Hippocampal sclerosis of aging is a key alzheimer's disease mimic: Clinical-pathologic correlations and comparisons with both alzheimer's disease and non-tauopathic frontotemporal lobar degeneration

Willa D. Brenowitz, Sarah E. Monsell, Frederick A. Schmitt, Walter A. Kukull, Peter T. Nelson

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

Hippocampal sclerosis of aging (HS-Aging) neuropathology was observed in more than 15% of aged individuals in prior studies. However, much remains unknown about the clinical correlates of HS-Aging pathology or the association(s) between HS-Aging, Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD) pathology. Clinical and comorbid pathological features linked to HS-Aging pathology were analyzed using National Alzheimer's Coordinating Center (NACC) data. From autopsy data extending back to 1990 (n = 9,817 participants), the neuropathological diagnoses were evaluated from American AD Centers (ADCs). Among participants who died between 2005-2012 (n = 1,422), additional analyses identified clinical and pathological features associated with HS-Aging pathology. We also compared cognitive testing and longevity outcomes between HS-Aging cases and a subsample with non-tauopathy FTLD (n = 210). Reporting of HS-Aging pathology increased dramatically among ADCs in recent years, to nearly 20% of autopsies in 2012. Participants with relatively 'pure' HS-Aging pathology were often diagnosed clinically as having probable (68%) or possible (15%) AD. However, the co-occurrence of HS-Aging pathology and AD neuropathology (AD-NP) did not indicate any pattern of correlation between the two pathologies. Compared with other pathologies, participants with HS-Aging pathology had higher overall cognitive/functional ability (versus AD-NP) and verbal fluency (versus both AD-NP and FTLD) but similar episodic memory impairment at one clinic visit 2-5 years prior to death. Patients with HS-Aging live considerably longer than patients with non-tauopathy FTLD. We conclude that the manifestations of HS-Aging, increasingly recognized in recent years, probably indicate a separate disease process of direct relevance to patient care, dementia research, and clinical trials. Supplementary Materials.

Original languageEnglish
Pages (from-to)691-702
Number of pages12
JournalJournal of Alzheimer's Disease
Volume39
Issue number3
DOIs
StatePublished - 2014

Keywords

  • APOE
  • TDP-43
  • hippocampus
  • human
  • oldest-old

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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