Fourteen-year longitudinal study of vascular risk factors, APOE genotype, and cognition: the ARIC MRI Study.
BACKGROUND
Strokes, vascular risk factors, and apolipoprotein E (APOE) genotype are associated with cognitive decline in the elderly, but definitive evidence that these affect cognition as early as middle age is limited.


OBJECTIVE
We describe the relationships of APOE genotype, stroke, and vascular risk factors with cognitive change over a 14-year follow-up in the Atherosclerosis Risk in Communities (ARIC) Study cohort recruited while in middle age.


METHODS
Participants included a subset of the ARIC Study who underwent assessments of cognitive function and vascular risk factors. Four cognitive assessments were performed between 1990-1992 and 2004-2006. Cognitive assessments included the Delayed Word Recall (DWR) Test, the Digit Symbol Substitution (DSS) Test, and the Word Fluency (WF) Test. Vascular risk factors were assessed during the baseline visit in 1990-1992. Incident stroke was recorded over the 14 years of follow-up.


RESULTS
There were 1130 participants (mean age, 59 +/- 4.3 [SD] years; 62% women; 52% African-American) with longitudinal data. In multivariate, random-effects linear models adjusted for age, education, gender, and race, the risk factors diabetes and APOE epsilon4 genotype were independently associated with a decline in performance on the DSS test (both P < .005), whereas hypertension and stroke were not. For DWR, stroke and APOE epsilon4 genotype were independent predictors of decline (both P < .001). For the WF test, metabolic syndrome, hypertension, and stroke were independently associated with decline (all P < .005). No evidence of differential effects of risk factors on cognitive decline by race, gender, or interactions between risk factors was found.


CONCLUSIONS
The vascular risk factors diabetes and hypertension, a history of stroke itself, and APOE epsilon4 genotype independently contribute to cognitive decline in late middle age and early elderly years.
Knopman
David S
DS
Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN, USA. knopman@mayo.edu
Mosley
Thomas H
TH
Catellier
Diane J
DJ
Coker
Laura H
LH
D000368:Aged; D053327:Apolipoprotein E4 / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D003072:Cognition Disorders / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D003920:Diabetes Mellitus / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics; D007807:Language Tests; D016014:Linear Models; D016015:Logistic Models; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009483:Neuropsychological Tests; D016017:Odds Ratio; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000235:genetics
D053327:Apolipoprotein E4; D002784:Cholesterol