Cerebrovascular Pathologies, Not Age-Adjusted AD, Rates Are Improving Over Time

No differences in AD or other neurodegenerative pathologies emerged over time, but cerebrovascular pathologies decreased.

Over a 25-year period, there were few differences in neurodegenerative pathology trends observed, but cerebrovascular pathologies tended to improve, indicating better brain health population-wide. These are the findings of a study published in JAMA Neurology.

Previous studies have suggested that rates of dementia in the United States may be declining. However, these temporal trends have not been sufficiently assessed.

Researchers from Rush Alzheimer’s Disease Center in the United States sourced data for this study from the Religious Orders Study and the Rush Memory and Aging Project, which were established in 1994 and 1997 in the US, respectively. In this study, participants (N=1554) were stratified by birth year and trends in Alzheimer disease (AD) pathology, neurodegenerative neuropathology, cerebrovascular pathology, and cognitive outcomes were evaluated.

A total of 374 individuals (65%-71% were women; 97%-99% were White) were born in 1905-1914, 360 in 1915-1919, 466 in 1920-1924, and 354 in 1925-1930. The median age at death decreased over time from 93 years for those born in 1905-1914 to 87 years for those born in 1925-1930. These individuals completed an average of 16.1-16.5 years of education and they had 1.9-2.2 comorbidities.

This indicates that any improvements over time in clinical dementia are likely associated with improved resilience to pathology over time.

The age-standardized prevalence of AD was similar for the first 3-birth cohorts (range, 68%-69%) but decreased to 64% for those born in 1925-1930 (P =.76). Age-standardized Alzheimer dementia slightly decreased from 46% for those born in 1905-1914 to 44% for 1915-1919, 42% for 1920-1924, and 41% for 1925-1930 (P =.18).

A significant trend was observed across birth cohorts for the level of amyloid beta (Ab; P <.001), in which those born in 1915-1919 (mean, 1.72) and 1920-1914 (mean, 1.65) had higher levels than those born in 1905-1914 (mean, 1.36) and 1925-1930 (mean, 1.41) as well as a significant increase in tau tangle density over time (P =.01).

For cerebrovascular pathologies, significant decreases in moderate or severe atherosclerosis from 54% to 22% (P <.001) and arteriosclerosis from 44% to 28% (P <.001) were observed, whereas the rate of chronic microinfarcts increased with time from 27% to 40% (P =.007).

These trends may have had effects on cognitive outcomes, as levels of cognition tended to increase over time from -1.07 standard units for those born in 1905-1914 to -0.93 standard units for 1915-1919, -0.93 standard units for 1920-1924, and -0.89 standard units for 1925-1930 (P =.05).

The major limitation of this study was the lack of diversity among the study population.

These data indicated that although no significant change in the rates of AD or Alzheimer dementia were observed, rates of cerebrovascular pathologies were decreasing over time, which led the researchers to conclude, “This indicates that any improvements over time in clinical dementia are likely associated with improved resilience to pathology over time.”


Grodstein F, Leurgans SE, Capuano AW, Schneider JA, Bennett DA. Trends in postmortem neurodegenerative and cerebrovascular neuropathologies over 25 years. JAMA Neurol. Published online February 23, 2023. doi:10.1001/jamaneurol.2022.5416