Associations between APOE and low-density lipoprotein cholesterol genotypes and cognitive and physical capability: the HALCyon programme

Tamuno Alfred*, Yoav Ben-Shlomo, Rachel Cooper, Rebecca Hardy, Cyrus Cooper, Ian J. Deary, Jane Elliott, David Gunnell, Sarah E. Harris, Mika Kivimaki, Meena Kumari, Richard M. Martin, Chris Power, Avan Aihie Sayer, John M. Starr, Diana Kuh, Ian N.M. Day, Catharine Gale, James Goodwin, Alison LennoxMarcus Richards, Thomas Von Zglinicki, John Gallacher, Gita Mishra, Paul Shiels, Humphrey Southall, Andrew Steptoe, Panos Demakakos, Kate Tilling, Lawrence Whalley, Geraldine McNeill, Leone Craig, Carmen Martin-Ruiz, Paula Aucott, Emily Murray, Zeinab Mulla, Mike Gardner, Sam Parsons

*Corresponding author for this work

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The APOE ε2/3/4 genotype has been associated with low-density lipoprotein cholesterol (LDL-C) and Alzheimer disease. However, evidence for associations with measures of cognitive performance in adults without dementia has been mixed, as it is for physical performance. Associations may also be evident in other genotypes implicated in LDL-C levels. As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, genotypic information was obtained for APOE ε2/3/4, rs515135 (APOB), rs2228671 (LDLR) and rs629301 (SORT1) from eight cohorts of adults aged between 44 and 90+years. We investigated associations with four measures of cognitive (word recall, phonemic fluency, semantic fluency and search speed) and physical capability (grip strength, get up and go/walk speed, timed chair rises and ability to balance) using meta-analyses. Overall, little evidence for associations between any of the genotypes and measures of cognitive capability was observed (e.g. pooled beta for APOE ε4 effect on semantic fluency z score=- 0.02; 95% CI=- 0.05 to 0.02; p value=0.3; n=18,796). However, there was borderline evidence within studies that negative effects of APOE ε4 on nonverbal ability measures become more apparent with age. Few genotypic associations were observed with physical capability measures. The findings from our large investigation of middle-aged to older adults in the general population suggest that effects of APOE on cognitive capability are at most modest and are domain- and age-specific, while APOE has little influence on physical capability. In addition, other LDL-C-related genotypes have little impact on these traits.

Original languageEnglish
Article number9673
Number of pages12
Issue number4
Early online date30 Jul 2014
Publication statusPublished - 31 Aug 2014


  • Ageing
  • Apolipoprotein E
  • Cognition
  • Single nucleotide polymorphism
  • RCUK
  • 15/SAG09977
  • BB/F019394/1
  • ESRC
  • MRC
  • Wellcome Trust
  • 068545/ Z /02
  • G0000934
  • K013351


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