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Cognitive impairment, decline and fluctuations in older community-dwelling subjects with Lewy bodies.
Brain. 2012 Oct; 135(Pt 10):3005-14.B

Abstract

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.

Authors+Show Affiliations

Rush Alzheimer’s Disease Centre, Rush University Medical Centre, Chicago, IL 60612, USA. julie_a_schneider@rush.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

23065790

Citation

Schneider, J A., et al. "Cognitive Impairment, Decline and Fluctuations in Older Community-dwelling Subjects With Lewy Bodies." Brain : a Journal of Neurology, vol. 135, no. Pt 10, 2012, pp. 3005-14.
Schneider JA, Arvanitakis Z, Yu L, et al. Cognitive impairment, decline and fluctuations in older community-dwelling subjects with Lewy bodies. Brain. 2012;135(Pt 10):3005-14.
Schneider, J. A., Arvanitakis, Z., Yu, L., Boyle, P. A., Leurgans, S. E., & Bennett, D. A. (2012). Cognitive impairment, decline and fluctuations in older community-dwelling subjects with Lewy bodies. Brain : a Journal of Neurology, 135(Pt 10), 3005-14. https://doi.org/10.1093/brain/aws234
Schneider JA, et al. Cognitive Impairment, Decline and Fluctuations in Older Community-dwelling Subjects With Lewy Bodies. Brain. 2012;135(Pt 10):3005-14. PubMed PMID: 23065790.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cognitive impairment, decline and fluctuations in older community-dwelling subjects with Lewy bodies. AU - Schneider,J A, AU - Arvanitakis,Z, AU - Yu,L, AU - Boyle,P A, AU - Leurgans,S E, AU - Bennett,D A, PY - 2012/10/16/entrez PY - 2012/10/16/pubmed PY - 2013/1/16/medline SP - 3005 EP - 14 JF - Brain : a journal of neurology JO - Brain VL - 135 IS - Pt 10 N2 - 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. SN - 1460-2156 UR - https://www.unboundmedicine.com/medline/citation/23065790/Cognitive_impairment_decline_and_fluctuations_in_older_community_dwelling_subjects_with_Lewy_bodies_ L2 - https://academic.oup.com/brain/article-lookup/doi/10.1093/brain/aws234 DB - PRIME DP - Unbound Medicine ER -