title: Cerebrovascular disease, APOE epsilon4 allele and cognitive decline in a cognitively normal population.
abstract: OBJECTIVE
  To investigate whether cerebrovascular disease (CVD) and apolipoprotein E (APOE) epsilon4 allele were associated with cognitive decline and whether the relationship between CVD and cognitive decline varied by APOE epsilon4 status.
  
  
  METHODS
  A total of 809 cognitively normal community-dwelling residents aged >75 years were followed to detect subjects with cognitive decline, defined as follow-up. Mini-mental state examination (MMSE) score was >10% decease of the baseline score. Logistic and multinomial logistic models were developed to estimate odds ratio (OR) and 95% confidence interval (CI) of cognitive decline related to a history of CVD and APOE epsilon4 by taking into account major potential confounders including baseline MMSE score.
  
  
  RESULTS
  During the mean 3.5 years of follow-up, 190 subjects experienced cognitive decline. Multi-adjusted ORs (95% CIs) of overall cognitive decline were 2.27 (1.23-4.17) for CVD and 1.69 (1.13-2.54) for APOE epsilon4, but no interaction was detected. Multinomial logistic analysis led to the CVD-related ORs of 1.42 (0.75-2.67) for cognitive decline without progression to dementia and 3.41 (1.55-7.55) for the decline progressing to dementia; similar analysis from a separate model led to adjusted OR of 2.28 (0.88-5.87; p=0.09) for the decline progressing to Alzheimer's disease. The risk effects of CVD on cognitive decline with progression to dementias were statistically significant mainly among individuals without APOE epsilon4 allele.
  
  
  CONCLUSIONS
  CVD is a major risk factor for cognitive decline associated with progression to dementia and Alzheimer's disease. There appears no interaction between CVD and APOE epsilon4 on cognitive decline in very old people.
authors.affiliation: Aging Research Center, Division of Geriatric Epidemiology and Medicine, Department of Neurotec, Karolinska Institutet and Stockholm Gerontology Research Center, Stockholm, Sweden. chengxuan.qui@ki.se
authors.forename: Chengxuan
authors.initials: C
authors.lastname: Qiu
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
authors.forename: Laura
authors.initials: L
authors.lastname: Fratiglioni
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics; D000483:Alleles; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D002561:Cerebrovascular Disorders / Q000453:epidemiology* / Q000235:genetics*; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000453:epidemiology* / Q000235:genetics*; D003704:Dementia / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E