Rationale

Little research has evaluated the life course drivers of cognitive aging in South Africa.

Objectives

We 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.

Methods

Data 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.

Results

Poor 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).

Conclusion

In 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.

Introduction

We evaluated whether competing risk of death or selective survival could explain the reported inverse association between cancer history and dementia incidence (incidence rate ratio [IRR] ≈ 0.62-0.85).

Methods

A multistate simulation model of a cancer- and dementia-free cohort of 65-year-olds was parameterized with real-world data (cancer and dementia incidence, mortality), assuming no effect of cancer on dementia (true IRR = 1.00). To introduce competing risk of death, cancer history increased mortality. To introduce selective survival, we included a factor (prevalence ranging from 10% to 50%) that reduced cancer mortality and dementia incidence (IRRs ranged from 0.30 to 0.90). We calculated IRRs for cancer history on dementia incidence in the simulated cohorts.

Results

Competing risk of death yielded unbiased cancer-dementia IRRs. With selective survival, bias was small (IRRs = 0.89 to 0.99), even under extreme scenarios.

Discussion

The bias induced by selective survival in simulations was too small to explain the observed inverse cancer-dementia link, suggesting other mechanisms drive this association.

Cancer diagnoses are associated with better long-term memory in older adults, possibly reflecting a range of social confounders that increase cancer risk but improve memory. We used spouse's memory as a negative control outcome to evaluate this possible confounding, since spouses share social characteristics and environments, and individuals' cancers are unlikely to cause better memory among their spouses. We estimated the association of an individual's incident cancer diagnosis (exposure) with their own (primary outcome) and their spouse's (negative control outcome) memory decline in 3601 couples from 1998 to 2014 in the Health and Retirement Study, using linear mixed-effects models. Incident cancer predicted better long-term memory for the diagnosed individual. We observed no association between an individual's cancer diagnosis and rate of spousal memory decline. This negative control study suggests that the inverse association between incident cancer and rate of memory decline is unlikely to be attributable to social/behavioral factors shared between spouses.

Background

Cancer is inversely associated with dementia. Using simulations, we examined whether this inverse association may be explained by dementia diagnosis timing, including death before dementia diagnosis and differential diagnosis patterns by cancer history.

Methods

We used multistate Markov simulation models to generate cohorts 65 years of age and free of cancer and dementia at baseline; follow-up for incident cancer (all cancers, breast, prostate, and lung cancer), dementia, dementia diagnosis among those with dementia, and death occurred monthly over 30 years. Models specified no true effect of cancer on dementia, and used age-specific transition rates calibrated to U.S. population and cohort data. We varied the average lapse between dementia onset and diagnosis, including nondifferential and differential delays by cancer history, and examined observed incidence rate ratios (IRRs) for the effect of cancer on dementia diagnosis.

Results

Nondifferential dementia diagnosis delay introduced minimal bias (IRRs = 0.98-1.02) for all cancer, breast, and prostate models and substantial bias (IRR = 0.78) in lung cancer models. For the differential dementia diagnosis delay model of all cancer types combined, simulation scenarios with ≥20% lower dementia diagnosis rate (additional 4.5-month delay) in those with cancer history versus without yielded results consistent with literature estimates. Longer dementia diagnosis delays in those with cancer and higher mortality in those with cancer and dementia yielded more bias.

Conclusions

Delays in dementia diagnosis may play a role in the inverse cancer-dementia relationship, especially for more fatal cancers, but moderate differential delays in those with cancer were needed to fully explain the literature-reported IRRs.

Objectives

To characterize the extent to which brief cognitive assessments administered in the population-representative U.S. Health and Retirement Study (HRS) and its International Partner Studies can be considered to be measuring a single, unidimensional latent cognitive function construct.

Methods

Cognitive function assessments were administered in face-to-face interviews in 12 studies in 26 countries (N = 155,690), including the U.S. HRS and selected International Partner Studies. We used the time point of the first cognitive assessment for each study to minimize differential practice effects across studies and documented cognitive test item coverage across studies. Using confirmatory factor analysis models, we estimated single-factor general cognitive function models and bifactor models representing memory-specific and nonmemory-specific cognitive domains for each study. We evaluated model fits and factor loadings across studies.

Results

Despite relatively sparse and inconsistent cognitive item coverage across studies, all studies had some cognitive test items in common with other studies. In all studies, the bifactor models with a memory-specific domain fit better than single-factor general cognitive function models. The data fit the models at reasonable thresholds for single-factor models in 6 of the 12 studies and for the bifactor models in all 12 of the 12 studies.

Discussion

The cognitive assessments in the U.S. HRS and its International Partner Studies reflect comparable underlying cognitive constructs. We discuss the assumptions underlying our methods, present alternatives, and future directions for cross-national harmonization of cognitive aging data.

Background

Intersectionality has rarely been considered in research studies of cognitive ageing. We investigated whether life-course financial mobility is differentially associated with later-life memory function and decline across intersectional identities defined by gender, and race and ethnicity.

Methods

Data were from two harmonised multiethnic cohorts (the Kaiser Healthy Aging and Diverse Life Experiences cohort and the Study of Healthy Aging in African Americans cohort) in northern California, USA (n=2340). Life-course financial mobility, measured using a combination of self-reported financial capital measures in childhood (from birth to age 16 years) and later adulthood (at the cohort baseline) was defined as consistently high, upwardly mobile, downwardly mobile, or consistently low. We clustered individuals into 32 strata representing intersectional identities defined by life-course financial mobility combined with gender, and race and ethnicity. Verbal episodic memory was assessed using the Spanish and English Neuropsychological Assessment Scales over four waves from 2017 to 2023. Adjusted mixed-effects linear regression models were estimated with and without fixed effects of gender, race and ethnicity, and financial mobility, to evaluate whether the random effects of the intersectional identity strata contributed variance to memory beyond individual fixed effects.

Findings

Mean age was 73·6 years (SD 8·1). Of 2340 individuals, 1460 (62·4%) were women, 880 (37·6%) were men, 388 (16·6%) were Asian, 1136 (48·5%) were Black, 334 (14·3%) were Latinx, and 482 (20·6%) were White. Consistently low and downwardly mobile financial capital were strongly negatively associated with later-life memory at baseline (-0·162 SD units [95% CI -0·273 to -0·051] for consistently low and -0·171 [-0·250 to -0·092] for downwardly mobile), but not rate of change over time. Intersectional identities contributed 0·2% of memory variance after accounting for the fixed effects of gender, race and ethnicity, and financial mobility.

Interpretation

Consistently low and downward life-course financial mobility are associated with lower later-life memory function. Intersectional identities defined by financial mobility in addition to gender, and race and ethnicity, contribute negligible additional variance to later-life memory in this study setting.

Funding

US National Institute on Aging, US National Institutes of Health.

Background

As global populations age, cross-national comparisons of cognitive health and dementia risk are increasingly valuable. It remains unclear, however, whether country-level differences in cognitive function are attributable to population differences or bias due to incommensurate measurement. To demonstrate an effective method for cross-national comparison studies, we aimed to statistically harmonize measures of episodic memory and language function across two population-based cohorts of older adults in the United States (HRS HCAP) and India (LASI-DAD).

Methods

Data for 3,496 HRS HCAP (≥65 years) and 3,152 LASI-DAD (≥60 years) participants were statistically harmonized for episodic memory and language performance using confirmatory factor analysis (CFA) methods. Episodic memory and language factor variables were investigated for differential item functioning (DIF) and precision.

Results

CFA models estimating episodic memory and language domains based on a priori adjudication of comparable items fit the data well. DIF analyses revealed that four out of ten episodic memory items and five out of twelve language items measured the underlying construct comparably across samples. DIF-modified episodic memory and language factor scores showed comparable patterns of precision across the range of the latent trait for each sample.

Conclusions

Harmonization of cognitive measures will facilitate future investigation of cross-national differences in cognitive performance and differential effects of risk factors, policies, and treatments, reducing study-level measurement and administrative influences. As international aging studies become more widely available, advanced statistical methods such as those described in this study will become increasingly central to making universal generalizations and drawing valid conclusions about cognitive aging of the global population.