Trajectories of cognitive decline differ in hippocampal sclerosis and Alzheimer's disease

Hippocampal sclerosis (HS) is a prevalent cause of dementia in the oldest old but is generally misdiagnosed as Alzheimer's disease (AD) due to similarities in clinical presentation. To determine if clinical and cognitive features diverge over time, we compared results from longitudinal evaluations of participants in the University of California, San Diego, Alzheimer's Disease Research Center with autopsy-confirmed AD (n = 195), HS (n = 21), or both HS + AD (n = 18). Each group exhibited decline in all cognitive measures, with HS declining at a slower rate than AD on the Mini-Mental State Examination, immediate recall condition of a word-list learning test, and Dementia Rating Scale total and subtest scores (except memory). Five years before the final evaluation, more prominent semantic and visuospatial deficits were apparent in AD participants than in HS participants despite comparable global cognitive impairment. Groups did not differ on any measure of executive function. HS + AD differed from AD only on the Boston Naming Test. Overall, results suggest that HS dementia is associated with cognitive deficits that progress more slowly than, but generally mimic, those observed in AD.