Document Detail

The greater sensitivity of elderly APOE ε4 carriers to anticholinergic medications is independent of cerebrovascular disease risk.
MedLine Citation:
PMID:  22534472     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Recent studies found use of anticholinergic medications to be associated with greater performance decrements in older persons who carry an ε4 allele of the apolipoprotein E (APOE) gene than in those carrying only ε2 or ε3 alleles.
OBJECTIVES: The present study examined whether the apparently greater behavioral toxicity of anticholinergic drugs in ε4 carriers may result from an increased risk of cerebrovascular disease, which is more common in ε4 carriers.
METHODS: Cross-sectional data were available from 240 elderly community volunteers who had participated in 2 different studies of the cognitive and motor effects of normal aging. As part of these studies, information was gathered on subjects' use of anticholinergic medications (based on an inventory of medications taken within 24 hours of testing), risk of cerebrovascular disease (Framingham Stroke Risk Profile), and APOE genotype. Performance data were also available from measures of general cognitive status (Mini-Mental State Examination), executive function (Trail Making Test), mood (Geriatric Depression Scale), sleep (Pittsburgh Sleep Quality Index), and walking speed. Logistic and linear regression models were used to examine how outcomes differed between genotypes and drug use, independent of the risk of cerebrovascular disease.
RESULTS: In persons with a non-ε4 genotype, anticholinergic medication use did not significantly affect any of the behavioral measures. By contrast, among ε4 carriers, those taking anticholinergic drugs performed significantly worse than did those not taking such drugs on tests of general cognitive status, executive function, mood, and sleep. Adjusting for participants' stroke risk had a minimal effect on these results.
CONCLUSIONS: Anticholinergic medication use was associated with poorer performance on measures of cognition, sleep, and mood only in older persons who carried 1 or more ε4 alleles of the APOE gene; this effect did not appear to be the result of an increased risk of cerebrovascular disease.
Robert D Nebes; Bruce G Pollock; Subashan Perera; Edythe M Halligan; Judith A Saxton
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-04-24
Journal Detail:
Title:  The American journal of geriatric pharmacotherapy     Volume:  10     ISSN:  1876-7761     ISO Abbreviation:  Am J Geriatr Pharmacother     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-04     Completed Date:  2012-10-01     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  101190325     Medline TA:  Am J Geriatr Pharmacother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  185-92     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.
Department of Psychiatry, University of Pittsburgh Medical School, Pennsylvania, USA.
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MeSH Terms
Affect / drug effects
Aged, 80 and over
Apolipoprotein E4 / genetics*
Cerebrovascular Disorders / epidemiology*,  genetics
Cholinergic Antagonists / adverse effects*
Cognition Disorders / epidemiology
Cross-Sectional Studies
Genetic Predisposition to Disease / epidemiology*
Psychiatric Status Rating Scales
Risk Factors
Grant Support
K07-AG033174/AG/NIA NIH HHS; P30 AG024827/AG/NIA NIH HHS; P30-AG024827/AG/NIA NIH HHS; R01 AG014051/AG/NIA NIH HHS; R01 AG019151/AG/NIA NIH HHS; R01 AG030452/AG/NIA NIH HHS; R01-AG019151/AG/NIA NIH HHS; R01-AG030452/AG/NIA NIH HHS
Reg. No./Substance:
0/Apolipoprotein E4; 0/Cholinergic Antagonists

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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