Cited by 516Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

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Alzheimer Neuropathologic Alterations in Aged Cognitively Normal Subjects

Davis, D G, Schmitt, F A, Wekstein, D R, Markesbery, W R·1999·Journal of Neuropathology and Experimental Neurology

DOI 10.1097/00005072-199904000-00008

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Abstract

The histopathologic changes distinguishing early Alzheimer disease (AD) from normal or pathologic aging are not clearly defined. This report describes the autopsy findings of 59 elderly, well-educated, volunteers. They were examined longitudinally with mental status testing, some for up to 8 years, as part of our normal aging study. This study reveals that (1) the brains of many subjects who did not show cognitive impairment on neuropsychologic testing contain abundant senile plaques (SP) and/or neurofibrillary tangles (NFT); (2) 29 subjects met Khachaturian criteria for AD, 15 met CERAD and 7 met National Institute on Aging-Reagan Institute guidelines; (3) Braak and Braak staging method included 9 in stage IV subjects, 4 in stage V, and 1 in stage VI; (4) there was a progression of NFT from entorhinal cortex to hippocampus and amygdala as a function of age; (5) 2 subjects met criteria for a diagnosis of dementia with Lewy bodies but were not demented; (6) cerebral amyloid angiopathy was present in leptomeningeal vessels in 75% of subjects and in parenchymal vessels in 62% of subjects; (7) only 10 of 59 subjects (17%) had no or few degenerative brain changes. Our study demonstrates that the brains of a large percentage of cognitively normal, relatively well-educated individuals contain numerous degenerative changes and only a small percentage are relatively free of these changes.

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Background

Authors: Davis, D. G., Schmitt, F. A., Wekstein, D. R., & Markesbery, W. R.
Affiliations: University of Kentucky HealthCare (US)
Corresponding author: Davis, D G
ORCID: Schmitt, F A
Venue: Journal of Neuropathology and Experimental Neurology
Publisher: Oxford University Press (OUP)
Published: 1999-04
Volume: 58
Issue: 4
Pages: 376-388
ISSN: 0022-3069 (ISSN-L)
DOI: 10.1097/00005072-199904000-00008
OpenAlex: W2009882167
Cited by: 516
References: 0
Citations by year: 2026: 2 · 2025: 6 · 2024: 6 · 2023: 12 · 2022: 7 · 2021: 13 · 2020: 14 · 2019: 16 · 2018: 22 · 2017: 16 · 2016: 26 · 2015: 18 · 2014: 30 · 2013: 25 · 2012: 19
FWCI: 15.68
Type: journal article
Language: en
Open access: closed
Locations: Journal of Neuropathology & Experimental Neurology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Aging (P50AG005144, P50-AGO5144, 1PO1-AGO51195)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords: Alzheimer's disease, normal aging, amyloid plaques, neurofibrillary tangles, Braak staging, dementia with Lewy bodies, cerebral amyloid angiopathy, entorhinal cortex, hippocampus, amygdala, neuropathology
MeSH terms: Aged, Aged, 80 and over, Aging, Alzheimer Disease, Amyloidosis, Apolipoproteins E, Brain, Cerebral Infarction, Chronic Disease, Cognition, Female, Genotype, Craniocerebral Trauma, Humans, Male, Mental Status Schedule, Middle Aged, Dementia, Vascular, Silver Staining, Lewy Bodies, Neurofibrillary Tangles

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Alzheimer Neuropathologic Alterations in Aged Cognitively Normal Subjects

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