Evidence for Reduced Dementia Incidence to be Driven by Improved Vascular Health

Dementia risk for individuals has decreased in recent decades, even as the population grows and ages to the point at which overall number of cases expands. Since individual risk of suffering cardiovascular disease has also decreased over the same period of time, it is reasonable to ask whether reduced dementia risk is a direct consequence of improvements in long term vascular health. Researchers here provide evidence to suggest that this is the case, noting that levels of amyloid-β aggregates in post-mortem brains are much the same across recent decades, while vascular health improves. Misfolding and aggregation of amyloid-β is still broadly thought to be the mechanism that produces Alzheimer's disease, though there is now considerable debate given the failure of amyloid-clearing immunotherapies to help patients. Is amyloid-β actually a meaningful cause, or is it only relevant in the early stages of Alzheimer's? The situation is complicated by the fact that a sizable fraction of Alzheimer's patients also exhibit clear signs of vascular dementia.

In Europe and the U.S., proportionately fewer people are developing dementia now than in the past. Is this driven by less-prevalent Alzheimer's disease (AD) pathology? No, say researchers, who reported that among 1,550 older Americans born over a 25-year period, all had similar amounts of amyloid plaques at death, which came at an average of 90 years. If less pathology does not explain falling dementia incidence, then what does? People born in the 1920s had healthier blood vessels in their brains when they died than did those born in the 1900s, the authors found. They think better cardiovascular health among people born in more recent decades may make them more resilient to AD pathology.

Dementia incidence has steadily fallen by 20 to 25 percent over the past three decades in the U.S., U.K., Sweden, and the Netherlands. Researchers suspect that this drop was due to better overall health - especially improvements in cardiovascular health - and higher levels of education . Might these factors stave off amyloid plaques and neurofibrillary tangles? To find out, researchers quantified the extent of amyloid plaques, neurofibrillary tangles, Lewy bodies, TDP-43 aggregates, infarcts, and the severity of atherosclerosis and arteriosclerosis in cortical tissue from 1,554 participants in the Religious Orders Study and the Rush Memory and Aging Project (ROSMAP) cohort. About one-quarter were born in each of four periods: 1905 to 1914, 1915 to 1919, 1920 to 1924, and 1925 to 1930. All died between 1997 and 2022.

The prevalence of postmortem AD diagnoses hovered between 64 and 68 percent in each birth epoch. The amount of Lewy bodies and TDP-43 inclusions remained the same across birth cohorts, as well. Notably, people born later had higher densities of neurofibrillary tangles than those born earlier. However, the extent of blood vessel damage, be it through atherosclerosis or arteriosclerosis, had decreased dramatically in participants born in the later cohorts. About half of those born from 1905 to 1914 had moderate to severe atherosclerosis, while only 22 percent of people born in the late 1920s did. All told, the researchers think that the declining prevalence of clinically diagnosed AD may be due to people having more cognitive reserve, which might be a product of better cardiovascular health and more education.

Link: https://www.alzforum.org/news/research-news/those-declining-dementia-rates-its-not-plaques-and-tangles

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