title: APOE and mild cognitive impairment: the Framingham Heart Study.
abstract: BACKGROUND
  The risk apolipoprotein E-4 (APOE4) poses for mild cognitive impairment (MCI) may vary based on the neuropsychological definition of MCI.
  
  
  METHODS
  A community-based cohort study.
  
  
  METHODS
  Using two psychometric neuropsychological impairment definitions, we examined APOE4 and prevalent MCI among older adults or pre-MCI among middle-aged adults. Neuropsychological, clinical and genetic data were collected on 2,239 Framingham Offspring Cohort participants free from clinical stroke or dementia (62±9 years; 54% women). Prevalent amnestic MCI was defined from neuropsychological performances≥1.5 SD below the mean based on (i) age and education or (ii) age and Wide Range Achievement Test-3 Reading (WRAT-3 Reading) performance adjustment.
  
  
  RESULTS
  In the entire sample, multivariable-adjusted logistic regressions found that APOE4 was associated with amnestic MCI when using the age and WRAT Reading definition (odds ratio [OR]=1.7, P=0.002) but not the age and education definition (OR=1.0, P=0.90). Results were modified by age, such that APOE4 was associated with amnestic MCI in participants≥65 years using both the age and WRAT Reading definition (OR=2.4, P<0.001) and the age and education definition (OR=1.7, P=0.04).
  
  
  CONCLUSIONS
  APOE4 risk for prevalent amnestic MCI varies depending on the definition of objective neuropsychological impairment for MCI. Our findings support existing literature emphasising the need to refine MCI neuropsychological profiling methods.
authors.affiliation: Vanderbilt Memory & Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, 2525 West End Avenue, Suite 1200, Nashville, TN 37203, USA.
authors.forename: Angela L
authors.initials: AL
authors.lastname: Jefferson
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Alexa S
authors.initials: AS
authors.lastname: Beiser
authors.affiliation: National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
authors.affiliation: National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Wolf
authors.affiliation: National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Rhoda
authors.initials: R
authors.lastname: Au
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D053327:Apolipoprotein E4 / Q000097:blood* / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D003071:Cognition; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000453:epidemiology* / Q000378:metabolism* / Q000523:psychology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008875:Middle Aged; D015999:Multivariate Analysis; D009483:Neuropsychological Tests; D016017:Odds Ratio; D015995:Prevalence; D011594:Psychometrics; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4; D015415:Biomarkers
keywords: APOE; Alzheimer's disease; genetic risk; mild cognitive impairment; older people; risk factors