title: Associations between APOE and low-density lipoprotein cholesterol genotypes and cognitive and physical capability: the HALCyon programme.
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.
authors: School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol, BS8 2PS, UK, tamuno.alfred@bristol.ac.uk.
authors: Tamuno
authors: T
authors: Alfred
authors: Yoav
authors: Y
authors: Ben-Shlomo
authors: Rachel
authors: R
authors: Cooper
authors: Rebecca
authors: R
authors: Hardy
authors: Cyrus
authors: C
authors: Cooper
authors: Ian J
authors: IJ
authors: Deary
authors: Jane
authors: J
authors: Elliott
authors: David
authors: D
authors: Gunnell
authors: Sarah E
authors: SE
authors: Harris
authors: Mika
authors: M
authors: Kivimaki
authors: Meena
authors: M
authors: Kumari
authors: Richard M
authors: RM
authors: Martin
authors: Chris
authors: C
authors: Power
authors: Avan Aihie
authors: AA
authors: Sayer
authors: John M
authors: JM
authors: Starr
authors: Diana
authors: D
authors: Kuh
authors: Ian N M
authors: IN
authors: Day
mesh_terms: D000328:Adult; D000375:Aging / Q000235:genetics*; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D053327:Apolipoprotein E4 / Q000235:genetics* / Q000378:metabolism; D008078:Cholesterol, LDL / Q000235:genetics* / Q000378:metabolism; D003071:Cognition / Q000502:physiology*; D004247:DNA / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D013997:Time Factors; D016138:Walking / Q000502:physiology
chemical_list: D053327:Apolipoprotein E4; D008078:Cholesterol, LDL; D004247:DNA