Hippocampal sclerosis of aging at post-mortem is evident on MRI more than a decade prior

Abstract

Introduction: Hippocampal sclerosis of aging (HS) is an important component of combined dementia neuropathology. However, the temporal evolution of its histologically-defined features is unknown. We investigated pre-mortem longitudinal hippocampal atrophy associated with HS, as well as with other dementia-associated pathologies.

Methods: We analyzed hippocampal volumes from MRI segmentations in 64 dementia patients with longitudinal MRI follow-up and post-mortem neuropathological evaluation, including HS assessment in the hippocampal head and body.

Results: Significant HS-associated hippocampal volume changes were observed thoughout the evaluated timespan, up to 11.75 years before death. These changes were independent of age and Alzheimer’s Disease (AD) burden, and specifically driven by CA1 and subiculum. AD burden, but not HS, significantly associated with the rate of hippocampal atrophy.

Discussion: HS-associated volume changes are detectable on MRI earlier than 10 years before death. These findings could contribute to the derivation of volumetric cut-offs for in vivo differentiation between HS and AD.

Figure 1.. Longitudinal progression of hippocampal volumes as a function of HS.

(A) HS groups defined as a function of HS staging including early and advanced stages (HS+ for those at stage>0) [23]. (B) HS groups determined by the classical definition of the pathology, by which only advanced cases with severe cell loss are included within the HS+ group. HS: hippocampal sclerosis of aging.

Figure 2.. Longitudinal progression of hippocampal subfields volumes as a function of HS staging.

(A) Volumes of CA1+subiculum in the head of the hippocampus. (B) Volumes of CA1+subiculum in the hippocampal body. (C) CA3+CA4 volumes in the head of the hippocampus. (D) CA3+CA4 volumes in the hippocampal body. CA1+Sub: CA1+subiculum.

Figure 3.. Longitudinal volumes of the whole hippocampus as a function of other neuropathologies in dementia.

(A) Differences between groups of low/intermediate and high probability of ADNC. (B) Groups of low and high vascular pathology burden, following the evaluation proposed by Deramecourt et al. [30] (C) Groups of low and high Lewy body pathology burden, as a function of Braak staging for α-synuclein. (D) Comparisons between groups of low and high TDP-43 pathology burden, evaluated through LATE staging. ADNC: Alzheimer’s disease neuropathological change. LATE: limbic age-related TDP-43 encephalopathy.