To examine the impact of common degenerative neuropathologies across the age spectrum using the National Alzheimer's Coordinating Center (NACC) database.

Few studies have assessed whether the impact of degenerative pathologies is different across different age groups.

NACC participants whose last visits occurred within two years of death (n=4,554) were divided into four age groups: ≤69 years, 70-79 years, 80-89 years, and 90+ years. Dichotomized pathologies included Alzheimer’s disease (AD), cerebral amyloid angiopathy (CAA), atherosclerosis, arteriolosclerosis, Lewy bodies (LB), hippocampal sclerosis (HS), frontotemporal lobar degeneration (FTLD), and primary age-related tauopathy (PART). Cognition was dichotomized as no dementia versus dementia. In each age group, we examined the relationship between cognition (outcome) and all neuropathologies (predictor) using logistic regressions that were adjusted for sex and education.

Average age at death was 80.14 years. AD, atherosclerosis, and arteriolosclerosis were more common in older groups, whereas FTLD became less prevalent with age. LB was more common in 70-89 group while CAA prevalence was stable across groups. Overall, PART and HS were uncommon but demonstrated greater prevalence in older groups. In terms of relationship with dementia, AD and LB had significant association in all ages but the association was stronger in younger groups. FTLD was significantly associated with dementia for all ages but HS relationship with dementia was only significant in those older than 70. CAA association was significant for the 80-89 group and arteriolosclerosis was significant for those over 80. PART and atherosclerosis were not significantly associated with dementia in any age group.

Despite greater prevalence in older age groups, the association between dementia and AD and LB was stronger in the younger groups. Resilience to AD in older age and higher prevalence of other pathologies such as HS are potential explanations.