title: The effect of the APOE-epsilon4 allele and ACE-I/D polymorphism on cognition during a two-year follow-up in first-ever stroke patients.
abstract: BACKGROUND
  Cognitive impairment is commonly observed after stroke and has a negative impact on survival and rehabilitation. Some stroke patients deteriorate in cognitive functioning whereas others do not. Environmental and demographic risk factors cannot fully explain this. There is growing evidence that a genetic predisposition plays a role in the pathogenesis of post-stroke cognitive decline.
  
  
  OBJECTIVE
  To study the influence of the APOE-epsilon4 allele and the ACE-I/D polymorphism on cognitive functioning after stroke.
  
  
  METHODS
  We included 194 first-ever stroke patients of whom information about APOE genotyping and ACE-I/D polymorphism was available in 92 and 129 patients, respectively. Patients were cognitively assessed at 1, 6, 12 and 24 months after the event. Linear mixed models with slope estimates were used to study the influence of the APOE-epsilon4 allele and the ACE-I/D polymorphism on the MMSE score, CAMCOG, executive functioning, psychomotor speed, and verbal memory function during follow-up.
  
  
  RESULTS
  Patients carrying the APOE-epsilon4 allele more often suffered a lacunar infarction than non-carriers. The APOE-epsilon4 allele had no effect on cognitive functioning during the follow-up. ACE-DD homozygosity was associated with a worse performance in executive functioning compared to patients with neither an APOE-epsilon4 allele nor the ACE-DD genotype. There was no interaction between the APOE-epsilon4 allele and the ACE-DD phenotype in the prediction of cognitive decline.
  
  
  CONCLUSIONS
  The ACE-DD genotype may be associated with post-stroke cognitive decline while the APOE-epsilon4 allele is not. Further research is needed to examine the role of genetic risk factors for post-stroke cognitive decline and to determine why some patients deteriorate cognitively after stroke but others do not.
authors.affiliation: Department of Clinical Neurophysiology, Maastricht University Medical Center, Maastricht, The Netherlands. a.bour@mumc.nl
authors.forename: A M J J
authors.initials: AM
authors.lastname: Bour
authors.forename: S M C
authors.initials: SM
authors.lastname: Rasquin
authors.forename: L
authors.initials: L
authors.lastname: Baars
authors.forename: M P J
authors.initials: MP
authors.lastname: van Boxtel
authors.forename: P J
authors.initials: PJ
authors.lastname: Visser
authors.forename: M
authors.initials: M
authors.lastname: Limburg
authors.forename: F R J
authors.initials: FR
authors.lastname: Verhey
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D053327:Apolipoprotein E4 / Q000235:genetics*; D016009:Chi-Square Distribution; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D012307:Risk Factors; D020521:Stroke / Q000150:complications / Q000235:genetics*
chemical_list: D053327:Apolipoprotein E4; D007703:Peptidyl-Dipeptidase A