School racial/ethnic composition, effect modification by caring teacher/staff presence, and mid-/late-life depressive symptoms: findings from the Study of Healthy Aging in 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. To our knowledge, no prior studies have evaluated the association between school racial/ethnic composition from kindergarten through grade 12 and later-life mental health. In a cohort of Black adults aged ≥50 years in Northern California who retrospectively reported (2017-2020) school racial/ethnic composition for grades 1, 6, 9, and 12, we assessed the association between attending a school with mostly Black students versus not and mid-/late-life depressive symptoms (8-item Patient-Reported Outcomes Measurement Information System (PROMIS) depression score, standardized to the 2000 US adult population) using age-, sex/gender-, southern US birth-, and parental education-adjusted generalized estimating equations, and assessed effect modification by the presence of a caring teacher/staff member. Levels of later-life depressive symptoms were lower among those who attended schools with mostly Black students in grades 1 and 6 (ß = -0.12 [95% CI, -0.23 to 0.00] and ß = -0.11 [95% CI, -0.22 to 0.00], respectively). In grade 6, this difference was larger for students without an adult at school who cared about them (ß = -0.29 [95% CI, -0.51 to -0.07] vs ß = -0.04 [95% CI, -0.17 to 0.09]). Among Black Americans, experiencing early schooling with mostly Black students may have later-life mental health benefits; this protective association appears more important for students without the presence of caring teachers/staff. This article is part of a Special Collection on Mental Health.

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.

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.

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.

School-based racial segregation, social support, and late-life cognitive function in the Study of Healthy Aging in African Americans (STAR).

INTRODUCTION: School-based social support for Black students may mediate or modify the association between school segregation and late-life cognition. METHODS: Study of Healthy Aging in African Americans participants (n = 574) reported segregated school attendance and school-based social support. Associations of segregated schooling with domain-specific cognitive outcomes and effect modification or mediation by school-based social support were evaluated with linear mixed models. RESULTS: Segregated school attendance was associated with increased likelihood of school-based social support. Segregated (vs. desegregated in 6th grade) school attendance was associated with lower executive function (ß = -0.18 [-0.34, -0.02]) and semantic memory z-scores (ß = -0.31 [-0.48, -0.13]). Social support did not mediate these associations. Estimates for segregated school attendance were attenuated among those who felt supported, although there was limited evidence of statistically significant effect modification. DISCUSSION: Early-childhood school segregation was associated with poorer cognitive function. Sources of resilience within racialized educational experiences should be further evaluated to bridge inequities. HIGHLIGHTS: School segregation is a form of structural racism that affected the educational experiences of Black youth with potentially lasting consequences for healthy brain aging. Black students who attended a segregated school experienced greater school-based social support, which may highlight a potential source of resilience and resistance against the effects of racism-related stressors on cognitive function. The estimated adverse association between attending a segregated school on cognition was larger for students without an adult at school who cared about them versus those with an adult at school who cared about them, but estimates were imprecise.

Cerebral amyloid angiopathy interacts with neuritic amyloid plaques to promote tau and cognitive decline.

Accumulating data suggest that cerebrovascular disease contributes to Alzheimer's disease pathophysiology and progression toward dementia. Cerebral amyloid angiopathy is a form of cerebrovascular pathology that results from the build-up of ß-amyloid in the vessel walls. Cerebral amyloid angiopathy commonly co-occurs with Alzheimer's disease pathology in the ageing brain and increases the risk of Alzheimer's disease dementia. In the present study, we examined whether cerebral amyloid angiopathy influences tau deposition and cognitive decline independently or synergistically with parenchymal ß-amyloid burden. Secondly, we examined whether tau burden mediates the association between cerebral amyloid angiopathy and cognitive decline. We included data from autopsied subjects recruited from one of three longitudinal clinical-pathological cohort studies: the Rush Memory and Aging Project, the Religious Orders Study and the Minority Aging Research Study. Participants completed annual clinical and cognitive evaluations and underwent brain autopsy. Cerebral amyloid angiopathy pathology was rated as none, mild, moderate or severe. Bielschowsky silver stain was used to visualize neuritic ß-amyloid plaques and neurofibrillary tangles. We used linear regression and linear mixed models to test independent versus interactive associations of cerebral amyloid angiopathy and neuritic plaque burden with tau burden and longitudinal cognitive decline, respectively. We used causal mediation models to examine whether tau mediates the association between cerebral amyloid angiopathy and cognitive decline. The study sample included 1722 autopsied subjects (age at baseline = 80.2 ± 7.1 years; age at death = 89.5 ± 6.7 years; 68% females). Cerebral amyloid angiopathy interacted with neuritic plaques to accelerate tau burden and cognitive decline. Specifically, those with more severe cerebral amyloid angiopathy pathology and higher levels of neuritic plaque burden had greater tau burden and faster cognitive decline. We also found that tau mediated the association between cerebral amyloid angiopathy and cognitive decline among participants with higher neuritic plaque burden. In summary, more severe levels of cerebral amyloid angiopathy and higher parenchymal ß-amyloid burden interacted to promote cognitive decline indirectly via tau deposition. These results highlight the dynamic interplay between cerebral amyloid angiopathy and Alzheimer's disease pathology in accelerating progression toward dementia. These findings have implications for Alzheimer's disease clinical trials and therapeutic development.

Sex-specific effects of microglial activation on Alzheimer's disease proteinopathy in older adults.

Females show a disproportionate burden of Alzheimer's disease pathology and higher Alzheimer's disease dementia prevalences compared to males, yet the mechanisms driving these vulnerabilities are unknown. There is sexual dimorphism in immunological functioning, and neuroimmune processes are implicated in Alzheimer's disease genesis. Using neuropathology indicators from human brain tissue, we examined the mediational role of microglial activation on the relationship between amyloid and tau and how it differs by sex. 187 decedents (64% female; 89 mean age at death; 62% non-demented) from the Rush Memory and Aging Project completed neuropathological evaluations with brain tissue quantified for microglial activation, amyloid-ß and tau. Proportion of morphologically activated microglia was determined via immunohistochemistry (HLA-DP-DQ-DR) and morphological staging (stage I, II or III). Amyloid-ß and tau burden were quantified via immunohistochemistry (M00872 or AT8, respectively). Using causal counterfactual modelling, we estimated the mediational effect of microglial activation on the amyloid-ß to tau relationship in the whole sample and stratified by sex (amyloid-ß â†’ microglial activation → tau). Alternative models tested the role of microglia activation as the precipitating event (microglial activation → amyloid-ß â†’ tau). Microglial activation significantly mediated 33% [95% confidence interval (CI) 10-67] of the relationship between amyloid-ß and tau in the whole sample; stratified analyses suggested this effect was stronger and only statistically significant in females. 57% (95% CI 22-100) of the effect of amyloid-ß on tau was mediated through microglial activation in females, compared to 19% (95% CI 0-64) in males. Regional analyses suggested that mediational effects were driven by greater cortical versus subcortical microglial activation. Relationships were independent of cerebrovascular disease indices. Alternative models suggested that in females, microglial activation was a significant exposure both preceding the amyloid-ß to tau relationship (mediational effect: 50%, 95% CI 23-90) and directly related to tau burden (microglia direct effect: 50%, 95% CI 10-77). By contrast, in males, only the direct effect of microglial activation to tau reached significance (74%, 95% CI 32-100) (mediational effect: 26%, 95% CI 0-68). Our models suggest a reciprocal, bidirectional relationship between amyloid-ß and microglial activation that significantly accounts for tau burden in females. By contrast, in males, direct independent (non-mediational) relationships between microglial activation or amyloid-ß with tau were observed. Microglial activation may be disproportionately important for Alzheimer's disease pathogenesis in females. Determining sex-specific vulnerabilities to Alzheimer's disease development both inform fundamental pathophysiology and support precision health approaches for this heterogeneous disease.

AD and non-AD mediators of the pathway between the APOE genotype and cognition.

INTRODUCTION: The apolipoprotein E (APOE) genotype is a driver of cognitive decline and dementia. We used causal mediation methods to characterize pathways linking the APOE genotype to late-life cognition through Alzheimer's disease (AD) and non-AD neuropathologies. METHODS: We analyzed autopsy data from 1671 individuals from the Religious Orders Study, Memory and Aging Project, and Minority Aging Research Study (ROS/MAP/MARS) studies with cognitive assessment within 5 years of death and autopsy measures of AD (amyloid beta (Aß), neurofibrillary tangles), vascular (athero/arteriolo-sclerosis, micro-infarcts/macro-infarcts), and non-AD neurodegenerative neuropathologies (TAR DNA protein 43 [TDP-43], Lewy bodies, amyloid angiopathy, hippocampal sclerosis). RESULTS: The detrimental effect of APOE ε4 on cognition was mediated by summary measures of AD and non-AD neurodegenerative neuropathologies but not vascular neuropathologies; effects were strongest in individuals with dementia. The protective effect of APOE ε2 was partly mediated by AD neuropathology and stronger in women than in men. DISCUSSION: The APOE genotype influences cognition and dementia through multiple neuropathological pathways, with implications for different therapeutic strategies targeting people at increased risk for dementia. HIGHLIGHTS: Both apolipoprotein E (APOE) ε2 and APOE ε4 effects on late-life cognition are mediated by AD neuropathology. The estimated mediated effects of most measures of AD neuropathology were similar. Non-Alzheimer's disease (AD) neurodegenerative pathologies mediate the effect of ε4 independently from AD. Non-AD vascular pathologies did not mediate the effect of the APOE genotype on cognition. The protective effect of APOE ε2 on cognition was stronger in women.

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 

Riding the merry-go-round of racial disparities in ADRD research.

INTRODUCTION: With the rapid expansion of the aging population, the burden of Alzheimer's disease related dementias (ADRD) is anticipated to increase in racialized and minoritized groups who are at disproportionately higher risk. To date, research emphasis has been on further characterizing the existence of racial disparities in ADRD through comparisons to groups racialized as White that are assumed to be normative. Much of the literature on this comparison insinuates that racialized and minoritized groups experience poorer outcomes due to genetics, culture, and/or health behaviors. METHODS: This perspective shines a light on a category of ADRD research that employs ahistorical methodological approaches to describe racial disparities in ADRD that puts us on a merry-go-round of research with no benefits to society. METHODS: This commentary provides historical context for the use of race in ADRD research and justification for the study of structural racism. The commentary concludes with recommendations to guide future research.

Pragmatic approaches to handling practice effects in longitudinal cognitive aging research.

INTRODUCTION: The challenge of accounting for practice effects (PEs) when modeling cognitive change was amplified by the COVID-19 pandemic, which introduced period and mode effects that may bias the estimation of cognitive trajectory. METHODS: In three Kaiser Permanente Northern California prospective cohorts, we compared predicted cognitive trajectories and the association of grip strength with cognitive decline using three approaches: (1) no acknowledgment of PE, (2) inclusion of a wave indicator, and (3) constraining PE based on a preliminary model (APM) fit using a subset of the data. RESULTS: APM-based correction for PEs based on balanced, pre-pandemic data, and with current age as the timescale produced the smallest discrepancy between within-person and between-person estimated age effects. Estimated associations between grip strength and cognitive decline were not sensitive to the approach used. DISCUSSION: Constraining PEs based on a preliminary model is a flexible, pragmatic approach allowing for meaningful interpretation of cognitive change. HIGHLIGHTS: The magnitude of practice effects (PEs) varied widely by study. When PEs were present, the three PE approaches resulted in divergent estimated age-related cognitive trajectories. Estimated age-related cognitive trajectories were sometimes implausible in models that did not account for PEs. The associations between grip strength and cognitive decline did not differ by the PE approach used. Constraining PEs based on estimates from a preliminary model allows for a meaningful interpretation of cognitive change.

The structural and social determinants of Alzheimer's disease related dementias.

INTRODUCTION: The projected growth of Alzheimer's disease (AD) and AD-related dementia (ADRD) cases by midcentury has expanded the research field and impelled new lines of inquiry into structural and social determinants of health (S/SDOH) as fundamental drivers of disparities in AD/ADRD. METHODS: In this review, we employ Bronfenbrenner's ecological systems theory as a framework to posit how S/SDOH impact AD/ADRD risk and outcomes. RESULTS: Bronfenbrenner defined the "macrosystem" as the realm of power (structural) systems that drive S/SDOH and that are the root cause of health disparities. These root causes have been discussed little to date in relation to AD/ADRD, and thus, macrosystem influences, such as racism, classism, sexism, and homophobia, are the emphasis in this paper. DISCUSSION: Under Bronfenbrenner's macrosystem framework, we highlight key quantitative and qualitative studies linking S/SDOH with AD/ADRD, identify scientific gaps in the literature, and propose guidance for future research. HIGHLIGHTS: Ecological systems theory links structural/social determinants to AD/ADRD. Structural/social determinants accrue and interact over the life course to impact AD/ADRD. Macrosystem is made up of societal norms, beliefs, values, and practices (e.g., laws). Most macro-level determinants have been understudied in the AD/ADRD literature.

Sex differences in associations between APOE ε2 and longitudinal cognitive decline.

INTRODUCTION: We examined whether sex modifies the association between APOE ε2 and cognitive decline in two independent samples. METHODS: We used observational data from cognitively unimpaired non-Hispanic White (NHW) and non-Hispanic Black (NHB) adults. Linear mixed models examined interactive associations of APOE genotype (ε2 or ε4 carrier vs. ε3/ε3) and sex on cognitive decline in NHW and NHB participants separately. RESULTS: In both Sample 1 (N = 9766) and Sample 2 (N = 915), sex modified the association between APOE ε2 and cognitive decline in NHW participants. Specifically, relative to APOE ε3/ε3, APOE ε2 protected against cognitive decline in men but not women. Among APOE ε2 carriers, men had slower decline than women. Among APOE ε3/ε3 carriers, cognitive trajectories did not differ between sexes. There were no sex-specific associations of APOE ε2 with cognition in NHB participants (N = 2010). DISCUSSION: In NHW adults, APOE ε2 may protect men but not women against cognitive decline. HIGHLIGHTS: We studied sex-specific apolipoprotein E (APOE) ε2 effects on cognitive decline. In non-Hispanic White (NHW) adults, APOE ε2 selectively protects men against decline. Among men, APOE ε2 was more protective than APOE ε3/ε3. In women, APOE ε2 was no more protective than APOE ε3/ε3. Among APOE ε2 carriers, men had slower decline than women. There were no sex-specific APOE ε2 effects in non-Hispanic Black (NHB) adults.

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.

Physical Performance and Cognition in a Diverse Cohort: Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study.

BACKGROUND: The authors assessed the cross-sectional association of physical function measures with cognition in the Kaiser Healthy Aging and Diverse Life Experiences Cohort. METHODS: Analyses included 1369 participants (24% Asian, 26% Black, 18% Latino, 32% White). Grip strength was measured using a hand-held dynamometer (kilograms) and gait speed was measured over a 4-m walk (seconds/meter). The Spanish and English Neuropsychological Assessment Scales was used to evaluate cognitive domains of executive function, semantic memory, and verbal episodic memory. Physical function measures (per SD) were associated with cognitive test z-scores in linear regression models adjusted for demographic, behavioral, and clinical factors. Racial/ethnic differences were tested using interaction terms and stratification. RESULTS: Stronger grip was associated with better executive function [ß=0.10 (95% confidence interval, 0.05-0.15)], semantic memory [ß=0.13 (0.09-0.18)] and verbal episodic memory [ß=0.07 (0.02-0.13)] with no racial/ethnic differences. Faster gait was associated with better executive function [ß=0.29 (0.22-0.36)], semantic memory [ß=0.23 (0.16-0.30)], and verbal episodic memory [ß=0.20 (0.13-0.27)]; however, the association between gait speed and executive function varied by race/ethnicity with the strongest associations in Asians and Whites. CONCLUSION: Across race/ethnicity, grip strength and gait speed were associated with cognition with racial/ethnic differences in the association of gait speed and executive function.

Racial/Ethnic Disparities in Young Adulthood and Midlife Cardiovascular Risk Factors and Late-life Cognitive Domains: The Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study.

BACKGROUND: Midlife cardiovascular risk factors (CVRF) increase dementia risk. Less is known about whether CVRF identified before midlife impact late-life cognition in diverse populations. METHODS: Linear regression models examined hypertension, hyperlipidemia, and overweight/obesity at ages 30 to 59 with late-life executive function, semantic memory, verbal episodic memory, and global cognition in a cohort of Asians, blacks, Latinos, and whites (n=1127; mean age=75.8, range=65 to 98). Models adjusted for age at CVRF, age at cognitive assessment, sex, race/ethnicity, participant education, and parental education. RESULTS: Overall, 34% had 1 CVRF at ages 30 to 59; 19% had 2+. Blacks (26%) and Latinos (23%) were more likely to have 2+ CVRF than Asians (14%) or whites (13%). Having 2+ CVRF was associated with lower global cognition [ß=-0.33; 95% confidence interval (CI)=-0.45, -0.21], executive function (ß=-0.26; 95% CI=-0.39, -0.13), verbal episodic memory (ß=-0.34; 95% CI=-0.48, -0.20), and semantic memory (ß=-0.20; 95% CI=-0.33, -0.07). Interaction by age (P=0.06) indicated overweight/obesity was negatively associated with executive function at ages 30 to 39 but not at ages 40 to 59. Race/ethnic-specific effects showed disparities in CVRF prevalence impact population disparities in late-life cognition. CONCLUSION: Being overweight/obese in early adulthood and having 2+ CVRF in early adulthood/midlife are modifiable targets to redress racial/ethnic disparities in cognitive impairment and dementia.

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.

Life-Course Individual and Neighborhood Socioeconomic Status and Risk of Dementia in the Atherosclerosis Risk in Communities Neurocognitive Study.

We examined associations of individual- and neighborhood-level life-course (LC) socioeconomic status (SES) with incident dementia in the Atherosclerosis Risk in Communities cohort. Individual- and neighborhood-level SES were assessed at 3 life epochs (childhood, young adulthood, midlife) via questionnaire (2001-2002) and summarized into LC-SES scores. Dementia was ascertained through 2013 using cognitive exams, telephone interviews, and hospital and death certificate codes. Cox regression was used to estimate hazard ratios of dementia by LC-SES scores in race-specific models. The analyses included data from 12,599 participants (25% Black) in the United States, with a mean age of 54 years and median follow-up of 24 years. Each standard-deviation greater individual LC-SES score was associated with a 14% (hazard ratio (HR) = 0.86, 95% confidence interval (CI): 0.81, 0.92) lower risk of dementia in White and 21% (HR = 0.79, 95% CI: 0.71, 0.87) lower risk in Black participants. Education was removed from the individual LC-SES score and adjusted for separately to assess economic factors of LC-SES. A standard-deviation greater individual LC-SES score, without education, was associated with a 10% (HR = 0.90, 95% CI: 0.84, 0.97) lower dementia risk in White and 15% (HR = 0.85, 95% CI: 0.76, 0.96) lower risk in Black participants. Neighborhood LC-SES was not associated with dementia. We found that individual LC-SES is a risk factor for dementia, whereas neighborhood LC-SES was not associated.

Migraine Headache and Risk of Dementia in the Atherosclerosis Risk in Communities Neurocognitive Study.

OBJECTIVE: We aimed to assess the association between migraine headache and incident dementia. BACKGROUND: Migraine is a risk factor for white matter hyperintensities and ischemic stroke, which are both associated with increased risk of dementia. However, it is unknown whether migraine is independently associated with dementia. METHODS: History of migraine was ascertained via questionnaire. Adjudicated cases of dementia were identified using cognitive tests, neuropsychological exams, and clinician review of suspected cases. Incident dementia was identified using adjudicated cases, follow-up calls, and surveillance of hospital and death codes. We assessed hazards of incident dementia by migraine status. Sex differences were also examined and stratified results were presented. RESULTS: Analysis included 12,495 White and African American participants ages 51-70 with a median follow-up time of 21 years. Prevalence of dementia was 18.5% (1821/9955) among those with no migraine history, 15.8% (196/1243) among those with severe non-migraine heading, and 16.7% (233/1397) among migraineurs. There was no association between migraine and incident dementia [hazard ratio: 1.04 (0.91, 1.20)]. There was also no statistically significant interaction between sex and migraine status on risk of dementia. CONCLUSION: Despite evidence of brain abnormalities in migraineurs, there was no association between migraine and incident dementia in this prospective cohort.

No Association Found Between Midlife Seropositivity for Infection and Subsequent Cognitive Decline: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS).

Infections of herpes simplex virus type 1 (HSV-1), cytomegalovirus (CMV), Helicobacter pylori, and Chlamydia pneumoniae may play a role in cognitive decline via systemic inflammation. We hypothesized that Atherosclerosis Risk in Communities study participants who were seropositive in midlife for antibodies to HSV-1, CMV, H pylori, or C pneumoniae would have an accelerated rate of cognitive decline over 20 years. Atherosclerosis Risk in Communities performed a case-cohort study involving a stratified random sample of participants tested for serum immunoglobulin G antibodies to the pathogens of interest. We conducted a longitudinal study using this cohort. Cognitive change was measured using Z scores from the Delayed Word Recall (DWR), Digit Symbol Substitution (DSS), and Word Fluency (WF) Tests administered at visits 2 (1990-1992), 4 (1996-1998), and 5 (2011-2013). Linear regression models with generalized estimating equations and inverse probability of attrition weights were used to evaluate associations between infection and cognitive performance. Four hundred twenty-six participants were analyzed, of which 3% were seronegative for all 4 infections, 14% seropositive for one, 33% and 34% seropositive for 2 and 3, respectively, and 16% seropositive for all infections. At baseline, test scores were significantly lower for participants seropositive for H pylori and C pneumoniae. After baseline covariate adjustment, the rate of decline in DWR, DSS, WF, and global Z scores did not differ significantly by infection status for any of the 4 infections. There was also no significant association between the number of infections for which participants were seropositive and cognitive decline. Our study provides no evidence supporting a longitudinal relationship between seropositivity and cognitive decline.