Alzheimer's & other dementias

Common health complaints increase Alzheimer's risk

October, 2011

Two large studies respectively find that common health complaints and irregular heartbeat are associated with an increased risk of developing Alzheimer’s, while a rat study adds to evidence that stress is also a risk factor.

A ten-year study involving 7,239 older adults (65+) has found that each common health complaint increased dementia risk by an average of about 3%, and that these individual risks compounded. Thus, while a healthy older adult had about an 18% chance of developing dementia after 10 years, those with a dozen of these health complaints had, on average, closer to a 40% chance.

It’s important to note that these complaints were not for serious disorders that have been implicated in Alzheimer’s. The researchers constructed a ‘frailty’ index, involving 19 different health and wellbeing factors: overall health, eyesight, hearing, denture fit, arthritis/rheumatism, eye trouble, ear trouble, stomach trouble, kidney trouble, bladder control, bowel control, feet/ankle trouble, stuffy nose/sneezing, bone fractures, chest problems, cough, skin problems, dental problems, other problems.

Not all complaints are created equal. The most common complaint — arthritis/rheumatism —was only slightly higher among those with dementia. Two of the largest differences were poor eyesight (3% of the non-demented group vs 9% of those with dementia) and poor hearing (3% and 6%).

At the end of the study, 4,324 (60%) were still alive, and of these, 416 (9.6%) had Alzheimer's disease, 191 (4.4%) had another sort of dementia and 677 (15.7%) had other cognitive problems (but note that 1,023 were of uncertain cognitive ability).

While these results need to be confirmed in other research — the study used data from broader health surveys that weren’t specifically designed for this purpose, and many of those who died during the study will have probably had dementia — they do suggest the importance of maintaining good general health.

Common irregular heartbeat raises risk of dementia

In another study, which ran from 1994 to 2008 and followed 3,045 older adults (mean age 74 at study start), those with atrial fibrillation were found to have a significantly greater risk of developing Alzheimer’s.

At the beginning of the study, 4.3% of the participants had atrial fibrillation (the most common kind of chronically irregular heartbeat); a further 12.2% developed it during the study. Participants were followed for an average of seven years. Over this time, those with atrial fibrillation had a 40-50% higher risk of developing dementia of any type, including probable Alzheimer's disease. Overall, 18.8% of the participants developed some type of dementia during the course of the study.

While atrial fibrillation is associated with other cardiovascular risk factors and disease, this study shows that atrial fibrillation increases dementia risk more than just through this association. Possible mechanisms for this increased risk include:

  • weakening the heart's pumping ability, leading to less oxygen going to the brain;
  • increasing the chance of tiny blood clots going to the brain, causing small, clinically undetected strokes;
  • a combination of these plus other factors that contribute to dementia such as inflammation.

The next step is to see whether any treatments for atrial fibrillation reduce the risk of developing dementia.

Stress may increase risk for Alzheimer's disease

And a rat study has shown that increased release of stress hormones leads to cognitive impairment and that characteristic of Alzheimer’s disease, tau tangles. The rats were subjected to stress for an hour every day for a month, by such means as overcrowding or being placed on a vibrating platform. These rats developed increased hyperphosphorylation of tau protein in the hippocampus and prefrontal cortex, and these changes were associated with memory deficits and impaired behavioral flexibility.

Previous research has shown that stress leads to that other characteristic of Alzheimer’s disease: the formation of beta-amyloid.




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Helping Alzheimer's sufferers

Behavioral and cognitive strategies that can help those suffering from Alzheimer's.

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

Memory grows less efficient very early in Alzheimer's

A study of 109 healthy older adults (average age 75), 41 older adults with very early Alzheimer's, 13 with early Alzheimer's, and 35 younger adults (25 or younger) has found that those with Alzheimer’s — even those in the very early stages — were significantly less efficient than their healthy age peers at remembering items according to their value. It may be that Alzheimer's makes it harder for people to encode what they learn in a strategic way. This research suggests the potential for improved memory training.

Castel, A.D., Balota, D.A. & McCabe, D.P. 2009. Memory Efficiency and the Strategic Control of Attention at Encoding: Impairments of Value-Directed Remembering in Alzheimer's Disease. Neuropsychology, 23 (3), 297-306.

Pictures better than words for memory-damaged patients

We’ve long known that pictures are remembered better than words. Now a study has found that this picture superiority still exists in those with mild cognitive impairment and very mild Alzheimer’s disease. Moreover, frontally-based brainwave patterns were similar to those of controls when pictures were being retrieved, but not for words. The findings support the idea that those with mild Alzheimer’s can successfully use implicit memory (memory without conscious awareness) to support recognition, and this may point to new strategies for dealing with their memory problems.

Castel, A.D., Balota, D.A. & McCabe, D.P. 2009. Memory Efficiency and the Strategic Control of Attention at Encoding: Impairments of Value-Directed Remembering in Alzheimer's Disease. Neuropsychology, 23 (3), 297-306.

Treating sleep apnea in Alzheimer's patients helps cognition

A study of 52 men and women with mild to moderate Alzheimer's disease and obstructive sleep apnea (OSA) has found significant improvement in patients' neurological test scores after continuous positive airway pressure (CPAP) treatment. CPAP also reduced daytime sleepiness, a common complaint of Alzheimer's patients and their caregivers. The prevalence of OSA in patients with dementia has been estimated to be as high as 70 to 80%.

Ancoli-Israel, S. et al. 2008. Cognitive Effects of Treating Obstructive Sleep Apnea in Alzheimer's Disease: A Randomized Controlled Study. Journal of the American Geriatrics Society, 56 (11),2076-2081.

Hypnosis shown to reduce symptoms of dementia

This one’s really quite weird. A study found that people living with dementia who received hypnosis therapy over a nine month period showed an improvement in concentration, memory and socialization compared to groups receiving the normal treatment (who declined in these measures) and those attending a regular discussion group (who stayed the same). Relaxation, motivation and daily living activities also improved with the use of hypnosis. The findings point to the role of depression and anxiety in worsening the symptoms of dementia. The latest follow-up study has found that many of the benefits in the hypnosis group were maintained 12 months later.

Duff, S.C. & Nightingale, D.J. 2008. Long-term outcomes of hypnosis in changing the quality of life in patients with dementia. European Journal of Clinical Hypnosis, 7 (1)

More sleep improves cognition in Alzheimer patients with OSA

A study involving 52 participants with an average age of 77.8 years who had Alzheimer disease and obstructive sleep apnea (OSA) has found that it was increases in total sleep time in those given continuous positive airway pressure treatment that was associated with improvements in cognition, rather than improvement in oxygen levels. This suggests that the cognitive dysfunction associated with OSA in patients with dementia may be in part an effect of short sleep time.

The findings were presented at SLEEP 2008, the 22nd Annual Meeting of the Associated Professional Sleep Societies (APSS).

Mediterranean diet may help Alzheimer's patients live longer

A study of 192 people with Alzheimer's disease has found that those who most closely followed a Mediterranean diet were 76% less likely to die during the 4 ½ year study period compared to those who followed the diet the least. A previous study by the same researchers found that healthy people who eat a Mediterranean diet lowered their risk of developing Alzheimer's disease. The Mediterranean diet includes a high intake of vegetables, legumes, fruits, cereals, fish, monounsaturated fatty acids; a low intake of saturated fatty acids, dairy products, meat and poultry; and a mild to moderate amount of alcohol.

Scarmeas, N., Luchsinger, J.A., Mayeux, R. & Stern, Y. 2007. Mediterranean diet and Alzheimer disease mortality. Neurology, 69, 1084-1093. 070910162411.htm

Alzheimer's weight gain initiative improved patients' intellectual abilities

In a small, three-month study, Swedish researchers have found a way to increase the weight of people with Alzheimer's, with consequent improved intellectual abilities, by improving communication and patient involvement, altering meal routines and providing a more homely eating environment.

Mamhidir et al. 2007. Weight increase in patients with dementia and alteration in meal routines and meal environment after integrity promoting care. Journal of Clinical Nursing, 16, 987-996.

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.

Computer-based 'games' enhance mental function in Alzheimer's patients

An interactive multimedia internet-based game has been shown to benefit cognition in patients with Alzheimer's disease more than classic exercises of mental stimulation commonly used with dementia patients. The study compared patients receiving no cognitive intervention, those enrolled in a daily program that included 2.5 to 3.5 hours of cognitive stimulation tasks, musical therapy, arts and crafts, physical activity and programs that reinforced instrumental activities of daily living, and those who also used an interactive multimedia internet-based system which allowed them to carry out a variety of different cognitive stimulation tasks at varying levels of difficulty throughout the day. After 12 weeks, both intervention groups performed better on tests than the control group; at 24 weeks, the dual-intervention group did better than the program-only group. The study points to the value of cognitive stimulation to slow the rate of cognitive loss.

Tárraga, L. et al. 2006. A randomised pilot study to assess the efficacy of an interactive, multimedia tool of cognitive stimulation in Alzheimer’s disease. Journal of Neurology, Neurosurgery and Psychiatry, 77, 1116-1121.

Elders with dementia can tap into memory stores to give advice

Surprisingly, it appears that the best way to converse with an Alzheimer’s patient may be to ask them for advice. In two studies, researchers found that adults with moderate to severe symptoms of dementia can still be quite coherent and informative when asked for advice. In the first study, 14 people with early to advanced stages of dementia were asked about marriage, children and church in a purely social way, such as "Tell me about your children," and then later were asked for advice on the same topics, as in, "I'm thinking about having children. What kind of advice can you give me on that?" Patients were more coherent, informative and focused on the topic when asked for advice as opposed to when they were simply asked about their children, church or marriage. In the second study, six adults with dementia and six older adults without dementia, were given a booklet of pictures to guide them in teaching someone a simple recipe. Both groups successfully taught students to prepare the recipes, although those with dementia did need more prompting to finish the task.

Dijkstra, K., Bourgeois, M., Youmans, G. & Hancock, A. 2006. Implications of an Advice-Giving and Teacher Role on Language Production in Adults With Dementia. Gerontologist, 46, 357-366.

Missing eyeglasses impair activities for a third of nursing home patients with Alzheimer's disease

A study of nearly 100 Alzheimer’s patients in nursing homes has determined that one third of them were not using or did not have glasses that were strong enough to correct their eyesight. Apart from causing disorientation, limiting mobility and increasing the chance of falls, the loss of vision is likely to impact on mental stimulation, by making it difficult or impossible to engage in mentally stimulating activities such as reading or watching television.

Koch, J.M., Datta, G., Makhdoom, S. & Grossberg, G.T. 2005. Unmet Visual Needs of Alzheimer’s Disease Patients in Long-term Care Facilities. Journal of the American Medical Directors Association, 6(4), 233-237.

New memory aid helps dementia sufferers remember

An innovative memory aid based on an interactive multimedia computer system aims to stimulate more enjoyable, rewarding conversation between sufferers and those who care for them. CIRCA (Computer Interactive Reminiscence and Conversation Aid) involves a simple touch-screen with easy-to-follow instructions; it displays a choice of three random categories (entertainment, local life etc) and three media (music, photo, video). The images, video or sound clips then act as a memory trigger and conversation prompt. During development, CIRCA was tested on 40 dementia sufferers with very encouraging results. CIRCA could become available on the market in 2-3 years.

Weight loss may be an early sign of dementia in the elderly

An analysis of data from 1,890 men who were participants in The Honolulu-Asia Aging Study has found that the weight loss common in people with dementia begins 2-4 years before the onset of clinical dementia symptoms. It’s possible that treatment interventions directed toward maintaining optimal nutrition and preventing excess weight loss could slow the disease.

Stewart, R., Masaki, K., Xue, Q-L., Peila, R., Petrovitch, H., White, L.R. & Launer, L.J. 2005. A 32-Year Prospective Study of Change in Body Weight and Incident Dementia: The Honolulu-Asia Aging Study. Archives of Neurology, 62, 55-60.

Studies suggest people with early AD can still learn

A new study suggests that people who have early stage Alzheimer's disease could be more capable of learning than previously thought. The study found that mildly impaired Alzheimer’s patients who participated in 3-to-4 months of cognitive rehabilitation had a 170% improvement, on average, in their ability to recall faces and names and a 71% improvement in their ability to provide proper change for a purchase. The participants also could respond to and process information more rapidly and were better oriented to time and place. These improvements were still evident 3 months after the cognitive training ended.

Loewenstein, D.A., Acevedo, A., Czaja, S.J. & Duara, R. 2004. Cognitive Rehabilitation of Mildly Impaired Alzheimer Disease Patients on Cholinesterase Inhibitors. American Journal of Geriatric Psychiatry, 12(4), 395-402.

Alzheimer's may leave some forms of memory intact

A new study has demonstrated that people with Alzheimer's disease retain the capability for a specific form of memory used for rote learning of skills, despite their other memory loss. The finding suggests new strategies to improve training and rehabilitative programs for Alzheimer's sufferers. It also confirms other studies suggesting that a number of brain systems are more intact in Alzheimer's than previously thought.

[1219] Lustig, C., & Buckner R. L.
(2004).  Preserved Neural Correlates of Priming in Old Age and Dementia.
Neuron. 42(5), 865 - 875.

Program helps physical and behavioral well-being of Alzheimer's patients

A controlled trial of 153 community-dwelling patients diagnosed with Alzheimer’s examined the effectiveness of a home-based exercise program combined with caregiver training in behavioral management techniques in reducing functional dependence and delay institutionalization. The program resulted in improved physical health and less depression. Specifically, after three months, those receiving the training were more likely to exercise at least 60 minutes a week, to have fewer days of restricted activity, to have improved scores for physical role functioning, and improved Cornell Depression Scale for Depression in Dementia scores, and have less institutionalization due to behavioral disturbance.

Teri, L. et al. 2003. Exercise Plus Behavioral Management in Patients With Alzheimer Disease: A Randomized Controlled Trial. JAMA, 290, 2015-2022.

Alzheimer patients who scored well on memory tests show unique compensatory brain activity

A study of 12 healthy older adults and 11 older patients with probable early-stage Alzheimer's compared their performance in a series of semantic and episodic memory tasks on a computer screen, using PET scans. Overall, Alzheimer's patients performed less accurately on the semantic and episodic tasks compared to the normal controls. However, the range of scores was quite large in the Alzheimer group, with some performing poorly and others performing within the normal range. For those patients who did better on the memory tasks, researchers found that their prefrontal network activity was more expansive compared to the error-prone patients. This additional activity was happening in the right frontal and temporoparietal areas. It was a unique neural pattern not found in the controls either. This provides the most direct evidence to date that Alzheimer's patients can use additional neural resources in the prefrontal cortex to compensate for losses attributable to the degenerative process of the disease.

Grady, C.L., McIntosh, A.R., Beig, S., Keightley, M.L., Burian, H. & Black, S.E. 2003. Evidence from Functional Neuroimaging of a Compensatory Prefrontal Network in Alzheimer's Disease. Journal of Neuroscience, 23, 986-993.

Memory training may help some Alzheimer's patients

Following anecdotal "success stories" of memory training provided by rehabilitation experts, researchers in London conducted a controlled study to see whether such training could be standardized for a larger group of people, and whether the benefits of training endured. The study involved 12 participants with probable Alzheimer's Disease (AD) at the minimal or mild stage, when they still had some capacity for learning. The researchers then trained participants to remember the names of people whom they had difficulty naming from a set of 12 photos that included people in their social network and famous people. They used such memory aids as mnemonic devices, which use the image to jog memory through some kind of meaningful association; "vanishing cues," a method in which participants fill in more and more letters in the person's name, until they can recall that name without any help; and "expanding rehearsal," in which people test themselves on what they've learned, in spaced intervals over time. All training minimized the chance of errors, which helped to reduce distress and raise confidence. By training participants' memory for just half of their photo sets, researchers were able to compare memory training with no training, for each participant. Participants learned the face-name association at the rate of one per week, adding each new pair to their practice until they worked at all six pairs. They continued practicing until a one-month follow-up test of the face-name pairs. Testing was repeated at three, six and 12 months. The memory training produced a statistically significant improvement in group performance on free recall of trained items. Participants kept their memory gains six months after training, and scores remained above baseline levels after 12 months -- even without further practice. Not all participants benefited from the training. Further research is needed to discover what distinguishes those who benefitted from those who didn’t. One factor that was found, was that those who were more aware of their memory problems were more likely to respond well to memory training.

Clare, L.,Wilson, B.A., Carter, G., Roth, I., Hodges & J.R. 2002. Relearning Face-Name Associations in Early Alzheimer's Disease. Neuropsychology, 16 (4), 538-47.

Helping Alzheimer's sufferers remember

Alzheimer sufferers recalled significantly more details of long-ago events when music was played during recall. Recent memory was not affected. It is suggested that music could be played at particular times when better recall is desirable, such as when relatives visit.

The study involved 23 older adults with mild-to-moderate dementia. Participants were tested in each of four auditory background conditions presented randomly, one week apart: quiet; cafeteria noise; familiar music (first movement of Vivaldi's “The Four Seasons”); novel music (Fitkin's “Hook”). Questions were drawn from three life eras: up to age 20; around ages 20—50; and recent past and present. Sound conditions (music or noise) were significantly better than quiet (mean recall 67% vs 61%). There was no difference between familiar and novel music, but there was a small difference between noise and music (66% vs 68%). This difference was greater for remote memory; there was no difference between noise and music for memory of recent past. Overall, the Alzheimer's patients had much better recall for older memories.

The improvement in recall for the sound conditions over quiet, and the similarity between all sound conditions, points to arousal as the crucial factor. The greater effectiveness of music compared to noise may signal an associational effect. Further research exploring the effects of different pieces of music would help clarify this.

Valentine, E. & Foster, N. 2000. Reported at the British Psychological Society's London Conference, December 20.

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

Close caregiver relationship may slow Alzheimer's decline

A study of 167 pairs of caregivers and Alzheimer's patients has found that by the end of the study patients whose caregivers had scored their relationship as particularly close lost less than half as many points on average on a common cognitive test called the Mini-Mental State Exam (MMSE) as patients with more distant caregivers. The scores were based on a survey in which caregivers rated their level of agreement or disagreement with six statements, such as "My relationship with the care recipient is close"; "The care recipient makes me feel like a special person"; and "The care recipient and I can always discuss things together." The effect was strongest when the caregiver was a spouse, as opposed to an adult child or in-law. Patients with close spouses showed rates of decline similar to patients taking Alzheimer's drugs called acetylcholinesterase inhibitors. However, it can’t be ruled out that the effect may be due to slower decline encouraging caregivers to remain close. A follow-up study is planned to answer this question.

Norton, M.C. et al. 2009. Caregiver–Recipient Closeness and Symptom Progression in Alzheimer Disease. The Cache County Dementia Progression Study. The Journals of Gerontology Series B: Psychological Sciences and Social Sciences, Advance Access published on June 29, 2009.

Results of caregiver survey

Results from the third annual Alzheimer’s Foundation of America Investigating Caregivers’ Attitudes and Needs Survey found that about three in five caregivers say their children aged 8 to 21 are involved in caring for a loved one with Alzheimer’s. Of the caregivers who feel they do a good job balancing the care of their loved ones with Alzheimer’s disease and children under 21, more than one-third (36%) specifically cited support from children as a contributor to their success. Additionally, nearly two-thirds (63%) would like more information about how to help their children cope when a loved one is diagnosed with Alzheimer’s. Caregivers of sufferers whose diagnosis was delayed for a year or more say the delay was most often due to lack of caregiver familiarity with symptoms or insufficient knowledge about Alzheimer’s. Additional key survey findings can be found at

Counseling Alzheimer's caregivers postpones the nursing home

A long-running study of 406 people caring for a spouse with dementia has found that a program of individual and family counseling sessions and ongoing support for caregivers delays by an average of 1.5 years the time when people with dementia are usually put in nursing homes.

Mittelman, M.S., Haley, W.E., Clay, O.J. & Roth, D.L. 2006. Improving caregiver well-being delays nursing home placement of patients with Alzheimer disease. Neurology, 67, 1592-1599.

Individualized counseling helps caregivers

A study of 642 people who were caring for a relative with Alzheimer's disease or a related disorder has found that those who participated in a counseling program were less likely to suffer depression and felt more confident and able to deal with caring for their relative. Hispanic and white participants saw the greatest benefit. In African-Americans, the intervention was effective among spouse-caregivers, but relatively ineffective among caregivers who were caring for a relative other than their husband or wife. Hispanics had the greatest improvement in reduction of caregiver depressive symptoms and problem behaviors of the recipient. Whites saw the most impact in the area of social support and African-American spouse-caregivers had the most positive outcome in reducing the caregiver burden and improving self-care.

Belle, S.H. et al. 2006. Enhancing the Quality of Life of Dementia Caregivers from Different Ethnic or Racial Groups: A Randomized, Controlled Trial. Annals of Internal Medicine, 145(10), 727-738.

Collaborative care has better outcomes for both patients and caregivers

An 18-month study involving 153 older adults with Alzheimer's disease and their caregivers has found that restructuring the primary care practice environment to emphasize a team approach to care significantly improved the quality of care and behavioral and psychological symptoms of dementia. Caregivers were also less stressed and less depressed.

Callahan, C.M. et al. 2006. Effectiveness of Collaborative Care for Older Adults With Alzheimer Disease in Primary Care: A Randomized Controlled Trial. JAMA, 295, 2148-2157.

Enhanced counseling eases depression among caregivers

A new report from of the NYU Spouse-Caregiver Intervention Study shows that a six-session counseling and long-term support program substantially eases the depression of people caring for a loved one with Alzheimer’s, and that the mental health benefits apparently are long lasting. The study involved 406 caregivers, half of whom received the usual counseling--sessions provided on an ad-hoc basis upon request (control group). The other half was given three additional types of counseling: two sessions of individual counseling, four sessions of counseling with their family, and then weekly meetings with a support group of fellow caregivers. After one year, some 45% of the control group had symptoms of clinical depression, compared with 30% of those who had received special counseling. This group still showed fewer symptoms of depression on average than those in the control group three years later. There was no difference after five years. It was suggested that key factors in the enhanced treatment program were having the same counselor for all sessions, the use of multiple types of coordinated therapy, and counseling tailored to the particular coping challenges that each of the caregivers and their families were dealing with.

Mittelman, M.S., Roth, D.L., Coon, D.W. & Haley, W.E. 2004. Sustained Benefit of Supportive Intervention for Depressive Symptoms in Caregivers of Patients With Alzheimer’s Disease. American Journal of Psychiatry, 161, 850-856.

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Alzheimer's disease symptoms more subtle in people over 80

September, 2011
  • A new study shows that, among the very old, it’s harder to distinguish between normal brain atrophy and cognitive impairment and that indicative of Alzheimer’s.

A study involving 105 people with Alzheimer's disease and 125 healthy older adults has compared cognitive function and brain shrinkage in those aged 60-75 and those aged 80+.

It was found that the association between brain atrophy and cognitive impairment typically found in those with Alzheimer’s disease was less evident in the older group. This is partly because of the level of brain atrophy in healthy controls in that age group — there was less difference between the healthy controls and those with Alzheimer’s. Additionally, when compared to their healthy counterparts, executive function, immediate memory and attention/processing speed were less abnormal in the older group than they were in the younger group.

The finding suggests that mild Alzheimer’s in the very old may go undetected, and emphasize the importance of taking age into account when interpreting test performance and brain measures.




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Sleep apnea and brain injury raise risk of later dementia

August, 2011

Recent studies add to the evidence that sleep apnea and even mild brain injury increase the risk of developing dementia.

Sleep apnea linked to later dementia

A study involving 298 older women with sleep problems found that those who had disordered breathing (such as sleep apnea) were significantly more likely to develop dementia or mild cognitive impairment.

Around a third of the women (average age 82) had disordered breathing (slowing down or stopping breathing during sleep and often having to gasp to catch up). None showed signs of cognitive impairment at the time of the sleep testing. When re-tested some five years later, 45% of those who had disordered breathing had developed dementia or MCI, compared with 31% of those with no breathing irregularities.

Those whose sleep irregularities had been particularly severe (15 or more breathing stoppages per hour and more than 7% of sleep time not breathing) during the earlier part of the study were nearly twice as likely as those without breathing problems to develop dementia or MCI. Other measures of sleep quality — waking after sleep onset, sleep fragmentation, sleep duration — were not associated with cognitive impairment.

The finding adds to the evidence for the importance of treating sleep apnea. Previous research has found that CPAP treatment effectively counteracts cognitive impairment caused by sleep apnea.

Brain injury raises dementia risk

Analysis of medical records on 281,540 U.S. military veterans aged at least 55 at the beginning of the study has found that over the next seven years those who had at one time suffered a traumatic brain injury were more than twice as likely to develop dementia than those who had not suffered such an injury. Around 1.7% (4,902) had incurred a traumatic brain injury, in many cases during the Vietnam War, and over 15% of these developed dementia. In contradiction of the prevailing belief that only moderate or severe brain injuries predispose people to dementia, severity of the injury made no difference.

Injuries due to strokes were weeded out of the study.

In another study, following up on nearly 4,000 retired National Football League players surveyed in 2001, 35% appeared to have significant cognitive problems (as assessed by questionnaire). When 41 of them were tested, they were found to have mild cognitive impairment that resembled a comparison group of much older patients from the general population.

The findings are a reminder of the importance of treating even mild head injuries, and of following a regime designed to mitigate damage: exercising, eating a healthy diet, reducing stress, and so on.


[2444] Yaffe, K., Laffan A. M., Harrison S L., Redline S., Spira A. P., Ensrud K. E., et al.
(2011).  Sleep-Disordered Breathing, Hypoxia, and Risk of Mild Cognitive Impairment and Dementia in Older Women.
JAMA: The Journal of the American Medical Association. 306(6), 613 - 619.

The brain injury studies were reported in July at the Alzheimer's Association International Conference in France.



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Diagnosis and prevalence of dementia & MCI — recent reports

August, 2011

Several recent reports point to the need for GPs to be better informed about the initial symptoms of dementia and mild cognitive impairment.

Functional impairment good indicator of mild cognitive impairment

Evaluation of 816 older adults, of whom 229 had no cognitive problems, 394 had a diagnosis of amnestic mild cognitive impairment, and 193 had a diagnosis of mild Alzheimer’s, has revealed that most of those with aMCI (72%) or AD (97%) had trouble with at least one type of function on the Pfeffer Functional Activities Questionnaire. Only 8% of controls had any difficulty. In both impaired groups, those who had the most difficulty functioning also tended to score worse on cognition tests, have smaller hippocampal volumes, and carry the APOe4 gene.

Two of the ten items in the questionnaire were specific in differentiating the control group from the impaired groups. Those items concerned "remembering appointments, family occasions, holidays, and medications” and "assembling tax records, business affairs, or other papers." Only 34% of those with aMCI and 3.6% of those with AD had no difficulty with these items.

The findings suggest that even mild disruptions in daily functioning may be an important clinical indicator of disease.

Early-onset Alzheimer’s poorly diagnosed when initial symptoms aren’t memory related

Post-mortem analysis of 40 people diagnosed  with early-onset Alzheimer’s has revealed that about 38% experienced initial symptoms other than memory problems, such as behavior, vision or language problems and a decline in executive function, or the ability to carry out tasks. Of these, 53% were incorrectly diagnosed when first seen by a doctor, compared to 4% of those who had memory problems. Of those with unusual initial symptoms, 47% were still incorrectly diagnosed at the time of their death.

The mean age at onset was 54.5 years (range 46-60). The average duration of the disease was 11 years, with an average diagnostic delay of 3 years.

GPs misidentify and fail to identify early dementia and MCI

A review of 30 studies involving 15,277 people seen in primary care for cognitive disorders, has found that while GPs managed to identify eight out of ten people with moderate to severe dementia, they only identified 45% of those with early dementia and mild cognitive impairment. Moreover, they were very poor at recording such diagnoses. Thus, though they recognized 45% of the MCI cases, they only recorded 11% of these cases in their medical notes. Although they identified 73% of people with dementia, they made correct annotations in medical records in only 38% of cases.

But the problem is not simply one of failing to diagnose — they were even more likely to misidentify dementia, and this was particularly true for those with depression or hearing problems.

The findings point to the need for more widespread use of simple cognitive screening tests.

Prevalence of dementia & MCI in 'oldest old' women

Data from 1,299 women enrolled in the Women Cognitive Impairment Study of Exceptional Aging suggests that the incidence of dementia almost doubles with every 5 years of age and prevalence rises from approximately 2-3% in those 65 to 75 years to 35% in those 85+.

Among those with mild cognitive impairment, amnestic multiple domain was most common (34%), followed by non-amnestic single domain (29%). Amnestic single domain (affecting only one type of cognitive function, including memory difficulty) affected 22%.

Alzheimer's disease and mixed dementia accounted for nearly 80% of dementia cases, and vascular dementia for 12.1%.

Those with dementia tended to be older, less likely to have completed high school, more likely to have reported depression, a history of stroke, and to have the APOEe4 gene.

The women in the study had an average age of 88.2 years and 27% were older than 90. 41% had clinical cognitive impairment (17.8% with dementia and 23.2% with mild cognitive impairment).

The high prevalence of cognitive impairment in this age group points to the importance of screening for cognitive disorders, particularly among high-risk groups.




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Discovery of more risky genes reveals more about the paths to Alzheimer’s

June, 2011

New genetic studies implicate myelin development, the immune system, inflammation, and lipid metabolism as critical pathways in the development of Alzheimer’s.

I commonly refer to ApoE4 as the ‘Alzheimer’s gene’, because it is the main genetic risk factor, tripling the risk for getting Alzheimer's. But it is not the only risky gene.

A mammoth genetic study has identified four new genes linked to late-onset Alzheimer's disease. The new genes are involved in inflammatory processes, lipid metabolism, and the movement of molecules within cells, pointing to three new pathways that are critically related to the disease.

Genetic analysis of more than 11,000 people with Alzheimer's and a nearly equal number of healthy older adults, plus additional data from another 32,000, has identified MS4A, CD2AP, CD33, and EPHA1 genes linked to Alzheimer’s risk, and confirmed two other genes, BIN1 and ABCA7.

A second meta-analysis of genetic data has also found another location within the MS4A gene cluster which is associated with Alzheimer's disease. Several of the 16 genes within the cluster are implicated in the activities of the immune system and are probably involved in allergies and autoimmune disease. The finding adds to evidence for a role of the immune system in the development of Alzheimer's.

Another study adds to our understanding of how one of the earlier-known gene factors works. A variant of the clusterin gene is known to increase the risk of Alzheimer’s by 16%. But unlike the ApoE4 gene, we didn’t know how, because we didn’t know what the CLU gene did. A new study has now found that the most common form of the gene, the C-allele, impairs the development of myelin.

The study involved 398 healthy adults in their twenties. Those carrying the CLU-C gene had poorer white-matter integrity in multiple brain regions. The finding is consistent with increasing evidence that degeneration of myelin in white-matter tracts is a key component of Alzheimer’s and another possible pathway to the disease. But this gene is damaging your brain (in ways only detectible on a brain scan) a good 50 years before any clinical symptoms are evident.

Moreover, this allele is present in 88% of Caucasians. So you could say it’s not so much that this gene variant is increasing your risk, as that having the other allele (T) is protective.


[2257] Naj, A. C., Jun G., Beecham G. W., Wang L-S., Vardarajan B. N., Buros J., et al.
(2011).  Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease.
Nat Genet. 43(5), 436 - 441.

Antunez, C. et al. 2011. The membrane-spanning 4-domains, subfamily A (MS4A) gene cluster contains a common variant associated with Alzheimer's disease. Genome Medicine,  3:33 doi:10.1186/gm249
Full text available at

[2254] Braskie, M. N., Jahanshad N., Stein J. L., Barysheva M., McMahon K. L., de Zubicaray G. I., et al.
(2011).  Common Alzheimer's Disease Risk Variant Within the CLU Gene Affects White Matter Microstructure in Young Adults.
The Journal of Neuroscience. 31(18), 6764 - 6770.



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Alzheimer's diagnostic guidelines updated

June, 2011
  • Updated clinical guidelines now cover three distinct stages of Alzheimer's disease.

For the first time in 27 years, clinical diagnostic criteria for Alzheimer's disease dementia have been revised, and research guidelines updated. They mark a major change in how experts think about and study Alzheimer's disease.

The updated guidelines now cover three distinct stages of Alzheimer's disease:

  • Preclinical – is currently relevant only for research. It describes the use of biomarkers that may precede the development of Alzheimer’s.
  • Mild Cognitive Impairment– Current biomarkers include elevated levels of tau or decreased levels of beta-amyloid in the cerebrospinal fluid, reduced glucose uptake in the brain, and atrophy of certain brain regions. Primarily for researchers, these may be used in specialized clinical settings.
  • Alzheimer's Dementia – Criteria outline ways clinicians should approach evaluating causes and progression of cognitive decline, and expand the concept of Alzheimer's dementia beyond memory loss to other aspects of cognition, such as word-finding, vision/spatial issues, and impaired reasoning or judgment.

The criteria are available at



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Brain starts shrinking long before Alzheimer's appears

June, 2011

A study following older adults for more than a decade has found that neural volume in specific brain regions markedly predicted later development of Alzheimer’s.

A long-term study of older adults with similar levels of education has found that those with the thinnest cerebral cortex in specific brain regions were the most likely to develop dementia. Among those in whom these signature brain areas were the thinnest at the beginning of the study, 55% developed dementia over the next decade, compared with 20% of those with average cortical thickness and none of those in whom cortical thickness was above average. Those with the thinnest cortical areas also developed Alzheimer's significantly faster.

The study involved two independent samples. In the first group, 33 people were followed for an average of 11 years, during which time eight developed Alzheimer's. In the second group, 32 people were followed for an average of seven years, and seven of them developed the disease. (So 23% developed Alzheimer’s in total.) Participants were divided into three groups based on cortical thickness in the key areas: 11 had the lowest levels, 9 had the highest, and 45 were average.




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Tobacco-derived compound prevents memory loss in Alzheimer's mice

June, 2011

A mouse study has found that a compound derived from tobacco reduced plaques associated with dementia and prevented memory loss.

Some epidemiological studies have showed that people who smoke tend to have lower incidences of Parkinson's disease and Alzheimer's disease; this has been widely attributed to nicotine. However, nicotine's harmful effects make it a poor drug candidate.

Cotinine, a byproduct of nicotine metabolism, is nontoxic and longer lasting than nicotine.

In the study, genetically engineered 2-month-old mice were given cotinine daily for five months. When tested, those treated with cotinine performed at the same level as normal mice on spatial memory tests, and showed a 26% reduction in deposits of amyloid plaques, compared to the genetically engineered mice who had not received the treatment. Cotinine also inhibited the accumulation of the amyloid peptide oligomers, and stimulated the signaling factor Akt, which promotes the survival of neurons and enhances attention and memory.

The researchers are hoping to carry out a pilot clinical trial to investigate cotinine's effectiveness in preventing progression to Alzheimer's dementia in patients with mild cognitive impairment.


Echeverria, V. et al. In press. Cotinine Reduces Amyloid-β Aggregation and Improves Memory in Alzheimer's Disease Mice. Journal of Alzheimer's Disease, 24 (4).



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