APOE and mild cognitive impairment: the Framingham Heart Study

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Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
09:38

Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease

Published on: November 14, 2017

Angela L Jefferson1, Alexa S Beiser2, Sudha Seshadri3

  • 1Vanderbilt Memory & Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, 2525 West End Avenue, Suite 1200, Nashville, TN 37203, USA.

Age and Ageing
|December 16, 2014
PubMed
Abstract

Insights

The apolipoprotein E-4 (APOE4) gene variant increases the risk of amnestic mild cognitive impairment (MCI) in older adults, but this association depends on how MCI is defined. Refined neuropsychological profiling is needed.

Area of Science:

  • Neuroscience
  • Genetics
  • Gerontology

Background:

  • The apolipoprotein E-4 (APOE4) genotype is a known risk factor for cognitive decline.
  • The association between APOE4 and mild cognitive impairment (MCI) may differ based on diagnostic criteria.
  • Mild cognitive impairment (MCI) is a transitional stage between normal aging and dementia.

Purpose of the Study:

  • To investigate the association between APOE4 and prevalent amnestic MCI.
  • To examine how different neuropsychological definitions of MCI affect the APOE4 association.
  • To explore age-related differences in the APOE4 risk for MCI.

Main Methods:

  • A community-based cohort study of 2,239 participants from the Framingham Offspring Cohort.
  • APOE genotyping, clinical, and neuropsychological assessments were performed.
  • Amnestic MCI was defined using two criteria: age/education adjustment and age/Wide Range Achievement Test-3 Reading (WRAT-3 Reading) adjustment.

Main Results:

  • APOE4 was significantly associated with amnestic MCI when defined by age and WRAT-3 Reading (OR=1.7, P=0.002).
  • No significant association was found using the age and education definition (OR=1.0, P=0.90).
  • In participants aged 65 and older, APOE4 was associated with amnestic MCI by both definitions (ORs 2.4 and 1.7, P<0.001 and P=0.04, respectively).

Conclusions:

  • The risk of APOE4 for prevalent amnestic MCI is definition-dependent.
  • The association is more pronounced in older adults (≥65 years).
  • Findings highlight the need for refined neuropsychological assessment methods for MCI.
Keywords:
APOEAlzheimer's diseasegenetic riskmild cognitive impairmentolder peoplerisk factors

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