title: 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.
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.
authors.affiliation: National Alzheimer's Coordinating Center (NACC), University of Washington, Seattle, WA, USA Department of Epidemiology, University of Washington, Seattle, WA, USA.
authors.forename: Willa D
authors.initials: WD
authors.lastname: Brenowitz
authors.affiliation: National Alzheimer's Coordinating Center (NACC), University of Washington, Seattle, WA, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Monsell
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Schmitt
authors.affiliation: National Alzheimer's Coordinating Center (NACC), University of Washington, Seattle, WA, USA Department of Epidemiology, University of Washington, Seattle, WA, USA.
authors.forename: Walter A
authors.initials: WA
authors.lastname: Kukull
authors.affiliation: Department of Pathology, Division of Neuropathology, University of Kentucky, Lexington, KY, USA Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Nelson
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000503:physiopathology*; D001344:Autopsy; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000150:complications*; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008297:Male; D016874:Neurofibrillary Tangles / Q000473:pathology; D011569:Psychiatric Status Rating Scales; D012598:Sclerosis / Q000209:etiology / Q000473:pathology; D013223:Statistics as Topic; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016875:tau Proteins
keywords: APOE; TDP-43; hippocampus; human; oldest-old