Mid-Life Household Food Insecurity and Subsequent Memory Function and Rate of Decline in Rural South Africa, 2004-2022.

INTRODUCTION: We aimed to investigate mid-life food insecurity over time in relation to subsequent memory function and rate of decline in Agincourt, rural South Africa. METHODS: Data from the longitudinal Agincourt Health and Socio-Demographic Surveillance System (Agincourt HDSS) were linked to the population-representative Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa (HAALSI). Food insecurity (yes vs. no) and food insecurity intensity (never/rarely/sometimes vs. often/very often) in the past month were assessed every 3 years from 2004 to 2013 in Agincourt HDSS. Cumulative exposure to each food insecurity measure was operationalized as 0, 1, and ≥2 time points. Episodic memory was assessed from 2014/15 to 2021/22 in HAALSI. Mixed-effects linear regression models were fitted to investigate the associations of each food insecurity measure with memory function and rate of decline over time. RESULTS: A total of 3,186 participants (mean age [SD] in 2004: 53 [12.87]; range: 30-96) were included and 1,173 (36%) participants experienced food insecurity in 2004, while this figure decreased to 490 (15%) in 2007, 489 (15%) in 2010, and 150 (5%) in 2013. Experiencing food insecurity at one time point (vs. never) from 2004 to 2013 was associated with lower baseline memory function (ß = -0.095; 95% CI: -0.159 to -0.032) in 2014/15 but not rate of memory decline. Higher intensity of food insecurity at ≥2 time points (vs. never) was associated with lower baseline memory function (ß = -0.154, 95% CI: -0.338 to 0.028), although the estimate was imprecise. Other frequencies of food insecurity and food insecurity intensity were not associated with memory function or decline in the fully adjusted models. CONCLUSION: In this setting, mid-life food insecurity may be a risk factor for lower later-life memory function, but not decline.

Incidence of Cognitive Impairment during Aging in Rural South Africa: Evidence from HAALSI, 2014 to 2019.

INTRODUCTION: Despite rapid population aging, there are currently limited data on the incidence of aging-related cognitive impairment in sub-Saharan Africa. We aimed to determine the incidence of cognitive impairment and its distribution across key demographic, social, and health-related factors among older adults in rural South Africa. METHODS: Data were from in-person interviews with 3,856 adults aged ≥40 who were free from cognitive impairment at baseline in the population-representative cohort, "Health and Aging in Africa: a Longitudinal Study of an INDEPTH Community in South Africa" (HAALSI), in Agincourt sub-district, Mpumalanga province, South Africa (2014-19). Cognitive impairment was defined as scoring <1.5 standard deviations below the mean of the baseline distribution of orientation and episodic memory scores. Incidence rates and rate ratios for cognitive impairment were estimated according to key demographic, social, and health-related factors, adjusted for age, sex/gender, and country of birth. RESULTS: The incidence of cognitive impairment was 25.7/1,000 person-years (PY; 95% confidence interval [CI]: 23.0-28.8), weighted for mortality (12%) and attrition (6%) over the 3.5-year mean follow-up (range: 1.5-4.8 years). Incidence increased with age, from 8.9/1,000 PY (95% CI: 5.2-16.8) among those aged 40-44 to 93.5/1,000 PY (95% CI: 75.9-116.3) among those aged 80+, and age-specific risks were similar by sex/gender. Incidence was strongly associated with formal education and literacy, as well as marital status, household assets, employment, and alcohol consumption but not with history of smoking, hypertension, stroke, angina, heart attack, diabetes, or prevalent HIV. CONCLUSIONS: This study presents some of the first incidence rate estimates for aging-related cognitive impairment in rural South Africa. Social disparities in incident cognitive impairment rates were apparent in patterns similar to those observed in many high-income countries.

Cognitive function and cardiometabolic disease risk factors in rural South Africa: baseline evidence from the HAALSI study.

BACKGROUND: Evidence on cognitive function in older South Africans is limited, with few population-based studies. We aimed to estimate baseline associations between cognitive function and cardiometabolic disease risk factors in rural South Africa. METHODS: We use baseline data from "Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa" (HAALSI), a population-based study of adults aged 40 and above in rural South Africa in 2015. Cognitive function was measured using measures of time orientation, immediate and delayed recall, and numeracy adapted from the Health and Retirement Study cognitive battery (overall total cognitive score range 0-26). We used multiple linear regression to estimate associations between cardiometabolic risk factors (including BMI, hypertension, dyslipidemia, diabetes, history of stroke, alcohol frequency, and smoking status) and the overall cognitive function score, adjusted for potential confounders. RESULTS: In multivariable-adjusted analyses (n = 3018; male = 1520; female = 1498; median age 59 (interquartile range 50-67)), cardiometabolic risk factors associated with lower cognitive function scores included: diabetes (b = - 1.11 [95% confidence interval: - 2.01, - 0.20] for controlled diabetes vs. no diabetes); underweight BMI (b = - 0.87 [CI: - 1.48, - 0.26] vs. normal BMI); and current and past smoking history compared to never smokers. Factors associated with higher cognitive function scores included: obese BMI (b = 0.74 [CI: 0.39, 1.10] vs. normal BMI); and controlled hypertension (b = 0.53 [CI: 0.11, 0.96] vs. normotensive). CONCLUSIONS: We provide an important baseline from rural South Africa on the associations between cardiometabolic disease risk factors and cognitive function in an older, rural South African population using standardized clinical measurements and cut-offs and widely used cognitive assessments. Future studies are needed to clarify temporal associations as well as patterns between the onset and duration of cardiometabolic conditions and cognitive function. As the South African population ages, effective management of cardiometabolic risk factors may be key to lasting cognitive health.

Decreasing Opioid Utilization in Rehabilitation Patients Using a Clinical Nurse Specialist Pain Consultant Program.

OBJECTIVE: To investigate whether access to a clinical nurse specialist (CNS) with expertise in pain management will result in more rapid decline in opioid use across the rehabilitation hospitalization. DESIGN: Retrospective chart review of patients discharged during 6 months prior to and 6 months after introduction of the CNS role. SETTING: Not-for-profit 98-bed community inpatient rehabilitation hospital. PARTICIPANTS: Two population-based samples of adult, inpatient rehabilitation patients (N=72) with daily opioid use ≥30mg morphine equivalent dose (MED) per day on admission and length of stay ≥24 days. INTERVENTIONS: Implementation of a CNS pain consult program. MAIN OUTCOME MEASURES: Change in average daily opioid use (milligrams of MED per day), measured at admission, week 1, week 2, and week 3. RESULTS: Linear mixed modeling was used to estimate individual and group average opioid trajectories, including individual patient intercepts (opioid use at admission) and slopes (change in opioid use over time). There was a significant interaction between group and time (b=5.75, t=2.52, P<.01), indicating faster change in opioid use for the CNS group (quadratic slope, -5.91) compared with the no CNS group (quadratic slope, -.16). Quadratic change in the CNS group reflected an initial increase in opioid use from admission to week 1, followed by a steady decline. Conversely, there was virtually no change in the no CNS group. Random effects revealed considerable variability in opioid trajectories across patients. CONCLUSIONS: Addition of a CNS pain consultant program to an inpatient rehabilitation hospital supported a distinct pattern of opioid tapering that promoted more rapid titration of daily opioid use across the rehabilitation hospitalization.

Examining the Pathways Between Self-Awareness and Well-Being in Mild to Moderate Alzheimer Disease.

OBJECTIVE: To investigate the relationship between awareness of memory loss and psychological well-being in a nonclinically depressed sample of participants with mild to moderate Alzheimer disease (AD). METHODS: Study participants (N = 104) enrolled through Columbia University Medical Center and the University of Pennsylvania completed clinical and cognitive assessments. Participants were rated with regard to their degree of awareness of memory deficits and completed questionnaires relating to their psychological well-being, including mood and quality of life (QOL). Mediating models were used to establish the relationship between awareness, depression, and QOL and to examine potential mediators of awareness and depression, including psychological distress, objective memory deficits, and negative self-ratings. RESULTS: There was a direct association between awareness of memory deficits and depressed mood but not awareness and QOL. However, there was an indirect association between awareness and QOL through depression. Neither psychological distress, memory deficits, nor negative self-ratings mediated the relationship between awareness and depression. CONCLUSION: Awareness is associated with depressed mood in nonclinically depressed participants with mild to moderate AD. However, depressed mood does not appear to reflect the direct psychological reaction to awareness of memory loss. Moreover, awareness has only an indirect association with QOL via depressed mood. These results suggest that preserved awareness does not have a direct negative impact on overall psychological well-being in AD.

Mid-life employment trajectories and subsequent memory function and rate of decline in rural South Africa, 2000-22.

AIM: To investigate mid-life employment trajectories in relation to later-life memory function and rate of decline in rural South Africa. METHODS: Data from the Agincourt Health and Socio-Demographic Surveillance System were linked to the 'Health and Ageing in Africa: A Longitudinal Study of an INDEPTH Community in South Africa' (HAALSI) in rural Agincourt, South Africa (N = 3133). Employment was assessed every 4 years over 2000-12 as being employed (0, 1, 2 and ≥3 time points), being employed in a higher-skill occupation (0, 1, 2 and ≥3 time points) and dynamic employment trajectories identified using sequence analysis. Latent memory z-scores were assessed over 2014-22. Mixed-effects linear regression models were fitted to examine the associations of interest. RESULTS: Sustained mid-life employment from 2000-12 (ß = 0.052, 95% CI: -0.028 to 0.132, 1 vs 0 time points; ß = 0.163, 95% CI: 0.077 to 0.250, 2 vs 0 time points; ß = 0.212, 95% CI: 0.128 to 0.296, ≥3 vs 0 time points) and greater time spent in a higher-skill occupation (ß = 0.077, 95% CI: -0.020 to 0.175, 1 vs 0 time points; ß = 0.241, 95% CI: 0.070 to 0.412, 2 vs 0 time points; ß = 0.361, 95% CI: 0.201 to 0.520, ≥3 vs 0 time points) were associated with higher memory scores in 2014/15, but not subsequent rate of memory decline. Moving from a lower-skill to higher-skill occupation was associated with higher memory function, but a faster rate of decline over 2014-22. CONCLUSIONS: Sustained mid-life employment, particularly in higher-skill occupations, may contribute to later-life memory function in this post-Apartheid South African setting.

Association of brain arterial diameters with demographic and anatomical factors in a multi-national pooled analysis of cohort studies.

BACKGROUND AND PURPOSE: Brain arterial diameters are markers of cerebrovascular disease. Demographic and anatomical factors may influence arterial diameters. We hypothesize that age, sex, height, total cranial volume (TCV), and persistent fetal posterior cerebral artery (fPCA) correlate with brain arterial diameters across populations. METHODS: Participants had a time-of-flight MRA from nine international cohorts. Arterial diameters of the cavernous internal carotid arteries (ICA), middle cerebral arteries (MCA), and basilar artery (BA) were measured using LAVA software. Regression models assessed the association between exposures and brain arterial diameters. RESULTS: We included 6,518 participants (mean age: 70 ± 9 years; 41% men). Unilateral fPCA was present in 13.2% and bilateral in 3.2%. Larger ICA, MCA, and BA diameters correlated with older age (Weighted average [WA] per 10 years: 0.18 mm, 0.11 mm, and 0.12 mm), male sex (WA: 0.24 mm, 0.13 mm, and 0.21 mm), and TCV (WA: for one TCV standard deviation: 0.24 mm, 0.29 mm, and 0.18 mm). Unilateral and bilateral fPCAs showed a positive correlation with ICA diameters (WA: 0.39 mm and 0.73 mm) and negative correlation with BA diameters (WA: -0.88 mm and -1.73 mm). Regression models including age, sex, TCV, and fPCA explained on average 15%, 13%, and 25% of the ICA, MCA, and BA diameter interindividual variation, respectively. Using height instead of TCV as a surrogate of head size decreased the R-squared by 3% on average. CONCLUSION: Brain arterial diameters correlated with age, sex, TCV, and fPCA. These factors should be considered when defining abnormal diameter cutoffs across populations.

Associations between cohort derived dementia and COVID-19 serological diagnosis among older Black adults in rural South Africa.

Objectives: This study investigates the association between cohort derived dementia and serologically confirmed SARS-CoV-2 infection, an underexplored phenomena in low-and middle-income countries. Examining this relationship in a rural South African community setting offers insights applicable to broader healthcare contexts. Methods: Data were collected from Black South Africans in the Mpumalanga province who participated in the Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa. Cohort derived dementia was developed using a predictive model for consensus-based dementia diagnosis. Multinomial logistic regression models estimated the association between predicted dementia probability in 2018 and SARS-CoV-2 infection risk in 2021, controlling for demographics, socioeconomic status, and comorbidities. Results: Fifty-two percent of the tested participants had serologically confirmed SARS-CoV-2 infections. In the fully adjusted model, cohort derived dementia was significantly associated with over twice the risk of serological diagnosis of COVID-19 (RRR = 2.12, p = 0.045). Conclusion: Complying with COVID-19 prevention recommendations may be difficult for individuals with impaired cognitive functioning due to their symptoms. Results can inform community-based public health initiatives to reduce COVID-19 transmission among South Africa's rapidly aging population.

Telomere Length, Health, and Mortality in a Cohort of Older Black South African Adults.

Telomere length (TL) may be a biomarker of aging processes as well as age-related diseases. However, most studies of TL and aging are conducted in high-income countries. Less is known in low- and middle-income countries (LMICs) such as South Africa, where life expectancy remains lower despite population aging. We conducted a descriptive analysis of TL in a cohort of older adults in rural South Africa. TL was assayed from venous blood draws using quantitative polymerase chain reaction (T/S ratio). We examined the correlation between TL and biomarkers, demographic characteristics, mental/cognitive health measures, and physical performance measures in a subsample of the Wave 1 2014-2015 "Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa" (HAALSI) cohort (n = 510). We used logistic regression to measure the association between TL and mortality through Wave 3 (2021-2022). In bivariate analyses, TL was significantly correlated with age (r = -0.29, p < .0001), self-reported female sex (r = 0.13, p = .002), mortality (r = -0.1297, p = .003), diastolic blood pressure (r = 0.09, p = .037), pulse pressure (r = -0.09, p = .045), and being a grandparent (r = -0.17, p = .0001). TL was significantly associated with age (ß = -0.003; 95% confidence interval [CI] = -0.005, -0.003). TL was significantly associated in unadjusted multivariate analyses with mortality, but the relationship between TL and mortality was attenuated after adjusting for age (odds ratio [OR] = 0.19; 95% CI = 0.03, 1.27) and other covariates (OR = 0.17; 95% CI = 0.02, 1.19). Our study is the first analysis of TL in an older adult South African population. Our results corroborate existing relationships between TL and age, sex, cardiometabolic disease, and mortality found in higher-income countries.

Feasibility of an online consensus approach for the diagnosis of cognitive impairment and dementia in rural South Africa.

INTRODUCTION: We describe the development and feasibility of using an online consensus approach for diagnosing cognitive impairment and dementia in rural South Africa. METHODS: Cognitive assessments, clinical evaluations, and informant interviews from Cognition and Dementia in the Health and Aging in Africa Longitudinal Study (HAALSI Dementia) were reviewed by an expert panel using a web-based platform to assign a diagnosis of cognitively normal, mild cognitive impairment (MCI), or dementia. RESULTS: Six hundred thirty-five participants were assigned a final diagnostic category, with 298 requiring adjudication conference calls. Overall agreement between each rater's independent diagnosis and final diagnosis (via the portal or consensus conference) was 78.3%. A moderate level of agreement between raters' individual ratings and the final diagnostic outcomes was observed (average κ coefficient = 0.50). DISCUSSION: Findings show initial feasibility in using an online consensus approach for the diagnosis of cognitive impairment and dementia in remote, rural, and low-resource settings.

Towards a consensus definition of allostatic load: a multi-cohort, multi-system, multi-biomarker individual participant data (IPD) meta-analysis.

BACKGROUND: Allostatic load (AL) is a multi-system composite index for quantifying physiological dysregulation caused by life course stressors. For over 30 years, an extensive body of research has drawn on the AL framework but has been hampered by the lack of a consistent definition. METHODS: This study analyses data for 67,126 individuals aged 40-111 years participating in 13 different cohort studies and 40 biomarkers across 12 physiological systems: hypothalamic-pituitary-adrenal (HPA) axis, sympathetic-adrenal-medullary (SAM) axis, parasympathetic nervous system functioning, oxidative stress, immunological/inflammatory, cardiovascular, respiratory, lipidemia, anthropometric, glucose metabolism, kidney, and liver. We use individual-participant-data meta-analysis and exploit natural heterogeneity in the number and type of biomarkers that have been used across studies, but a common set of health outcomes (grip strength, walking speed, and self-rated health), to determine the optimal configuration of parameters to define the concept. RESULTS: There was at least one biomarker within 9/12 physiological systems that was reliably and consistently associated in the hypothesised direction with the three health outcomes in the meta-analysis of these cohorts: dehydroepiandrosterone sulfate (DHEAS), low frequency-heart rate variability (LF-HRV), C-reactive protein (CRP), resting heart rate (RHR), peak expiratory flow (PEF), high density lipoprotein cholesterol (HDL-C), waist-to-height ratio (WtHR), HbA1c, and cystatin C. An index based on five biomarkers (CRP, RHR, HDL-C, WtHR and HbA1c) available in every study was found to predict an independent outcome - mortality - as well or better than more elaborate sets of biomarkers. DISCUSSION: This study has identified a brief 5-item measure of AL that arguably represents a universal and efficient set of biomarkers for capturing physiological 'wear and tear' and a further biomarker (PEF) that could usefully be included in future data collection.

Associations between cognitive function and marital status in the United States, South Africa, Mexico, and China.

We investigate the associations between marital status and cognitive well-being among adults aged 50 and older across four settings: the United States, rural South Africa, Mexico, and China. Using a standardized measure of immediate word recall, we assess whether people in each non-married status have worse cognitive function than their married counterparts, and the extent to which these associations vary across settings. We theorize that the practices around marriage in each setting, as well as the social stigma attached to marital dissolution, will reveal differing associations between marital status and cognition. Results suggest that, among women, being in a widowed marital status is associated with lower cognitive function in each setting except Mexico (after accounting for education and employment), while being separated/divorced or never married is associated with lower cognitive function only among women in the U.S. and Mexico. Among men, being widowed is associated with lower cognitive function relative to being married in each setting except South Africa (after accounting for education and employment), and being never married is associated with lower cognitive function in the U.S. and China (but not in South Africa or Mexico, after accounting for education and employment). Men also face relatively lower cognitive function if separated/divorced in the U.S. and South Africa. We discuss possible reasons for these associations across settings.

Corrigendum: Apolipoprotein E Genetic Variation and its Association With Cognitive Function in Rural-Dwelling Older South Africans.

[This corrects the article DOI: 10.3389/fgene.2021.689756.].

Protocol: the complexity of informal caregiving for Alzheimer's disease and related dementias in rural South Africa.

BACKGROUND:  With aging, many people develop Alzheimer's disease or related dementias (ADRD) as well as chronic physical health problems. The consequent care needs can be complicated, with heavy demands on families, households and communities, especially in resource-constrained settings with limited formal care services. However, research on ADRD caregiving is largely limited to primary caregivers and high-income countries. Our objectives are to analyse in a rural setting in South Africa: (1) how extended households provide care to people with ADRD; and (2) how the health and wellbeing of all caregivers are affected by care roles. METHODS:  The study will take place at the Agincourt health and socio-demographic surveillance system site of the MRC/Wits Rural Public Health and Health Transitions Research Unit in Mpumalanga Province, northeast South Africa. We will recruit 100 index individuals predicted to currently have ADRD or cognitive impairment using data from a recent dementia survey. Quantitative surveys will be conducted with each index person's nominated primary caregiver, all other household members aged over 12, and caregiving non-resident kin and non-kin to determine how care and health are patterned across household networks. Qualitative data will be generated through participant observation and in-depth interviews with caregivers, select community health workers and key informants. Combining epidemiological, demographic and anthropological methods, we will build a rich picture of households of people with ADRD, focused on caregiving demands and capacity, and of caregiving's effects on health. DISCUSSION:  Our goal is to identify ways to mitigate the negative impacts of long-term informal caregiving for ADRD when formal supports are largely absent. We expect our findings to inform the development of locally relevant and community-oriented interventions to improve the health of caregivers and recipients, with implications for other resource-constrained settings in both higher- and lower-income countries.

Subjective social position and cognitive function in a longitudinal cohort of older, rural South African adults, 2014-2019.

BACKGROUND: The relationship between subjective social position (SSP) and cognitive ageing unclear, especially in low-income settings. We aimed to investigate the relationship between SSP and cognitive function over time among older adults in rural South Africa. METHODS: Data were from 3771 adults aged ≥40 in the population-representative 'Health and Ageing in Africa: A Longitudinal Study of an INDEPTH Community in South Africa' from 2014/2015 (baseline) to 2018/2019 (follow-up). SSP was assessed at baseline with the 10-rung MacArthur Network social position ladder. Outcomes were composite orientation and episodic memory scores at baseline and follow-up (range: 0-24). Mortality- and attrition-weighted linear regression estimated the associations between baseline SSP with cognitive scores at each of the baseline and follow-up. Models were adjusted for age, age2, sex, country of birth, father's occupation, education, employment, household assets, literacy, marital status and health-related covariates. RESULTS: SSP responses ranged from 0 (bottom ladder rung/lowest social position) to 10 (top ladder rung/highest social position), with a mean of 6.6 (SD: 2.3). SSP was positively associated with baseline cognitive score (adjusted ß=0.198 points per ladder rung increase; 95% CI 0.145 to 0.253) and follow-up cognitive score (adjusted ß=0.078 points per ladder rung increase; 95% CI 0.021 to 0.136). CONCLUSION: Independent of objective socioeconomic position measures, SSP is associated with orientation and episodic memory scores over two time points approximately 3 years apart among older rural South Africans. Future research is needed to establish the causality of the observed relationships, whether they persist over longer follow-up periods and their consistency in other populations.

Grandchild Caregiving and Cognitive Health Among Grandparents in Rural South Africa.

Objectives: We investigate how caregiving for grandchildren is associated with cognitive function among rural South Africans, and whether the association differs by gender. We further investigate whether measures of physical activity or social engagement mediate this association. Methods: Data were from interviews with 3668 Black, South African grandparents in the "Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa" study, conducted between 2014 and 2015. Results: We find that caregiving grandparents have better cognitive function than non-caregiving grandparents, and this association does not differ by grandparent gender. Although grandchild caregiving is associated with physical activity and social engagement measures, and some of these measures are associated with cognitive function, we do not find conclusive evidence of mediation. Discussion: Providing care for grandchildren may stimulate cognitive function for both grandmothers and grandfathers. Neither physical activity nor social engagement explains the association between caregiving and cognitive function.

Do You See What Eye See? Measurement, Correlates, and Functional Associations of Objective and Self-Reported Vision Impairment in Aging South Africans.

Objectives: Our study investigates measurement, correlates, and functional associations of vision impairment (VI) in an aging population in rural South Africa. Methods: 1582 participants aged 40-69 reported on near (NVI) and distance vision impairment (DVI) and completed objective vision tests. Logistic and linear regression were used to evaluate sociodemographic, health, and psychosocial correlates of VI and assess relationships between VI and cognitive and physical function. Results: VI prevalence was considerably higher according to objective testing (56%) versus self-reports (18%). Older adults were especially likely to underreport impairment. Objective VI was associated with age, education, cardiometabolic disease, and female sex. Conversely, self-reported VI was associated with psychosocial factors. Objective NVI and both types of DVI were associated with worse visual cognition and slower gait speed, respectively. Discussion: Self-reported and objective VI measures should not be used interchangeably in this context. Our findings highlight extensive burden of untreated VI in this region.

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

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.

Dimensionality and differential item endorsement of depressive symptoms among aging Black populations in South Africa: Findings from the HAALSI study.

BACKGROUND: The Center for Epidemiologic Studies-Depression (CES-D) scale is a widely used measure of depressive symptoms, but its construct validity has not been adequately assessed in sub-Saharan Africa. This study validates the CES-D among an aging Shangaan-speaking and predominantly Black African sample in rural South Africa, with a special emphasis on gender differences. METHODS: An 8-item CES-D scale was administered in Shangaan to 5059 respondents, aged 40+ years, residing in Agincourt, South Africa. We used Cronbach's alpha and exploratory and confirmatory factor analysis to examine and confirm dimensionality of the CES-D scale. Differential endorsement of CES-D items by gender were assessed using the Mantel-Haenszel (MH) odds ratio test. RESULTS: Reliability of the CES-D scale differed by gender with women reporting higher internal consistency on items than men. A two-factor solution was retained and confirmed representing two latent factors: (1) Negative Affect (six items) and (2) Diminished Positive Affect (two items). MH results showed that men exhibited significantly higher odds of putting an effort in everything that they did (OR: 1.33, 95% CI: 1.15-1.54) and lower odds of feeling depressed (OR: 0.71, 95% CI: 0.56-0.89) and having restless sleep (OR: 0.67, 95% CI:0.58-0.77) than women. LIMITATIONS: Analyses were limited to a dichotomous, short form of the CES-D, a self-reported population-based measure. CONCLUSION: Aging Black Africans differ in endorsing affective and somatic items on the CES-D scale by gender, which may lead to skewed population-level estimates of depression in key subpopulations. These findings highlight the importance of continued research disentangling cross-cultural and gendered nuances of depression measurements.

Disparity in Educational Attainment Partially Explains Cognitive Gender Differences in Older Rural South Africans.

OBJECTIVES: Direction and magnitude of gender differences in late-life cognitive function are inextricably tied to sociocultural context. Our study evaluates education and literacy as primary drivers of gender equality in cognitive performance among middle-aged and older adults in rural South Africa. METHOD: Data were collected on 1,938 participants aged 40-79 from Agincourt, South Africa. Cognitive function was measured via the Oxford Cognitive Screen-Plus, a tablet-based assessment with low literacy demands. Four cognitive domains were derived through confirmatory factor analysis: episodic memory, executive function, visual spatial, and language. Structural equation models tested domain-specific gender effects, incrementally controlling for demographic, education, health, and socioeconomic variables. RESULTS: In the model adjusting only for demographic factors, men outperformed women on executive function and visual-spatial domains. Adding education and literacy to the model revealed a robust female advantage in episodic memory, and reduced the magnitude of male advantage in executive function and visual and spatial by 47% and 42%, respectively. Health and socioeconomic factors did not alter patterns of gender associations in subsequent models. DISCUSSION: In this older South African cohort, gender inequality in cognitive performance was partially attributable to educational differences. Understanding biopsychosocial mechanisms that promote cognitive resilience in older women is critically important given the predominantly female composition of aging populations worldwide.