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(Stroke. 1999;30:1548-1553.)
© 1999 American Heart Association, Inc.
Original Contributions |
Impact of Apolipoprotein E 
4 and Vascular Disease on Brain Morphology in Men From the NHLBI Twin Study
From the Department of Neurology, University of Kansas, Kansas City (C.D.); Department of Medical and Molecular Genetics, Indiana University, Indianapolis (T.R.); Department of Neurology, University of California at San Francisco–Mt Zion (B.L.M.); Department of Neurology, Boston University (Mass) (P.A.W.); and Health Sciences Division, SRI International, Menlo Park, Calif (G.E.S., D.C.).
Correspondence to Charles DeCarli, MD, Department of Neurology, Kansas University Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160-7314. E-mail cdecarli{at}kumc.edu
Background and
Purpose—Apolipoprotein E 
4 genotype (ApoE4) has been
associated with increased risk for cardiovascular
disease morbidity or mortality. This appears to be mediated by an
ApoE4-related increase in cardiovascular
atherosclerosis. Given the similarities between risk
factors for heart disease and risk factors for stroke, a positive
association between ApoE4 and stroke would be expected. Since
age-related brain atrophy and the extent of white matter
hyperintensities (WMH) share similar risk factors, we examined the
combined effect of ApoE4 and history of vascular disease on brain
volume, WMH, and MRI evidence of stroke.
Methods—Subjects were the surviving members of the National Heart, Lung, and Blood Institute Twin Study. This is a longitudinal study of the effects of cardiovascular disease risk factors in community-dwelling male veterans. The fourth and final examination of this cohort included cerebral MRI and was completed in 1997. Apolipoprotein E (ApoE) genotype, quantitative measures of brain volume, WMH, and the presence of stroke on MRI were obtained from the 396 participants in the final examination. The presence or absence of a history of coronary heart disease, cerebrovascular disease, peripheral arterial disease, and ApoE genotype were determined for each subject.
Results—Of the 396 men, 88 (22%) had at least 1 ApoE4 allele. ApoE4 was not associated with differences in age or education. While the prevalence of vascular disease was generally greater in the ApoE4 group, this was only significant for coronary heart disease (29.8% in subjects without ApoE4 versus 40.7% in subject with ApoE4; P=0.03). ApoE4 subjects had significantly smaller brain volumes (942.4±34.5 versus 952.2±40.1 cm3; P=0.02). MRI evidence of stroke was detected in 88 (22%) of the subjects. The distribution of ApoE genotype was marginally different between subjects with MRI-detected stroke compared with those without. Further analysis revealed that the co-occurrence of cerebrovascular disease and ApoE4 was associated with significantly greater brain atrophy and WMH than either ApoE4 or cerebrovascular disease alone. Similar relations were seen for coronary heart disease and peripheral arterial disease.
Conclusions—We conclude that ApoE4 enhances the extent of brain abnormalities in the presence of various vascular diseases. We speculate that this effect may be mediated by an increased susceptibility to brain injury or impaired repair mechanisms associated with ApoE4.
Key Words: apolipoproteins • brain injuries • cerebrovascular disorders • epidemiology • magnetic resonance imaging
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