Does neighborhood socioeconomic status alter memory change associated with a cancer diagnosis? Preliminary evidence from the US Health and Retirement Study.

BACKGROUND: Neighborhood disadvantage has been linked to cognitive impairment, but little is known about the effect of neighborhood disadvantage on long-term cancer-related memory decline. METHODS: Incident cancer diagnosis and memory (immediate and delayed recall, combined with proxy-reported memory) were assessed at biennial interviews in the U.S. Health and Retirement Study (N=13,293, 1998-2016). Neighborhood disadvantage was measured using the National Neighborhood Data Archive disadvantage index, categorized into tertiles (T1: least disadvantaged - T3: most disadvantaged). Linear mixed-effects models estimated the standardized memory trajectories in participants with or without cancer, by neighborhood disadvantage. RESULTS: Living in more disadvantaged neighborhoods was associated with worse mean memory function and steeper memory declines, regardless of cancer status. An incident cancer diagnosis was associated with an acute memory drop for those living in least disadvantaged neighborhoods but not more disadvantaged neighborhoods (T1: -0.05, 95% CI: -0.08, -0.01; T3: -0.13, 95% CI: -0.06, 0.03). Cancer survivors in the least disadvantaged neighborhoods had a slight memory advantage in the years prior to diagnosis (T1: 0.09, 95% CI: 0.04, 0.13) and after diagnosis (T1: 0.07, 95% CI: 0.01, 0.13). CONCLUSIONS: An incident cancer diagnosis among those living in the least disadvantaged neighborhoods was associated with an acute memory drop at the time of diagnosis and a long-term memory advantage before and after diagnosis compared to cancer-free individuals in similar neighborhoods. IMPACT: These findings could inform interventions to promote cancer survivor's long-term aging. Future studies should investigate the social and biological pathways through which nSES could influence cancer-related memory changes.

The association of pre-cancer diagnosis cardiovascular risk factors with memory aging after a cancer diagnosis, overall and by race/ethnicity.

PURPOSE: Cardiovascular risk factors (CVRFs) are associated with increased risk for cognitive impairment and decline in the general population, but less is known about how CVRFs might influence cognitive aging among older cancer survivors. We aimed to determine how CVRFs prior to a cancer diagnosis affect post-cancer diagnosis memory aging, compared to cancer-free adults, and by race/ethnicity. METHODS: Incident cancer diagnoses and memory (immediate and delayed recall) were assessed biennially in the US Health and Retirement Study (N = 5,736, 1998-2018). CVRFs measured at the wave prior to a cancer diagnosis included self-reported cigarette smoking, obesity, diabetes, heart disease, hypertension, and stroke. Multivariable-adjusted linear mixed-effects models evaluated the rate of change in standardized memory score (SD/decade) post-cancer diagnosis for those with no, medium, and high CVRFs, compared to matched cancer-free adults, overall and stratified by sex and race/ethnicity. RESULTS: Higher number of CVRFs was associated with worse baseline memory for both men and women, regardless of cancer status. Cancer survivors with medium CVRFs had slightly slower rates of memory decline over time relative to cancer-free participants (0.04 SD units/decade [95% CI: 0.001, 0.08]). Non-Hispanic Black (NHB) and Hispanic cancer-free participants and cancer survivors had worse baseline memory than their Non-Hispanic White (NHW) counterparts. CONCLUSIONS: CVRFs were associated with worse baseline memory function, but not decline, for cancer-free adults and cancer survivors. Racial disparities were largely similar between cancer survivors and cancer-free adults. IMPLICATIONS FOR CANCER SURVIVORS: These findings may inform hypotheses about pre-diagnosis multimorbidity and cognitive aging of cancer survivors from diverse groups.

The Impact of Old Age Pension Eligibility on Alcohol Consumption: Evidence From a Population-Based Study in Rural South Africa.

Background and Objectives: Alcohol causes more than 3 million deaths a year globally and contributes to over 5% of global disease and injury. Heavy drinking and alcohol use disorders among older adults have increased in the last 10-15 years. For individuals living in low-income countries, where wages are low and unemployment is high, old age pensions may provide a significant increase in household income. In turn, the receipt of supplementary income may increase spending on alcohol. Earlier life factors and socioeconomic status may affect alcohol consumption, making it difficult to directly assess the impact of income on alcohol consumption. This study reduces the potential for endogeneity with other life factors by exploiting an exogenous increase in income from old age pensions to isolate the impact of extra income on alcohol consumption for older adults. Research Design and Methods: We used a regression discontinuity design to assess changes in drinking patterns among rural, low-income adults who were 3 years below and 3 years above South Africa's Old Age Pension Grant eligibility threshold (age 60). We assessed this relationship separately by gender and for employed and unemployed individuals. Results: We observed a significantly increased alcohol use associated with the Old Age Pension Grant eligibility for employed men (ß = 4.57, 95% confidence interval: 1.72-12.14). We did not observe this same trend for unemployed men or for women. Discussion and Implications: The analysis in this study indicates that increased income from reaching the pension eligibility age may contribute to an increase in alcohol consumption for employed men. Interventions, such as informational campaigns on the risks of alcohol consumption for older adults or age-appropriate health interventions to help individuals reduce alcohol consumption, targeted around the time of pension eligibility age for employed men may help to reduce alcohol-related harms in low-income, rural sub-Saharan African settings.

The Impact of the Older Person's Grant Expansion on Hypertension Among Older Men in Rural South Africa: Findings From the HAALSI Cohort.

Background and Objectives: Hypertension is a major modifiable contributor to disease burden in sub-Saharan Africa. We exploited an expansion to age eligibility for men in South Africa's noncontributory public pension to assess the impact of pension eligibility on hypertension in a rural, low-income South African setting. Research Design and Methods: Data were from 1 247 men aged ≥60 in the population-representative Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa in 2014/2015. We identified cohorts of men from 0 (controls, aged ≥65 at pension expansion) through 5 years of additional pension eligibility based on their birth year. Using the modified Framingham Heart Study hypertension risk prediction model, and the Wand et al. model modified for the South African population, we estimated the difference in the probabilities of hypertension for men who benefitted from the pension expansion relative to the control. We conducted a negative control analysis among older women, who were not eligible for pension expansion, to assess the robustness of our findings. Results: Older men with 5 additional years of pension eligibility had a 6.9-8.1 percentage point greater probability of hypertension than expected without the pension expansion eligibility. After accounting for birth cohort effects through a negative control analysis involving older women reduced estimates to a 3.0-5.2 percentage point greater probability of hypertension than expected. We observed a mean 0.2 percentage point increase in the probability of hypertension per additional year of pension eligibility, but this trend was not statistically significant. Discussion and Implications: Although the Older Person's Grant is important for improving the financial circumstances of older adults and their families in South Africa, expanded pension eligibility may have a small, negative short-term effect on hypertension among older men in this rural, South African setting.

Child support grant expansion and cognitive function among women in rural South Africa: Findings from a natural experiment in the HAALSI cohort.

BACKGROUND: Cash transfers are a promising but understudied intervention that may protect cognitive function in adults. Although South Africa has a rapidly ageing population, little is known about the nature of association between cash transfers and cognitive function in this setting. OBJECTIVES: We leveraged age-eligibility expansions to South Africa's Child Support Grant (CSG) to investigate the association between duration of CSG eligibility and cognitive function of biological mothers of child beneficiaries in South Africa. METHODS: We analysed 2014/2015 baseline data from 944 women, aged 40-59 years with at least one CSG-eligible child, enrolled in the population-representative HAALSI cohort in Agincourt, South Africa. Duration of CSG eligibility for each mother was calculated based on the birth dates of all their children and the CSG age-eligibility expansion years (2003-2012). Cognitive function was measured using a cognitive battery administered at the HAALSI baseline interview. Linear regression was used to estimate the association between duration of CSG eligibility, dichotomized as low (≤10 years) and high (>10 years) eligibility, and cognitive function z-scores of the mothers. RESULTS: High vs. low duration of CSG eligibility, was associated with higher cognitive function z-scores in the full sample [ß: 0.15 SD units; 95% CI: 0.04, 0.26; p-value = 0.01]. In mothers with one to four lifetime children, but not five or more, high vs. low duration of CSG eligibility, was associated with higher cognitive function z-scores [ß: 0.19 SD units; 95% CI: 0.05, 0.34, p-value = 0.02]. CONCLUSION: Government cash transfers given to support raising children may confer substantial protective effects on the subsequent cognitive function of mothers. Further studies are needed to understand how parity may influence this relationship. Our findings bring evidence to policymakers for designing income supplementation programmes to promote healthy cognitive ageing in low-income settings.

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.

Educational Attainment and Later-Life Cognitive Function in High- and Middle-Income Countries: Evidence From the Harmonized Cognitive Assessment Protocol.

OBJECTIVES: Identifying social policies that can promote cognitive health is crucial for reducing the global burden of dementia. We evaluated the importance of educational attainment for later-life cognitive function in various social and geographic settings. METHODS: Using harmonized data for individuals aged ≥65 years from the United States Health and Retirement Study (HRS) and its international partner studies in England, Mexico, China, and India, and each study's respective Harmonized Cognitive Assessment Protocol (HCAP), we conducted a cross-national comparative study to examine the role of educational attainment in later-life cognitive function across countries (n = 14,980, 2016-2019). We used multivariable-adjusted regression to estimate associations between educational attainment and harmonized global cognitive function scores. RESULTS: In Mexico, China, and India, the general cognitive function scores on average are approximately one standard deviation of the HRS-HCAP cognitive function score distribution lower compared to the United States and England, paralleling patterns of educational attainment across countries. In all countries, higher educational attainment was associated with progressively higher later-life cognitive function scores. Population-level differences in educational attainment explained about 50%-90% of the observed differences in cognitive function scores across countries. DISCUSSION: The relationship between education and later-life cognitive function across social and geographic contexts underscores the crucial role of education to promote cognitive health and reduce dementia risk. Continual improvement of educational attainment in low- and middle-income settings may yield a significant pay-off in later-life cognitive health.

Cross-national comparisons of later-life cognitive function using data from the Harmonized Cognitive Assessment Protocol (HCAP): Considerations and recommended best practices.

The Harmonized Cognitive Assessment Protocol (HCAP) is a major innovation that provides, for the first time, harmonized data for cross-national comparisons of later-life cognitive functions that are sensitive to linguistic, cultural, and educational differences across countries. However, cognitive function does not lend itself to direct comparison across diverse populations without careful consideration of the best practices for such comparisons. This perspective discusses theoretical and methodological considerations and offers a set of recommended best practices for conducting cross-national comparisons of risk factor associations using HCAP data. Because existing and planned HCAP studies provide cognition data representing an estimated 75% of the global population ≥65 years of age, these recommended best practices will support high-quality comparative analyses of cognitive aging around the world. The principles described in this perspective are applicable to any researcher aiming to integrate or compare harmonized data on cognitive outcomes and their risk and protective factors across diverse populations.

Does education moderate gender disparities in later-life memory function? A cross-national comparison of harmonized cognitive assessment protocols in the United States and India.

INTRODUCTION: We compared gender disparities in later-life memory, overall and by education, in India and the United States (US). METHODS: Data (N = 7443) were from harmonized cognitive assessment protocols (HCAPs) in the Longitudinal Aging Study of India-Diagnostic Assessment of Dementia (LASI-DAD; N = 4096; 2017-19) and US Health and Retirement Study HCAP (HRS-HCAP; N = 3347; 2016-17). We derived harmonized memory factors from each study using confirmatory factor analysis. We used multivariable-adjusted linear regression to compare gender disparities in memory function between countries, overall and by education. RESULTS: In the United States, older women had better memory than older men (0.28 SD-unit difference; 95% CI: 0.22, 0.35). In India, older women had worse memory than older men (-0.15 SD-unit difference; 95% CI: -0.20, -0.10), which attenuated with increasing education and literacy. CONCLUSION: We observed gender disparities in memory in India that were not present in the United States, and which dissipated with education and literacy.

Association of cancer history with structural brain aging markers of Alzheimer's disease and related dementias risk.

INTRODUCTION: Cancer survivors are less likely than comparably aged individuals without a cancer history to develop Alzheimer's disease and related dementias (ADRD). METHODS: In the UK Biobank, we investigated associations between cancer history and five structural magnetic resonance imaging (MRI) markers for ADRD risk, using linear mixed-effects models to assess differences in mean values and quantile regression to examine whether associations varied across the distribution of MRI markers. RESULTS: Cancer history was associated with smaller mean hippocampal volume (b = -19 mm3 , 95% CI = -36, -1) and lower mean cortical thickness in the Alzheimer's disease signature region (b = -0.004 mm, 95% CI = -0.007, -0.000). Quantile regressions indicated individuals most vulnerable to ADRD were more affected by cancer history. DISCUSSION: Some brain MRI markers associated with ADRD risk were elevated in adults with a history of cancer. The magnitude of the adverse associations varied across quantiles of neuroimaging markers, and the pattern suggests possible harmful associations for individuals already at high ADRD risk. HIGHLIGHTS: We found no evidence of an inverse association between cancer history and ADRD-related neurodegeneration. Cancer history was associated with smaller mean hippocampal volume and lower mean cortical thickness in the Alzheimer's disease signature region. Quantile regressions indicated individuals most vulnerable to ADRD were more affected by cancer history.

Lifetime occupational skill and later-life cognitive function among older adults in the United States, Mexico, India, and South Africa.

INTRODUCTION: We conducted a cross-national comparison of the association between main lifetime occupational skills and later-life cognitive function across four economically and socially distinct countries. METHODS: Data were from population-based studies of aging and their Harmonized Cognitive Assessment Protocols (HCAPs) in the US, South Africa, India, and Mexico (N = 10,037; Age range: 50 to 105 years; 2016 to 2020). Main lifetime occupational skill was classified according to the International Standard Classification of Occupations. Weighted, adjusted regression models estimated pooled and country-specific associations between main lifetime occupational skill and later-life general cognitive function in men and women. RESULTS: We observed positive gradients between occupational skill and later-life cognitive function for men and women in the US and Mexico, a positive gradient for women but not men in India, and no association for men or women in South Africa. DISCUSSION: Main lifetime occupations may be a source of later-life cognitive reserve, with cross-national heterogeneity in this association. HIGHLIGHTS: No studies have examined cross-national differences in the association of occupational skill with cognition. We used data from Harmonized Cognitive Assessment Protocols in the US, Mexico, India, and South Africa. The association of occupational skill with cognitive function varies by country and gender.

Spousal Concordance of Hypertension Among Middle-Aged and Older Heterosexual Couples Around the World: Evidence From Studies of Aging in the United States, England, China, and India.

BACKGROUND: Health concordance within couples presents a promising opportunity to design interventions for disease management, including hypertension. We compared the concordance of prevalent hypertension within middle-aged and older heterosexual couples in the United States, England, China, and India. METHODS AND RESULTS: Cross-sectional dyadic data on heterosexual couples were used from contemporaneous waves of the HRS (US Health and Retirement Study, 2016/17, n=3989 couples), ELSA (English Longitudinal Study on Aging, 2016/17, n=1086), CHARLS (China Health and Retirement Longitudinal Study, 2015/16, n=6514), and LASI (Longitudinal Aging Study in India, 2017/19, n=22 389). Concordant hypertension was defined as both husband and wife in a couple having hypertension. The prevalence of concordant hypertension within couples was 37.9% (95% CI, 35.8-40.0) in the United States, 47.1% (95% CI, 43.2-50.9) in England, 20.8% (95% CI, 19.6-21.9) in China, and 19.8% (95% CI, 19.0-20.5) in India. Compared with wives married to husbands without hypertension, wives married to husbands with hypertension were more likely to have hypertension in the United States (prevalence ratio, 1.09 [95% CI, 1.01- 1.17), England (prevalence ratio, 1.09, 95% CI, 0.98-1.21), China (prevalence ratio, 1.26 [95% CI, 1.17-1.35), and India (prevalence ratio, 1.19 [95% CI, 1.15-1.24]). Within each country, similar associations were observed for husbands. Across countries, associations in the United States and England were similar, whereas they were slightly larger in China and India. CONCLUSIONS: Concordance of hypertension within heterosexual couples was consistently observed across these 4 socially and economically diverse countries. Couple-centered interventions may be an efficient strategy to prevent and manage hypertension in these countries.

Association of cumulative loneliness with all-cause mortality among middle-aged and older adults in the United States, 1996 to 2019.

Loneliness is a growing public health concern worldwide. We characterized the association between cumulative loneliness and subsequent all-cause mortality, using data from 9,032 participants aged 50+ in the population-based US Health and Retirement Study (HRS) from 1996 to 2019. Loneliness status (yes; no) was measured biennially from 1996 to 2004, and we categorized the experience of cumulative loneliness over the 8-y period as never, one time point, two time points, and ≥three time points. A multivariable-adjusted age-stratified Cox proportional hazards regression model was fitted to examine the association between cumulative loneliness from 1996 to 2004 and all-cause mortality from 2004 to 2019. Excess deaths due to each category of cumulative loneliness were calculated. Compared to those who never reported loneliness from 1996 to 2004, participants experiencing loneliness at one time point, two time points, and ≥three time points respectively had 1.05 (95% CI: 0.96 to 1.15), 1.06 (95% CI: 0.95 to 1.19), and 1.16 (95% CI: 1.02 to 1.33) times higher hazards of mortality from 2004 to 2019 (P trend = 0.01). These results correspond to 106 (95% CI: 68 to 144), 202 (95% CI: 146 to 259), and 288 (95% CI: 233 to 343) excess deaths per 10,000 person-years, for those experiencing loneliness at each of one, two, or ≥three time points from 1996 to 2004. Cumulative loneliness in mid-to-later life may thus be a mortality risk factor with a notable impact on excess mortality. Loneliness may be an important target for interventions to improve life expectancy in the United States.

Harmonisation of later-life cognitive function across national contexts: results from the Harmonized Cognitive Assessment Protocols.

BACKGROUND: The Harmonized Cognitive Assessment Protocol (HCAP) is an innovative instrument for cross-national comparisons of later-life cognitive function, yet its suitability across diverse populations is unknown. We aimed to harmonise general and domain-specific cognitive scores from HCAP studies across six countries, and evaluate reliability and criterion validity of the resulting harmonised scores. METHODS: We statistically harmonised general and domain-specific cognitive function scores across publicly available HCAP partner studies in China, England, India, Mexico, South Africa, and the USA conducted between October, 2015 and January, 2020. Participants missing all cognitive test items in a given HCAP were excluded. We used an item banking approach that leveraged common cognitive test items across studies and tests that were unique to studies. We generated harmonised factor scores to represent a person's relative functioning on the latent factors of general cognitive function, memory, executive function, orientation, and language using confirmatory factor analysis. We evaluated the marginal reliability, or precision, of the factor scores using test information plots. Criterion validity of factor scores was assessed by regressing the scores on age, gender, and educational attainment in a multivariable analysis adjusted for these characteristics. FINDINGS: We included 21 144 participants from the six HCAP studies of interest (11 480 women [54·3%] and 9664 [45·7%] men), with a median age of 69 years (IQR 64-76). Confirmatory factor analysis models of cognitive function in each country fit well: 31 (88·6%) of 35 models had adequate or good fit to the data (comparative fit index ≥0·90, root mean square error of approximation ≤0·08, and standardised root mean residual ≤0·08). Marginal reliability of the harmonised general cognitive function factor was high (>0·9) for 19 044 (90·1%) of 21 144 participant scores across the six countries. Marginal reliability of the harmonised factor was above 0·85 for 19 281 (91·2%) of 21 142 participant factor scores for memory, 7805 (41·0%) of 19 015 scores for executive function, 3446 (16·3%) of 21 103 scores for orientation, and 4329 (20·5%) of 21 113 scores for language. In each country, general cognitive function scores were lower with older age and higher with greater levels of educational attainment. INTERPRETATION: We statistically harmonised cognitive function measures across six large population-based studies of cognitive ageing. These harmonised cognitive function scores empirically reflect comparable domains of cognitive function among older adults across the six countries, have high reliability, and are useful for population-based research. This work provides a foundation for international networks of researchers to make improved inferences and direct comparisons of cross-national associations of risk factors for cognitive outcomes in pooled analyses. FUNDING: US National Institute on Aging.

The Joys and Stresses of Social Relationships and the Effect on Resiliency During the Covid-19 Pandemic: A National Survey of US Older Adults.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic placed unprecedented stress on older adults. Resiliency could mitigate deleterious effects of pandemic stressors. We described trends in resilience among US adults aged 50-80 years approximately one and half years after the onset of the pandemic, compared with before the pandemic, and evaluated associations between relationships and resilience. RESEARCH DESIGN AND METHODS: Data were from the National Poll on Healthy Aging (N=2,100) in August 2021. Respondents rated their resiliency as compared with before the pandemic (more, about the same, or less) and different types of relationships (spouse/partner, friends, neighbors) as sources of joy and/or stress during the pandemic (a lot, some, very little, and not at all). Multinomial logistic regressions (complete-case analysis) estimated the relationships between each joyful and stressful relationships and resiliency. RESULTS: Most participants reported feeling as resilient as before the pandemic (70.6%) with 14.5% feeling less resilient. More women than men felt less resilient than before the pandemic (16.7% vs. 12.8%, p=0.006). Feeling a lot of stress from one's spouse or neighbors was associated with increased likelihood of feeling less resilient than before the pandemic (OR=3.7; 95% CI: 1.8, 7.7 and OR=4.5; 95% CI: 1.5, 13.9, respectively) which was stronger among women (OR=15.1; 95% CI: 4.8, 45.6) than men (OR=1.03; 95% CI: 0.4, 2.7). DISCUSSION AND IMPLICATIONS: Social relationships may have been more important for women than for men in supporting resiliency during the pandemic. Understanding patterns of resiliency can help to inform policymaking and support the well-being of older adults.

Memory and language cognitive data harmonization across the United States and Mexico.

INTRODUCTION: We used cultural neuropsychology-informed procedures to derive and validate harmonized scores representing memory and language across population-based studies in the United States and Mexico. METHODS: Data were from the Health and Retirement Study Harmonized Cognitive Assessment Protocol (HRS-HCAP) and the Mexican Health and Aging Study (MHAS) Ancillary Study on Cognitive Aging (Mex-Cog). We statistically co-calibrated memory and language domains and performed differential item functioning (DIF) analysis using a cultural neuropsychological approach. We examined relationships among harmonized scores, age, and education. RESULTS: We included 3170 participants from the HRS-HCAP (Mage = 76.6 [standard deviation (SD): 7.5], 60% female) and 2042 participants from the Mex-Cog (Mage = 68.1 [SD: 9.0], 59% female). Five of seven memory items and one of twelve language items demonstrated DIF by study. Harmonized memory and language scores showed expected associations with age and education. DISCUSSION: A cultural neuropsychological approach to harmonization facilitates the generation of harmonized measures of memory and language function in cross-national studies. HIGHLIGHTS: We harmonized memory and language scores across studies in the United States and Mexico.A cultural neuropsychological approach to data harmonization was used.Harmonized scores showed minimal measurement differences between cohorts.Future work can use these harmonized scores for cross-national studies of Alzheimer's disease and related dementias.

The Mediating Roles of Neurobiomarkers in the Relationship Between Education and Late-Life Cognition.

BACKGROUND: The mediating roles of neuropathologies and neurovascular damage in the relationship between early-life education and later-life cognitive function are unknown. OBJECTIVE: To examine whether Alzheimer's and neurovascular biomarkers mediate the relationships between education and cognitive functions. METHODS: Data were from 537 adults aged 55-94 in the Alzheimer's Disease Neuroimaging Initiative 3. We tested whether the relationships between education (continuous, years) and cognitive function (memory, executive functioning, and language composites) were mediated by neuroimaging biomarkers (hippocampal volumes, cortical gray matter volumes, meta-temporal tau PET standard uptake value ratio, and white matter hyperintensity volumes). Models were adjusted for age, race, sex/gender, cardiovascular history, body mass index, depression, and Apolipoprotein E-ɛ4 status. RESULTS: Hippocampal volumes and white matter hyperintensities partially mediated the relationships between education and cognitive function across all domains (6.43% to 15.72% mediated). The direct effects of education on each cognitive domain were strong and statistically significant. CONCLUSIONS: Commonly measured neurobiomarkers only partially mediate the relationships between education and multi-domain cognitive function.

Association between cancer and dementia risk in the UK Biobank: evidence of diagnostic bias.

Epidemiological studies have identified an inverse association between cancer and dementia. Underlying methodological biases have been postulated, yet no studies have systematically investigated the potential for each source of bias within a single dataset. We used the UK Biobank to compare estimates for the cancer-dementia association using different analytical specifications designed to sequentially address multiple sources of bias, including competing risk of death, selective survival, confounding bias, and diagnostic bias. We included 140,959 UK Biobank participants aged ≥ 55 without dementia before enrollment and with linked primary care data. We used cancer registry data to identify cancer cases prevalent before UK Biobank enrollment and incident cancer diagnosed after enrollment. We used Cox models to evaluate associations of prevalent and incident cancer with all-cause dementia, Alzheimer's disease (AD), and vascular dementia. We used time-varying models to evaluate diagnostic bias. Over a median follow-up of 12.3 years, 3,310 dementia cases were diagnosed. All-site incident cancer was positively associated with all-cause dementia incidence (hazard ratio [HR] = 1.14, 95% CI: 1.02-1.29), but prevalent cancer was not (HR = 1.04, 95% CI: 0.92-1.17). Results were similar for vascular dementia. AD was not associated with prevalent or incident cancer. Dementia diagnosis was substantially elevated in the first year after cancer diagnosis (HR = 1.83, 95% CI: 1.42-2.36), after which the association attenuated to null, suggesting diagnostic bias. Following a cancer diagnosis, health care utilization or cognitive consequences of diagnosis or treatment may increase chance of receiving a dementia diagnosis, creating potential diagnostic bias in electronic health records-based studies.

Comparison of Particulate Air Pollution From Different Emission Sources and Incident Dementia in the US.

Importance: Emerging evidence indicates that exposure to fine particulate matter (PM2.5) air pollution may increase dementia risk in older adults. Although this evidence suggests opportunities for intervention, little is known about the relative importance of PM2.5 from different emission sources. Objective: To examine associations of long-term exposure of total and source-specific PM2.5 with incident dementia in older adults. Design, Setting, and Participants: The Environmental Predictors of Cognitive Health and Aging study used biennial survey data from January 1, 1998, to December 31, 2016, for participants in the Health and Retirement Study, which is a nationally representative, population-based cohort study in the US. The present cohort study included all participants older than 50 years who were without dementia at baseline and had available exposure, outcome, and demographic data between 1998 and 2016 (N = 27 857). Analyses were performed from January 31 to May 1, 2022. Exposures: The 10-year mean total PM2.5 and PM2.5 from 9 emission sources at participant residences for each month during follow-up using spatiotemporal and chemical transport models. Main Outcomes and Measures: The main outcome was incident dementia as classified by a validated algorithm incorporating respondent-based cognitive testing and proxy respondent reports. Adjusted hazard ratios (HRs) were estimated for incident dementia per IQR of residential PM2.5 concentrations using time-varying, weighted Cox proportional hazards regression models with adjustment for the individual- and area-level risk factors. Results: Among 27 857 participants (mean [SD] age, 61 [10] years; 15 747 [56.5%] female), 4105 (15%) developed dementia during a mean (SD) follow-up of 10.2 [5.6] years. Higher concentrations of total PM2.5 were associated with greater rates of incident dementia (HR, 1.08 per IQR; 95% CI, 1.01-1.17). In single pollutant models, PM2.5 from all sources, except dust, were associated with increased rates of dementia, with the strongest associations for agriculture, traffic, coal combustion, and wildfires. After control for PM2.5 from all other sources and copollutants, only PM2.5 from agriculture (HR, 1.13; 95% CI, 1.01-1.27) and wildfires (HR, 1.05; 95% CI, 1.02-1.08) were robustly associated with greater rates of dementia. Conclusion and Relevance: In this cohort study, higher residential PM2.5 levels, especially from agriculture and wildfires, were associated with higher rates of incident dementia, providing further evidence supporting PM2.5 reduction as a population-based approach to promote healthy cognitive aging. These findings also indicate that intervening on key emission sources might have value, although more research is needed to confirm these findings.

Negative wealth shocks in later life and subsequent cognitive function in older adults in China, England, Mexico, and the USA, 2012-18: a population-based, cross-nationally harmonised, longitudinal study.

BACKGROUND: Household wealth is positively related to cognitive health outcomes in later life. However, the association between negative wealth shocks and cognitive function in later life, and whether this association might differ across countries at different levels of economic development, is unclear. We aimed to investigate whether negative wealth shocks in later life are associated with cognitive function in older adults in China, England, Mexico, and the USA, and whether this association is modified by country income level. METHODS: For this population-based, cross-nationally harmonised, longitudinal study, data were analysed from core interviews of the population-based US Health and Retirement Study (2012 and 2016) and its partner studies in China (the China Health and Retirement Longitudinal Study; 2015 and 2018), England (the English Longitudinal Study of Ageing; 2012 and 2016), and Mexico (Mexican Health and Aging Study; 2012 and 2015-16), and their respective Harmonized Cognitive Assessment Protocols (HCAPs). Negative wealth shocks over the follow-up periods of the respective cohorts were defined in two ways: an extreme loss of 75% or greater from the baseline amount of wealth, and a decline in within-population wealth quintile rank. The primary outcome was the harmonised general cognitive function (GCF) factor score, which was constructed with factor analysis on the HCAP neuropsychological assessments of memory, orientation, attention, executive function, and verbal fluency performance (mean 0; SD 1). We used sampling-weighted, multivariable-adjusted linear models to examine associations. FINDINGS: Data from 9465 participants were included in this analysis: 3796 from China, 1184 from England, 1193 from Mexico, and 3292 from the USA. The mean baseline age of participants was 68·5 (SD 5·4) years in China (49·8% women), 72·0 (7·0) years in England (54·6% women), 70·6 (6·8) years in Mexico (55·1% women), and 72·7 (7·5) years in the USA (60·4% women). A wealth loss of 75% or greater was negatively associated with subsequent cognitive function in the USA (ß -0·16 SD units; 95% CI -0·29 to -0·04) and China (-0·14; -0·21 to -0·07), but not in England (-0·01; -0·24 to 0·22) or Mexico (-0·11; -0·24 to 0·03). Similarly, within-population wealth quintile rank declines were negatively associated with subsequent cognitive function in the USA (ß -0·07 per quintile rank decline; 95% CI -0·11 to -0·03) and China (ß -0·07; -0·09 to -0·04), but not in England (-0·05; -0·11 to 0·01) or Mexico (-0·03; -0·07 to 0·01). INTERPRETATION: The impact of wealth shocks in later life on subsequent lower level of cognitive function of older adults in China, England, Mexico, and the USA differed across macro-level socioeconomic structures. These findings suggest that government policies and social safety nets in countries with different levels of economic development might have a role in protecting older adults from adverse health effects of wealth losses in later life. FUNDING: US National Institute on Aging, US National Institutes of Health.