TY - JOUR
T1 - Associations between APOE and low-density lipoprotein cholesterol genotypes and cognitive and physical capability
T2 - the HALCyon programme
AU - Alfred, Tamuno
AU - Ben-Shlomo, Yoav
AU - Cooper, Rachel
AU - Hardy, Rebecca
AU - Cooper, Cyrus
AU - Deary, Ian J
AU - Elliott, Jane
AU - Gunnell, David
AU - Harris, Sarah E
AU - Kivimaki, Mika
AU - Kumari, Meena
AU - Martin, Richard M
AU - Power, Chris
AU - Sayer, Avan Aihie
AU - Starr, John M
AU - Kuh, Diana
AU - Day, Ian N M
AU - the HALCyon Study Team
PY - 2014/8
Y1 - 2014/8
N2 - 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.
AB - 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.
KW - synthetic biology
U2 - 10.1007/s11357-014-9673-9
DO - 10.1007/s11357-014-9673-9
M3 - Article (Academic Journal)
C2 - 25073452
SN - 0161-9152
VL - 36
SP - 9673
JO - AGE
JF - AGE
IS - 4
ER -