Sex differences in mixed neuropathologies in community-dwelling older adults

Alzheimer's dementia is the leading cause of dementia in older adults and women are disproportionately burdened. It is increasingly recognized that dementia in older persons is related to the co-occurrence of mixed pathologies in the brain, but few studies have examined whether the frequency of common pathologies vary by sex. We examined the frequency of the most common mixed pathologies that underlie Alzheimer's dementia in aging, including Alzheimer's disease (AD) in combination with Lewy Bodies, cerebrovascular disease (CVD) pathology, or TDP-43/Hippocampal sclerosis, and determined whether the patterns differed for women and men in a combined cohort of over 1500 older community-dwelling adults. We found in separate models that women were significantly more likely to have AD and CVD pathology than men, and men were more likely to have "pure" Lewy Body disease, in models adjusted for age at death, education, race, and the APOE-e4 allele. Although AD with TDP-43/Hippocampal sclerosis pathology was greater in number in women than men, the difference was not significant after adjustments for age at death and other confounders. Together these findings suggest sex differences in mixed pathology, specifically AD with CVD in older adults from the community.