Interactive Effects of Apolipoprotein E Type 4 Genotype and Cerebrovascular Risk on Neuropsychological Performance and Structural Brain Changes

David Zade, Alexa Beiser, Regina McGlinchey, Rhoda Au, Sudha Seshadri, Carole Palumbo, Philip A. Wolf, Charles DeCarli, William Milberg

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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 ≤ .001), verbal organization (P ≤ .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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)261-268
Number of pages8
JournalJournal of Stroke and Cerebrovascular Diseases
Volume19
Issue number4
DOIs
StatePublished - Jul 2010

Fingerprint

Apolipoprotein E4
Genotype
Blood Pressure
Alleles
Magnetic Resonance Imaging
Brain
Stroke
Alzheimer Disease
Linear Models
Cross-Sectional Studies
Organizations
Hypertension

Keywords

  • Alzheimer
  • Apolipoprotein E type 4
  • cerebrovascular disease
  • cognition
  • diabetes
  • magnetic resonance imaging
  • neuropsychology

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery
  • Rehabilitation
  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

Interactive Effects of Apolipoprotein E Type 4 Genotype and Cerebrovascular Risk on Neuropsychological Performance and Structural Brain Changes. / Zade, David; Beiser, Alexa; McGlinchey, Regina; Au, Rhoda; Seshadri, Sudha; Palumbo, Carole; Wolf, Philip A.; DeCarli, Charles; Milberg, William.

In: Journal of Stroke and Cerebrovascular Diseases, Vol. 19, No. 4, 07.2010, p. 261-268.

Research output: Contribution to journalArticle

Zade, David ; Beiser, Alexa ; McGlinchey, Regina ; Au, Rhoda ; Seshadri, Sudha ; Palumbo, Carole ; Wolf, Philip A. ; DeCarli, Charles ; Milberg, William. / Interactive Effects of Apolipoprotein E Type 4 Genotype and Cerebrovascular Risk on Neuropsychological Performance and Structural Brain Changes. In: Journal of Stroke and Cerebrovascular Diseases. 2010 ; Vol. 19, No. 4. pp. 261-268.
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AB - 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 ≤ .001), verbal organization (P ≤ .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. Conclusion: 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.

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