Subsequent Cognitive Function Research Articles

A developmental neurotoxicity adverse outcome pathway (DNT-AOP) with voltage gate sodium channel (VGSC) inhibition as a molecular initiating event (MiE).

The adverse outcome pathway (AOP) framework serves as a practical tool for organising scientific knowledge that can be used to infer cause-effect relationships between stressor events and toxicity outcomes in intact organisms. However, a major challenge in the broader application of the AOP concept within regulatory toxicology is the development of a robust AOPs that can withstand peer review and acceptance. This is mainly due to the considerable amount of work required to substantiate the modular units of a complete AOP, which can take years from inception to completion. The methodology used here consisted of an initial assessment of a single chemical hazard using the Integrated Approach to Testing and Assessment (IATA) framework. An evidence-based approach was then used to gather empirical evidence combining systematic literature review methods with expert knowledge to ensure the effectiveness of the AOP development methodology. The structured framework used assured transparency, objectivity and comprehensiveness, and included expert knowledge elicitation for the evaluation of key event relationships (KERs). This stepwise approach led to the development of an AOP that begins with binding of chemicals to Voltage Gate Sodium Channels (VGSC/Nav) during mammalian development leading to adverse consequences in neurodevelopment evidenced as deficits in cognitive functions. Disruption of the formation of precise neural circuits by alterations in VGSC kinetics during the perinatal stages of brain development may also underlie neurodevelopmental disorders. Gaps in our understanding include the specific critical developmental windows and the quantitative relationship of binding to VGSC and subsequent disruption and cognitive function. Despite the limited quantitative information at all KER levels, regulatory applications of this AOP for DNT assessment have been identified.

Cross-sectional and longitudinal associations between late-life depressive symptoms and cognitive deficits: 20-year follow-up of the Kuakini Honolulu-Asia aging study

ObjectiveTo examine depressed affect, somatic complaints, and positive affect as longitudinal predictors of fluid, crystallized and global cognitive performance in the Kuakini Honolulu-Asia Aging Study (HAAS), a large prospective cohort study of Japanese-American men. MethodsWe assessed 3,088 dementia-free Kuakini-HAAS participants aged 71–93 (77.1 ± 4.2) years at baseline (1991–1993). Depressive symptoms were evaluated by the Center for Epidemiologic Studies Depression (CES-D) Scale. Baseline CES-D depression subscales (depressed and positive affects; somatic complaints) were computed. The Cognitive Abilities Screening Instrument (CASI) measured cognitive performance on a 100-point scale; fluid and crystallized cognitive abilities were derived from CASI factor analysis. Cognition was also evaluated at 4 follow-up examinations over a 20-year period. Multiple regression assessed baseline CES-D subscales as predictors of cognitive change. The baseline covariates analyzed were CASI, age, education, prevalent stroke, APOE ε4 presence, and the longevity-associated FOXO3 genotype. ResultsCross-sectionally, baseline CES-D subscales were related to cognitive measures; e.g., higher depressed affect was associated with lower crystallized ability (β = −0.058, p ≤ 0.01), and somatic complaints were linked to poorer fluid ability (β = −0.045, p ≤ 0.05) and to worse global cognitive function as measured by total CASI score (β = −0.038, p ≤ 0.05). However, depression subscales did not significantly or consistently predict fluid ability, crystallized ability, or global cognitive performance over time. ConclusionPsychological and physical well-being were associated with contemporaneous but not subsequent cognitive functioning. Assessment of depressive symptoms may identify individuals who are likely to benefit from interventions to improve mood and somatic health and thereby maintain or enhance cognition.

Social health and subsequent cognitive functioning in people aged 50 years and older: examining the mediating roles of depressive symptoms and inflammatory biomarkers in two European longitudinal studies

Social health markers, including marital status, contact frequency, network size, and social support, have been shown to be associated with cognition. However, the mechanisms underlying these associations remain poorly understood. We investigated whether depressive symptoms and inflammation mediated associations between social health and subsequent cognition. In the English Longitudinal Study of Ageing (ELSA), a nationally representative longitudinal study in England, UK, we sampled 7136 individuals aged 50 years or older living in private households without dementia at baseline or at the intermediate mediator assessment timepoint, who had recorded information on at least one social health marker and potential mediator. We used four-way decomposition to examine to what extent depressive symptoms, C-reactive protein, and fibrinogen mediated associations between social health and subsequent standardised cognition (verbal fluency and delayed and immediate recall), including cognitive change, with slopes derived from multilevel models (12-year slope). We examined whether findings were replicated in the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), a population-based longitudinal study in Sweden, in a sample of 2604 individuals aged 60 years or older living at home or in institutions in Kungsholmen (central Stockholm) without dementia at baseline or at the intermediate mediator assessment timepoint (6-year slope). Social health exposures were assessed at baseline, potential mediators were assessed at an intermediate timepoint (wave 2 in ELSA and 6-year follow-up in SNAC-K); cognitive outcomes were assessed at a single timepoint (wave 3 in ELSA and 12-year follow-up in SNAC-K), and cognitive change (between waves 3 and 9 in ELSA and between 6-year and 12-year follow-ups in SNAC-K). The study sample included 7136 participants from ELSA, of whom 3962 (55·5%) were women and 6934 (97·2%) were White; the mean baseline age was 63·8 years (SD 9·4). Replication analyses included 2604 participants from SNAC-K, of whom 1604 (61·6%) were women (SNAC-K did not collect ethnicity data); the mean baseline age was 72·3 years (SD 10·1). In ELSA, we found indirect effects via depressive symptoms of network size, positive support, and less negative support on subsequent verbal fluency, and of positive support on subsequent immediate recall (pure indirect effect [PIE] 0·002 [95% CI 0·001-0·003]). Depressive symptoms also partially mediated associations between less negative support and slower decline in immediate recall (PIE 0·001 [0·000-0·002]) and in delayed recall (PIE 0·001 [0·000-0·002]), and between positive support and slower decline in immediate recall (PIE 0·001 [0·000-0·001]). We did not observe mediation by inflammatory biomarkers. Findings of mediation by depressive symptoms in the association between positive support and verbal fluency and between positive support and change in immediate recall were replicated in SNAC-K. The findings of this study provide new insights into mechanisms linking social health with cognition, suggesting that associations between interactional aspects of social health, especially social support, and cognition are partly underpinned by depressive symptoms. EU Joint Programme-Neurodegenerative Disease Research (JPND) and Alzheimer's Society. For the Swedish translation of the abstract see Supplementary Materials section.

Social isolation and cognitive function in patients with schizophrenia: A two years follow-up study

Cognitive impairment is a core characteristic of schizophrenia. Social isolation has been linked to impaired cognitive function among the general population. In this longitudinal study, we examined the association between social isolation and cognitive function among inpatients with schizophrenia. Two waves of data (2019 and 2021) were collected from chronic psychiatric wards. A total of 166 inpatients completed all measurements at baseline and follow-up. Social isolation was measured by incorporating the frequency of social contact and participation, while cognitive functions were assessed by the Taiwan version of the Montreal Cognitive Assessment (MoCA-T). We used multiple linear regression to evaluate the link between baseline social isolation and cognitive function. For the total sample, social isolation was significantly related to poor language abilities (β = −0.17, p = 0.013) and delayed recall (β = −0.15, p = 0.023). Sex-stratified analysis showed that social isolation was significantly related to poor global cognitive function (β = −0.14, p = 0.021) and domain-specific cognitive functions including language abilities (β = −0.26, p = 0.003) and delayed recall (β = −0.19, p = 0.045) in male inpatients. No significant association was found between social isolation and global cognitive function or any cognitive domain (all ps > 0.05) for females. All associations were independent of loneliness and other covariates. These findings suggested that social isolation could predict poor subsequent cognitive function in inpatients with schizophrenia, especially in males. Interventions aimed at enhancing social connections could potentially improve cognitive function in this population.

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

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. 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. 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. High vs. low duration of CSG eligibility, was associated with higher cognitive function z-scores in the full sample [β: 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 [β: 0.19 SD units; 95% CI: 0.05, 0.34, p-value = 0.02]. 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.

SOCIAL INTEGRATION, COGNITION, AND FUNCTIONAL OUTCOME IN OLDER ADULTS FOLLOWING TRAUMATIC BRAIN INJURY

Abstract Persons aged 65 and older have the highest rates of traumatic brain injury (TBI), and this injury is known to be related to significant, persistent functional changes. What is not known is what factors may mediate these changes. The current study aimed 1) to examine interrelationships among social integration, functional outcome, and cognition in older adults at years 1, 2, and 5 post-traumatic brain injury (TBI) and 2) to examine if functional outcome mediates the concurrent and longitudinal relationships between social integration and cognitive function post-TBI in older adults. This is a secondary analysis of data obtained from Traumatic Brain Injury Model System National Database (TBIMS-NDB). Included subjects from the database were persons aged 65 years and older at the time of injury (N=1469). We used longitudinal mediation analysis to address study aims. We found that social integration had a direct effect on functional outcome and cognition at 1, 2, and 5-years post-TBI. Functional outcome had a positive direct effect on concurrent cognitive function. Regarding mediation, social integration and cognition were mediated by concurrent functional outcome. However, there were no significant mediating effects of concurrent functional outcome on concurrent social integration or subsequent cognitive function. Our findings suggest there are positive relationships between social integration, functional outcome, and cognition over time. With a better understanding of these interrelationships, tailored interventions that target social integration, such as activities fostering a sense of belonging in the community and cultural diversity programs may promote improved functional and cognitive outcomes.

THE DYNAMIC AND RECIPROCAL RELATIONSHIP BETWEEN PERCEIVED DISCRIMINATION AND COGNITIVE FUNCTION IN LATER LIFE

Abstract Studies have suggested that perceived discrimination is a potentially modifiable risk factor for cognitive health in later life. However, there is a lack of focus in the literature on the changes and directionality of the relationship between these two constructs. This study, based on socioemotional selectivity theory, investigates the dynamic and reciprocal relationship between perceived discrimination and cognitive function in later life. Data were drawn from four waves of the Health and Retirement Study (HRS; 2006, 2010, 2014, and 2018). We utilized a subsample of respondents who completed the psychosocial and lifestyle questionnaire in at least three waves. A total of 4,101 people who were 51 and older were included. Cognitive function was measured by the abbreviated version of the telephone interview for cognitive status (TICS-27). Perceived discrimination was measured using scores of the perceived everyday discrimination scale. Random intercept cross-lagged panel model (RI-CLPM) was utilized. Age was associated with lower perceived discrimination (b=-0.224, p<.0001). While lower cognitive function was cross-sectionally associated with higher perceived discrimination in all racial/ethnic groups, higher everyday discrimination predicted subsequent lower cognitive function only among White respondents. The model fit statistics were favorable: CFI=0.968; SRMR=0.045. Results suggested that a decline in cognitive function may exacerbate perceived discrimination which may result in further reduction of cognitive function in general. Lifetime experience of discrimination was discussed as a possible source of the racial/ethnic variations in the relationship. Further study is needed to examine whether this relationship holds among people with cognitive impairment or dementia.

The relationship between handgrip strength and cognitive function among older adults in China: Functional limitation plays a mediating role

BackgroundThe deterioration of cognitive function with age has become a major public health issue. To date, the underlying mechanisms of the association between handgrip strength and cognitive function were poorly understood. This study aimed to examine the mediating effect of functional limitation in the longitudinal relationship between handgrip strength and subsequent cognitive function. MethodsThis research recruited 4416 participants aged 60 and above from wave 2015 and 2018 of the China Longitudinal Study of Health and Retirement (CHARLS). We conducted the linear regression model and bootstrap analyses to test the mediating role of functional limitation in the relationship between handgrip strength and cognitive function. ResultsAfter adjusting the confounders, handgrip strength was positively associated with subsequent cognitive function (β = 0.12, P < 0.001) and was negatively associated with functional limitation (β = −0.14, P < 0.001). The mediation effect of functional limitation accounted for 23.33 % of the total effect regarding the handgrip strength with cognitive function, and the magnitude of mediation effect was a*b = 0.021 (95%CI: 0.017–0.027). LimitationsThe variable of functional limitations was self-reported. And this study did not analyse the severity and duration of handgrip strength loss and functional limitations, which may lose some information. ConclusionsOur findings revealed that handgrip strength not only directly influenced cognitive function among older individuals but also indirectly via functional limitation over 3-year follow-up. Physical exercise targeting handgrip strength and functional limitation may be an effective approach to prevent and delay cognitive decline.

Can introduction of sleep hygiene videos improve sleep and concentration in 5th and 6th graders? Interventional study

BackgroundInsomnia is a very common condition in childhood with a prevalence of 25–50%. It can present as difficulty with initiating and maintaining sleep with frequent disruptions throughout the night. Sleep insomnia is known to affect children’s development and contribute to poor attention and memory. Establishing a good sleep routine will have a beneficial effect not just on the child’s wellbeing and development but the whole family.The objective of the study was to assess the effectiveness of sleep hygiene videos in improving sleep quality and subsequent cognitive function in children aged 10–11 years.Two cartoon videos on sleep hygiene were designed along with a child-friendly questionnaire to be filled by grade 5 and 6 students in two different schools in the city of Leeds, England. Questionnaires were filled prior to viewing the videos and 2 to 3 weeks afterward to assess response to the video contents. The videos were viewed in April and May 2022.ResultsIn the East of Leeds School, 49 students participated. In the North of Leeds School, 45 students participated. Significance of outcomes were analysed using the Wilcoxon signed-rank test. In the first school, there was a significant improvement in sleep duration, sleep disturbance, sleep latency, daytime dysfunction due to sleepiness and sleep efficiency (p < 0.05). In the second school, there was a significant improvement in sleep duration, sleep disturbance and sleep latency (p < 0.05).ConclusionPoor sleep function is a major issue in children. The results demonstrated that the use of sleep hygiene videos can support children with sleep difficulties and help them to modify their behaviour through self-health promotion.

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

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. 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. 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 (β -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 (β -0·07 per quintile rank decline; 95% CI -0·11 to -0·03) and China (β -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). 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. US National Institute on Aging, US National Institutes of Health.

Temporal relationship between depression and cognitive decline in the elderly: a two-wave cross-lagged study in a Chinese sample

Objectives: Less information is available about the temporal relationship between depression in the elderly and cognitive decline. In the current study, we (1) evaluated the temporal association between depression and cognitive decline in older adults over a 4-year period; (2) indicated which cognitive domains have a strong temporal relationship with depression.Methods: Using data from China Family Panel Studies, we examined the relationship between depression and cognition among adults aged 65 and older with a cross-lagged design.Results: The results showed that initial depression affected subsequent cognitive function, especially immediate and delayed recall, but that cognition decline did not predict depression over time.Conclusion: The findings suggest that depression precedes cognitive decline in older adults, which is of great significance for the future research of mild cognitive impairment and dementia in the elderly.

Targeting the gut-microbiota-brain axis in irritable bowel disease to improve cognitive function- recent knowledge and emerging therapeutic opportunities.

The brain-gut axis forms a bidirectional communication system between the gastrointestinal (GI) tract and cognitive brain areas. Disturbances to this system in disease states such as inflammatory bowel disease haveconsequences for neuronal activity and subsequent cognitive function. The gut-microbiota-brain axis refers to the communication between gut-resident bacteria and the brain. This circuits exists to detect gut microorganisms andrelay information to specific areas of the central nervous system (CNS) that in turn, regulate gut physiology. Changes in both the stability and diversity of the gut microbiota have been implicated in several neuronal disorders, including depression, autism spectrum disorder Parkinson's disease, Alzheimer's disease and multiple sclerosis. Correcting this imbalance with medicinal herbs, the metabolic products of dysregulated bacteria and probiotics have shown hope for the treatment of these neuronal disorders. In this review, we focus on recent advances in our understanding of the intricate connections between the gut-microbiota and the brain. We discuss the contribution of gut microbiota to neuronal disorders and the tangible links between diseases of the GI tract with cognitive function and behaviour. In this regard, we focus on irritable bowel syndrome (IBS) given its strong links tobrain function and anxiety disorders. This adds to the growing body of evidence supporting targeted therapeutic strategies to modulate the gut microbiota for the treatment of brain/mental-health-related disease.

Domains of Sedentary Behavior and Cognitive Function: The Health, Aging, and Body Composition Study, 1999/2000 to 2006/2007.

This study examines the relationship between various domains of sedentary behavior and subsequent cognitive function to evaluate whether different sedentary activities have specific associations with future cognitive performance. Data were from 1 261 older adults participating in the Health, Aging, and Body Composition (Health ABC) Study between 1999/2000 and 2006/2007. Total sitting time (hours/day), reading time (hours/week), and TV time (≤27/≥28 h/wk) were self-reported at baseline and 3 years later. At follow-up, cognitive function was evaluated using the Teng Mini-Mental State Examination (3MS) and the Digit Symbol Substitution Test (DSST). Multivariable linear regression modeling examined the independent associations of baseline sedentary behaviors and 3-year change in those behaviors with cognitive function scores at follow-up, adjusting for important covariables. Baseline total sitting time was positively associated with 3MS (β = 0.14 ± 0.07; p < .05) and DSST (β = 0.20 ± 0.10; p < .05) scores at follow-up, as was reading time (β = 0.09 ± 0.03; p < .05 for 3MS score and β = 0.14 ± 0.04; p < 0.01 for DSST score). Participants who increased their TV watching time over 3 years had a significantly lower 3MS score (β = -1.45 ± 0.71; p < .05) at follow-up, compared with those who maintained a low level of TV time (referent). These findings were independent of age, sex, race, education level, health status, depressive symptoms, and physical activity. Some types of sedentary behavior may have benefits for cognitive function in older age, thus highlighting the importance of measuring different domains of sitting time.

Social Isolation, Sleep Disturbance, and Cognitive Functioning (HRS): ALongitudinal MediationStudy.

Social isolation is prevalent and associated with dementia, yet the directionality and mechanisms are less understood. This study examined the association between social isolation and cognitive functioning and explored the mediating role of sleep disturbance on the social isolation-cognition relationship. Data from 5753 dementia-free Americans aged ≥50 of 2006 (T1), 2010 (T2), and 2014 (T3) waves of the Health and Retirement Study. Social isolation was measured by the Steptoe Social Isolation Index. Cognitive functioning was measured by the Telephone Interview of Cognitive Status. Sleep disturbance was measured with the modified Jenkins Sleep Scale. We used cross-lagged panel models to determine the associations between social isolation, sleep disturbance, and cognitive functioning. Social isolation is significantly associated with subsequent cognitive functioning (T1 to T2: β=-0.055, standard error [SE]=0.014, p < .001; T2 to T3: β=-0.044, SE=0.016, p < .001). Lower cognitive functioning is significantly associated with greater subsequent social isolation (T1 to T2: β=-0.101, SE=0.020, p < .001; T2 to T3: β=-0.058, SE=.011, p < .001). Sleep disturbance at T2 partially mediated the effect of social isolation (T1) on cognitive functioning (T3), accounting for 6.2% of the total effect (β=-0.003, SE=0.001, p < .01). Social isolation may deteriorate cognitive functioning and vice versa. The association between social isolation and cognition is partially explained by sleep disturbance.

TRENDS IN HOUSEHOLD MATERIAL RESOURCES AND COGNITIVE HEALTH IN A LONGITUDINAL COHORT STUDY OF AGING IN SOUTH AFRICA

Abstract Material resources that affect daily living conditions may be salient for cognitive aging in low-income settings, but evidence is limited on this topic. We investigated relationships between long-term trends in household material resources and subsequent cognitive function among 4,580 adults aged ≥40 in a population-representative cohort in Agincourt sub-district, South Africa, from 2001-2015. Household material resources (dwelling materials, water, sanitation, sources of power, modern amenities, and livestock) were assessed biennially from 2001-2013. We evaluated mean resources, volatility in resources, and change in resources over this period in relation to cognitive function in 2014/2015. Higher mean household resources and larger improvements over time in resources were positively associated with subsequent cognitive function, independent of confounders. Findings were largely driven by modern amenities for food preparation, transportation, and communication outside of the household. Access to these amenities may support cognitive aging through boosting nutrition and cognitive reserve and should be investigated further.

COGNITIVE AGING ACROSS NATIONAL CONTEXTS: EVIDENCE FROM THE HARMONIZED COGNITIVE ASSESSMENT PROTOCOLS

Abstract The global burden of dementia is rapidly rising and shifting to low- and middle-income countries. The triangulation of evidence across country contexts is essential for unlocking the causes of dementia and reducing its global burden. The Harmonized Cognitive Assessment Protocol (HCAP) is a recent innovation administered in the US Health and Retirement Study and several of its International Partner Studies. For the very first time, these HCAPs provide high-quality data for cross-national comparisons of later-life cognitive function that are sensitive to linguistic, cultural, and educational differences across diverse country contexts. However, despite the common HCAP protocols, human cognitive function does not lend itself to direct comparison across diverse populations without careful consideration of necessary test adaptations. This symposium presents results from analyses of the HCAP data in the US, England, Mexico, South Africa, China, and India, highlighting cross-national differences in later-life cognition identified using the HCAP data, and presenting key methodological concerns for cross-national comparisons of cognitive aging. First, Zhang will present findings comparing education gradients in later-life cognitive function across countries. Next, Cho will present longitudinal data comparing the relationships between short-term changes in household wealth in later-life and subsequent cognitive function across countries. Third, Avila-Rieger will present findings comparing sex/gender disparities in later-life cognitive function in the US and India and how they differ by education. Finally, Nichols will conclude the session by discussing differences in the measurement of cognition for the assessment of dementia across countries and implications for data interpretation and the design of future instruments.

DOES THE MICROBIOME INFLUENCE THE DEVELOPMENT OF DEMENTIA IN OLDER ADULTS?

Abstract Some data implicate microbes in the pathogenesis of Alzheimer’s Disease and Related Dementias (ADRD). Whether the use of antibiotics predisposes to ADRD remains unknown. To investigate the relationship between antibiotics and subsequent cognitive function, we analyzed data from a longitudinal, nationally representative sample of older US adults (N=2,906, the National Social Life, Health and Aging Project). The use of antibiotic medications was collected by home interview at baseline. Five years later, cognition was assessed using a survey adapted version of the Montreal Cognitive Assessment (MoCA). Additionally, ADRD status was measured by a report of a physician’s diagnosis (self or proxy). The association between baseline antibiotic use and an interval dementia diagnosis/MoCA scores was tested using multivariate logistic regression, controlling for age, sex, race and ethnicity, education, co-morbidities (modified Charlson Comorbidity Index), and cognition at baseline (Short Portable Mental Status Questionnaire). Older US adults who used antibiotics had lower MoCA-SA scores at 5-year follow-up (OR=3.94, 95% CI= 1.79-8.66). However, the use of antibiotics did not predict a subsequent diagnosis of dementia (OR=1.48, 95% CI= 0.44-4.95). Thus, antibiotic use may cause deleterious effects on cognitive function, but does not appear to have a clinical impact in terms of diagnosis of dementia. Further study of the role of microbes and drugs that modulate them may be useful in understanding ADRD.

SHORT-TERM WEALTH CHANGES AND SUBSEQUENT COGNITIVE HEALTH AMONG OLDER ADULTS IN CHINA, ENGLAND, MEXICO, AND THE US

Abstract Household wealth is positively associated with later-life cognitive health, but little is known about the effects of changes in wealth over time and whether they differ across populations. In this study, we evaluated the within- and between-country relationships between short-term changes in household wealth and subsequent cognitive function among adults aged ≥65 years in China, England, Mexico, and the US. We used sampling-weighted, multivariable-adjusted linear models to estimate the relationships between household wealth change over 3- to 4-year periods and subsequent harmonized general cognitive performance factor scores using HCAP measures. We found that short-term decreases in household wealth were associated with poor subsequent cognitive health in the US and China, but not in England or Mexico. The observed associations were weaker in Mexico than in the US. In summary, macro-level social and economic structures may modify the association between wealth changes and cognitive health, although further investigation is needed.

COGNITIVE AGING IN LOW- AND MIDDLE-INCOME COUNTRIES

Abstract Cognitive aging is a highly complex, dynamic, and context-dependent process; and is influenced by individual and community characteristics and experiences across the life course. Low- and middle-income countries (LMICs) are critical components of the international dementia research community because the burden of dementia is rapidly rising in LMICs, and low-resource settings may have unique social and economic determinants of cognitive health. However, little population-based research focuses on these regions. The papers in this symposium use high-quality population survey data from Mexico, Brazil, South Africa, and China to study critical social determinants of cognitive function in countries across the globe. These papers cover a range of social and economic factors, including food insecurity, education, household material resources, and urban-rural settings and policy. First, Saenz will present findings on how food insecurity, throughout life, relates with cognitive function among older Mexican adults. Next, Farina will present evidence on both indirect and direct pathways from education to cognitive function among older Brazilians. Third, Kobayashi will present longitudinal data evaluating level and change in household resources in relation to subsequent cognitive function in South Africa. Finally, Zhang will present evidence on the interplay of rural/urban residence and household registration system across the life-course in creating cumulative advantage/disadvantage in cognitive aging using longitudinal data from China. The papers in this symposium provide new insights into social determinants of cognitive health in diverse contexts and have significant policy implications for improving cognitive health in LMICs across the globe.

Sex-specific impacts of social isolation on loneliness, depressive symptoms, cognitive impairment, and biomarkers: Results from the social environment and biomarker of aging study

ObjectivesTo investigate sex-specific associations between social isolation and psychological outcomes and biomarkers among community-dwelling middle-aged and older adults using a nationally representative population-based cohort study. MethodsData from 757 participants from the Social Environment and Biomarkers of Aging Study (SEBAS) were retrieved for analysis, and all participants were stratified by sex. The associations between social isolation and psychological outcomes (loneliness, depressive symptoms, and cognitive impairment) at the 4-year follow-up were examined by multivariate logistic regression models, and associations between social isolation and biomarkers at the 4-year follow-up were examined by multivariate generalized linear models (GLMs). ResultsFor men, social isolation was not associated with the development of loneliness. However, being married (adjusted odds ratio (aOR) 0.32 [95% confidence interval (CI) 0.13-0.74], p<0.001) was associated with a lower risk of loneliness, indicating potential protective effects of marriage for men. On the other hand, social isolation was associated with a 2-fold higher risk of loneliness in women (aOR 2.26 [1.01-5.09], p<0.001). Social isolation was not associated with depressive symptoms after adjusting for other demographics. For men, being married (aOR 0.51 [0.26-0.99], p<0.05) or having good self-reported health (aOR 0.44 [0.21-0.92], p<0.05) was protective against depressive symptoms. For women, only good self-reported health (aOR 0.30 [0.13-0.70], p<0.01) provided protective effects against depressive symptoms. Similarly, other demographic factors (being married and having a higher educational level) but not social isolation were associated with lower risks of cognitive impairment. No significant associations were noted between social isolation and selected biomarkers. ConclusionsSex-different associations between social isolation and loneliness were noted; the effects of demographic factors, such as being married, self-reported health status, and high education levels, on subsequent loneliness, depression, and cognitive function were also sex-different. Further intervention studies are needed to explore sex-specific approaches to deal with the interplay of social isolation, loneliness, psychological outcomes and other demographic factors.