APOE E4 status predicts age-related cognitive decline in the ninth decade: longitudinal follow-up of the Lothian Birth Cohort 1921

Mol Psychiatry. 2012 Mar;17(3):315-24. doi: 10.1038/mp.2010.137. Epub 2011 Jan 25.

Abstract

Carriers of the APOE E4 allele have an increased risk of developing Alzheimer's disease. However, it is less clear whether APOE E4 status may also be involved in non-pathological cognitive ageing. The present study investigated the associations between APOE genotypes and cognitive change over 8 years in older community-dwelling individuals. APOE genotype was determined in 501 participants of the Lothian Birth Cohort 1921, whose intelligence had been measured in childhood in the Scottish Mental Survey 1932. A polymorphic variant of TOMM40 (rs10524523) was included to differentiate between the effects of the APOE E3 and E4 allelic variants. Cognitive performance on the domains of verbal memory, abstract reasoning and verbal fluency was assessed at mean age 79 years (n=501), and again at mean ages of 83 (n=284) and 87 (n=187). Using linear mixed models adjusted for demographic variables, vascular risk factors and IQ at age 11 years, possession of the APOE E4 allele was associated with a higher relative rate of cognitive decline over the subsequent 8 years for verbal memory and abstract reasoning. Individuals with the long allelic variant of TOMM40, which is linked to APOE E4, showed similar results. Verbal fluency was not affected by APOE E4 status. APOE E2 status was not associated with change in cognitive performance over 8 years. In non-demented older individuals, possession of the APOE E4 allele predicted a higher rate of cognitive decline on tests of verbal memory and abstract reasoning between 79 and 87 years. Thus, possession of the APOE E4 allele may not only predispose to Alzheimer's disease, but also appears to be a risk factor for non-pathological decline in verbal memory and abstract reasoning in the ninth decade of life.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Aging / genetics
  • Aging / psychology
  • Alleles
  • Apolipoprotein E2 / genetics
  • Apolipoprotein E4 / genetics*
  • Apolipoprotein E4 / physiology
  • Cognition Disorders / epidemiology
  • Cognition Disorders / genetics*
  • Cohort Studies
  • Comorbidity
  • Female
  • Follow-Up Studies
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Membrane Transport Proteins / genetics
  • Memory Disorders / epidemiology
  • Memory Disorders / genetics
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Neuropsychological Tests
  • Risk Factors
  • Scotland / epidemiology
  • Speech Disorders / epidemiology
  • Speech Disorders / genetics

Substances

  • Apolipoprotein E2
  • Apolipoprotein E4
  • Membrane Transport Proteins
  • Mitochondrial Precursor Protein Import Complex Proteins
  • TOMM40 protein, human