School racial composition, effect modification by caring teacher/staff presence, and mid/late-life depressive symptoms: findings from the Study of Healthy Aging among African Americans.

For Black students in the United States, attending schools with a higher proportion of White students is associated with worse mental and physical health outcomes in adolescence/early adulthood. No prior studies evaluate K-12 school racial composition and later-life mental health. In a cohort of Black adults ages 50+ in Northern California who retrospectively self-reported school racial composition for grades 1, 6, 9, and 12, we assessed the association between attending a school with mostly Black students vs. not and mid/late-life depressive symptoms (8-item PROMIS depression score, standardized to US adult population) using age-, sex/gender-, southern US birth-, and parental education-adjusted generalized estimating equations, and assessed effect modification by caring teacher/staff presence. Later-life depressive symptoms were lower among those who attended schools with mostly Black students in grades 1 and 6 (b=-0.12, 95% CI: -0.23, 0.00 and b=-0.11, 95% CI: -0.22, 0.00, respectively). In grade 6, this difference was larger for students without an adult at school who cared about them (b=-0.29, 95% CI: -0.51, -0.07 vs. b=-0.04, 95% CI: -0.17, 0.09). Among Black Americans, attending early school with mostly Black students may have later life mental health benefits; this protective association appears more important for students without caring teachers/staff.

The Association Between Physical Activity and Cognition in a Racially/Ethnically Diverse Cohort of Older Adults: Results From the Kaiser Healthy Aging and Diverse Life Experiences Study.

OBJECTIVE: Most prior research on physical activity (PA) and cognition is based on predominantly white cohorts and focused on associations of PA with mean (average) cognition versus the distribution of cognition. Quantile regression offers a novel way to quantify how PA affects cognition across the entire distribution. METHODS: The Kaiser Healthy Aging and Diverse Life Experiences study includes 30% white, 19% black, 25% Asian, and 26% Latinx adults age 65+ living in Northern California (n = 1600). The frequency of light or heavy PA was summarized as 2 continuous variables. Outcomes were z-scored executive function, semantic memory, and verbal episodic memory. We tested associations of PA with mean cognition using linear regression and used quantile regression to estimate the association of PA with the 10th-90th percentiles of cognitive scores. RESULTS: Higher levels of PA were associated with higher mean semantic memory (b = 0.10; 95% CI: 0.06, 0.14) and executive function (b = 0.05; 95% CI: 0.01, 0.09). Associations of PA across all 3 cognitive domains were stronger at low quantiles of cognition. CONCLUSION: PA is associated with cognition in this racially/ethnically diverse sample and may have larger benefits for individuals with low cognitive scores, who are most vulnerable to dementia.

Timing and level of educational attainment and late-life cognition in the KHANDLE study.

INTRODUCTION: The timing of educational attainment may modify its effects on late-life cognition, yet most studies evaluate education only at a single time point. METHODS: Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study cohort participants (N = 554) reported educational attainment (dichotomized at any college education) at two time points, and we classified them as having low, high, or later-life high educational attainment. Linear mixed-effects models estimated associations between educational attainment change groups and domain-specific cognitive outcomes (z-standardized). RESULTS: Compared to low educational attainment, high (ß= 0.59 SD units; 95% confidence interval [CI]: 0.39, 0.79) and later-life high educational attainment (ß = 0.22; 95% CI: 0.00, 0.44) were associated with higher executive function. Only high educational attainment was associated with higher verbal episodic memory (ß = 0.27; 95% CI: 0.06, 0.48). DISCUSSION: Level and timing of educational attainment are both associated with domain-specific cognition. A single assessment for educational attainment may inadequately characterize protective associations with late-life cognition. HIGHLIGHTS: Few studies have examined both level and timing of educational attainment on cognition. Marginalized populations are more likely to attain higher education in adulthood. Higher educational attainment in late life is also associated with higher cognition.

Race, community disadvantage, and cognitive decline: Findings from KHANDLE and STAR.

INTRODUCTION: Community disadvantage is associated with late-life cognition. Few studies examine its contribution to racial disparities in cognition/cognitive change. METHODS: Inverse probability weighted models estimated expected mean differences in cognition/cognitive change attributed to residing in less advantaged communities, defined as cohort top quintile of Area Deprivation Indices (ADI): childhood 66-100; adulthood ADI 5-99). Interactions by race tested. RESULTS: More Black participants resided in less advantaged communities. Semantic memory would be lower if all participants had resided in less advantaged childhood (b = -0.16, 95% confidence interval [CI] = -0.30, -0.03) or adulthood (b = -0.14, 95% CI = -0.22, -0.04) communities. Race interactions indicated that, among Black participants, less advantaged childhood communities were associated with higher verbal episodic memory (interaction p-value = 0.007) and less advantaged adulthood communities were associated with lower semantic memory (interaction p-value = 0.002). DISCUSSION: Examining racial differences in levels of community advantage and late-life cognitive decline is a critical step toward unpacking community effects on cognitive disparities.

What is the association between adverse childhood experiences and late-life cognitive decline? Study of Healthy Aging in African Americans (STAR) cohort study.

OBJECTIVES: Adverse childhood experiences (ACEs) are associated with higher risk of chronic disease, but little is known about the association with late life cognitive decline. We examined the longitudinal association between ACEs and late-life cognitive decline in the Study of Healthy Aging in African Americans (STAR). DESIGN: Linear mixed models with random intercepts and slope examined the association of individual and composite ACEs with cognitive change adjusting for years from baseline (timescale), baseline age, sex, parental education, childhood socioeconomic status and childhood social support. Participants reported whether they had experienced nine types of ACEs. Executive function and verbal episodic memory were measured up to three times over a 3-year period using the Spanish and English Neuropsychological Assessment Scales. SETTINGS: Kaiser Permanente Northern California members living in the Bay Area. PARTICIPANTS: STAR is a cohort study of cognitive ageing launched in 2018 that has enrolled 764 black Americans ages ≥50 years (mean age=67.5; SD=8.5). RESULTS: Twenty-one per cent of participants reported no ACEs, 24% one ACE, 20% two ACEs, 17% three ACEs and 17% four or more ACEs. Compared with no ACEs, two ACEs (ß=0.117; 95% CI 0.052 to 0.182), three ACEs (ß=0.075; 95% CI 0.007 to 0.143) and four or more ACEs (ß=0.089; 95% CI 0.002 to 0.158) were associated with less decline in executive function. There were no significant associations between number of ACEs and baseline or longitudinal verbal episodic memory or between individual ACEs and executive function or verbal episodic memory. CONCLUSION: In this cohort of older black Americans, there was no association between ACEs and baseline cognition or cognitive change in verbal episodic memory; however, experiencing ≥ 2 ACEs was associated with less decline in executive function. These results may indicate that participants who survived to age 50+ and experienced ACEs may have cognitive resilience that warrants further investigation.

Short-Term Dietary Intervention with Whole Oats Protects from Antibiotic-Induced Dysbiosis.

Antibiotic-induced gut microbiome dysbiosis (AID) is known to be influenced by host dietary composition. However, how and when diet modulates gut dysbiosis remains poorly characterized. Thus, here, we utilize a multi-omics approach to characterize how a diet supplemented with oats, a rich source of microbiota-accessible carbohydrates, or dextrose impacts amoxicillin-induced changes to gut microbiome structure and transcriptional activity. We demonstrate that oat administration during amoxicillin challenge provides greater protection from AID than the always oats or recovery oats diet groups. In particular, the group in which oats were provided at the time of antibiotic exposure induced the greatest protection against AID while the other oat diets saw greater effects after amoxicillin challenge. The oat diets likewise reduced amoxicillin-driven elimination of Firmicutes compared to the dextrose diet. Functionally, gut communities fed dextrose were carbohydrate starved and favored respiratory metabolism and consequent metabolic stress management while oat-fed communities shifted their transcriptomic profile and emphasized antibiotic stress management. The metabolic trends were exemplified when assessing transcriptional activity of the following two common gut commensal bacteria: Akkermansia muciniphila and Bacteroides thetaiotaomicron. These findings demonstrate that while host diet is important in shaping how antibiotics effect the gut microbiome composition and function, diet timing may play an even greater role in dietary intervention-based therapeutics. IMPORTANCE We utilize a multi-omics approach to demonstrate that diets supplemented with oats, a rich source of microbiota-accessible carbohydrates, are able to confer protection against antibiotic-induced dysbiosis (AID). Our findings affirm that not only is host diet important in shaping antibiotics effects on gut microbiome composition and function but also that the timing of these diets may play an even greater role in managing AID. This work provides a nuanced perspective on dietary intervention against AID and may be informative on preventing AID during routine antibiotic treatment.

Association of Early Adulthood Hypertension and Blood Pressure Change With Late-Life Neuroimaging Biomarkers.

Importance: The association between hypertension developed before midlife and late-life brain health is understudied and, because of the cardioprotective benefits of estrogen before menopause, may differ by sex. Objective: To assess the association of early adulthood hypertension and blood pressure (BP) change with late-life neuroimaging biomarkers and examine potential sex differences. Design, Setting, and Participants: This cohort study used data from the Study of Healthy Aging in African Americans (STAR) and Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study, which were harmonized longitudinal cohorts of racially and ethnically diverse adults aged 50 years and older from the San Francisco Bay area and Sacramento Valley in California. The STAR was conducted from November 6, 2017, to November 5, 2021, and the KHANDLE study was conducted from April 27, 2017, to June 15, 2021. The current study included 427 participants from the KHANDLE and STAR studies who received health assessments between June 1, 1964, and March 31, 1985. Regional brain volumes and white matter (WM) integrity were measured via magnetic resonance imaging between June 1, 2017, and March 1, 2022. Exposures: Hypertension status (normotension, transition to hypertension, and hypertension) and BP change (last measure minus first measure) were assessed at 2 multiphasic health checkups (MHCs; 1964-1985) in early adulthood (ages 30-40 years). Main Outcomes and Measures: Regional brain volumes and WM integrity were measured using 3T magnetic resonance imaging and z standardized. General linear models adjusted for potential confounders (demographic characteristics and study [KHANDLE or STAR]) were used to assess the association of hypertension and BP change with neuroimaging biomarkers. Sex interactions were tested. Results: Among 427 participants, median (SD) ages were 28.9 (7.3) years at the first MHC, 40.3 (9.4) years at the last MHC, and 74.8 (8.0) years at neuroimaging. A total of 263 participants (61.6%) were female and 231 (54.1%) were Black. Overall, 191 participants (44.7%) had normotension, 68 (15.9%) transitioned to hypertension, and 168 (39.3%) had hypertension. Compared with participants who had normotension, those who had hypertension and those who transitioned to hypertension had smaller cerebral volumes (hypertension: ß = -0.26 [95% CI, -0.41 to -0.10]; transition to hypertension: ß = -0.23 [95% CI, -0.44 to -0.23]), with similar differences in cerebral gray matter volume (hypertension: ß = -0.32 [95% CI, -0.52 to -0.13]; transition to hypertension: ß = -0.30 [95% CI, -0.56 to -0.05]), frontal cortex volume (hypertension: ß = -0.43 [95% CI, -0.63 to -0.23]; transition to hypertension: ß = -0.27 [95% CI, -0.53 to 0]), and parietal cortex volume (hypertension: ß = -0.22 [95% CI, -0.42 to -0.02]; transition to hypertension: ß = -0.29 [95% CI, -0.56 to -0.02]). Participants with hypertension also had smaller hippocampal volume (ß = -0.22; 95% CI, -0.42 to -0.02), greater ventricular volumes (lateral ventricle: ß = 0.44 [95% CI, 0.25-0.63]; third ventricle: ß = 0.20 [95% CI, 0.01-0.39]), larger free water volume (ß = 0.35; 95% CI, 0.18-0.52), and lower fractional anisotropy (ß = -0.26; 95% CI, -0.45 to -0.08) than those who had normotension. Holding hypertension status constant, a 5-mm Hg increase in systolic BP was associated with smaller temporal cortex volume (ß = -0.03; 95% CI, -0.06 to -0.01), while a 5-mm Hg increase in diastolic BP was associated with smaller parietal cortex volume (ß = -0.06; 95% CI, -0.10 to -0.02). The negative association of hypertension and BP change with regional brain volumes appeared stronger in men than women for some regions. Conclusions and Relevance: In this cohort study, early adulthood hypertension and BP change were associated with late-life volumetric and WM differences implicated in neurodegeneration and dementia. Sex differences were observed for some brain regions whereby hypertension and increasing BP appeared more detrimental for men. These findings suggest that prevention and treatment of hypertension in early adulthood is important for late-life brain health, particularly among men.

Association of primary lifetime occupational cognitive complexity and cognitive decline in a diverse cohort: Results from the KHANDLE study.

INTRODUCTION: Higher occupational complexity has been linked to favorable cognitive outcomes, but rarely examined in racially and ethnically diverse populations. METHODS: In a diverse cohort (n = 1536), linear mixed-effects models estimated associations between main lifetime occupational complexity and domain-specific cognitive decline (z-standardized). Occupational complexity with data, people, and things were classified using the Dictionary of Occupational Titles. RESULTS: For occupational complexity with data, highest tertile (vs. lowest) was associated with higher baseline executive function (ß = 0.11; 95% confidence interval [CI] 0.00-0.22) and slower annual rate of decline (ß = 0.03; 95% CI 0.01-0.06), and higher baseline semantic memory (ß = 0.14; 95% CI 0.04-0.25). Highest tertile of occupational complexity with people was associated with higher baseline executive function (ß = 0.29; 95% CI 0.18-0.40), verbal episodic memory (ß = 0.12; 95% CI 0.00-0.24), and semantic memory (ß = 0.23; 95% CI 0.12-0.34). DISCUSSION: In a diverse cohort, higher occupational complexity is associated with better cognition. Findings should be verified in larger cohorts. HIGHLIGHT: Few studies have examined associations of occupational complexity with cognition in diverse populations. Racial and ethnic minorities are disproportionately exposed to lower occupational complexity. Occupational complexity with data and people are associated with better cognition.

Rural residence across the life course and late-life cognitive decline in KHANDLE: A causal inference study.

Background: Modifiable risks for dementia are more prevalent in rural populations, yet there is a dearth of research examining life course rural residence on late-life cognitive decline. Methods: The association of rural residence and socioeconomic status (SES) in childhood and adulthood with late-life cognitive domains (verbal episodic memory, executive function, and semantic memory) and cognitive decline in the Kaiser Healthy Aging and Diverse Life Experiences cohort was estimated using marginal structural models with stabilized inverse probability weights. Results: After adjusting for time-varying SES, the estimated marginal effect of rural residence in childhood was harmful for both executive function (ß = -0.19, 95% confidence interval [CI] = -0.32, -0.06) and verbal episodic memory (ß = -0.22, 95% CI = -0.35, -0.08). Effects of adult rural residence were imprecisely estimated with beneficial point estimates for both executive function (ß = 0.19; 95% CI = -0.07, 0.44) and verbal episodic memory (ß = 0.24, 95% CI = -0.07, 0.55). Conclusions: Childhood rurality is associated with poorer late-life cognition independent of SES.

State-Level Indicators of Childhood Educational Quality and Incident Dementia in Older Black and White Adults.

Importance: Higher educational attainment is associated with reduced dementia risk, but the role of educational quality is understudied, presenting a major evidence gap, especially as it may contribute to racial inequities. Objective: To evaluate the association between state-level educational quality during childhood and dementia risk. Design, Setting, and Participants: This cohort study analyzed longitudinal data collected from January 1, 1997, through December 31, 2019 (23-year follow-up period). The sample comprised members of Kaiser Permanente Northern California (KPNC), a large integrated health care delivery system, who completed an optional survey during 1964-1972. Eligible individuals were US born; non-Hispanic Black or non-Hispanic White; aged 65 years or older as of January 1, 1996; were still alive; and did not have a dementia diagnosis or lapse in KPNC membership greater than 90 days between January 1 and December 31, 1996. Exposures: Historical state-level administrative indicators of school quality (school term length, student-teacher ratio, and attendance rates) linked to participants using birth state and birth year (with a 6-year lag) and divided into tertiles using the pooled sample. Main Outcomes and Measures: Dementia diagnoses from electronic health records between 1997 and 2019 were analyzed between March 1 and August 31, 2022. The associations of educational quality with incident dementia were estimated using Cox proportional hazards regression models. Results: Among 21 450 KPNC members who participated in the optional survey, individuals born before availability of educational quality records (n = 87) and missing educational attainment (n = 585) were excluded. The final analytic sample was 20 778 individuals (56.5% women, 43.5% men; mean [SD] age, 74.7 [6.5] years; 18.8% Black; 81.2% White; 41.0% with less than high school education). Among Black individuals, 76.2% to 86.1% (vs 20.8%-23.3% of White individuals) attended schools in states in the lowest educational quality tertiles. Highest (vs lowest) educational quality tertiles were associated with lower dementia risk (student-teacher ratio: hazard ratio [HR], 0.88 [95% CI, 0.83-0.94]; attendance rates: HR, 0.80 [95% CI, 0.73-0.88]; term length: HR, 0.79 [95% CI, 0.73-0.86]). Effect estimates did not differ by race and were not attenuated by adjustment for educational attainment. Conclusions and Relevance: In this cohort study, lower state-average educational quality was more common among Black individuals and associated with higher dementia risk. Differential investment in high-quality education due to structural racism may contribute to dementia disparities.

Evaluating interpersonal discrimination and depressive symptoms as partial mediators of the effects of education on cognition: Evidence from the Study of Healthy Aging in African Americans (STAR).

INTRODUCTION: Education is correlated with positive health outcomes, but associations are sometimes weaker among African Americans. The extent to which exposure to discrimination and depressive symptoms attenuates the education-cognition link has not been investigated. METHODS: Study of Healthy Aging in African Americans (STAR) participants (n = 764; average age 69 years) completed the Spanish and English Neuropsychological Assessment Scales. We assessed everyday and major lifetime discrimination and depressive symptoms as mediators of education effects on cognition using G-estimation with measurement error corrections. RESULTS: Education was correlated with greater major lifetime and everyday discrimination but lower depressive symptoms. Accounting for discrimination and depressive symptoms slightly reduced the estimated effect of education on cognition. The estimated total effect of graduate education (vs 

Streptozotocin-Induced Hyperglycemia Is Associated with Unique Microbiome Metabolomic Signatures in Response to Ciprofloxacin Treatment.

It is well recognized that the microbiome plays key roles in human health, and that damage to this system by, for example, antibiotic administration has detrimental effects. With this, there is collective recognition that off-target antibiotic susceptibility within the microbiome is a particularly troublesome side effect that has serious impacts on host well-being. Thus, a pressing area of research is the characterization of antibiotic susceptibility determinants within the microbiome, as understanding these mechanisms may inform the development of microbiome-protective therapeutic strategies. In particular, metabolic environment is known to play a key role in the different responses of this microbial community to antibiotics. Here, we explore the role of host dysglycemia on ciprofloxacin susceptibility in the murine cecum. We used a combination of 16S rRNA sequencing and untargeted metabolomics to characterize changes in both microbiome taxonomy and environment. We found that dysglycemia minimally impacted ciprofloxacin-associated changes in microbiome structure. However, from a metabolic perspective, host hyperglycemia was associated with significant changes in respiration, central carbon metabolism, and nucleotide synthesis-related metabolites. Together, these data suggest that host glycemia may influence microbiome function during antibiotic challenge.

Association of Social Integration with Cognitive Status in a Multi-Ethnic Cohort: Results From the Kaiser Healthy Aging and Diverse Life Experiences Study.

We evaluated overall and race-specific relationships between social integration and cognition in older adults. Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) cohort participants included 1343 Asian, Black, Latino, or non-Latino White Kaiser Permanente Northern California members. We estimated the effect of social integration on verbal episodic memory, semantic memory, and executive function derived from the Spanish and English Neuropsychological Assessment (SENAS) Scales. Social integration scores included marital status; volunteer activity; and contact with children, relatives, friends, and confidants. We estimated covariate-adjusted linear mixed-effects models for baseline and 17-month follow-up cognition. Social integration was associated with higher baseline cognitive scores (average  ß = 0.066 (95% confidence interval: 0.040, 0.092)) overall and in each racial/ethnic group. The association did not vary by race/ethnicity. Social integration was not associated with the estimated rate of cognitive change. In this cohort, more social integration was similarly associated with better late-life cognition across racial/ethnic groups.

Streptozotocin-induced hyperglycemia alters the cecal metabolome and exacerbates antibiotic-induced dysbiosis.

It is well established in the microbiome field that antibiotic (ATB) use and metabolic disease both impact the structure and function of the gut microbiome. But how host and microbial metabolism interacts with ATB susceptibility to affect the resulting dysbiosis remains poorly understood. In a streptozotocin-induced model of hyperglycemia (HG), we use a combined metagenomic, metatranscriptomic, and metabolomic approach to profile changes in microbiome taxonomic composition, transcriptional activity, and metabolite abundance both pre- and post-ATB challenge. We find that HG impacts both microbiome structure and metabolism, ultimately increasing susceptibility to amoxicillin. HG exacerbates drug-induced dysbiosis and increases both phosphotransferase system activity and energy catabolism compared to controls. Finally, HG and ATB co-treatment increases pathogen susceptibility and reduces survival in a Salmonella enterica infection model. Our data demonstrate that induced HG is sufficient to modify the cecal metabolite pool, worsen the severity of ATB dysbiosis, and decrease colonization resistance.

Association of Timing of School Desegregation in the United States With Late-Life Cognition in the Study of Healthy Aging in African Americans (STAR) Cohort.

Importance: Prior research suggests schooling differences for Black individuals in the US are associated with worse cognitive aging. It is unknown whether age when experiencing school desegregation is associated with differences in late-life cognition in this population. Objective: To examine patterns of association between age of school desegregation in grades 1 to 12 and late-life cognition. Design, Setting, and Participants: This cohort study analyzed baseline data from the Study of Healthy Aging in African Americans (STAR) cohort collected from 2018 through 2019 in Northern California, primarily in the cities of Richmond and Oakland. Participants were 699 self-identified Black individuals aged 50 years or older who were community-dwelling, long-term members of Kaiser Permanente Northern California and dementia free at baseline. Exposures: Participants reported whether they attended a segregated school in grades 1, 6, 9, and 12 and were placed in 1 of 6 transition categories: (1) always attended integrated schools; (2) integrated between grades 1 through 5; (3) integrated between grades 6 through 8; (4) integrated between grades 9 through 12; (5) ever moved from integrated to segregated school; (6) never attended integrated schools. Main Outcomes and Measures: Executive function, semantic memory, and verbal episodic memory ascertained via the Spanish and English Neuropsychological Assessment Battery and z standardized for analyses. Results: The mean (SD) age of the 699 participants was 68.5 (8.7) years, and 484 (69.2%) were female. Most participants transitioned from segregated to integrated schools owing to historical timing and cohort geography. Compared with 111 participants who never attended integrated schools (reference group), executive function was better among 50 participants who transitioned to integrated schools between grades 1 and 5 (ß = 0.35; 95% CI, 0.08-0.61; P = .01). Semantic memory was better among 435 participants who only attended integrated schools (ß = 0.34; 95% CI, 0.14-0.54; P = .001) or among 50 participants who transitioned to integrated schools between grades 1 and 5 (ß = 0.43; 95% CI, 0.15-0.72; P = .003). However, no significant differences were found by group for verbal episodic memory function (eg, for 50 participants who transitioned to integrated schools between grades 1 and 5: ß = 0.07; 95% CI, -0.22 to 0.35; P = .66). No significant differences were found when testing for potential interactions by sex, Southern birth, or baseline age. Conclusions and Relevance: The STAR cohort data indicated that executive function and semantic memory were higher among Black individuals with some integrated school experience. These results suggest that racially segregated schooling experiences, including de facto segregation present today, may be associated with worse late-life cognition.

Stroke Belt birth state and late-life cognition in the Study of Healthy Aging in African Americans (STAR).

PURPOSE: We examined the association of Stroke Belt birth state with late-life cognition in The Study of Healthy Aging in African Americans (STAR). METHODS: STAR enrolled 764 Black Americans ages 50+ who were long-term Kaiser Permanente Northern California members. Participants completed Multiphasic Health Check-ups (MHC; 1964-1985) where early-life overweight/obesity, hypertension, diabetes, and hyperlipidemia were measured. At STAR (2018), birth state, self-reported early-life socioeconomic status (SES), and executive function, verbal episodic memory, and semantic memory scores were collected. We used linear regression to examine the association between Stroke Belt birth and late-life cognition adjusting for birth year, gender, and parental education. We evaluated early-life SES and cardiovascular risk factors (CVRF) as potential mechanisms. RESULTS: Twenty-seven percent of participants were born in the Stroke Belt with a mean age of 69 (standard deviation = 9) at STAR. Stroke Belt birth was associated with worse late-life executive function (ß [95% confidence interval]: -0.18 [-0.33, -0.02]) and semantic memory (-0.37 [-0.53, -0.21]), but not verbal episodic memory (-0.04 [-0.20, 0.12]). Adjustment for SES and CVRF attenuated associations of Stroke Belt birth with cognition (executive function [-0.05 {-0.25, 0.14}]; semantic memory [-0.28 {-0.49, -0.07}]). CONCLUSIONS: Black Americans born in the Stroke Belt had worse late-life cognition than those born elsewhere, underscoring the importance of early-life exposures on brain health.

Loss of tumor protein 53 protects against alcohol-induced facial malformations in mice and zebrafish.

BACKGROUND: Alcohol exposure during the gastrulation stage of development causes the craniofacial and brain malformations that define fetal alcohol syndrome. These malformations, such as a deficient philtrum, are exemplified by a loss of midline tissue and correspond, at least in part, to regionally selective cell death in the embryo. The tumor suppressor protein Tp53 is an important mechanism for cell death, but the role of Tp53 in the consequences of alcohol exposure during the gastrulation stage has yet to be examined. The current studies used mice and zebrafish to test whether genetic loss of Tp53 is a conserved mechanism to protect against the effects of early developmental stage alcohol exposure. METHODS: Female mice, heterozygous for a mutation in the Tp53 gene, were mated with Tp53 heterozygous males, and the resulting embryos were exposed during gastrulation on gestational day 7 (GD 7) to alcohol (two maternal injections of 2.9 g/kg, i.p., 4 h apart) or a vehicle control. Zebrafish mutants or heterozygotes for the tp53zdf1  M214K mutation and their wild-type controls were exposed to alcohol (1.5% or 2%) beginning 6 h postfertilization (hpf), the onset of gastrulation. RESULTS: Examination of GD 17 mice revealed that eye defects were the most common phenotype among alcohol-exposed fetuses, occurring in nearly 75% of the alcohol-exposed wild-type fetuses. Tp53 gene deletion reduced the incidence of eye defects in both the heterozygous and mutant fetuses (to about 35% and 20% of fetuses, respectively) and completely protected against alcohol-induced facial malformations. Zebrafish (4 days postfertilization) also demonstrated alcohol-induced reductions of eye size and trabeculae length that were less common and less severe in tp53 mutants, indicating a protective effect of tp53 deletion. CONCLUSIONS: These results identify an evolutionarily conserved role of Tp53 as a pathogenic mechanism for alcohol-induced teratogenesis.

Impact of Cardiovascular Risk Factors in Adolescence, Young Adulthood, and Midlife on Late-Life Cognition: Study of Healthy Aging in African Americans.

BACKGROUND: Midlife cardiovascular risk factors (CVRFs) increase risk of dementia. Black Americans experience an elevated prevalence of CVRFs and dementia. However, little is known of how CVRFs prior to midlife affect late-life cognition. We examined CVRFs in adolescence, young adulthood, and midlife with late-life cognition in the Study of Healthy Aging in African Americans (STAR). METHOD: STAR assesses cognitive aging among 764 Black Americans aged ≥50 (mean age = 69; SD = 9; range = 53-95). Participants' body mass index, blood pressure, glucose, and total cholesterol were collected during Multiphasic Health Checkups (MHC; 1964-1985). At STAR baseline (2018-2019), executive function, verbal episodic memory, and semantic memory were measured using the Spanish and English Neuropsychological Assessment Scales. Linear regression models examined associations between CVRFs and cognition adjusting for demographics and years since MHC. RESULTS: At MHC, 36% of participants had 1 CVRF and 26% had ≥2. Twenty-two percent of participants were adolescents (age 12-20), 62% young adults (age 21-34), and 16% midlife adults (age 35-56). Overweight/obesity was not associated with cognition. Hypertension was associated with worse executive function (ß [95% CI]: -0.14 [-0.28, -0.0003]) and verbal episodic memory (ß [95% CI]: -0.22 [-0.37, -0.07]) compared to normotension. Diabetes was associated with worse executive function (ß [95% CI]: -0.43 [-0.83, -0.03]). Having ≥2 CVRFs (vs 0) was associated with worse executive function (ß [95% CI]: -0.19 [-0.34, -0.03]) and verbal episodic memory (ß [95% CI]: -0.25 [-0.41, -0.08]). Adolescents with hypertension had lower late-life executive function compared to normotensive adolescents (ß [95% CI]: -0.39 [-0.67, -0.11]). Young adulthood hypertension (ß [95% CI]: -0.29 [-0.49, -0.09]) and midlife hyperlipidemia (ß [95% CI]: -0.386 [-0.70, -0.02]) were associated with lower verbal episodic memory. CONCLUSIONS: Among Black Americans, life-course CVRFs were associated with poorer executive function and verbal episodic memory emphasizing the importance of cardiovascular health on the aging brain.

Operationalizing Social Environments in Cognitive Aging and Dementia Research: A Scoping Review.

BACKGROUND: Social environments are a contributing determinant of health and disparities. This scoping review details how social environments have been operationalized in observational studies of cognitive aging and dementia. METHODS: A systematic search in PubMed and Web of Science identified studies of social environment exposures and late-life cognition/dementia outcomes. Data were extracted on (1) study design; (2) population; (3) social environment(s); (4) cognitive outcome(s); (5) analytic approach; and (6) theorized causal pathways. Studies were organized using a 3-tiered social ecological model at interpersonal, community, or policy levels. RESULTS: Of 7802 non-duplicated articles, 123 studies met inclusion criteria. Eighty-four studies were longitudinal (range 1-28 years) and 16 examined time-varying social environments. When sorted into social ecological levels, 91 studies examined the interpersonal level; 37 examined the community/neighborhood level; 3 examined policy level social environments; and 7 studies examined more than one level. CONCLUSIONS: Most studies of social environments and cognitive aging and dementia examined interpersonal factors measured at a single point in time. Few assessed time-varying social environmental factors or considered multiple social ecological levels. Future studies can help clarify opportunities for intervention by delineating if, when, and how social environments shape late-life cognitive aging and dementia outcomes.

Lifecourse socioeconomic changes and late-life cognition in a cohort of U.S.-born and U.S. immigrants: findings from the KHANDLE study.

BACKGROUND: Low socioeconomic status (SES) in early and late life has been associated with lower late-life cognition. Less is known about how changes in SES from childhood to late life are associated with late-life cognition, especially among diverse populations of older adults. METHODS: In a multi-ethnic sample (n = 1353) of older adults, we used linear regression to test associations of change in comprehensive measures of SES (financial, cultural, and social domains) from childhood to late life with semantic memory, episodic memory, and executive function. We tested whether the association between SES trajectory and late-life cognition differed by populations who resided in the U.S. during childhood or immigrated to the U.S. as adults. RESULTS: Participants with low childhood/high late-life financial capital had better semantic memory (ß = 0.18; 95% CI: 0.04, 0.32) versus those with low financial capital in both childhood and late life, regardless of childhood residence. We observed a significant interaction in the association of verbal episodic memory and cultural capital by childhood residence (p = 0.08). Participants with a foreign childhood residence had higher verbal episodic memory if they had low childhood/high late-life cultural capital (ß = 0.32; 95% CI: 0.01, 0.63), but lower verbal episodic memory if they had high childhood/low late-life cultural capital (ß = - 0.40; 95% CI: - 0.94, 0.13). Having high lifecourse social capital was associated with better verbal episodic memory scores among those with a U.S. childhood (ß = 0.34; 95% CI: 0.14, 0.55), but lower verbal episodic memory among those with a foreign childhood (ß = - 0.10; 95% CI: - 0.51, 0.31). CONCLUSIONS: High financial and cultural capital in late life is associated with better cognition, regardless of early childhood SES or childhood residence.