APOE genotype and cognitive decline in a middle-aged cohort
C. K. Blair, MPH,
A. R. Folsom, MD,
D. S. Knopman, MD,
M. S. Bray, PhD,
T. H. Mosley, PhD and
E. Boerwinkle, PhD for the Atherosclerosis Risk in Communities (ARIC) Study Investigators
From the Division of Epidemiology (Dr. Folsom, C.K. Blair), School of Public Health, University of Minnesota, Minneapolis; Department of Neurology (Dr. Knopman), Mayo Clinic, Rochester, MN; Children’s Nutrition Research Center (Dr. Bray), Department of Pediatrics, Baylor College of Medicine, Houston; Department of Medicine (Geriatrics) (Dr. Mosley), University of Mississippi Medical Center, Jackson; and Human Genetics Center and Institute of Molecular Medicine (Dr. Boerwinkle), Houston Health Sciences Center, University of Texas, Houston.
Address correspondence and reprint requests to Dr. A.R. Folsom, Division of Epidemiology, University of Minnesota, 1300 S. Second St., Suite 300, Minneapolis, MN 55454; e-mail: folsom{at}epi.umn.edu
Background: Most longitudinal studies of nondemented personshave reported greater cognitive decline among APOE4 carriersvs noncarriers. However, most studies involved elderly samples(aged 65+) and were not large enough to examine the three APOEalleles separately.
Methods: Change in cognitive function was examined over a 6-yearperiod using three neuropsychological tests among four APOEgenotype groups (2/2 + 2/3, 3/3 (referent), 4/2 + 4/3, 4/4).The population-based sample included 1,693 African Americansand 6,202 Caucasians initially ages 47 to 68.
Results: There was increasingly greater cognitive decline fromthe 2 group to the 4/4 group in Caucasians for two of the threetests. The combination of APOE4 with hypercholesterolemia ordiabetes showed the greatest cognitive decline. Among AfricanAmericans, only the test measuring psychomotor speed showedassociations with APOE genotype.
Conclusions:APOE4 is associated with greater cognitive declinein middle-aged Caucasian individuals, with a reduced declineamong 2 carriers. This suggests that the processes by whichAPOE genotype mediates dementia risk are operative well in advanceof overt dementia.
Supported by contracts N01-HC-55015, N01-HC-55016, N01-HC-55018,N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022 fromthe National Heart, Lung, and Blood Institute, NIH, as wellas by contracts UR6/CCU617218 and HL073366.
Received May 10, 2004. Accepted in final form October 8, 2004.
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4 carriers vs noncarriers. However, most studies involved elderly samples (aged 65+) and were not large enough to examine the three APOE alleles separately. 
