We May Be Better at Fending Off Dementia, Autopsies Suggest

Neurodegenerative pathologies have shown few differences over time despite falling dementia incidence rates, brain autopsy data suggested.

In over 1,500 deceased people from birth epochs spanning 25 years (1905-1930), no significant differences in global Alzheimer’s disease pathology or other neurodegenerative pathologies emerged over time, according to Francine Grodstein, ScD, of Rush University Medical Center in Chicago, and colleagues.

However, brain atherosclerosis and arteriosclerosis were dramatically lower over the years. The age-standardized prevalence of moderate to severe atherosclerosis, for example, ranged from 54% for people born from 1905-1914 to 22% for those born from 1925-1930 (χ² test: P<0.001 across birth epochs), the researchers reported in JAMA Neurology.

Recent studies have indicated that the incidence of dementia may be declining in the U.S., but have not explained the mechanisms behind this shift, Grodstein noted.

“Its important to understand what may be driving any decreases, so we might learn some lessons about dementia prevention,” she told MedPage Today. “We examined trends over time in the prevalence of dementia-related neuropathologies as a way to understand how some of the pathways underlying dementia may or may not be changing over time.”

“We did not find any decrease over time in neurodegenerative neuropathologies, which indicates that any decreases in clinical dementia are likely due — at least in part — to resilience against pathology, rather than to changes in pathology itself,” Grodstein said.

“We did, however, find substantial decreases over time in brain atherosclerosis and arteriosclerosis,” she continued. “This finding suggests that national efforts to reduce vascular risk factors and improve vascular health are extremely important.”

The researchers analyzed autopsy data from two longitudinal cohorts — the Religious Orders Study and the Rush Memory and Aging Project — from 1997 to 2022 with up to 27 years of follow-up. Both are prospective studies enrolling older adults who agree to annual clinical evaluations and brain donation at death.

A total of 1,554 participants were included; most were female (67%) and median age at death was 90. Participants were distributed fairly evenly across four birth epochs of 1905-1914, 1915-1919, 1920-1924, and 1925-1930.

The prevalence of pathologic Alzheimer’s diagnosis was similar over time, at 68% for those born from 1905-1914, 68% for 1915-1919 births, 69% for 1920-1924 births, and 64% for 1925-1930 births (χ² test: P=0.76 across year of birth groups).

There also was no significant difference across epochs in mean levels of overall pathological burden of amyloid-beta and tau. Higher levels of tau tangle density emerged over time, with those in more recent birth year categories showing higher density than those in the earliest epoch (analysis of variance test: P=0.01 across birth year categories). “Given our finding of better cognitive function across birth epochs, this further supports the likelihood of an increase in resilience to pathology over time,” Grodstein and colleagues wrote.

No differences in other neurodegenerative pathologies emerged over time.

The prevalence of moderate to severe brain atherosclerosis was 54% among 1905-1914 births, 37% for 1915-1919, 30% for 1920-1924, and 22% for 1925-1930, while moderate/severe arteriolosclerosis ranged from 44% for those born from 1905-1914 to 28% from 1925-1930 (χ² test: P<0.001 across birth year categories). However, there were no differences in age-standardized prevalence of gross chronic infarcts over time, and microinfarcts were more prevalent with later year of birth.

Clinical data suggested better levels of cognition over time. The age-standardized prevalence of Alzheimer’s dementia appeared to slightly but continuously fall over time, but did not reach statistical significance.

Participants in these cohorts may be healthier than the general population, the researchers acknowledged. “However, since neuropathology is so common in aging regardless of health or dementia status, the results here regarding trends in neuropathology likely provide important and relevant insights,” they wrote. In addition, participants mainly were white.