Utility of MRI in the identification of hippocampal sclerosis of aging

Woodworth, Davis C.; Nguyen, Hannah L.; Khan, Zainab; Kawas, Claudia H.; Corrada, María M.

doi:10.1002/alz.12241

Cited by 22 publications

(21 citation statements)

References 30 publications

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“…This trend suggests larger sample sizes could reveal pairwise volume differences among HS stages and enable its in vivo classification. In agreement with histological findings, volume effects were not restricted to CA1 and subiculum, also in line with previously reported lower CA3 and CA4 volumes in HS 49 .…”

Section: Discussionsupporting

confidence: 92%

A novel histological staging of hippocampal sclerosis that is evident in grey matter lossin vivo

Ortega-Cruz

Uceda-Heras

Iglesias

et al. 2022

Preprint

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INTRODUCTION: Hippocampal sclerosis of aging (HS) is defined by end-stage histological findings, strongly associated with limbic-predominant age-related TDP-43 encephalopathy (LATE). We aimed to characterize features of early HS to refine the understanding of its role within combined pathology. METHODS: We studied 159 brain donations from the multimodal Vallecas Alzheimers Center Study. A staging system (0 to IV) was developed to account for HS progression and analyzed in relation to pre-mortem cognitive and MRI data. RESULTS: Our HS staging system displayed a significant correlation with disease duration, cognitive performance and combined neuropathologies, especially with LATE. Two-level assessment along the hippocampal longitudinal axis revealed an anterior-posterior gradient of HS severity. In vivo MRI showed focally reduced hippocampal grey matter density as a function of HS staging. DISCUSSION: The association of this staging system with clinical progression and structural differences supports its utility in the characterization and potential in vivo monitoring of HS.

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Section: Discussionsupporting

confidence: 92%

A novel histological staging of hippocampal sclerosis that is evident in grey matter lossin vivo

Ortega-Cruz

Uceda-Heras

Iglesias

et al. 2022

Preprint

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“…Our results of associations between medial temporal lobe structures and hippocampal sclerosis of aging are also of interest. Many previous studies have noted that HS is associated with hippocampal atrophy 31-33 and one study has even noted associations outside the medial temporal lobe 34 . Also, other studies have found TDP-43, the proteinopathy signature of HS, to be associated with hippocampal 29 and additional brain atrophy 35 .…”

Section: Discussionmentioning

confidence: 99%

Dementia is strongly associated with medial temporal atrophy even after accounting for neuropathologies

Woodworth¹,

Sheikh‐Bahaei

Ka³

et al. 2021

Preprint

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Objective: Brain atrophy is associated with degenerative neuropathologies as well as clinical status of dementia. Whether dementia influences atrophy independent of neuropathologies is not known. In this study, we examined the pattern of atrophy associated with dementia while accounting for the most common dementia-related neuropathologies. Methods: We used data from National Alzheimer's Coordinating Center (NACC, N=129) and Alzheimer's Disease Neuroimaging Initiative (ADNI, N=47) participants with suitable in-vivo 3D-T1w MRI and autopsy data. We determined dementia status at visit closest to MRI. We examined the following dichotomized neuropathological variables: Alzheimer's disease neuropathology, hippocampal sclerosis, Lewy Bodies, cerebral amyloid angiopathy, atherosclerosis. Voxel-based morphometry (VBM) identified areas associated with dementia after accounting for neuropathologies. Identified regions of interest were further analyzed. We used multiple linear regression models adjusted for neuropathologies and demographic variables. Results: We found strong associations for dementia with volumes of the hippocampus, amygdala, and parahippocampus (semi-partial correlations≥0.28, P<0.0001 for all regions in NACC; semi-partial correlations≥0.35, P≤0.01 for hippocampus and parahippocampus in ADNI). Dementia status accounted for more unique variance in atrophy in these structures (~8%) compared with neuropathological variables; the only exception was hippocampal sclerosis which accounted for more variance in hippocampal atrophy (10%). Conclusion: Even after accounting for the most common neuropathologies, dementia still had among the strongest correlations with atrophy of medial temporal lobe structures. This suggests that atrophy of the medial temporal lobe is most related to clinical status of dementia as opposed to Alzheimer's or other neuropathologies.

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“…Additionally, there is an increasing awareness that certain age-related neuropathologies such as TAR DNAbinding protein (TDP-43) and hippocampal sclerosis of aging (HS) are of greater importance in advanced age as they are much more common and strongly related to dementia in the oldest-old. Some in vivo neuroimaging studies in younger cohorts have begun to identify atrophy patterns on MRI related to TDP-43 [67][68][69] and HS [70,71]. However, given the importance and prevalence of TDP-43 and HS, more in vivo neuroimaging research focused specifically on the oldest-old and followed by pathological assessment is needed to try to identify biomarkers for these pathologies that cannot be identified during life.…”

Section: Summary and Future Directionsmentioning

confidence: 99%

Neuroimaging in the Oldest-Old: A Review of the Literature

Woodworth

Scambray

Corrada

et al. 2021

JAD

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The oldest-old, those 85 years and older, are the fastest growing segment of the population and present with the highest prevalence of dementia. Given the importance of neuroimaging measures to understand aging and dementia, the objective of this study was to review neuroimaging studies performed in oldest-old participants. We used PubMed, Google Scholar, and Web of Science search engines to identify in vivo CT, MRI, and PET neuroimaging studies either performed in the oldest-old or that addressed the oldest-old as a distinct group in analyses. We identified 60 studies and summarized the main group characteristics and findings. Generally, oldest-old participants presented with greater atrophy compared to younger old participants, with most studies reporting a relatively stable constant decline in brain volumes over time. Oldest-old participants with greater global atrophy and atrophy in key brain structures such as the medial temporal lobe were more likely to have dementia or cognitive impairment. The oldest-old presented with a high burden of white matter lesions, which were associated with various lifestyle factors and some cognitive measures. Amyloid burden as assessed by PET, while high in the oldest-old compared to younger age groups, was still predictive of transition from normal to impaired cognition, especially when other adverse neuroimaging measures (atrophy and white matter lesions) were also present. While this review highlights past neuroimaging research in the oldest-old, it also highlights the dearth of studies in this important population. It is imperative to perform more neuroimaging studies in the oldest-old to better understand aging and dementia.

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Utility of MRI in the identification of hippocampal sclerosis of aging

Cited by 22 publications

References 30 publications

A novel histological staging of hippocampal sclerosis that is evident in grey matter lossin vivo

A novel histological staging of hippocampal sclerosis that is evident in grey matter lossin vivo

Dementia is strongly associated with medial temporal atrophy even after accounting for neuropathologies

Neuroimaging in the Oldest-Old: A Review of the Literature

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