Alzheimer's & other dementias
As we all know, people are living longer and obesity is at appalling levels. For both these (completely separate!) reasons, we expect to see growing rates of dementia. A new analysis using data from the long-running Framingham Heart Study offers some hope to individuals, however.
Looking at the rate of dementia during four distinct periods in the late 1970s, late 1980s, 1990s, and 2000s, using data from 5205 older adults (60+), the researchers found that there was a progressive decline in the incidence of dementia at a given age, with an average reduction of 20% per decade since the 1970s (22%, 38%, and 44% during the second, third, and fourth epochs, respectively).
There are two important things to note about this finding:
The cumulative risk over five years, adjusted for age and gender, were:
Part of the reason for the decline is put down to the decrease in vascular risk factors other than obesity and diabetes, and better management of cardiovascular diseases and stroke. But this doesn't completely explain the decrease. I would speculate that other reasons might include:
The finding is not completely unexpected. Recent epidemiological studies in the U.S., Canada, England, the Netherlands, Sweden and Denmark have all suggested that “a 75- to 85-year-old has a lower risk of having Alzheimer’s today than 15 or 20 years ago.” Which actually cuts to the heart of the issue: individual risk of dementia has gone down (for those taking care of their brain and body), but because more and more people are living longer, the numbers of people with dementia are increasing.
 Satizabal, C. L., Beiser A. S., Chouraki V., Chêne G., Dufouil C., & Seshadri S.
(2016). Incidence of Dementia over Three Decades in the Framingham Heart Study.
New England Journal of Medicine. 374(6), 523 - 532.
I've spoken before about how the presence or absence of the “Alzheimer's gene” may affect which lifestyle changes are beneficial for you. A new study has added to that idea with a finding that seafood consumption was associated with fewer signs of Alzheimer's-related pathology, but only among those with the APOEe4 gene.
Seafood consumption was also associated with increased mercury levels in the brain, with levels rising the more seafood was consumed. However, higher levels of mercury were not correlated with any neuropathologies.
Fish oil supplementation was not associated with any differences in neuropathology. However, higher levels of alpha-linolenic acid (an omega-3 fatty acid found in flaxseed, chia seeds, walnuts, etc) were associated with a reduced chance of cerebral infarctions.
The study involved 554 deceased participants (average age 89.9 years) from the long-running Memory and Aging Project (MAP) conducted by Rush University Medical Center. The participants had completed annual dietary questionnaires over a number of years. The brains of 286 participants were autopsied, to assess neuropathologies and mercury levels.
The average educational attainment of the participants was 14.6 years; 67% were women.
The finding tempers the evidence from many studies that eating fish reduces Alzheimer's risk. However, it is consistent with what I believe is becoming apparent: that there are different paths to Alzheimer's, and thus different factors involved in preventing it, depending on your own particular gene-environment attributes.
 Morris, M., Brockman J., Schneider JA., & et al
(2016). ASsociation of seafood consumption, brain mercury level, and apoe ε4 status with brain neuropathology in older adults.
JAMA. 315(5), 489 - 497.
A study involving 14 years of health records from more than 274,000 Northern Californians has assessed the relative dementia risk of six different ethnicities.
The average annual rate of dementia was:
But this is an annual rate, not particularly useful at a practical level. How do these numbers convert to lifetime risk? Statistical calculations estimate that among those who reach age 65 dementia-free, the following percentages of each ethnicity will develop dementia in the next 25 years:
The study population included 18,778 African-Americans, 4543 American Indians/Alaskan Natives, 21,000 Latinos, 206,490 white Americans, 23,032 Asian-Americans, and 440 Pacific Islanders.
 Mayeda, E. Rose, M. Glymour M., Quesenberry C. P., & Whitmer R. A.
(2016). Inequalities in dementia incidence between six racial and ethnic groups over 14 years.
Alzheimer's & Dementia: The Journal of the Alzheimer's Association.
After Alzheimer's disease, the next most common type of dementia is Lewy Body disease. Far less widely known, this form of dementia is often diagnosed quite late. A new study has validated a simple rating scale that non-specialist clinicians can use to quickly and effectively diagnose LBD in about three minutes.
The Lewy Body Composite Risk Score (LBCRS) is a simple, one-page survey with structured yes/no questions for six non-motor features that are present in patients with LBD, but are much less commonly found in other forms of dementia.
The study involved 256 patients referred from the community. The LBCRS was able to discriminate between Alzheimer's disease and LBD with 96.8% accuracy, and provided sensitivity of 90% and specificity of 87%.
Earlier diagnosis will not only reduce the strain on sufferers and their families, but also reduce the risk of inappropriate medications that can have potentially serious adverse consequences, and increase the opportunity to receive appropriate symptomatic therapies at the earliest stages when they are likely to be most effective.
 Galvin, J. E.
(2015). Improving the clinical detection of Lewy body dementia with the Lewy body composite risk score.
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. 1(3), 316 - 324.
We know that traumatic brain injury increases the risk of later developing neurodegenerative disorders such as Alzheimer's disease, but we haven't known why. New mouse studies suggest a reason.
In the research, mice who had a toxic form of tau protein (taken from mice who had suffered TBI) injected into their hippocampus, showed impaired memory and cognition. Moreover, levels of the aggregated tau protein not only increased in the hippocampus, but also in the cerebellum (which is quite some distance away from the hippocampus). This is consistent with other research showing that tau tangles spread from the initial injection site, using mice modeling Alzheimer's disease.
The study followed on from previous research showing that this form of tau protein increases after a traumatic brain injury and may contribute to development of chronic traumatic encephalopathy (a condition experienced by many professional athletes and military personnel).
The findings support the hypothesis that many of the symptoms of TBI may be down to an increase in these tau tangles, and that this may also be responsible for the increased risk for neurodegenerative disease. As an obvious corollary, it also suggests that the tau tangles are an important therapeutic target.
 Gerson, J. E., Castillo-Carranza D. L., Sengupta U., Bodani R., Prough D. S., DeWitt D., et al.
(2016). Tau oligomers derived from Traumatic Brain Injury cause cognitive impairment and accelerate onset of pathology in Htau mice.
Journal of Neurotrauma.
A study involving both mice and human cells adds to evidence that stress is a risk factor for Alzheimer's.
The study found that mice who were subjected to acute stress had more amyloid-beta protein in their brains than a control group. Moreover, they had more of a specific form of the protein, one that has a particularly pernicious role in the development of Alzheimer's disease.
When human neurons were treated with the stress hormone corticotrophin releasing factor (CRF), there was also a significant increase in the amyloid proteins.
It appears that CRF causes the enzyme gamma secretase to increase its activity. This produces more amyloid-beta.
The finding supports the idea that reducing stress is one part of reducing your risk of developing Alzheimer's.
An interesting study last year supports this.
The study, involving 800 women who were followed up some 40 years after taking a personality test, found that women who scored highly in "neuroticism" in middle age, have a greater chance of later developing Alzheimer's. People who have a tendency to neuroticism are more readily worried, distressed, and experience mood swings. They often have difficulty in managing stress.
The women, aged 38 to 54, were first tested in 1968, with subsequent examinations in 1974, 1980, 1992, 2000, and 2005. Neuroticism and extraversion were assessed in 1968 using the Eysenck Personality Inventory. The women were asked whether they had experienced long periods of high stress at each follow-up.
Over the 38 years, 153 developed dementia (19%), of whom 104 were diagnosed with Alzheimer's (13% of total; 68% of those with dementia).
A greater degree of neuroticism in midlife was associated with a higher risk of Alzheimer's and long-standing stress. This distress accounted for a lot of the link between neuroticism and Alzheimer's.
Extraversion, while associated with less chronic stress, didn't affect Alzheimer's risk. However, high neuroticism/low extraversion (shy women who are easily worried) was associated with the highest risk of Alzheimer's.
The finding supports the idea that long periods of stress increase the risk of Alzheimer's, and points to people with neurotic tendencies, who are more sensitive to stress, as being particularly vulnerable.
 Park, H-J., Ran Y., Jung J. In, Holmes O., Price A. R., Smithson L., et al.
(2015). The stress response neuropeptide CRF increases amyloid-β production by regulating γ-secretase activity.
The EMBO Journal. 34(12), 1674 - 1686.
 Johansson, L., Guo X., Duberstein P. R., Hällström T., Waern M., Östling S., et al.
(2014). Midlife personality and risk of Alzheimer disease and distress A 38-year follow-up.
Neurology. 83(17), 1538 - 1544.
A ten-year study involving 2,092 older adults (average age 76) has found that people tended to lose awareness of memory problems two to three years before the onset of dementia.
Being unaware of your own memory problems is common in dementia, but previous research has focused on those already diagnosed with dementia. In this study, participants had no cognitive impairment at the beginning of the study.
Overall, subjective memory ratings taken annually were modestly correlated with performance (only modestly — people tend not to be that great at accurately assessing their own memory!), and this awareness was stable with age. However, in the subset of those who developed dementia (239 participants; 11%), this awareness started to deteriorate an average of 2.6 years before dementia was diagnosed (after which it dropped rapidly).
In a subset of those who died and had their brains examined (385 participants), a decline in memory awareness was associated with three pathologies:
There was no decline in memory awareness in those who didn't show any of these pathologies.
Those who were older at the beginning of the study were more likely to retain memory awareness longer, perhaps because they were more alert to memory problems.
 Wilson, R. S., Boyle P. A., Yu L., Barnes L. L., Sytsma J., Buchman A. S., et al.
(2015). Temporal course and pathologic basis of unawareness of memory loss in dementia.
A new questionnaire has been developed that very quickly determines whether or not a person has dementia and whether it's very mild, mild, moderate or severe. The 10-item questionnaire takes only 3-5 minutes and can be completed by a caregiver, friend or family member.
Testing on 239 individuals with various forms of dementia and 28 healthy controls has shown the results are comparable to the gold standard used presently, which takes several hours for an experienced professional to administer, interpret and score.
The "Quick Dementia Rating System" (QDRS) was developed by a leading neuroscientist, James E. Galvin, who has developed a number of dementia screening tools. The questionnaire covers:
The total score is derived by summing up the 10 fields and each area has five possible answers increasing in severity of symptoms. The 10 areas capture the prominent symptoms of mild cognitive impairment, Alzheimer's disease, and non-Alzheimer's neurocognitive disorders including Lewy Body Dementia, frontotemporal degeneration, vascular dementia, chronic traumatic encephalopathy and depression.
The speed and ease of this questionnaire makes it a very useful initial screening tool. However, there are several caveats to its use now. At the moment, it has only been validated in the context of a memory disorders clinic, where prevalence of MCI and dementia is high. The next step would be to evaluate it in the context of settings where dementia prevalence is lower, such as 'ordinary' health clinics. Additionally, most of the study participants were Caucasian. Most importantly, inter-rater reliability has not yet been assessed (that is, the degree to which different scorers agree).
The Quick Dementia Rating System is copyrighted and permission to use this tool is required. QDRS is available at no cost to clinicians, researchers and not-for-profit organizations.
 Galvin, J. E.
(2015). The Quick Dementia Rating System (QDRS): A rapid dementia staging tool.
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. 1(2), 249 - 259.
A long-running study comparing African-Americans and Nigerians has found the incidence of dementia has fallen significantly over two decades among the African-Americans, but remained the same for the Nigerians (for whom it was lower anyway).
The study enrolled two cohorts, one in 1992 and one in 2001, who were evaluated every 2–3 years until 2009. The 1992 cohort included 1440 older African-Americans (70+) and 1774 Nigerian Yoruba; the 2001 cohort included 1835 African-Americans and 1895 Yoruba. None of the participants had dementia at study beginning.
The overall standardized annual incidence rate was 3.6% for the 1992 African-American cohort, and 1.4% for the 2001 cohort. For the Yoruba, it was 1.7% and 1.4%, respectively.
It's suggested that one reason for the improvement among African-Americans may be medications for cardiovascular conditions. Although both groups had similar rates of high blood pressure, this was recognized and treated in the American group but not in the Nigerian.
As you can see, African-Americans in the earlier cohort were more than twice as likely as Africans to develop dementia. Their decrease has brought them into line with the African rate.
Although the rate of new cases of dementia decreased, the African-Americans enrolling in 2001 had significantly higher rates of diabetes, hypertension and stroke, but also higher treatment rates, than the African-Americans who enrolled in 1992.
The finding offers hope that treatment can offset the expected increase in dementia resulting from the rise in lifestyle diseases.
 Gao, S., Ogunniyi A., Hall K. S., Baiyewu O., Unverzagt F. W., Lane K. A., et al.
(Submitted). Dementia incidence declined in African-Americans but not in Yoruba.
Alzheimer's & Dementia.
A post-mortem study of five Alzheimer's and five control brains has revealed the presence of iron-containing microglia in the subiculum of the Alzheimer's brains only. The subiculum lies within the hippocampus, a vital memory region affected early in Alzheimer's. None of the brains of those not diagnosed with Alzheimer's had the iron deposits or the microglia, in that brain region, while four of the five Alzheimer's brains contained the iron-containing microglia.
The microglia were mostly in an inflamed state. Growing evidence implicates brain inflammation in the development of Alzheimer's.
There was no consistent association between iron-laden microglia and amyloid plaques or tau in the same area.
Obviously, this is only a small study, and more research needs to be done to confirm the finding. However, this is consistent with previous findings of higher levels of iron in the hippocampi of Alzheimer's brain.
At the moment, we don't know how the iron gets into brain tissue, or why it accumulates in the subiculum. However, the researchers speculate that it may have something to do with micro-injury to small cerebral blood vessels.
This is an interesting finding that may lead to new treatment or prevention approaches if confirmed in further research.
 Zeineh, M. M., Chen Y., Kitzler H. H., Hammond R., Vogel H., & Rutt B. K.
(Submitted). Activated iron-containing microglia in the human hippocampus identified by magnetic resonance imaging in Alzheimer disease.
Neurobiology of Aging.
Dr McPherson's practical, research-based books are instantly available as digital downloads from the Mempowered store (all formats), Kindle Store, Kobo Store, and iTunes. They are also available in paperback.