Longitudinal hippocampal atrophy in hippocampal sclerosis of aging vs. Alzheimer’s disease

Abstract

AbstractBackgroundHippocampal sclerosis of aging (HS) is a common degenerative neuropathology in older individuals and is strongly associated with dementia. HS is characterized by disproportionate hippocampal atrophy at autopsy but cannot be diagnosed during life. Therefore, little is known about the onset and progression of hippocampal atrophy and how it relates with stages of cognitive impairment in individuals with HS. We performed a longitudinal case‐series study of hippocampal atrophy and its progression in participants with HS at autopsy compared with matched participants with Alzheimer’s disease (AD) and those without HS or AD to better understand the longitudinal pattern of hippocampal atrophy in HS.MethodsWe used data from Alzheimer’s Disease Neuroimaging Initiative (ADNI‐1, http://adni.loni.usc.edu/) participants with both 3D‐T1w MRIs and autopsy data. Of 47 total participants, 6 had HS. 12 comparison cases were matched by age, sex, and education: 6 with AD, and 6 with neither HS nor AD (No‐HS/AD). We calculated total hippocampal volume using FreeSurfer v6.0 (https://surfer.nmr.mgh.harvard.edu/fswiki/LongitudinalHippocampalSubfields). We plotted hippocampal volumes with respect to age labeled by cognitive status, and compared average volumes and slopes using paired T‐tests.ResultsParticipant characteristics are shown in Table‐1. Three HS participants also had AD. All except one HS participants had lower hippocampal volumes compared to the matched AD and No‐HS/AD participants (Figure‐1). HS3 participant maintained a high hippocampal volume and normal cognition throughout follow‐up. When excluding participants with normal cognition at the time of imaging (HS3, N5), paired T‐tests for average hippocampal volume trended towards significance (HSvsAD P=0.060, HSvsNo‐HS/AD P=0.12), but there were no significant differences in slopes of volume change with age (Figure‐2).ConclusionThe results of this case‐series suggest that individuals with HS have MRI detectable smaller hippocampi than individuals with AD or other pathologies at corresponding stages of cognitive impairment. Our findings also suggest that hippocampal atrophy may begin several years before dementia onset in individuals with HS, supporting the potential utility of hippocampal atrophy as an early biomarker for HS.