Associations between APOE and low-density lipoprotein cholesterol genotypes and cognitive and physical capability: the HALCyon programme
Year: 2014
Type: article
Abstract: 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.
Source: AGE
Institutions: University of Bristol, MRC Unit for Lifelong Health and Ageing, University College London, MRC Lifecourse Epidemiology Unit, University of Southampton, University of Oxford, University of Edinburgh, University of London, Western General Hospital, Southampton General Hospital, Alzheimer Scotland
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $2,135
Funders: John D. and Catherine T. MacArthur Foundation, Wellcome Trust, National Institute for Health and Care Research, British Heart Foundation, University of Southampton, University College London, University of Edinburgh, Health and Safety Executive, University of Bristol, Versus Arthritis, Centre for Cognitive Ageing and Cognitive Epidemiology, National Institutes of Health, Directorate for Biological Sciences, Medical Research Council, Engineering and Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council, Economic and Social Research Council, World Cancer Research Fund, National Institute on Aging, National Heart, Lung, and Blood Institute
Awards: G1093300281, G1137313802, G1167024831, G1269020986, G1466358154, G1492072473, Understanding Society Waves 6 to 8, G1896713975, G2029631211, G2294100661, G2425175678, Health behaviors over the adult lifecourse and cognitive aging, G2507151542, G2594517499, G269567959, G2719016821, G2751663742, Determinants of healthy ageing in the Whitehall II study, G2824707892, G2928833717, G2953502109, G3251713059, G3278553629, G3349769430, G3812491970, Conducting a genome-wide association study (GWAS) in the English Longitudinal Study of Ageing (ELSA): a unique resource for UK social science, G400652325, G4237323377, G443238052, G4522451727, G4641403149, G4746977625, G4856618060, G4942547004, G4950536974, G5067462658, G5208912463, NIHR Senior Investigator Award, G5365760627, G538581767, G5412976545, G5503240538, G5568298347, A national DNA control series for genetic case-control studies based on the British 1958 birth cohort, G6060264546, G6122601559, G6172210748, G6239859655, G6276181198, G6354209809, G643113813, G6803116133, G680566116, NIHR Senior Investigator Award, G6883877472, G690763772, G695167419, A genome-wide association study of non-pathological cognitive ageing, G7243315025, G7374949320, G7572990571, G7627314639, G7782480062, Socio-economic status and heterogeneity in aging, G7900679853, G8158107655, G8301108051, NIHR Senior Investigator Award, Socioeconomic gradient in CHD in early old age, G8648435156, Understanding Society and the UK Longitudinal Studies Centre, G9000120579, G9000178614
OpenAlex ID: W1991044584