Interactive effects of apolipoprotein E type 4 genotype and cerebrovascular risk on neuropsychological performance and structural brain changes.
OBJECTIVE
We sought to determine whether the presence of the apolipoprotein E type 4 (apoE4) allele, a known risk factor for Alzheimer disease, interacts with cerebrovascular risk factors to produce a disproportionate impairment in neuropsychological (NP) performance and alterations in structural morphometry as measured by magnetic resonance imaging (MRI).


METHODS
In all, 1995 participants from the community-based Framingham Offspring Cohort participants (mean age 61 years; 1063 women) underwent NP testing and structural MRI in 1999 to 2002. Multivariate linear regression was used to estimate the relationships among Framingham Stroke Risk Profile scores, NP variables, and MRI measures; interaction terms were included to examine modification of these relationships by the presence of the apoE4 allele. All analyses were cross sectional.


RESULTS
We found significant interactions between the presence of the apoE4 allele and the top sex-specific quartile of the stroke risk profile and their effects on verbal memory (P <or= .001), verbal organization (P <or= .001), nonverbal memory (P=.015), as well as set shifting and complex attention (P=.005). Systolic blood pressure (SBP) was the only individual risk factor significantly linked to these cognitive measures. With the exception of lateral ventricular volume, there were no significant interactions among presence of apoE4, the top sex-specific quartile of the stroke risk profile, and any of the MRI variables.


CONCLUSIONS
The apoE4 allele exacerbates the effects of cerebrovascular risk factors on NP function. This relationship appears to be driven by SBP, suggesting that treatment of high SBP could potentially reduce risk of cognitive impairment among those already at increased risk for Alzheimer disease.
Zade
David
D
Department of Veterans Affairs Boston Medical Center, Geriatric Research Education and Clinical Center, Framingham, Massachusetts, USA. david.zade@gmail.com
Beiser
Alexa
A
McGlinchey
Regina
R
Au
Rhoda
R
Seshadri
Sudha
S
Palumbo
Carole
C
Wolf
Philip A
PA
Decarli
Charles
C
Milberg
William
W
D000368:Aged; D000483:Alleles; D053327:Apolipoprotein E4 / Q000235:genetics*; D001794:Blood Pressure; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D002561:Cerebrovascular Disorders / Q000235:genetics* / Q000473:pathology; D003071:Cognition; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D009929:Organ Size; D012306:Risk; D012307:Risk Factors; D012737:Sex Factors
D053327:Apolipoprotein E4
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