Cognitive impairment, decline and fluctuations in older community-dwelling subjects with Lewy bodies
Open accessAbstract
Lewy bodies are common in the ageing brain and often co-occur with Alzheimer's disease pathology. There is little known regarding the independent role of Lewy body pathology in cognition impairment, decline and fluctuations in community-dwelling older persons. We examined the contribution of Lewy body pathology to dementia, global cognition, cognitive domains, cognitive decline and fluctuations in 872 autopsied subjects (mean age = 87.9 years) from the Rush Religious Order Study (n = 491) and Memory and Aging Project (n = 381) longitudinal community-based clinical-pathological studies. Dementia was based on a clinical evaluation; annual cognitive performance tests were used to create a measure of global cognition and five cognitive domains. Lewy body type was determined by using α-synuclein immunostained sections of substantia nigra, limbic and neocortical regions. Statistical models included multiple regression models for dementia and cognition and mixed effects models for decline. Cognitive fluctuations were estimated by comparing standard deviations of individual residuals from mean trajectories of decline in those with and without Lewy bodies. All models controlled for age, sex, education, Alzheimer's disease pathology and infarcts. One hundred and fifty-seven subjects (18%) exhibited Lewy body pathology (76 neocortical-type, 54 limbic-type and 27 nigra-predominant). One hundred and three (66%) subjects with Lewy body pathology had a pathologic diagnosis of Alzheimer's disease. Neocortical-type, but not nigral-predominant or limbic-type Lewy body pathology was related to an increased odds of dementia (odds ratio = 3.21; 95% confidence interval = 1.78-5.81) and lower cognition (P < 0.001) including episodic memory function (P < 0.001) proximate to death. Neocortical-type Lewy body pathology was also related to a faster decline in global cognition (P < 0.001), decline in all five specific cognitive domains (all P-values < 0.001), and to fluctuations in decline of working and semantic memory (P-values < 0.001). Limbic-type Lewy body pathology was related to lower and faster decline in visuospatial skills (P = 0.042). The relationship of Lewy body pathology to cognition and dementia was not modified by Alzheimer's disease pathology. Neocortical-type Lewy body pathology is associated with increased odds of dementia; lower and more rapid decline in all cognitive domains including episodic memory and fluctuations in decline in semantic and working memory. Limbic-type Lewy body pathology is specifically associated with lower and more rapid decline in visuospatial skills. The effect of Lewy body pathology on cognition appears to be independent of Alzheimer's disease pathology.
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The dichotomous summary variable for neocortical-type Lewy body pathology was previously shown to be associated with dementia.
“In this study, a dichotomous summary variable was used indicative of presence or absence of neocortical-type Lewy body pathology which we previously showed to be associated with dementia [57].”
From Sex differences in Alzheimer’s disease and common neuropathologies of aging (2018) · cites this paper as [57]
Levels of posttranslationally modified IGF1 receptor were positively related to β-amyloid and negatively related to episodic and working memory, after adjusting for AD pathology.
“Specifically, levels of postranslationally modified forms of the IGF1 receptor were positively related to β-amyloid and negatively related to episodic and working memory, after adjusting for AD pathology.”
From A molecular network of the aging human brain provides insights into the pathology and cognitive decline of Alzheimer’s disease (2018) · cites this paper as [38]
Prior work found decreased response to IGF1 in brains from persons with MCI and AD dementia relative to controls, regardless of diabetes status.
“In prior work, we found evidence of decreased response to insulin growth factor 1 (IGF1) in brains from persons with mild cognitive impairment and AD dementia relative to controls, regardless of diabetes status.38”
From A molecular network of the aging human brain provides insights into the pathology and cognitive decline of Alzheimer’s disease (2018) · cites this paper as [38]
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“38 In this study, we used a dichotomous variable toindicatethepresenceorabsenceofneocortical-typeLewybodies.”
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- Authors
- Schneider, J. A., Arvanitakis, Z., Yu, L., Boyle, P. A., Leurgans, S. E., & Bennett, D. A.
- Affiliations
- Rush University Medical Center (US)
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-10-01
- Volume
- 135
- Issue
- 10
- Pages
- 3005-3014
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC3470712
- OpenAlex
- W2151689101
- Cited by
- 273
- References
- 55
- Citations by year
- 2026: 12 · 2025: 22 · 2024: 30 · 2023: 17 · 2022: 31 · 2021: 21 · 2020: 18 · 2019: 22 · 2018: 19 · 2017: 21 · 2016: 18 · 2015: 18 · 2014: 11 · 2013: 11 · 2012: 1
- FWCI
- 9.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG017917, P30-AG 10161, R01-AG34374, R01‐AG17917, R01 AG15819, R01AG015819, P30AG010161, R01AG034374)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Lewy body pathology, cognitive impairment, cognitive decline, cognitive fluctuations, dementia with Lewy bodies, Alzheimer's disease pathology, episodic memory, visuospatial ability, brain aging, alpha-synuclein, substantia nigra
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Cognition Disorders, Female, Humans, Longitudinal Studies, Male, Neuropsychological Tests, Comorbidity, Lewy Bodies, Lewy Body Disease
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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