CVD IS PATHOLOGICALLY ASSOCIATED WITH GREATER ALZHEIMER'S DISEASE IN NON-DEMENTED OLDER ADULTS

Abstract

To investigate the association between cerebrovascular disease (CVD) and Alzheimer's Disease (AD)-related neuropathological changes in non-demented older adults drawn from the Framingham Brain Donation Program (FBDP). Autopsy data from 76 dementia-free participants were evaluated for AD-related neuropathological changes (i.e., density of neurofibrillary tangles [NFT], diffuse plaques [DP] and neuritic plaques [NP]) and CVD burden reflected by the Ischemic Injury Score (IIS; infarcts, microinfarcts, white matter lesions [WMLs], cerebral amyloid angiopathy [CAA], atherosclerosis, arteriosclerosis, and hippocampal sclerosis [HS]). After adjusting for age, sex, and APOE-e4 genotypes, the IIS score was significantly associated with Total-NFT, Total-DP, and Total-NP as well as medial temporal lobe NFT (MTL-NFT) and MTL-DP (all p-values < 0.05), but not MTL-NP. Examined separately, CAA was linked to elevations in all whole brain AD-related neuropathological indices (p-values < 0.05) as well as MTL-DP and MTL-NP (p-values < 0.01). Additionally, HS was associated with NFT counts in both the MTL and whole brain but was not related to plaque density. Finally, increased WML volume was related to Total NP, but neither infarcts, microinfarcts, atherosclerosis, nor arteriosclerosis were associated with AD-related neuropathological changes. Results suggest that CVD and AD-related neuropathological changes commonly co-occur, even in non-demented participants. Importantly, our data indicate that CAA and hippocampal sclerosis, and to some extent WML, are tightly linked with AD-related neuropathological changes. Taken together, our findings underscore the importance of comprehensive evaluation of CVD to elucidate our understanding of the prevalence of mixed pathologies, even among those who are clinically asymptomatic.