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To investigate the association of hippocampal sclerosis (HS) with TAR‐DNA binding protein of 43kDa (TDP‐43) and other common age‐related pathologies, dementia, probable Alzheimer disease (AD), mild cognitive impairment (MCI), and cognitive domains in community‐dwelling older subjects.

Diagnoses of dementia, probable AD, and MCI in 636 autopsied subjects from the Religious Order Study and the Rush Memory and Aging Project were based on clinical evaluation and cognitive performance tests. HS was defined as severe neuronal loss and gliosis in the hippocampal CA1 and/or subiculum. The severity and distribution of TDP‐43 were assessed, and other age‐related pathologies were also documented.

HS was more common in those aged >90 years (18.0%) compared to younger subjects (9.2%). HS cases commonly coexisted with TDP‐43 pathology (86%), which was …