risk factors

Vascular & Mixed Dementia

alence

Vascular dementia, as its name suggests, is caused by poor blood flow, produced by a single, localized stroke, or series of strokes.

It is the second most common dementia, accounting for perhaps 17% of dementias. It also co-occurs with Alzheimer's in 25-45% of cases. Although there are other types of dementia that also co-occur with Alzheimer's, mixed dementia generally refers to the co-occurrence of Alzheimer's and vascular dementia.

Risk factors

In general, unsurprisingly, vascular dementia has the same risk factors as cerebrovascular disease.

A study1 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. Because this was not true for those with Alzheimer's disease, it suggests that low childhood IQ may act as a risk factor for vascular dementia through vascular risks rather than the "cognitive reserve" theory.

Prevention

The exciting thing about vascular dementia is that it is far more preventable than other forms of dementia. As with risk, as a general rule, the same things that help you protect you from heart attacks and stroke will help protect you from vascular dementia. This means diet, and it means exercise.

A four-year study2 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.

Treatment

Apart from normal medical treatment for cerebrovascular problems, there are a couple of interesting Chinese studies that have looked specifically at vascular dementia.

The herb gastrodine has been used in China for centuries to treat disorders such as dizziness, headache and even ischemic stroke. A 12-week, randomized, double-blind trial3 involving 120 stroke patients who were diagnosed with mild to moderate vascular dementia has found that  gastrodine and Duxil® (a drug used to treat stroke patients in China) produced similar overall levels of cognitive improvement -- although more patients showed 'much improvement' with gastrodine (23% vs 14%).

A Chinese pilot study4 involving 25 patients with mild to moderate vascular dementia found that ginseng compound significantly improved their average memory function after 12 weeks, but more research (larger samples, placebo-controls) is needed before this finding can be confirmed. Five years on I have still not seen such a study.

References: 

  1. 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
  2. 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.
  3. Tian, J.Z. et al. 2003. A double-blind, randomized controlled clinical trial of compound of Gastrodine in treatment of mild and moderate vascular dementia in Beijing, China. Presented at the American Heart Association's Second Asia Pacific Scientific Forum in Honolulu on June 10.
  4. Tian, J.Z. et al. 2003. Presented at the American Stroke Association's 28th International Stroke Conference on February 14 in Phoenix. Press release

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Dementia: A general introduction

alence of dementia

Dementia is estimated1 to afflict over 35.5 million people worldwide -- this includes nearly 10 million people in Europe, nearly 4.4 million in North America, nearly 7 million in South and Southeast Asia, about 5.5 million in China and East Asia and about 3 million in Latin America.

The estimated prevalence for over 60s is 4.7% worldwide. Because this is a disorder of age, prevalence is of course greatly affected by the proportion of people reaching their senior years. Hence the prevalence is higher in the more developed countries: the estimated prevalence in Western Europe and North America is 7.2% and 6.9% respectively, compared to 2.6% in Africa.

What kinds of dementia are most common?

The prevalence of the various dementia types is a complicated story. Certainly Alzheimer's disease is by far the most common type of dementia, accounting for perhaps 70% of all dementias (although a 2006 study13 suggested that non-Alzheimer dementias were as common as Alzheimer's — however this was based on dementia among military veterans). The second most common dementia is almost certainly vascular dementia, which may account for some 17% of dementias. However, the actual numbers are made uncertain by the fact that these two dementias often occur together.

At minimum, around a quarter of Alzheimer's cases have been found, on autopsy, to also have vascular pathology; this proportion reaches higher levels when the samples are not restricted to dementia clinics. One such community-based study2, for example, found 45% of the Alzheimer's cases also showed significant vascular pathology. Another, U.K., study3 found a similar proportion (46%).

Another, large long-running, study14 has found that only 30% of people with signs of dementia had Alzheimer’s disease alone. 42% had Alzheimer’s disease with cerebral infarcts (strokes) and 16% had Alzheimer’s disease with Parkinson’s disease (including two people with all three conditions). Infarcts alone caused another 12% of the cases. Vascular dementia caused another 12%.

Although there are other types of dementia that also co-occur with Alzheimer's, mixed dementia generally refers to the co-occurrence of Alzheimer's and vascular dementia.

The other important dementia type that co-occurs with Alzheimer's at a high rate is dementia with Lewy bodies, also considered to be one of the most common dementias (although, due to inconsistent criteria, estimates of its actual prevalence vary wildly). It is estimated to co-occur with Alzheimer's pathology around half the time. At a lesser frequency, but still high, is Parkinson's disease dementia — about 20% of Alzheimer's patients also have Parkinson's disease.

But it is probably fair to say that the distinction between these dementia types is not clear-cut. Lewy bodies are found in a high proportion of both Alzheimer's and Parkinson's patients — the number of cases of 'pure' Lewy body dementia is much smaller. It's been said, in fact, that the main difference between Lewy body dementia and Parkinson's disease dementia lies in the timing — Parkinson's disease dementia will be preceded by at least a year and more likely a number of years, by full-blown Parkinson's disease.

Regardless of the difficulties in establishing clear clinical criteria, however, there is no doubt that Alzheimer's co-occurs with vascular pathology or Lewy body pathology at a startlingly high rate.

One of the problems with clearly distinguishing between these types of dementia is a happy one: vascular and Alzheimer's pathology can be found, at autopsy, in many elderly brains that have not shown symptoms of dementia.

For example, in one community-based study4, in which the median age at death was around 85 for the 209 individuals, 48% had had dementia, of whom 64% showed Alzheimer's pathology. However, 33% of those who had not had dementia showed similar levels of Alzheimer's plaques. Similarly, some amount of tau tangles (another aspect of Alzheimer's pathology) was found in 61% of the demented and 34% of the non-demented individuals. Finally, multiple vascular pathology was found in 46% of the demented group and 33% of the non-demented, and vascular lesions were equally common in both.

And in the large long-running study mentioned earlier14, in those without dementia, brain autopsy revealed the presence of Alzheimer’s in 24% of cases, and infarctions in 18%.

How likely am I to develop dementia?

The question of how likely any person is to develop dementia must begin with estimates of prevalence, but this of course is only the very beginning of the story.

Estimating prevalence is complicated by the fact that dementia is greatly affected by lifestyle, environmental, and genetic factors, and consequently prevalence varies a lot depending on geographic region.

Different dementia sub-types have different causes, and some give a much greater weight to genetic or environmental factors than others. However, the finding that dementia risk is much greater in those with more than one pathology, and that Alzheimer’s pathology with cerebral infarcts is a very common combination, adds to growing evidence that dementia risk might be reduced with the same tools we use for cardiovascular disease such as control of blood cholesterol levels and hypertension.

Age as a factor

The first American study to use nationally representative data5 (rather than extrapolating from regional data) came up with a figure of 13.9% of those aged 71 and older (one in seven). But age of course makes all the difference in the world. The study found 5% of those aged 71 to 79, rising to 37.4% of those age 90 and older.

Although all the dementia types show an increase with age, Alzheimer's is particularly a disorder of age: although the study found only 46.7% of those with dementia in their 70s had Alzheimer's, for those in their 90s, Alzheimer's was the dementia type for 79.5% of them.

An Italian study of over 2000 seniors over 80 years old6 confirms that dementia does indeed keep increasing with age (it had been thought that risk leveled off for those who reached their 90s). The study found that 13.5% of those aged 80 to 84 had dementia, rising sharply to 30.8% of those 85 to 89, 39.5% of those 90 to 94, and 52.8% among those older than 94.

Gender as a factor

A number of studies have found differences between men and women, or between difference ethnicities, but this large, nationally representative study found that, although on the face of it there were race and gender differences, these differences disappeared once age, years of education, and presence of at least one "Alzheimer's gene" was taken into account.

However, an American study of over 900 seniors over 90 years old7 found that women of this age were much more likely to have dementia than men (some 45% of them, compared to 28% of the men), and that the likelihood of having dementia kept increasing with age for the women, but not for the men. Of course, more women than men survive to this age (some two-thirds of the participants were women).

Interestingly, education was protective for the women (the risk of dementia decreasing the more years of education the individual had had) but not for the men. The study participants were not, however, a random sampling -- they all came from the same retirement community, and most were white and of high socioeconomic status. Given that, and considering the times in which they were born, it seems likely that there would be far more variability in educational level among the women than the men. The men, while less likely to develop dementia, did tend to decline faster if they did develop it.

The Italian oldest-old study, too, found more women than men had dementia: across all ages, 25.8% of the women and 17.1% of the men.

These figures don't of course tell us how many develop dementia at those ages. Obviously, survival rates are a factor, and as we saw in the other study, male and female survival rates do vary. The figures for new cases of dementia developing in these age bands were:

  • 6% at 80 to 84 years;
  • 12.4% at 85 to 89 years;
  • 13.1% from 90 to 94 years; and
  • 20.7% among those over 94.

These figures make even more clear what was apparent in the earlier figures: dementia jumps suddenly in the later half of the 80s, and again in the later half of the 90s.

Importantly, however, the incidence of new cases shows us how important the gender difference in survival rates is: the difference in prevalence is much smaller in these terms --9.2% among women and 7.2% among men.

The study, which canvassed everyone in the age group within a specific geographical area and had an 88% response rate, had a ratio of 74 women to 26 men. Because the number of men at the very highest ages was so small, we can't draw any firm conclusions about gender differences at those ages.

The Italian study involves a very different population from that of the American study: Varese is in a heavily industrialised part of northern Italy, with a high immigrant population, and the average amount of education was only 5.1 years.

A review of 26 studies looking at dementia prevalence in Europe8 confirmed rates for men rising from 1.8% in the 65-69 years age range up to 30% in the over 90 years age group, and for women rising from 1.5% to 30% in the 80-85 years age band. However (and confirming the American study), rates in the oldest old for women rose to over 50% in those over 95 years.

Early onset of dementia

The average age at the onset of dementia is around 80 years. Early-onset dementia is defined arbitrarily (and variably) as occurring before 60-65. Early-onset cases have been estimated to make up about 6-7% of all cases of Alzheimer's disease, and though a lot of attention has been given to them, only about 7% of early-onset cases are in fact familial9.

Familial cases involve mutations in specific genes (the APP or presenilin genes); they do not include what is popularly referred to as the "Alzheimer's gene" — variants of APOE. A 1995 study10 calculated that a person with no family history of Alzheimer's disease who has an e4 allele has a lifetime risk of 29%, compared to a risk of 9% if they don't have an e4 allele. In other words, if you don't have any of the Alzheimer's risk genes, or any family history, you only have a 9% risk of developing Alzheimer's, and even if you do have the "Alzheimer's gene", your chance of not getting Alzheimer's is still over 70%. Your risk does, however, go up dramatically if both your APOE alleles are e4.

A large study11 found, however, that there were both ethnic and gender differences for the risk of this genetic factor. The effect of having an e4 allele was much greater among Japanese compared to Caucasian, and greater for Caucasian compared to African American and Hispanic. Additionally, the effect of having an e4 allele becomes less significant after 70.

There is evidence12 that the age of onset for both Alzheimer's and Parkinson's diseases, for those genetically disposed, is controlled by genes on chromosome 10.

References: 

  1. From the 2009 World Alzheimer's Report: http://www.alz.co.uk/research/worldreport/
  2. Lim A, Tsuang D, Kukull W, et al. 1999. Cliniconeuropathological correlation of Alzheimer’s disease in a community-based case series. Journal of the American Geriatric Society, 47, 564-569.
  3. Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS). 2001. Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales. Lancet, 357, 169-175.
  4. Langa, K.M., Foster, N.L. & Larson, E.B. 2004. Mixed Dementia: Emerging Concepts and Therapeutic Implications. JAMA, 292(23), 2901-2908.
  5. Plassman, B.L. et al. 2007. Prevalence of Dementia in the United States: The Aging, Demographics, and Memory Study. Neuroepidemiology, 29, 125-132. 
  6. Lucca, U. et al. 2009. Risk of dementia continues to rise in the oldest old: The Monzino 80-plus Study. Presented on July 14, 2009, at the annual International Conference on Alzheimer's Disease in Vienna. http://www.alz.org/icad/documents/abstracts/abstracts_prev_ICAD09.pdf
  7. Corrada, M.M. et al. 2008. Prevalence of dementia after age 90: Results from The 90+ Study. Neurology, 71 (5), 337-343.
  8. Reynish, E. et al. 2009. Systematic Review and Collaborative Analysis of the Prevalence of Dementia in Europe. Presented on July 14, 2009, at the annual International Conference on Alzheimer's Disease in Vienna. http://www.alz.org/icad/documents/abstracts/abstracts_prev_ICAD09.pdf
  9. Nussbaum, R.L. & Ellis, C.E. 2003. Alzheimer's Disease and Parkinson's Disease. New England Journal of Medicine, 348 (14), 1356-1364. http://content.nejm.org/cgi/content/full/348/14/1356#R23
  10. Seshadri S, Drachman DA, Lippa CF. 1995. Apolipoprotein E epsilon 4 allele and the lifetime risk of Alzheimer's disease: what physicians know, and what they should know. Archives of Neurology, 52, 1074-1079. http://tinyurl.com/ya7vss7
  11. Farrer LA, Cupples LA, Haines JL, et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease: a meta-analysis. JAMA 1997;278:1349-1356. http://tinyurl.com/yb9tdju
  12. Li, Y. et al. 2002. Age at Onset in Two Common Neurodegenerative Diseases Is Genetically Controlled. American Journal of Human Genetics, 70, 985-993. Press release
  13. Ross, E.D. et al. 2006. Changing Relative Prevalence of Alzheimer Disease versus Non-Alzheimer Disease Dementias: Have We Underestimated the Looming Dementia Epidemic? Dementia and Geriatric Cognitive Disorders, 22 (4), 273-277.
  14. Schneider, J.A., Arvanitakis, Z., Bang, W. & Bennett, D.A. 2007. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology, published ahead of print June 13.

 

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Hearing loss linked to increased cognitive decline & dementia risk

  • A very large Taiwanese study found that adults with hearing loss had a higher dementia risk, and this was particularly so for those aged 45-64.
  • A very large Japanese study found that a dramatically greater proportion of older adults (65+) with hearing loss reported memory loss, compared to much fewer of those without hearing loss.
  • A very large study found that older adults (50+) who used hearing aids for hearing loss showed better performance on tests of working memory and attention compared with those who didn't use hearing aids for their hearing loss.
  • A large long-running study found that, while hearing impairment was associated with accelerated cognitive decline in older adults (mean age 73.5), the impact might be lessened by higher education.
  • A very large 8-year study found that hearing loss was associated with higher risk of subjective cognitive decline in older men (62+).
  • A very small study suggests that cognitive problems in some older adults may derive directly from hearing impairments, and may be fixed by addressing this.
  • A large, long-running study found that eating a healthy diet was associated with a lower risk of acquired hearing loss in women.

Hearing loss linked to increased dementia risk

A Taiwanese study involving 16,270 adults, of whom half had newly diagnosed hearing loss, found that those with hearing loss had a higher risk of dementia, particularly among those aged 45-64. Six comorbidities (cerebrovascular disease, diabetes, anxiety, depression, alcohol-related illnesses, and head injury) were also significantly associated with a higher dementia risk.

Among the study participants, 1,868 developed dementia during the 13-year study period.

https://www.eurekalert.org/pub_releases/2019-07/jn-hld072919.php

Hearing loss linked to limitations, distress, and memory loss in older people

Data from the 2016 Comprehensive Survey of Living Conditions of Japan has found that, of those 137,723 respondents who were aged 65 or older, about 9% reported hearing loss. There were substantial differences between those with hearing loss and those without:

  • 28.9% of those with hearing loss reported limitations in outdoor activities such as shopping or travel, vs. 9.5% of those without hearing loss
  • 39.7% of those with hearing loss reported psychological distress, vs 19.3%
  • 37.7% of those with hearing loss reported memory loss, vs only 5.2% of those without hearing loss.

https://www.eurekalert.org/pub_releases/2019-07/uot-hlt071919.php

Wearing hearing aid may help protect brain in later life

Data from the PROTECT online study of 25,000 older adults (50+) has found that those who wear a hearing aid for age-related hearing problems maintain better brain function over time than those who do not.

Participants undertook annual cognitive tests over two years. After that time, the group who wore hearing aids performed better in measures assessing working memory and aspects of attention than those who did not.

The findings were presented at the 2019 annual Alzheimer's Association International Conference, Los Angeles.

https://www.eurekalert.org/pub_releases/2019-07/uoe-wha071219.php

Hearing loss linked to greater cognitive decline but education mitigates effect

A large, long-running study, involving 1,164 older adults (mean age 73.5), found that, while hearing impairment was associated with accelerated cognitive decline, the impact might be lessened by higher education.

The study found that almost half of the participants (49.8%) had mild hearing impairment, with 16.8% suffering moderate-to-severe hearing loss. Those with more serious hearing impairment showed worse performance on the MMSE and the Trail-Making Test, Part B. Hearing impairment was also associated with greater decline in performance over time, for both the mildly and more severely impaired.

However, the association of mild hearing impairment with rate of cognitive decline was found only among those without a college education, while moderate-to-severe hearing impairment was associated with steeper MMSE decline regardless of education level.

Somewhat surprisingly, degree of social engagement did not affect the association of hearing impairment with cognitive decline.

https://www.eurekalert.org/pub_releases/2019-02/uoc--wac021219.php

Male hearing loss linked to cognitive decline

An eight-year longitudinal study among 10,107 older men (62+) found that hearing loss was associated with higher risk of subjective cognitive decline.

Compared with men with no hearing loss, the relative risk of cognitive decline was 30% higher among men with mild hearing loss, 42% higher among men with moderate hearing loss, and 54% higher among men with severe hearing loss but who did not use hearing aids. While those who did use hearing aids showed a reduced risk of cognitive decline (37%), this wasn’t statistically significant (not enough men in these groups, I assume).

The men were all health professionals. Subjective cognitive function was assessed using a six-item questionnaire, which was administered three times, at four-yearly intervals.

https://www.eurekalert.org/pub_releases/2019-01/bawh-etc012819.php

Signs of memory problems could be symptoms of hearing loss instead

A very small study found that 11 out of 20 participants being evaluated for cognitive concerns had some form of mild to severe hearing loss, but only 4 of them used hearing aids. A quarter of the participants didn’t show any signs of memory loss due to a brain disorder. It’s suggested that, for some, cognitive problems may derive directly from hearing impairments, and can be fixed by addressing this issue.

Hearing loss is the third most common chronic health condition in older adults, which is experienced by 50% of individuals over the age of 65 and 90% of people over the age of 80. It takes an average of 10 years before people seek treatment and fewer than 25% of those who need hearing aids will buy them.

https://www.eurekalert.org/pub_releases/2019-01/bcfg-som011819.php

Healthy diet may lower risk of hearing loss in women

A large, long-running study (the Nurses' Health Study II ) has found that eating a healthy diet was associated with a lower risk of acquired hearing loss in women. Women whose diets most closely resembled the AMED or DASH dietary patterns had an approximately 30% lower risk of moderate or worse hearing loss, compared with women whose diets resembled these dietary patterns the least.

The Alternate Mediterranean diet (AMED) diet includes extra virgin olive oil, grains, legumes, vegetables, fruits, nuts, fish and moderate intake of alcohol. The Dietary Approaches to Stop Hypertension (DASH) diet is high in fruits and vegetables and low-fat dairy, and low in sodium.

https://www.eurekalert.org/pub_releases/2018-05/bawh-hdm051118.php

Reference: 

[4479] Liu, C-M., & Lee C. Tzu- Chi
(2019).  Association of Hearing Loss With Dementia.
JAMA Network Open. 2(7), e198112 - e198112.

Iwagami, M., Kobayashi, Y., Tsukazaki, E., Watanabe, T., Sugiyama, T., Wada, T., … Tamiya, N. (2019). Associations between self-reported hearing loss and outdoor activity limitations, psychological distress and self-reported memory loss among older people: Analysis of the 2016 Comprehensive Survey of Living Conditions in Japan. Geriatrics & Gerontology International, 19(8), 747–754. https://doi.org/10.1111/ggi.13708

Alattar, A. A., Bergstrom, J., Laughlin, G. A., Kritz-Silverstein, D., Richard, E. L., Reas, E. T., … McEvoy, L. K. (n.d.). Hearing impairment and cognitive decline in older, community-dwelling adults. The Journals of Gerontology: Series A. https://doi.org/10.1093/gerona/glz035

Curhan, S et al. Longitudinal study of hearing loss and subjective cognitive function decline in men. Alzheimer's & Dementia DOI: 10.1016/j.jalz.2018.11.004

Dupuis, K., Yusupov, I., Vandermorris, S., Murphy, K., Rewilak, D., Stokes, K., & Reed, M. (2019). Considering Age-Related Hearing Loss in Neuropsychological Practice: Findings from a Feasibility Study. Canadian Journal on Aging / La Revue Canadienne Du Vieillissement, 38(2), 245-252. doi:10.1017/S0714980818000557

[4480] Curhan, S. G., Wang M., Eavey R. D., Stampfer M. J., & Curhan G. C.
(2018).  Adherence to Healthful Dietary Patterns Is Associated with Lower Risk of Hearing Loss in Women.
The Journal of Nutrition. 148(6), 944 - 951.

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More studies linking poor sleep to Alzheimer's risk

  • Adults whose sleep quality declined in their 40s and 50s had more amyloid-beta in their brains later in life, while those reporting poorer sleep in their 50s and 60s had more tau tangles.
  • Greater tau protein was associated with less synchronized brainwaves during sleep.
  • Both amyloid-beta and tau levels increase dramatically after a single night of sleep deprivation, suggesting good sleep helps remove these proteins.
  • A large study found that older adults who consistently slept more than nine hours every night had twice the risk of developing dementia and Alzheimer’s disease within the next 10 years.
  • A large Japanese study found that those with sleep durations of less than 5 hours or more than 10 hours were more likely to develop dementia. However, those with short sleep could mitigate the effect with high physical activity.
  • A largish 12-year study found that poorer REM sleep was associated with an increased dementia risk.
  • Sleep apnea has been linked to higher levels of tau in the entorhinal cortex, poorer attention and memory, and slower processing speed.
  • Those with the APOE4 gene may be particularly vulnerable to the ill effects of sleep apnea.

Disrupted sleep in one's 50s, 60s raises Alzheimer's risk

A study involving 95 healthy older adults found that adults reporting a decline in sleep quality in their 40s and 50s had more amyloid-beta in their brains later in life, while those reporting poorer sleep in their 50s and 60s had more tau tangles. Those with high levels of tau protein were more likely to lack the synchronized brain waves during deep NREM sleep that are associated with a good night's sleep, and the more tau protein, the less synchronized these brain waves were.

Previous research has found that a dip in the amplitude of slow wave activity during deep NREM sleep was associated with higher amounts of beta-amyloid in the brain and memory impairment.

https://www.eurekalert.org/pub_releases/2019-06/uoc--dsi062619.php

Studies of healthy animals and humans have reported higher levels of amyloid beta after a single night of sleep deprivation, and that disruption of slow-wave sleep causes amyloid beta levels to rise as much as 30%. Moreover, a single night’s sleep deprivation has been found to increase tau levels by as much as 50% in cerebrospinal fluid.

These findings suggest that quality sleep helps the body clear excess amyloid and tau proteins.

https://www.eurekalert.org/pub_releases/2019-03/aps-spa032119.php

A preliminary study involving 20 healthy subjects aged 22 to 72 found beta-amyloid increases of about 5% after losing a night of sleep.

Many researchers believe the link between sleep disorders and Alzheimer's risk is "bidirectional," since elevated beta-amyloid may also lead to sleep disturbances.

https://www.eurekalert.org/pub_releases/2018-04/nioa-los041318.php

A very small study involving eight people aged 30-60, who experienced (over time) two or three different sleep situations, found that amyloid beta levels were 25-30% higher when individuals had a a sleepless night — putting those amyloid beta levels on par with the levels seen in people genetically predisposed to develop Alzheimer’s at a young age.

http://www.futurity.org/sleep-alzheimers-amyloid-beta-1642332/

A sleep study involving 17 healthy adults aged 35 to 65, found that those whose slow-wave sleep was disrupted (by a beeping sound that moved them into a shallower sleep) found a 10% increase in amyloid beta levels after a single night of interrupted sleep, but no corresponding increase in tau levels. However, participants whose activity monitors showed they had slept poorly at home for the week before showed a spike in levels of tau.

http://www.futurity.org/sleep-alzheimers-proteins-1485152-2/

https://www.theguardian.com/science/2017/jul/10/poor-sleep-increases-risk-of-alzheimers-research-reveals

Is too much sleep an early sign of dementia?

Data from 2,457 older adults (65+) in the Framingham study found that those who consistently slept more than nine hours every night had twice the risk of developing dementia and Alzheimer’s disease within the next 10 years, compared to those who slept less than nine hours a night.

Over the 10-year study period, 234 were diagnosed with dementia.

It’s suggested that one reason might be that those with depression tend to sleep longer. In any case, it’s thought that the longer sleep sessions reflect something else going on, rather than being a cause.

Education level also affected the degree of risk. Those without a high school degree who slept more than nine hours nightly had a 600% greater risk of later receiving a dementia diagnosis than people with a high school degree.

http://www.futurity.org/too-much-sleep-dementia-1439122/

Optimal sleep linked to lower dementia risk

A ten-year Japanese study involving 1,517 older adults (60+) found that dementia rates were higher in those with daily sleep duration of less than 5 hours or more than 10 hours, compared with those with daily sleep duration of 5-6.9 hours. However, those with short sleep duration who had high physical activity did not have a greater risk of dementia.

294 participants (19%) developed dementia in the 10 year period.

https://www.eurekalert.org/pub_releases/2018-06/w-osl060518.php

Lack of REM sleep linked to higher dementia risk

A study involving 321 older adults (60+; average age 67), who participated in a sleep study between 1995 and 1998, found poorer REM sleep was associated with an increased risk of developing dementia over 12 years.

During that period, 32 people were diagnosed with some form of dementia (24 with Alzheimer’s)

Those who developed dementia spent an average of 17% of their sleep time in REM sleep, compared with 20% for those who didn’t develop dementia. For every percent that REM sleep was reduced, there was a 9% increase in dementia risk, and an 8% increase in Alzheimer’s risk specifically.

No such associations were found for other stages of sleep, although that shouldn’t be taken to mean that other sleep stages don’t affect key features of Alzheimer’s.

http://www.futurity.org/rem-sleep-dementia-risk-1524842/

Sleep apnea linked to higher tau levels

A study involving 288 cognitively healthy older adults (65+) found that those who had sleep apneas had on average 4.5% higher levels of tau in the entorhinal cortex than those who did not have apneas, after controlling for several other factors that could affect levels of tau in the brain, such as age, sex, education, cardiovascular risk factors and other sleep complaints.

15% (43 participants) were reported by their bed partners as having sleep apneas.

This preliminary study was presented at the American Academy of Neurology's 71st Annual Meeting in Philadelphia, May 4-10, 2019.

https://www.eurekalert.org/pub_releases/2019-03/aaon-sam022619.php

Data from 1,752 older adults found that sleep-disordered breathing was associated with poorer attention and processing speed. In particular, increased overnight hypoxemia (oxygen saturation below 90%) was linked with poorer attention and memory, and more daytime sleepiness associated with poorer attention and memory and slower cognitive processing speed.

These associations were strongest in APOE-ε4 carriers.

https://www.eurekalert.org/pub_releases/2017-07/ats-sdm071817.php

Reference: 

[4468] Winer, J. R., Mander B. A., Helfrich R. F., Maass A., Harrison T. M., Baker S. L., et al.
(2019).  Sleep as a Potential Biomarker of Tau and β-Amyloid Burden in the Human Brain.
Journal of Neuroscience. 39(32), 6315 - 6324.

[4469] Ning, S., & Jorfi M.
(2019).  Beyond the sleep-amyloid interactions in Alzheimer’s disease pathogenesis.
Journal of Neurophysiology. 122(1), 1 - 4.

[4413] Shokri-Kojori, E., Wang G-J., Wiers C. E., Demiral S. B., Guo M., Kim S. Won, et al.
(2018).  β-Amyloid accumulation in the human brain after one night of sleep deprivation.
Proceedings of the National Academy of Sciences. 115(17), 4483 - 4488.

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(2018).  Effect of sleep on overnight cerebrospinal fluid amyloid β kinetics.
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Poor sleep drives Alzheimer’s progression

  • Getting a good night’s sleep is given greater importance with the discovery that sleep deprivation appears to rapidly increase the spread of tau tangles.

Poor sleep has been associated with the development of Alzheimer's disease, and this has been thought to be in part because the protein amyloid beta increases with sleep deprivation. A new study explains more.

Experiments with mice show that sleep deprivation also rapidly increases levels of the other key Alzheimer’s disease protein, tau tangles.

The work built on findings that tau is high in older people who sleep poorly, and that, when people are kept awake all night, their tau levels rise by about 50%.

When mice had tau proteins seeded in the hippocampus of their brains, those who were kept awake for long periods each day (mice are nocturnal), showed significantly greater spread of tau tangles than those mice allowed to sleep normally. Moreover, the new tangles appeared in the same areas of the brain affected in people with Alzheimer’s.

Disrupted sleep also increased release of synuclein protein, a hallmark of Parkinson’s disease. People with Parkinson’s—like those with Alzheimer’s—often have sleep problems.

All of this supports the idea that sleep directly protects against the development of Alzheimer's.

https://www.futurity.org/alzheimers-disease-sleep-tau-1966962/

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Gut microbiome a risk factor for dementia

  • Preliminary research suggests that microbes in the gut directly affects dementia risk.

A Japanese study looking at 128 patients' fecal samples, found that fecal concentrations of ammonia, indole, skatole and phenol were higher in dementia patients compared to those without dementia, while levels of beneficial Bacteroides were lower in dementia patients.

https://www.eurekalert.org/pub_releases/2019-01/aha-it012519.php

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The findings were presented at the American Stroke Association's annual conference.

 

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Psychological distress a risk factor for dementia

  • A large Danish study has found that the greater number of symptoms of distress in late midlife, the more likely the individual was to develop dementia later in life.

Survey data from 6,807 Danish older adults (average age 60) in the Copenhagen City Heart Study, has found that being distressed in late midlife is associated with a higher risk of dementia in later life.

The survey measured “vital exhaustion”, which is operationalized as feelings of unusual fatigue, increased irritability and demoralization and can be considered an indicator of psychological distress. Vital exhaustion is suggested to be a response to unsolvable problems in individuals' lives, in particular when being incapable of adapting to prolonged exposure to stressors.

The study found a dose-response relation between symptoms of vital exhaustion reported in late midlife and the risk of dementia later in life:

  • for every additional symptom, dementia incidence increased by 2%
  • those reporting 5 to 9 symptoms had a 25% higher risk of dementia compared to those with no symptoms
  • those reporting 10 to 17 symptoms (the maximum) had a 40% higher risk of dementia compared with not having symptoms.

Results were adjusted for gender, marital status, lower educational level, lifestyle factors and comorbidities.

https://www.eurekalert.org/pub_releases/2019-01/ip-pdi011719.php

Full paper available at: https://content.iospress.com/articles/journal-of-alzheimers-disease/jad180478

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Poor sleep in older adults may increase Alzheimer’s risk

  • Older people who spend less time in slow-wave sleep (deep sleep) have higher levels of the Alzheimer’s brain protein tau.

Poor sleep has been associated with Alzheimer's disease risk, but a new study suggests a specific aspect of sleep is important.

The study, involving 119 older adults (60+), of whom 80% were cognitively normal and the remainder very mildly impaired, found that decreased slow-wave sleep coincided with higher levels of tau in the brain and a higher tau-to-amyloid ratio in the cerebrospinal fluid.

Amyloid plaques and tau tangles develop for decades before cognitive symptoms of dementia emerge. Identifying the process at an early stage offers a possible window of opportunity for successful intervention.

Participants’ sleep at home was monitored over the course of a normal week, and participants also kept sleep logs of nighttime sleep and daytime napping. Thirty-eight people underwent PET brain scans for amyloid-beta and tau proteins, and 104 people underwent spinal taps to provide cerebrospinal fluid. Twenty-seven did both.

Those with increased tau pathology actually slept more, during both night and day, but their quality of sleep was poorer. In fact, daytime napping alone was significantly associated with high levels of tau, making it a useful indicator of risk.

https://www.futurity.org/alzheimers-disease-sleep-1954732/

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Cholesterol genes link risk of heart disease & Alzheimer’s

  • A very large genetic study provides evidence that cardiovascular disease risk and Alzheimer's risk are related because of one shared element: genes involved in cholesterol and lipid metabolism.

The APOE gene, the strongest genetic risk factor for Alzheimer’s disease, is known to be involved in cholesterol and lipid metabolism. Now the largest ever genetic study of Alzheimer’s disease, using DNA from more than 1.5 million people, has identified 90 points across the genome that were associated with an increased risk of both cardiovascular disease and Alzheimer’s disease.

The study focused on specific risk factors for heart disease (e.g., high BMI, type 2 diabetes, high cholesterol) to see if any were genetically related to Alzheimer’s risk. It was found that only those genes involved in lipid metabolism also related to Alzheimer's risk.

Six of the 90 regions had very strong effects on Alzheimer’s and heightened blood lipid levels, including several points within the CELF1/MTCH2/SPI1 region on chromosome 11 that was previously linked to the immune system.

The same genetic risk factors were also more common in people with a family history of Alzheimer’s, even though they had not themselves developed dementia or MCI.

The findings suggest that cardiovascular and Alzheimer's risk co-occur because of a shared genetic basis.

They also suggest a therapeutic target — namely, pathways involved in lipid metabolism.

https://www.futurity.org/alzheimers-disease-heart-disease-cholesterol-1913312-2/

https://www.eurekalert.org/pub_releases/2018-11/wuso-cda111118.php

Reference: 

Broce I, Karch C, Desikan R, et al. Dissecting the genetic relationship between cardiovascular risk factors and Alzheimer's disease. Acta Neuropathologica, published online Nov. 9, 2018.

 

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Lower tau levels may obscure early Alzheimer’s in black patients

  • Two large studies show an association between the Alzheimer's protein tau and the Alzheimer's gene APOE4, but the association varies across race and gender.

Data from 1,215 older adults, of whom 173 (14%) were African-American, has found that, although brain scans showed no significant differences between black and white participants, cerebrospinal fluid (CSF) showed significantly lower levels of the brain protein tau in African-Americans.

While both groups showed the same (expected) pattern of higher tau levels being associated with greater chance of cognitive impairment, the absolute amounts of tau protein were consistently lower in African-Americans.

However, when APOE status was taken into account, it was found that those who held the low-risk variants of the “Alzheimer’s gene” had similar levels of tau, regardless of race. It was only African-Americans with the APOE4 gene variant that showed lower levels of tau.

This suggests that the APOE4 risk factor has different effects in African-Americans compared to non-Hispanic white Americans, and points to the need for more investigation into how Alzheimer’s develops in various populations.

Interestingly, another study, using data from 1798 patients (of whom 1690 were white), found that there was a strong gender difference in the association between APOE status and tau levels in the CSF.

Previous research has shown that the link between APOE4 and Alzheimer's is stronger in women than men. This study points to a connection with tau levels, as there was no gender difference in the association between APOE and amyloid-beta levels, amyloid plaques, or tau tangles.

https://www.futurity.org/alzheimers-disease-black-patients-1951502/

Reference: 

Morris JC, Schindler SE, McCue LM, et al. Assessment of Racial Disparities in Biomarkers for Alzheimer Disease. JAMA Neurol. Published online January 07, 2019. doi:10.1001/jamaneurol.2018.4249

Hohman TJ, Dumitrescu L, Barnes LL, et al. Sex-Specific Association of Apolipoprotein E With Cerebrospinal Fluid Levels of Tau. JAMA Neurol. 2018;75(8):989–998. doi:10.1001/jamaneurol.2018.0821

 

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