Hippocampal Sclerosis of Aging, a Prevalent and High-Morbidity Brain Disease

Authors

Peter T. Nelson, University of KentuckyFollow
Charles D. Smith, University of KentuckyFollow
Erin L. Abner, University of KentuckyFollow
Bernard J. Wilfred, University of Kentucky
Wang-Xia Wang, University of KentuckyFollow
Janna H. Neltner, University of KentuckyFollow
Michael Baker, University of Kentucky
David W. Fardo, University of KentuckyFollow
Richard J. Kryscio, University of KentuckyFollow
Stephen W. Scheff, University of KentuckyFollow
Gregory A. Jicha, University of KentuckyFollow
Kurt A. Jellinger, Institute of Clinical Neurobiology, Austria
Linda J. Van Eldik, University of KentuckyFollow
Frederick A. Schmitt, University of KentuckyFollow

Abstract

Hippocampal sclerosis of aging (HS-Aging) is a causative factor in a large proportion of elderly dementia cases. The current definition of HS-Aging rests on pathologic criteria: neuronal loss and gliosis in the hippocampal formation that is out of proportion to AD-type pathology. HS-Aging is also strongly associated with TDP-43 pathology. HS-Aging pathology appears to be most prevalent in the oldest-old: autopsy series indicate that 5-30 % of nonagenarians have HS-Aging pathology. Among prior studies, differences in study design have contributed to the study-to-study variability in reported disease prevalence. The presence of HS-Aging pathology correlates with significant cognitive impairment which is often misdiagnosed as AD clinically. The antemortem diagnosis is further confounded by other diseases linked to hippocampal atrophy including frontotemporal lobar degeneration and cerebrovascular pathologies. Recent advances characterizing the neurocognitive profile of HS-Aging patients have begun to provide clues that may help identify living individuals with HS-Aging pathology. Structural brain imaging studies of research subjects followed to autopsy reveal hippocampal atrophy that is substantially greater in people with eventual HS-Aging pathology, compared to those with AD pathology alone. Data are presented from individuals who were followed with neurocognitive and neuroradiologic measurements, followed by neuropathologic evaluation at the University of Kentucky. Finally, we discuss factors that are hypothesized to cause or modify the disease. We conclude that the published literature on HS-Aging provides strong evidence of an important and under-appreciated brain disease of aging. Unfortunately, there is no therapy or preventive strategy currently available.

Document Type

Article

Publication Date

8-2013

Notes/Citation Information

Published in Acta Neuropathologica, v. 126, issue 2, p. 161-177.

© Springer-Verlag Berlin Heidelberg 2013

The copyright holder has granted the permission for posting the article here.

The document available for download is the authors' post-peer-review final draft of the article.

Digital Object Identifier (DOI)

https://doi.org/10.1007/s00401-013-1154-1

Funding Information

Research reported in this publication was supported by National Institutes of Health under award numbers P30 AG028383, R01 NR014189, R01 AG038651, TR000117, and S10 RR26489.

Repository Citation

Nelson, Peter T.; Smith, Charles D.; Abner, Erin L.; Wilfred, Bernard J.; Wang, Wang-Xia; Neltner, Janna H.; Baker, Michael; Fardo, David W.; Kryscio, Richard J.; Scheff, Stephen W.; Jicha, Gregory A.; Jellinger, Kurt A.; Van Eldik, Linda J.; and Schmitt, Frederick A., "Hippocampal Sclerosis of Aging, a Prevalent and High-Morbidity Brain Disease" (2013). Sanders-Brown Center on Aging Faculty Publications. 98.
https://uknowledge.uky.edu/sbcoa_facpub/98