocial factors, such as social disengagement and depressed mood, are associated with both poorer cognitive and emotional health in late life. Increased mental activity throughout life, such as learning new things, may also benefit brain health.
 Wagster, M., Hendrie H., Albert M., Butters M., Gao S., Knopman D. S., et al.
(2006). The NIH Cognitive and Emotional Health ProjectReport of the Critical Evaluation Study Committee.
Alzheimer's and Dementia. 2(1), 12 - 32.
A study involving a subset of men (average age 67 years) in the VA Normative Aging Study has found that those men with uncontrolled hypertension performed significantly worse on tests of verbal fluency and short-term memory. Those whose hypertension was controlled did as well as those with normal blood pressure. In the United States, hypertension affects 60% of adults age 60 and older, and a high proportion of these are untreated or inadequately treated.
Brady, C.B., Spiro, A. III & Gaziano, J.M. 2005. Effects of Age and Hypertension Status on Cognition: The Veterans Affairs Normative Aging Study. Neuropsychology, 19 (6).
Analysis of a large longitudinal study (the Maine-Syracuse Longitudinal Study 1976—2002) has found significant associations of high blood pressure to lower cognitive performance in the areas of abstract reasoning, psychomotor skills and visual organization skills. This association, moreover, was significantly greater for African-Americans, although it should be noted that there were only 147 African-Americans among the 1,563 participants. The effect was independent of age.
 Robbins, M. A., Elias M. F., Elias P. K., & Budge M. M.
(2005). Blood pressure and cognitive function in an African-American and a Caucasian-American sample: the Maine-Syracuse Study.
Psychosomatic Medicine. 67(5), 707 - 714.
An imaging study of seniors (average age 60) found that those with high blood pressure showed reduced blood flow to active brain areas when performing various everyday memory tasks, such as looking up a phone number then walking to another room to pick up the phone and dial the number. The diminished blood flow correlated to slightly worse scores on the memory tests. The differences weren’t large, but may help account for "senior moments" - memory problems commonly associated with age. It’s estimated that as many as a third of those with high blood pressure are not aware they have it.
Jennings, J.R., Muldoon, M.F., Meltzer, C.C., Ryan, C. & Price, J. 2003. Human Cerebral Blood Flow Responses to Information Processing Tasks are Decreased in Hypertensives Relative to Normotensives. Report presented at the American Heart Association's 57th Annual High Blood Pressure Research Conference, September 23.
Epidemiological studies have suggested hypertensive patients perform worse than individuals with normal blood pressure on cognition tests. A new study has investigated performance on specific cognitive tasks (visual and memory search involving computer displays) by those with high blood pressure who were not on medication and had no detectable cardiovascular disease. Participants ranged in age from 20 to 80. Contrary to expectation, high blood pressure slowed performance only in the middle-aged group (40-59), not in those younger or older.
Madden, D., Langley, L., Thurston, R., Whiting, W. & Blumenthal, J. 2003. Interaction of Blood Pressure and Adult Age in Memory Search and Visual Search Performance. Aging, Neuropsychology and Cognition, 10 (4), 241-54.
High blood pressure and stroke are associated with increased risks of dementia and cognitive impairment. In a study aimed to determine whether blood pressure lowering would reduce the risks of dementia and cognitive decline among individuals with cerebrovascular disease, 6105 people with prior stroke or transient ischemic attack were given either active treatment (perindopril for all participants and indapamide for those with neither an indication for nor a contraindication to a diuretic) or matching placebo(s). Over some 4 years, dementia was found in 6.3% of those given active treatment and 7.1% of those in the placebo group. Cognitive decline occurred in 9.1% of the actively treated group and 11.0% of the placebo group. The researchers concluded that blood pressure lowering with perindopril and indapamide therapy was helpful for those with cerebrovascular disease, in terms of reduced risks of dementia and cognitive decline.
 The PROGRESS Collaborative Group*
(2003). Effects of Blood Pressure Lowering With Perindopril and Indapamide Therapy on Dementia and Cognitive Decline in Patients With Cerebrovascular Disease.
Arch Intern Med. 163(9), 1069 - 1075.
From around age 60, "white-matter lesions" appear in the brain, significantly affecting cognitive function. But without cognitive data from childhood, it is hard to know how much of the difference in cognitive abilities between elderly individuals is due to aging. A longitudinal study has been made possible by the Scottish Mental Survey of 1932, which gave 11-year-olds a validated cognitive test. Scottish researchers have tracked down healthy living men and women who took part in this Survey and retested 83 participants. Testing took place in 1999, when most participants were 78 years old.It was found that the amount of white-matter lesions made a significant contribution to general cognitive ability differences in old age, independent of prior ability. The amount of white-matter lesions contributed 14.4% of the variance in cognitive scores; early IQ scores contributed 13.7%. The two factors were independent.Although white-matter lesions are viewed as a normal part of aging, they are linked with other health problems, in particular to circulatory problems (including hypertension, diabetes, heart disease and cardiovascular risk factors).
 Deary, I. J., Leaper S. A., Murray A. D., Staff R. T., & Whalley L. J.
(2003). Cerebral white matter abnormalities and lifetime cognitive change: a 67-year follow-up of the Scottish Mental Survey of 1932.
Psychology and Aging. 18(1), 140 - 148.
Research in rats has found that linoleic acid improved not only blood pressure, but also hypertension-induced memory decline, suggesting that the early incorporation of linoleic acid in the diet, may not only help in controlling hypertension, but may also improve hypertension-induced cognitive impairment. Linoleic acid is found in vegetable seed oils, such as safflower, sunflower, and hemp seed.
Holloway, V. 2002. Effects of early nutritional supplementation of linoleic acid in Hypertension. Paper presented at an American Physiological Society (APS) conference, "The Power of Comparative Physiology: Evolution, Integration and Application", August 24-28 in San Diego, CA.
A large-scale six-year study of people aged 40 to 70 years old found that people with diabetes and high blood pressure are more likely to experience cognitive decline. Diabetes was associated with greater cognitive decline for those younger than 58 as well as those older than 58, but high blood pressure was a risk factor only for the 58 and older group.
 Knopman, D. S., Boland L. L., Mosley T., Howard G., Liao D., Szklo M., et al.
(2001). Cardiovascular risk factors and cognitive decline in middle-aged adults.
Neurology. 56(1), 42 - 48.
A large-scale study of French people aged 59 to 71 found that, after four years, 21.7% of those with untreated high blood pressure experienced severe cognitive decline. Of those with high blood pressure whose treatment didn't bring the blood pressure down to normal, 12.5% had severe cognitive decline. Of those whose high blood pressure was successfully treated, 7.8% had severe cognitive decline. Only 7.3% of those with normal blood pressure had severe cognitive decline.
Tzourio, C., Dufouil, C., Ducimetière, P., Alpérovitch, A. and for the EVA Study Group. 1999. Cognitive decline in individuals with high blood pressure: A longitudinal study in the elderly. Neurology, 53, 1948.
A study involving 1,575 older adults (aged 58-76) has found that those with DHA levels in the bottom 25% had smaller brain volume (equivalent to about 2 years of aging) and greater amounts of white matter lesions. Those with levels of all omega-3 fatty acids in the bottom quarter also scored lower on tests of visual memory, executive function, and abstract thinking.
The finding adds to the evidence that higher levels of omega-3 fatty acids reduce dementia risk.
For more about omega-3 oils and cognition
 Tan, Z. S., Harris W. S., Beiser A. S., Au R., Himali J. J., Debette S., et al.
(2012). Red Blood Cell Omega-3 Fatty Acid Levels and Markers of Accelerated Brain Aging.
Neurology. 78(9), 658 - 664.
A review supports cognitive stimulation therapy for those with mild to moderate dementia.
A review of 15 randomized controlled trials in which people with mild to moderate dementia were offered mental stimulation has concluded that such stimulation does indeed help slow down cognitive decline.
In total, 718 people with mild to moderate dementia, of whom 407 received cognitive stimulation, were included in the meta-analysis. The studies included in the review were identified from a search of the Cochrane Dementia and Cognitive Improvement Group Specialized Register, and included all randomized controlled trials of cognitive stimulation for dementia which incorporated a measure of cognitive change.
Participants were generally treated in small groups and activities ranged from discussions and word games to music and baking. Treatment was compared to those seen without treatment, with "standard treatments" (such as medicine, day care or visits from community mental health workers), or with alternative activities such as watching TV and physical therapy.
There was a “clear, consistent benefit” on cognitive function for those receiving cognitive stimulation, and these benefits were still seen one to three months after the treatment. Benefits were also seen for social interaction, communication and quality of life and well-being.
While no evidence was found for improvements in the mood of participants, or their ability to care for themselves or function independently, or in problem behaviors, this is not to say that lengthier or more frequent interventions might not be beneficial in these areas (that’s purely my own suggestion).
In one study, family members were trained to deliver cognitive stimulation on a one-to-one basis, and the reviewers suggested that this was an approach deserving of further attention.
The reviewers did note that the quality of the studies was variable, with small sample sizes. It should also be noted that this review builds on an earlier review, involving a subset of these studies, in which the opposite conclusion was drawn — that is, at that time, there was insufficient evidence that such interventions helped people with dementia. There is no doubt that larger and lengthier trials are needed, but these new results are very promising.
 Woods, B., Aguirre E., Spector A. E., Orrell M., Woods B., Aguirre E., et al.
(Submitted). Cognitive stimulation to improve cognitive functioning in people with dementia.
The Cochrane Library.
A large Swedish twin study reveals the prevalence of age-related cognitive impairment and points to the greater importance of environment over genes. Another very large study points to marked regional variation in mild cognitive impairment.
Data from 11,926 older twins (aged 65+) has found measurable cognitive impairment in 25% of them and subjective cognitive impairment in a further 39%, meaning that 64% of these older adults were experiencing some sort of cognitive impairment.
Although subjective impairment is not of sufficient magnitude to register on our measurement tools, that doesn’t mean that people’s memory complaints should be dismissed. It is likely, given the relative crudity of standard tests, that people are going to be aware of cognitive problems before they grow large enough to be measurable. Moreover, when individuals are of high intelligence or well-educated, standard tests can be insufficiently demanding. [Basically, subjective impairment can be thought of as a step before objective impairment, which itself is a step before mild cognitive impairment (MCI is a formal diagnosis, not simply a descriptive title), the precursor to Alzheimer’s. Note that I am calling these “steps” as a way of describing a continuum, not an inevitable process. None of these steps means that you will inevitably pass to the next step, but each later step will be preceded by the earlier steps.]
Those with subjective complaints were younger, more educated, more likely to be married, and to have higher socio-economic status, compared to those with objective impairment — supporting the idea that these factors provide some protection against cognitive decline.
The use of twins reveals that environment is more important than genes in determining whether you develop cognitive impairment in old age. For objective cognitive impairment, identical twins had a concordance rate of 52% compared to 50% in non-identical same-sex twins and 29% in non-identical different-gender twins. For subjective impairment, the rates were 63%, 63%, and 42%, respectively.
Another very large study, involving 15,376 older adults (65+), has explored the prevalence of amnestic MCI in low- and middle-income countries: Cuba, Dominican Republic, Peru, Mexico, Venezuela, Puerto Rico, China, and India. Differences between countries were marked, with only 0.6% of older adults in China having MCI compared to 4.6% in India (Cuba 1.5%, Dominican Republic 1.3%, Peru 2.6%, Mexico 2.8%, Venezuela 1%, Puerto Rico 3% — note that I have selected the numbers after they were standardized for age, gender, and education, but the raw numbers are not greatly different).
Studies to date have focused mainly on European and North American populations, and have provided prevalence estimates ranging from 2.1%-11.5%, generally hovering around 3-5% (for example, Finland 5.3%, Italy 4.9%, Japan 4.9%, the US 6% — but note South Korea 9.7% and Malaysia 15.4%).
What is clear is that there is considerable regional variation.
Interestingly, considering their importance in Western countries, the effects of both age and education on prevalence of aMCI were negligible. Granted that age and education norms were used in the diagnosis, this is still curious. It may be that there was less variance in educational level in these populations. Socioeconomic status was, however, a factor.
Participants were also tested on the 12-item WHO disability assessment schedule (WHODAS-12), which assesses five activity-limitation domains (communication, physical mobility, self-care, interpersonal interaction, life activities and social participation). MCI was found to be significantly associated with disability in Peru, India, and the Dominican Republic (but negatively associated in China). Depression (informant-rated) was also only associated with MCI in some countries.
All of this, I feel, emphasizes the situational variables that determine whether an individual will develop cognitive impairment.
Caracciolo B, Gatz M, Xu W, Pedersen NL, Fratiglioni L. 2012. Differential Distribution of Subjective and Objective Cognitive Impairment in the Population: A Nation-Wide Twin-Study. Journal of Alzheimer's Disease, 29(2), 393-403.
 Sosa, A L., Albanese E., Stephan B. C. M., Dewey M., Acosta D., Ferri C. P., et al.
(2012). Prevalence, Distribution, and Impact of Mild Cognitive Impairment in Latin America, China, and India: A 10/66 Population-Based Study.
PLoS Med. 9(2), e1001170 - e1001170.
Full text available at http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed....
The protein associated with Alzheimer's disease appears to impair cognitive function many years before symptoms manifest. Higher levels of this protein are more likely in carriers of the Alzheimer’s gene, and such carriers may be more affected by the protein’s presence.
Another study adds to the evidence that changes in the brain that may lead eventually to Alzheimer’s begin many years before Alzheimer’s is diagnosed. The findings also add to the evidence that what we regard as “normal” age-related cognitive decline is really one end of a continuum of which the other end is dementia.
In the study, brain scans were taken of 137 highly educated people aged 30-89 (participants in the Dallas Lifespan Brain Study). The amount of amyloid-beta (characteristic of Alzheimer’s) was found to increase with age, and around a fifth of those over 60 had significantly elevated levels of the protein. These higher amounts were linked with worse performance on tests of working memory, reasoning and processing speed.
More specifically, across the whole sample, amyloid-beta levels affected processing speed and fluid intelligence (in a dose-dependent relationship — that is, as levels increased, these functions became more impaired), but not working memory, episodic memory, or crystallized intelligence. Among the elevated-levels group, increased amyloid-beta was significantly associated with poorer performance for processing speed, working memory, and fluid intelligence, but not episodic memory or crystallized intelligence. Among the group without elevated levels of the protein, increasing amyloid-beta only affected fluid intelligence.
These task differences aren’t surprising: processing speed, working memory, and fluid intelligence are the domains that show the most decline in normal aging.
Those with the Alzheimer’s gene APOE4 were significantly more likely to have elevated levels of amyloid-beta. While 38% of the group with high levels of the protein had the risky gene variant, only 15% of those who didn’t have high levels carried the gene.
Note that, while the prevalence of carriers of the gene variant matched population estimates (24%), the proportion was higher among those in the younger age group — 33% of those under 60, compared to 19.5% of those aged 60 or older. It seems likely that many older carriers have already developed MCI or Alzheimer’s, and thus been ineligible for the study.
The average age of the participants was 64, and the average years of education 16.4.
Amyloid deposits varied as a function of age and region: the precuneus, temporal cortex, anterior cingulate and posterior cingulate showed the greatest increase with age, while the dorsolateral prefrontal cortex, orbitofrontal cortex, parietal and occipital cortices showed smaller increases with age. However, when only those aged 60+ were analyzed, the effect of age was no longer significant. This is consistent with previous research, and adds to evidence that age-related cognitive impairment, including Alzheimer’s, has its roots in damage occurring earlier in life.
In another study, brain scans of 408 participants in the Mayo Clinic Study of Aging also found that higher levels of amyloid-beta were associated with poorer cognitive performance — but that this interacted with APOE status. Specifically, carriers of the Alzheimer’s gene variant were significantly more affected by having higher levels of the protein.
This may explain the inconsistent findings of previous research concerning whether or not amyloid-beta has significant effects on cognition in normal adults.
As the researchers of the first study point out, what’s needed is information on the long-term course of these brain changes, and they are planning to follow these participants.
In the meantime, all in all, the findings do provide more strength to the argument that your lifestyle in mid-life (and perhaps even younger) may have long-term consequences for your brain in old age — particularly for those with a genetic susceptibility to Alzheimer’s.
 Rodrigue, K. M., Kennedy K. M., Devous M. D., Rieck J. R., Hebrank A. C., Diaz-Arrastia R., et al.
(2012). Β-Amyloid Burden in Healthy Aging Regional Distribution and Cognitive Consequences.
Neurology. 78(6), 387 - 395.
 Kantarci, K., Lowe V., Przybelski S. a, Weigand S. d, Senjem M. l, Ivnik R. J., et al.
(2012). APOE modifies the association between Aβ load and cognition in cognitively normal older adults.
Neurology. 78(4), 232 - 240.
Two recent studies add to the evidence linking sleep disorders to the later development of Alzheimer’s disease.
A small study of the sleep patterns of 100 people aged 45-80 has found a link between sleep disruption and level of amyloid plaques (characteristic of Alzheimer’s disease). The participants were recruited from the Adult Children Study, of whom half have a family history of Alzheimer’s disease.
Sleep was monitored for two weeks. Those who woke frequently (more than five times an hour!) and those who spent less than 85% of their time in bed actually asleep, were more likely to have amyloid plaques. A quarter of the participants had evidence of amyloid plaques.
The study doesn’t tell us whether disrupted sleep leads to the production of amyloid plaques, or whether brain changes in early Alzheimer's disease lead to changes in sleep, but evidence from other studies do, I think, give some weight to the first idea. At the least, this adds yet another reason for making an effort to improve your sleep!
The abstract for this not-yet-given conference presentation, or the press release, don’t mention any differences between those with a family history of Alzheimer’s and those without, suggesting there was none — but since the researchers made no mention either way, I wouldn’t take that for granted. Hopefully we’ll one day see a journal paper providing more information.
The main findings are supported by another recent study. A Polish study involving 150 older adults found that those diagnosed with Alzheimer’s after a seven-year observation period were more likely to have experienced sleep disturbances more often and with greater intensity, compared to those who did not develop Alzheimer’s.
Ju, Y., Duntley, S., Fagan, A., Morris, J. & Holtzman, D. 2012. Sleep Disruption and Risk of Preclinical Alzheimer Disease. To be presented April 23 at the American Academy of Neurology's 64th Annual Meeting in New Orleans.
Bidzan L, Grabowski J, Dutczak B, Bidzan M. 2011. [Sleep disorders in the preclinical period of the Alzheimer's disease]. Psychiatria Polska, 45(6), 851-60. http://www.ncbi.nlm.nih.gov/pubmed/22335128
A brief questionnaire designed to identify those with Alzheimer’s has been found to be useful in also identifying those with MCI. A large study confirms the value of such tools but also points to their limitations
New data from the ongoing validation study of the Alzheimer's Questionnaire (AQ), from 51 cognitively normal individuals (average age 78) and 47 aMCI individuals (average age 74), has found that the AQ is effective in identifying not only those with Alzheimer’s but also those older adults with mild cognitive impairment.
Of particular interest is that four questions were strong indicators of aMCI. These related to:
The AQ consists of 21 yes/no questions designed to be answered by a relative or carer. The questions fall into five categories: memory, orientation, functional ability, visuospatial ability, and language. Six of these questions are known to be predictive of AD and are given extra weighting, resulting in a score out of 27. A score above 15 was indicative of AD, and between 5 and 14 of aMCI. Scores of 4 or lower indicate that the person does not have significant memory problems.
The questionnaire is not of course definitive, but is intended as an indicator for further testing. Note, too, that all participants in this study were Caucasian.
The value of brief cognitive screenings combined with offering further evaluation is demonstrated in a recent large VA study, which found that, of 8,342 Veterans aged 70+ who were offered screening (the three-minute Mini-Cog), 8,063 (97%) accepted, 2,081 (26%) failed the screen, and 580 (28%) agreed to further evaluation. Among those accepting further evaluation, 93% were found to have cognitive impairment, including 75% with dementia.
Among those who declined further evaluation, 17% (259/1,501) were diagnosed with incident cognitive impairment through standard clinical care. In total, the use of brief cognitive screenings increased the numbers with cognitive impairment to 11% (902/8,063) versus 4% (1,242/28,349) in similar clinics without this program.
Importantly, the limits of such questionnaires were also demonstrated: 118 patients who passed the initial screen nevertheless requested further evaluation, and 87% were found to have cognitive impairment, including 70% with dementia.
This should not be taken as a reason not to employ such cognitive tests! There are two points that should, I think, be taken from this:
 Malek-Ahmadi, M., Davis K., Belden C. M., Jacobson S., & Sabbagh M. N.
(2012). Informant-reported cognitive symptoms that predict amnestic mild cognitive impairment.
BMC Geriatrics. 12(1), 3 - 3.
Full text available at http://www.biomedcentral.com/1471-2318/12/3
 Riley McCarten, J., Anderson P., Kuskowski M. A., McPherson S. E., Borson S., & Dysken M. W.
(2012). Finding Dementia in Primary Care: The Results of a Clinical Demonstration Project.
Journal of the American Geriatrics Society. 60(2), 210 - 217.
First study: http://www.eurekalert.org/pub_releases/2012-02/bc-htt020112.php
Second study: http://www.eurekalert.org/pub_releases/2012-02/w-cii020712.php
A pilot study suggests that wearing a nicotine patch may help improve memory loss in older adults with mild cognitive impairment.
The study involved 74 non-smokers with amnestic MCI (average age 76), of whom half were given a nicotine patch of 15 mg a day for six months and half received a placebo. Cognitive tests were given at the start of the study and again after three and six months.
After 6 months of treatment, the nicotine-treated group showed significant improvement in attention, memory, speed of processing and consistency of processing. For example, the nicotine-treated group regained 46% of normal performance for age on long-term memory, whereas the placebo group worsened by 26%.
Nicotine is an interesting drug, in that, while predominantly harmful, it can have positive effects if the dose is just right, and if the person’s cognitive state is at a particular level (slipping below their normal state, but not too far below). Too much nicotine will make things worse, so it’s important not to self-medicate.
Nicotine has been shown to improve cognitive performance in smokers who have stopped smoking and previous short-term studies with nicotine have shown attention and memory improvement in people with Alzheimer's disease. Nicotine receptors in the brain are reduced in Alzheimer’s brains.
Because the dose is so crucial, and the effects so dependent on brain state (including, one assumes, whether the person has been a smoker or not), more research is needed before this can be used as a treatment.
 Newhouse, P., Kellar K., Aisen P., White H., Wesnes K., Coderre E., et al.
(2012). Nicotine treatment of mild cognitive impairment.
Neurology. 78(2), 91 - 101.
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