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Apolipoprotein E Genetic Variation and Its Association With Cognitive Function in Rural-Dwelling Older South Africans

ABSTRACT: Apolipoprotein E (APOE) 𝜀4 allele carrier status is well known for its association with an increased likelihood of developing Alzheimer’s disease, but its independent role in cognitive function is unclear. APOE genetic variation is understudied in African populations; hence, this cross-sectional study in a rural South African community examined allele and genotype frequencies, and their associations with cognitive function. Cognitive function was assessed using two different screening methods to produce a total cognition score and four domain-specific cognition scores for verbal episodic memory, executive function, language, and visuospatial ability. Cognitive phenotype and APOE genotype data were used to determine whether APOE variation was significantly associated with cognitive function in this population. Observed allele frequencies for 1776 participants from the HAALSI study [age 40–80years (mean=56.19); 58.2% female] were 58.1% (𝜀3), 25.4% (𝜀4) and 16.5% (𝜀2). Allele distributions were similar to the African super population, but different from all non-African super populations from the 1,000 Genomes Project. The 𝜀3 homozygous genotype was most common (34.9%) and used as the base genotype for comparison in regression models. Four models were tested for each of the five cognitive phenotypes to explore association of APOE variation with cognitive function. In the first model assessing association with all genotypes for all individuals, marginally significant associations were observed for 𝜀2 homozygotes where executive function scored higher by ~0.5 standard deviations (p=0.037, SE=0.23), and for 𝜀3/𝜀4 heterozygotes where visuospatial ability scores were lower (p=0.046, SE=0.14). These did not survive correction for multiple testing. Regional African population differences were observed at the APOE locus. Marginally, significant associations between APOE genotype, and executive function and visuospatial ability indicate the need for larger studies to better examine these associations in African populations. Furthermore, longitudinal data could shed light on APOE genetic association with rate of change, or decline, in cognitive function.

SUBMITTER: Soo C

PROVIDER: S-EPMC8551631 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:RationaleLittle research has evaluated the life course drivers of cognitive aging in South Africa.ObjectivesWe investigated the relationships of self-rated childhood health and father's occupation during childhood with later-life cognitive function score and whether educational attainment mediated these relationships among older South Africans living in a former region of Apartheid-era racial segregation.MethodsData were from baseline assessments of "Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community" (HAALSI), a population-based study of 5059 men and women aged ≥40 years in 2015 in rural Agincourt sub-district, South Africa. Childhood health, father's occupation during childhood, and years of education were self-reported in study interviews. Cognitive measures assessed time orientation, numeracy, and word recall, which were included in a z-standardized latent cognitive function score variable. Linear regression models adjusted for age, sex, and country of birth were used to estimate the total and direct effects of each childhood risk factor, and the indirect effects mediated by years of education.ResultsPoor childhood health predicted lower cognitive scores (total effect = -0.28; 95% CI = -0.35, -0.21, versus good); this effect was not mediated by educational attainment. Having a father in a professional job during childhood, while rare (3% of sample), predicted better cognitive scores (total effect = 0.25; 95% CI = 0.10, 0.40, versus unskilled manual labor, 29% of sample). Half of this effect was mediated by educational attainment. Education was linearly associated with later-life cognitive function score (0.09; 95% CI = 0.09, 0.10 per year achieved).ConclusionIn this post-Apartheid, rural South African context, older adults with poor self-reported childhood health or whose father worked in unskilled manual labor had relatively poor cognitive outcomes. Educational attainment strongly predicted cognitive outcomes, and appeared to be, in part, a mechanism of social stratification in later-life cognitive health in this context.

Project description:BACKGROUND:Physical frailty, characterized by reduced physiologic complexity and ability to cope with stressors, is closely associated with cognitive impairment, which increases the risk of poor clinical outcomes. To better capture the association between frailty and cognitive impairment, a new construct, cognitive frailty, has been proposed. Cognitive frailty is a clinical condition characterized by the simultaneous presence of physical frailty and cognitive impairment. There is little evidence on the relationship between physical frailty and cognition, as well as cognitive frailty, in Chinese older adults. We aimed to elucidate whether physical frailty is associated with cognitive impairment in an older Chinese population. METHODS:Data were obtained from the China Comprehensive Geriatric Assessment Study. The sample comprised 3202 community-dwelling adults, aged 60 years and older, from seven Chinese cities. Physical frailty was assessed using a modified, four-item version of the Fried criteria, according to frailty phenotype. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). RESULTS:The prevalence of physical frailty, prefrailty, cognitive impairment, and cognitive frailty was 9.9, 33.9, 7.5, and 2.3%, respectively (weighted: 8.8, 33.8, 6.5, and 2.0%). The prevalence of the combination of prefrail/frail and cognitive impairment was 5.1% (weighted 4.5%). Frail participants performed worse on global cognition and all cognitive domains than robust and prefrail participants. The MMSE total score was positively correlated with walking speed and negatively correlated with age and frailty. A multivariate logistic regression revealed that after adjusting for age, gender, education level, living area, and chronic diseases, frailty, exhaustion, slowness, and inactivity were significantly associated with poor global cognition. CONCLUSIONS:The standard prevalence of physical frailty, prefrailty, cognitive impairment, and cognitive frailty in community-dwelling older adults in China was 8.8, 33.8, 6.5, and 2.0%, respectively. Frailty, exhaustion, slowness, and inactivity were significantly associated with poor global cognition.

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Apolipoprotein E Genetic Variation and Its Association With Cognitive Function in Rural-Dwelling Older South Africans

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