Natural history of mild cognitive impairment in older persons

Bennett, D. A.; Wilson, R. S.; Schneider, J. A.; Evans, D. A.; Beckett, L. A.; Aggarwal, N. T.; Barnes, L. L.; Fox, J. H.; Bach, J.

doi:10.1212/wnl.59.2.198

Cited by 1,037Dementia and Cognitive Impairment ResearchCancer-related cognitive impairment studiesCognitive Abilities and Testing

Natural history of mild cognitive impairment in older persons

Bennett, D. A., Wilson, R. S., Schneider, J. A., Evans, D. A., Beckett, L. A., Aggarwal, N. T., Barnes, L. L., Fox, J. H. +1 more·2002·Neurology

DOI 10.1212/wnl.59.2.198

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Abstract

BACKGROUND: Cognitive abilities of older persons range from normal, to mild cognitive impairment, to dementia. Few large longitudinal studies have compared the natural history of mild cognitive impairment with similar persons without cognitive impairment. METHODS: Participants were older Catholic clergy without dementia, 211 with mild cognitive impairment and 587 without cognitive impairment, who underwent annual clinical evaluation for AD and an assessment of different cognitive abilities. Cognitive performance tests were summarized to yield a composite measure of global cognitive function and separate summary measures of episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability. The authors compared the risk of death, risk of incident AD, and rates of change in global cognition and different cognitive domains among persons with mild cognitive impairment to those without cognitive impairment. All models controlled for age, sex, and education. RESULTS: On average, persons with mild cognitive impairment had significantly lower scores at baseline in all cognitive domains. Over an average of 4.5 years of follow-up, 30% of persons with mild cognitive impairment died, a rate 1.7 times higher than those without cognitive impairment (95% CI, 1.2 to 2.5). In addition, 64 (34%) persons with mild cognitive impairment developed AD, a rate 3.1 times higher than those without cognitive impairment (95% CI, 2.1 to 4.5). Finally, persons with mild cognitive impairment declined significantly faster on measures of episodic memory, semantic memory, and perceptual speed, but not on measures of working memory or visuospatial ability, as compared with persons without cognitive impairment. CONCLUSIONS: Mild cognitive impairment is associated with an increased risk of death and incident AD, and a greater rate of decline in selected cognitive abilities.

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Tangles are first seen in the entorhinal cortex (Braak stages I-II), then the hippocampus and thalamus (Braak stages III-IV) and finally the neocortex (Braak stages V-VI), a sequence typically synchronous with cognitive decline from mild cognitive impairment to severe dementia.
“Tangles are first seen in the entorhinal cortex (EC) (Braak stages I–II), then the hippocampus and thalamus (Braak stages III–IV) and finally the neocortex (Braak stages V–VI), a sequence that is typically synchronous with cognitive decline from mild cognitive impairment to severe dementia1,2,4–7.”
From Single-cell multiregion dissection of Alzheimer’s disease (2024) · cites this paper as [5]
Clinical evaluations in the Religious Orders Study were performed by personnel blinded to previous evaluations.
“Annual evaluations included a uniform structured interview and examination consisting of medical history, neurological examination and cognitive testing by trained personnel who are blind to previous evaluations, as previously described (Bennett, et al., 2002).”
From Cellular, synaptic, and biochemical features of resilient cognition in Alzheimer’s disease (2013) · cites this paper as Bennett, et al., 2002

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Authors: Bennett, D. A., Wilson, R. S., Schneider, J. A., Evans, D. A., Beckett, L. A., Aggarwal, N. T., Barnes, L. L., Fox, J. H., & Bach, J.
Affiliations: University of California System (US)
ORCID: Bennett, D. A.
Wilson, R. S.
Schneider, J. A.
Evans, D. A.
Beckett, L. A.
Aggarwal, N. T.
Barnes, L. L.
Fox, J. H.
Bach, J.
Venue: Neurology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2002-07-23
Volume: 59
Issue: 2
Pages: 198-205
ISSN: 0028-3878 (ISSN-L)
1526-632X
DOI: 10.1212/wnl.59.2.198
OpenAlex: W2075464796
Cited by: 1,037
References: 46
Citations by year: 2026: 40 · 2025: 50 · 2024: 47 · 2023: 47 · 2022: 31 · 2021: 35 · 2020: 34 · 2019: 31 · 2018: 36 · 2017: 37 · 2016: 40 · 2015: 32 · 2014: 52 · 2013: 41 · 2012: 54
FWCI: 24.41
Type: journal article
Language: en
Open access: closed
Locations: Neurology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Aging (AG-15819, AG 10161, AG-14449, P01AG014449, P30AG010161)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
Keywords: mild cognitive impairment, natural history (disease), older adults, Alzheimer's disease, dementia risk, mortality, cognitive decline, episodic memory, semantic memory, perceptual speed, working memory, visuospatial ability, global cognitive function
MeSH terms: Aged, Aged, 80 and over, Cognition, Cognition Disorders, Female, Humans, Male, Memory, Psychometrics, Risk Factors, Severity of Illness Index, Risk Assessment

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Natural history of mild cognitive impairment in older persons

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