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
Affiliations: [a] National Alzheimer's Coordinating Center (NACC), University of Washington, Seattle, WA, USA | [b] Department of Epidemiology, University of Washington, Seattle, WA, USA | [c] Department of Pathology, Division of Neuropathology, University of Kentucky, Lexington, KY, USA | [d] Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA
Correspondence:
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Correspondence to: Peter T. Nelson, MD, PhD, Department of Pathology, Division of Neuropathology and the Sanders-Brown Center on Aging, Rm 311, Sanders-Brown Building, 800 S. Limestone, University of Kentucky, Lexington, KY 40536-0230, USA. Tel.: +1 859 218 3862; Fax: +1 859 257 6054; E-mail: pnels2@email.uky.edu.
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.
