Polygenic risk for Alzheimer's disease is not associated with cognitive ability or cognitive aging in non-demented older people

J Alzheimers Dis. 2014;39(3):565-74. doi: 10.3233/JAD-131058.


Alzheimer's disease (AD) and non-pathological cognitive aging have phenotypic similarities which may be influenced by an overlapping set of genetic variants. Genome-wide complex trait analysis estimates that common genetic variants account for about 24% of the variation contributing to liability for AD. It is also estimated that 24% of the variance of non-pathological cognitive aging is accounted for by common single nucleotide polymorphisms. However, although the APOE locus is associated with both AD and cognitive aging, it is not known to what extent other common genetic variants, with smaller effect sizes that influence both, overlap. We test the hypothesis that polygenic risk for AD is associated with cognitive ability and cognitive change in about 3,000 non-demented older people (Cognitive Ageing Genetics England and Scotland-CAGES-consortium). We found no significant association of polygenic risk for AD with cognitive ability or cognitive change in CAGES, indicating that the genetic etiologies of AD and non-pathological cognitive decline differ.

Keywords: Aging; Alzheimer's disease; cognition; cohort studies; genetics; polygenic traits.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • Aging / genetics*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / physiopathology*
  • Apolipoproteins E / genetics
  • Cognition / physiology*
  • Cohort Studies
  • Databases, Factual / statistics & numerical data
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Neuropsychological Tests
  • Polymorphism, Single Nucleotide


  • Apolipoproteins E