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Relation of neuropathology to cognition in persons without cognitive impairment.
Ann Neurol. 2012 Oct; 72(4):599-609.AN

Abstract

OBJECTIVE

A study was undertaken to examine the relation of Alzheimer disease (AD) pathology, cerebral infarcts, and Lewy body (LB) pathology to cognition in persons without cognitive impairment.

METHODS

Persons without dementia from 2 cohort studies of aging, the Religious Orders Study and the Memory and Aging Project, agreed to annual clinical evaluation and brain donation. The studies had 19 neuropsychological performance tests in common that assessed 5 cognitive domains. For 296 persons without cognitive impairment who died and underwent postmortem assessment, we quantified AD pathology as a global pathology score, and as amyloid load, paired helical filament tau-positive (PHFtau) tangle density, cerebral infarcts, and LB pathology. Linear regression was used to examine the relation of neuropathology to cognitive abilities, controlling for demographics.

RESULTS

Nearly all persons had AD pathology with >¾ exhibiting amyloid; 22% had macroscopic and 24% had microscopic infarctions, and 13% had LB pathology. The global measure of AD pathology was related to global cognition (p = 0.008), whereas infarcts and Lewy bodies were not. Amyloid load was related to global cognition (p < 0.05), with only a trend for tangles (p = 0.08). In analyses of cognitive domains, AD pathology (p = 0.006), PHFtau tangles (p = 0.03), and macroscopic infarctions (p = 0.02) were related to episodic memory, with a trend for amyloid load (p = 0.06); AD pathology (p = 0.02) and amyloid load (p = 0.03) were related to working memory. Findings for global cognition and episodic memory were stronger in additional analyses with neocortical amyloid and mesial temporal tangles.

INTERPRETATION

AD pathology and macroscopic infarctions are common in older persons without cognitive impairment and are related to episodic and working memory.

Authors+Show Affiliations

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 60612, USA. David_A_Bennett@rush.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23109154

Citation

Bennett, David A., et al. "Relation of Neuropathology to Cognition in Persons Without Cognitive Impairment." Annals of Neurology, vol. 72, no. 4, 2012, pp. 599-609.
Bennett DA, Wilson RS, Boyle PA, et al. Relation of neuropathology to cognition in persons without cognitive impairment. Ann Neurol. 2012;72(4):599-609.
Bennett, D. A., Wilson, R. S., Boyle, P. A., Buchman, A. S., & Schneider, J. A. (2012). Relation of neuropathology to cognition in persons without cognitive impairment. Annals of Neurology, 72(4), 599-609. https://doi.org/10.1002/ana.23654
Bennett DA, et al. Relation of Neuropathology to Cognition in Persons Without Cognitive Impairment. Ann Neurol. 2012;72(4):599-609. PubMed PMID: 23109154.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Relation of neuropathology to cognition in persons without cognitive impairment. AU - Bennett,David A, AU - Wilson,Robert S, AU - Boyle,Patricia A, AU - Buchman,Aron S, AU - Schneider,Julie A, PY - 2012/10/31/entrez PY - 2012/10/31/pubmed PY - 2013/1/4/medline SP - 599 EP - 609 JF - Annals of neurology JO - Ann Neurol VL - 72 IS - 4 N2 - OBJECTIVE: A study was undertaken to examine the relation of Alzheimer disease (AD) pathology, cerebral infarcts, and Lewy body (LB) pathology to cognition in persons without cognitive impairment. METHODS: Persons without dementia from 2 cohort studies of aging, the Religious Orders Study and the Memory and Aging Project, agreed to annual clinical evaluation and brain donation. The studies had 19 neuropsychological performance tests in common that assessed 5 cognitive domains. For 296 persons without cognitive impairment who died and underwent postmortem assessment, we quantified AD pathology as a global pathology score, and as amyloid load, paired helical filament tau-positive (PHFtau) tangle density, cerebral infarcts, and LB pathology. Linear regression was used to examine the relation of neuropathology to cognitive abilities, controlling for demographics. RESULTS: Nearly all persons had AD pathology with >¾ exhibiting amyloid; 22% had macroscopic and 24% had microscopic infarctions, and 13% had LB pathology. The global measure of AD pathology was related to global cognition (p = 0.008), whereas infarcts and Lewy bodies were not. Amyloid load was related to global cognition (p < 0.05), with only a trend for tangles (p = 0.08). In analyses of cognitive domains, AD pathology (p = 0.006), PHFtau tangles (p = 0.03), and macroscopic infarctions (p = 0.02) were related to episodic memory, with a trend for amyloid load (p = 0.06); AD pathology (p = 0.02) and amyloid load (p = 0.03) were related to working memory. Findings for global cognition and episodic memory were stronger in additional analyses with neocortical amyloid and mesial temporal tangles. INTERPRETATION: AD pathology and macroscopic infarctions are common in older persons without cognitive impairment and are related to episodic and working memory. SN - 1531-8249 UR - https://www.unboundmedicine.com/medline/citation/23109154/Relation_of_neuropathology_to_cognition_in_persons_without_cognitive_impairment_ L2 - https://doi.org/10.1002/ana.23654 DB - PRIME DP - Unbound Medicine ER -