Longitudinal hippocampal atrophy in hippocampal sclerosis of aging

Abstract

Hippocampal sclerosis of aging (HS-A) is a common degenerative neuropathology in older individuals and is associated with dementia. HS-A 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 in individuals with HS-A. To better understand the onset and progression of hippocampal atrophy in HS-A, we examined longitudinal hippocampal atrophy using serial MRI in participants with HS-A at autopsy (HS-A+, n = 8) compared to participants with limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) without HS-A (n = 13), Alzheimer's disease neuropathologic change (ADNC) without HS-A or LATE-NC (n = 16), and those without these pathologies (n = 7). We found that participants with HS-A had lower hippocampal volumes compared to the other groups, and this atrophy preceded the onset of dementia. There was also some evidence that rates of hippocampal volume loss were slightly slower in those with HS-A. Together, these results suggest that the disproportionate hippocampal atrophy seen in HS-A may begin early prior to dementia.

Keywords: Alzheimer’s Disease; Dementia; Hippocampal sclerosis of aging; Hippocampus; LATE-NC; MRI.

Fig. 1

Total hippocampal volume (A) and smallest hippocampal volume (B) as percentage of total intracranial volume (%TIV) plotted against age at visit. Total hippocampal volume (C) and smallest hippocampal volume (D) as percentage of total intracranial volume (%TIV) plotted against CDR-SB. HS-A participants are shown in red, ADNC participants are shown in blue, LATE-NC participants are shown in orange, and no pathology participants are shown in purple. Marker shapes denote cognition at time of visit. Abbreviations: HS-A: Hippocampal sclerosis of aging, ADNC: Alzheimer’s disease neuropathologic change, LATE-NC: limbic-predominant age-related TDP-43 encephalopathy neuropathologic change, CN: cognitively normal, MCI: mild cognitive impairment. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)