title: The greater sensitivity of elderly APOE ε4 carriers to anticholinergic medications is independent of cerebrovascular disease risk.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Psychiatry, University of Pittsburgh Medical School, Pennsylvania, USA. nebesrd@upmc.edu
authors.forename: Robert D
authors.initials: RD
authors.lastname: Nebes
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Pollock
authors.forename: Subashan
authors.initials: S
authors.lastname: Perera
authors.forename: Edythe M
authors.initials: EM
authors.lastname: Halligan
authors.forename: Judith A
authors.initials: JA
authors.lastname: Saxton
mesh_terms: D000339:Affect / Q000187:drug effects; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D053327:Apolipoprotein E4 / Q000235:genetics*; D002561:Cerebrovascular Disorders / Q000453:epidemiology* / Q000235:genetics; D018680:Cholinergic Antagonists / Q000009:adverse effects*; D003072:Cognition Disorders / Q000453:epidemiology; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005838:Genotype; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors; D016138:Walking
chemical_list: D053327:Apolipoprotein E4; D018680:Cholinergic Antagonists