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

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

Bilingualism does not alter cognitive decline or dementia risk among Spanish-speaking immigrants

Objective: Clinic-based studies suggest that dementia is diagnosed at older ages in bilinguals compared with monolinguals. The current study sought to test this hypothesis in a large, prospective, community-based study of initially nondemented Hispanic immigrants living in a Spanish-speaking enclave of northern Manhattan. Method: Participants included 1,067 participants in the Washington/Hamilton Heights Inwood Columbia Aging Project (WHICAP) who were tested in Spanish and followed at 18–24 month intervals for up to 23 years. Spanish-English bilingualism was estimated via both self-report and an objective measure of English reading level. Multilevel models for change estimated the independent effects of bilingualism on cognitive decline in 4 domains: episodic memory, language, executive function, and speed. Over the course of the study, 282 participants developed dementia. Cox regression was used to estimate the independent effect of bilingualism on dementia conversion. Covariates included country of origin, gender, education, time spent in the United States, recruitment cohort, and age at enrollment. Results: Independent of the covariates, bilingualism was associated with better memory and executive function at baseline. However, bilingualism was not independently associated with rates of cognitive decline or dementia conversion. Results were similar whether bilingualism was measured via self-report or an objective test of reading level. Conclusions: This study does not support a protective effect of bilingualism on age-related cognitive decline or the development of dementia. In this sample of Hispanic immigrants, bilingualism is related to higher initial scores on cognitive tests and higher educational attainment and may not represent a unique source of cognitive reserve

Incident cognitive impairment in a longitudinal cohort of older adults in rural South Africa, 2014‐19

BackgroundWe aimed to determine the incidence of cognitive impairment and its key sociodemographic, social, and health‐related predictors at the first longitudinal follow‐up of the population‐representative “Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa” (HAALSI) cohort in South Africa.MethodData were from 3,861 adults aged ≥40 in rural Agincourt sub‐district, South Africa from 2014‐19, who were free from cognitive impairment at baseline. Cognitive impairment was defined as scoring ≥1.5 SD below the baseline mean composite time orientation and episodic memory score, or requiring a proxy interview with “fair” or “poor” proxy‐reported memory. Limitations to activities of daily living (ADLs) were compared according to incident cognitive impairment status. Incidence rates (IRs), incidence rate ratios (IRRs), and 95% confidence intervals (CIs) for cognitive impairment were estimated according to sociodemographic, social, and health‐related characteristics using modified Poisson regression. IRs and IRRs were weighted to account for mortality over the follow‐up. IRRs were adjusted for age, sex/gender, and country of birth.ResultOver a mean follow‐up of 3.7 years, 309/3,861 at‐risk participants newly developed cognitive impairment (IR=24.0 per 1000 person‐years (PY); 95% CI: 21.6‐26.8). Incidence increased steadily with age, from IR=9.1 per 1000 PY (95% CI: 5.5‐16.1) among those aged 40‐44 years at baseline to IR=76.5 per 1000 PY (95% CI: 63.2‐93.4) among those aged 80+. At least one ADL limitation was prevalent at follow‐up in 39% of those with an incident cognitive impairment, compared to 7% of non‐cognitively impaired participants. The incidence of cognitive impairment did not vary by sex/gender, HIV infection status, or cardiovascular risk factors, but was strongly graded according to education, literacy, household assets, employment, marital status, and frequency of alcohol consumption. For example, IRR=1.13 (95% CI: 0.91‐1.40) for female vs. male, IRR=1.05 (95% CI: 0.77‐1.43) for HIV‐positive vs. HIV‐negative, IRR=2.40 (95% CI: 1.81‐3.17) for illiterate vs. literate.ConclusionThis study presents one of the first incidence rate estimates for cognitive impairment in sub‐Saharan Africa, where populations are beginning to rapidly age. Social and socioeconomic disparities in incident cognitive impairment rates were apparent in a similar pattern as in many high‐income countries.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163880/1/alz043215.pd

Social contact, social support, and cognitive health in a population-based study of middle-aged and older men and women in rural South Africa

Background: Several theories seek to explain how social connections and cognitive function are interconnected in older age. These include that social interaction protects against cognitive decline, that cognitive decline leads to shedding of social connections and that cognitive decline leads to increased instrumental support. We investigated how patterns of social contact, social support and cognitive health in rural South Africa fit with these three theories. Method: We used data from the baseline of "Health and Aging in Africa: a Longitudinal Study of an INDEPTH community in South Africa" (HAALSI), a population-based study of 5059 individuals aged >= 40 years. We evaluated how a range of egocentric social connectedness measures varied by respondents' cognitive function. Results: We found that respondents with lower cognitive function had smaller, denser social networks that were more local and more kin-based than their peers. Lower cognitive function was associated with receipt of less social support generally, but this difference was stronger for emotional and informational support than for financial and physical support. Impairment was associated with greater differences among those aged 40-59 and those with any (versus no) educational attainment. Conclusions: The patterns we found suggest that cognitively impaired older adults in this setting rely on their core social networks for support, and that theories relating to social connectedness and cognitive function developed in higher-income and higher-education settings may also apply in lower-resource settings elsewhere

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

INTRODUCTIONWe describe the development and feasibility of using an online consensus approach for diagnosing cognitive impairment and dementia in rural South Africa.METHODSCognitive 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.RESULTSSix 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).DISCUSSIONFindings show initial feasibility in using an online consensus approach for the diagnosis of cognitive impairment and dementia in remote, rural, and low-resource settings.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/176243/1/dad212420_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/176243/2/dad212420.pd

Abstract TMP64: Association Of Brain Arterial Diameters With Demographic And Anatomical Factors In A Multi-national Pooled Analysis Of Cohort Studies

Byline: Victor J Del Brutto, Univ of Miami, Miami, FL; Farid Khasiyev, SLU Sch of Medicine, St. Louis, MT; Minghua Liu, Columbia Univ, New York, NY; Antonio Spagnolo-Allende, New York, NY; Ye Qiao, JOHNS HOPKINS UNIVERISITY, Baltimore, MD; Jesus D Melgarejo Arias, Universidad del Zulia, Maracaibo, Venezuela, Bolivarian Republic of; Vanessa A Guzman, Columbia university medical center, New York, NY; Danurys Sanchez, New York, NY; Howard Andrews, New York State Psychiatric Institute, New York, NY; Jeffrey D Pyne, Columbia Univ, New York, NY; Clarissa D Morales, Columbia Univ, New York, NY; Tatjana Rundek, MILLER SCHL OF MEDICINE UNIV M, Miami, FL; Clinton B Wright, NATIONAL INSTITUTES OF HEALTH, Rockville, MD; Meagan T Farrell, Harvard T.H. Chan Sch of Public Health, Boston, MA; Sudha Seshadri; Jose R Romero, BOSTON UNIVERSITY SCHOOL OF MEDICIN, Boston, MA; Gladys E Maestre, Univ of Texas Rio Grande Vall, Brownsville, TX; OSCAR DEL BRUTTO, CLINICA KENNEDY, Guayaquil, Ecuador; Adam Brickman, Columbia Univ, New York, NY; Jennifer Manly, New York, NY; Richard P Mayeux, Columbia Univ, New York, NY; Ralph L Sacco, UNIVERSITY OF MIAMI, Miami, FL; Mitchell Elkind; Christopher Chen, NATIONAL UNIVERSITY OF SINGAPORE, Singapore; Hilal Saima, National Univ of Singapore, Singapore, Singapore; Bruce Wasserman, John Hopkins Med Institute, Baltimore, MD; Jose Gutierrez, COLUMBIA UNIVERSITY MEDICAL CE, New York, NY Objectives: Brain arterial dilation is an increasingly recognized cerebrovascular disease marker. However, demographic and anatomical factors may influence brain arterial diameters within the normal spectrum. We hypothesize that age, sex, height, total cranial volume (TCV) and fetal posterior cerebral arteries (fPCA) presence correlate with brain arterial diameters across diverse populations. Methods: We included participants with available time-of-flight MRA from 9 cohort studies across the United States (4), Ecuador (1), Venezuela (1), South Africa (1) and Singapore (2). Arterial diameters of the basilar artery (BA), cavernous internal carotid arteries (ICAs) and middle cerebral arteries (MCAs) were measured using LKEB Automated Vessel Analysis (LAVA) software. Linear regression models were fitted to assess the association between brain arterial diameters and exposures. The R-squared was calculated to assess the extent of brain arterial diameter variation explained by the variables studied. Results: The sample included 6,269 participants (mean age 68 years; 42% men). Unilateral fPCA was found in 12.6% and bilateral fPCAs in 3.0%. Older age, male sex and TCV were uniformly correlated with larger BA, ICA and MCA diameters (Table). Unilateral and bilateral fPCAs showed a negative correlation with BA diameter and a positive correlation with ICA diameters in a dose-dependent manner. Models fitted for age, sex, TCV, and fPCA presence explained on average 24, 16 and 12 % of the BA, ICAs and MCA diameter interindividual variation, respectively. Using height instead of TCV decreased the R-squared by 2% on average. Conclusions: In this pooled analysis of cohort studies, we found brain arterial diameters consistently correlate with age, sex, TCV and fPCA presence. These factors should be considered to define abnormal arterial diameter cut-offs across populations. If resources are limited or if bedside applicability is desired, height could be used instead of TCV.Academi

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

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. 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. 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. Brain arterial diameters correlated with age, sex, TCV, and fPCA. These factors should be considered when defining abnormal diameter cutoffs across populations