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.

Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis: a genome-wide study.

AIMS: Although highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS. METHODS AND RESULTS: A genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10-8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2-SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26-1.35; P = 2.7 × 10-51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08-1.37; P = 1.4 × 10-3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90-5.12; P = 2.1 × 10-20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17-1.23; P = 4.8 × 10-73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05-1.9; P = 1.9 × 10-12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS. CONCLUSION: Dyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies.

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.

Racial and ethnic differences in the association between depressive symptoms and cognitive outcomes in older adults: Findings from KHANDLE and STAR.

INTRODUCTION: Depressive symptoms are associated with higher risk of dementia, but how they impact cognition in diverse populations is unclear. METHODS: Asian, Black, Latino, or White participants (n = 2227) in the Kaiser Healthy Aging and Diverse Life Experiences (age 65+) and the Study of Healthy Aging in African Americans (age 50+) underwent up to three waves of cognitive assessments over 4 years. Multilevel models stratified by race/ethnicity were used to examine whether depressive symptoms were associated with cognition or cognitive decline and whether associations differed by race/ethnicity. RESULTS: Higher depressive symptoms were associated with lower baseline verbal episodic memory scores (-0.06, 95% CI: -0.12, -0.01; -0.15, 95% CI: -0.25, -0.04), and faster decline annually in semantic memory (-0.04, 95% CI: -0.07, -0.01; -0.10, 95% CI: -0.15, -0.05) for Black and Latino participants. Depressive symptoms were associated with lower baseline but not decline in executive function. DISCUSSION: Depressive symptoms were associated with worse cognitive outcomes, with some evidence of heterogeneity across racial/ethnic groups. HIGHLIGHTS: We examined whether baseline depressive symptoms were differentially associated with domain-specific cognition or cognitive decline by race/ethnicity. Depressive symptoms were associated with worse cognitive scores for all racial/ethnic groups across different domains examined. Higher depressive symptoms were associated with faster cognitive decline for semantic memory for Black and Latino participants. The results suggest a particularly harmful association between depressive symptoms and cognition in certain racial/ethnic groups.

Clinical validation of the PrecivityAD2 blood test: A mass spectrometry-based test with algorithm combining %p-tau217 and Aß42/40 ratio to identify presence of brain amyloid.

BACKGROUND: With the availability of disease-modifying therapies for Alzheimer's disease (AD), it is important for clinicians to have tests to aid in AD diagnosis, especially when the presence of amyloid pathology is a criterion for receiving treatment. METHODS: High-throughput, mass spectrometry-based assays were used to measure %p-tau217 and amyloid beta (Aß)42/40 ratio in blood samples from 583 individuals with suspected AD (53% positron emission tomography [PET] positive by Centiloid > 25). An algorithm (PrecivityAD2 test) was developed using these plasma biomarkers to identify brain amyloidosis by PET. RESULTS: The area under the receiver operating characteristic curve (AUC-ROC) for %p-tau217 (0.94) was statistically significantly higher than that for p-tau217 concentration (0.91). The AUC-ROC for the PrecivityAD2 test output, the Amyloid Probability Score 2, was 0.94, yielding 88% agreement with amyloid PET. Diagnostic performance of the APS2 was similar by ethnicity, sex, age, and apoE4 status. DISCUSSION: The PrecivityAD2 blood test showed strong clinical validity, with excellent agreement with brain amyloidosis by PET.

Study design and methods: U.S. study to protect brain health through lifestyle intervention to reduce risk (U.S. POINTER).

INTRODUCTION: The U.S. study to protect brain health through lifestyle intervention to reduce risk (U.S. POINTER) is conducted to confirm and expand the results of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) in Americans. METHODS: U.S. POINTER was planned as a 2-year randomized controlled trial of two lifestyle interventions in 2000 older adults at risk for dementia due to well-established factors. The primary outcome is a global cognition composite that permits harmonization with FINGER. RESULTS: U.S. POINTER is centrally coordinated and conducted at five clinical sites (ClinicalTrials.gov: NCT03688126). Outcomes assessments are completed at baseline and every 6 months. Both interventions focus on exercise, diet, cognitive/social stimulation, and cardiovascular health, but differ in intensity and accountability. The study partners with a worldwide network of similar trials for harmonization of methods and data sharing. DISCUSSION: U.S. POINTER is testing a potentially sustainable intervention to support brain health and Alzheimer's prevention for Americans. Impact is strengthened by the targeted participant diversity and expanded scientific scope through ancillary studies.

APOE Effects on Late Life Cognitive Trajectories in Diverse Racial/Ethnic Groups.

OBJECTIVE: This study evaluated: (1) apolipoprotein E (APOE) ϵ4 prevalence among Black, Latino, and White older adults, (2) associations of APOE ϵ4 status with baseline level and change over time of cognitive outcomes across groups, and (3) combined impact of APOE ϵ4 prevalence and magnitude of effect on cognitive decline within each racial/ethnic group. METHOD: Participants included 297 White, 138 Latino, and 149 Black individuals from the longitudinal UC Davis Diversity Cohort who had APOE genotyping and ≥2 cognitive assessments. Magnitude of associations of ϵ4 with cognitive baseline and change across racial/ethnic groups was tested with multilevel parallel process longitudinal analyses and multiple group models. RESULTS: ϵ4 prevalence in Black (46%) and White participants (46%) was almost double that of Latino participants (24%). ϵ4 was associated with poorer baseline episodic memory only in White participants (p = .001), but had a moderately strong association with episodic memory change across all racial/ethnic groups (Blacks= -.061 SD/year, Latinos = -.055,Whites= -.055). ϵ4 association with semantic memory change was strongest in White participants (-.071), intermediate in Latino participants (-.041), and weakest in Black participants (-.022). CONCLUSION: Calculated cognitive trajectories across racial/ethnic groups were influenced in an additive manner by ϵ4 prevalence and strength of association with cognitive decline within the group. Group differences in ϵ4 prevalences and associations of ϵ4 with cognition may suggest different pathways from APOE to cognitive decline, and, AD possibly having less salient impact on cognitive decline in non-White participants. Differential effects of APOE on episodic memory and non-memory cognition have important implications for understanding how APOE influences late life cognitive decline.

Effects of early-life environment and adulthood SES on cognitive change in a multiethnic cohort.

OBJECTIVES: Early-life socioeconomic status (SES) and adversity are associated with late-life cognition and risk of dementia. We examined the association between early-life SES and adversity and late-life cross-sectional cognitive outcomes as well as global cognitive decline, hypothesizing that adulthood SES would mediate these associations. METHODS: Our sample (N = 837) was a racially and ethnically diverse cohort of non-Hispanic/Latino White (48%), Black (27%), and Hispanic/Latino (19%) participants from Northern California. Participant addresses were geocoded to the level of the census tract, and US Census Tract 2010 variables (e.g., percent with high school diploma) were extracted and combined to create a neighborhood SES composite. We used multilevel latent variable models to estimate early-life (e.g., parental education, whether participant ever went hungry) and adult (participant's education, main occupation) SES factors and their associations with cross-sectional and longitudinal cognitive outcomes of episodic memory, semantic memory, executive function, and spatial ability. RESULTS: Child and adult factors were strongly related to domain-specific cognitive intercepts (0.20-0.48 SD per SD of SES factor); in contrast, SES factors were not related to global cognitive change (0.001-0.01 SD per year per SD of SES factor). Adulthood SES mediated a large percentage (68-75%) of the total early-life effect on cognition. CONCLUSIONS: Early-life sociocontextual factors are more strongly associated with cross-sectional late-life cognitive performance compared to cognitive change; this effect is largely mediated through associations with adulthood SES.

Generation and age of immigration on later life cognitive performance in KHANDLE.

OBJECTIVES: We examined the association of generational status and age at immigration with later life cognitive outcomes in a diverse sample of Latinos and Asian Americans. DESIGN: Baseline data were obtained from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study, and a prospective cohort is initiated in 2017. SETTING: Older adults in Northern California. PARTICIPANTS: Our cohort consisted of Asians (n = 411) and Latinos (n = 340) who were on average 76 years old (SD = 6.8). MEASUREMENTS: We used multivariable linear regression models to estimate associations between generational status and age at immigration (collapsed into one five-level variable) with measures of verbal episodic memory, semantic memory, and executive function, adjusting for age, gender, race and ethnicity, and own- and parental education. RESULTS: Generational status and age at immigration were associated with cognitive outcomes in a graded manner. Compared to third-generation or higher immigrants, first-generation immigration in adulthood was associated with lower semantic memory (ß = -0.96; 95% CI: -1.12, -0.81) than immigration in adolescence (ß = -0.68; 95% CI: -0.96, -0.41) or childhood (ß = -0.28; 95% CI: -0.49, -0.06). Moreover, immigration in adulthood was associated with lower executive function (ß = -0.63; 95% CI: -0.78, -0.48) than immigration in adolescence (ß = -0.49; 95% CI: -0.75, -0.23). Similarly, compared to third-generation individuals, first-generation immigrants had lower executive functioning scores. CONCLUSIONS: Our study supports the notion that sociocontextual influences in early life impact later life cognitive scores. Longitudinal studies are needed to further clarify how immigration characteristics affect cognitive decline.

Assessing cognitive impairment in an ethnically diverse cohort of oldest-old: the life after 90 study.

BACKGROUND: Though dementia rates vary by racial or ethnic groups, it is unknown if these disparities remain among those aged 90 or older. AIMS: To test this hypothesis, we used baseline clinical evaluation of 541 ethnically and racially diverse individuals participating in the LifeAfter90 Study to assess how associations between core demographic characteristics and measures of physical and cognitive performance differ across the racial/ethnic groups. METHODS: Participants in this study were long-term non-demented members of Kaiser Permanente Northern California. They were clinically evaluated and diagnosed with normal or impaired cognition (mild cognitive impairment and dementia) through an in-person comprehensive clinical assessment consisting of a detailed medical history, physical and neurological examination, functional, and cognitive tests. RESULTS: The average age at enrollment was 93.0 ± 2.6 years, 62.4% female and 34.2% non-Hispanic White. At initial evaluation 301 participants had normal cognition and 165 had mild cognitive impairment (MCI) and despite screening, 69 participants were determined to have dementia. Age, education, 3MS, FAQ and CDR scores were significantly associated with cognitive impairment (normal versus MCI and dementia), but not gender. There was a significant univariate association between race/ethnicity and cognitive impairment (p < 0.02) being highest among Black (57.4%) and lowest among Asian (32.7%) individuals. After adjustment for age, gender, and education, however, prevalence of cognitive impairment was not influenced by race or ethnicity. CONCLUSION: Our results confirm the ability to reliably assess clinical diagnosis in a diverse sample of very old individuals.

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.

Neighborhood disadvantage and dementia incidence in a cohort of Asian American and non-Latino White older adults in Northern California.

INTRODUCTION: Some evidence suggests that neighborhood socioeconomic disadvantage is associated with dementia-related outcomes. However, prior research is predominantly among non-Latino Whites. METHODS: We evaluated the association between neighborhood disadvantage (Area Deprivation Index [ADI]) and dementia incidence in Asian American (n = 18,103) and non-Latino White (n = 149,385) members of a Northern California integrated health care delivery system aged 60 to 89 at baseline. Race/ethnicity-specific Cox proportional hazards models adjusted for individual-level age, sex, socioeconomic measures, and block group population density estimated hazard ratios (HRs) for dementia. RESULTS: Among non-Latino Whites, ADI was associated with dementia incidence (most vs. least disadvantaged ADI quintile HR = 1.09, 95% confidence interval [CI] = 1.02-1.15). Among Asian Americans, associations were close to null (e.g., most vs. least disadvantaged ADI quintile HR = 1.01, 95% CI = 0.85-1.21). DISCUSSION: ADI was associated with dementia incidence among non-Latino Whites but not Asian Americans. Understanding the potentially different mechanisms driving dementia incidence in these groups could inform dementia prevention efforts.

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 

The impact of attending historically Black colleges and universities on cognitive decline in Black adults: A longitudinal analysis in the KHANDLE and STAR cohorts.

INTRODUCTION: Black students attending predominantly White institutions (PWIs) versus historically Black colleges and universities (HBCUs) report more harmful discrimination and develop worse mental health outcomes, potentially offsetting the established benefits of college for lowering dementia incidence. METHODS: Black participants in two cohorts (the Kaiser Healthy Aging and Diverse Life Experiences [KHANDLE] and the Study of Healthy Aging in African Americans [STAR]) who had attended college (N = 716) self-reported the college name (classified as HBCU vs. PWI) and completed three waves of executive function (EF) and verbal episodic memory (VEM) assessments. HBCU effects on cognitive level and decline were estimated using adjusted linear mixed-effects models. RESULTS: HBCU (vs. PWI) attendees averaged better EF (ß = 0.05 [-0.22, 0.32]) and VEM (ß = 0.21 [-0.06, 0.46]) at age 70 though neither association was statistically significant. HBCU attendance was associated with slightly faster VEM decline (ß = -0.03 [-0.05, 0.00]). DISCUSSION: Harmonized analyses with larger studies are needed to estimate important effects of HBCU attendance. HIGHLIGHTS: Higher education is robustly linked to lower dementia risk, yet Black-White inequities persist among college-educated adults. Black students attending predominantly White institutions (PWIs) versus historically Black colleges and universities (HBCUs) report more harmful discrimination and develop worse mental health outcomes, which may offset the established benefits of college for lowering dementia incidence. HBCU (vs. non-HBCU) attendees averaged better executive function and verbal episodic memory (VEM) at average age 70, though confidence intervals were wide and associations were not statistically significant, and averaged slightly faster decline in VEM. Harmonized analyses using larger nationally representative studies are likely needed to avoid underestimating the health effects of HBCU attendance.

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.

rPOP: Robust PET-only processing of community acquired heterogeneous amyloid-PET data.

The reference standard for amyloid-PET quantification requires structural MRI (sMRI) for preprocessing in both multi-site research studies and clinical trials. Here we describe rPOP (robust PET-Only Processing), a MATLAB-based MRI-free pipeline implementing non-linear warping and differential smoothing of amyloid-PET scans performed with any of the FDA-approved radiotracers (18F-florbetapir/FBP, 18F-florbetaben/FBB or 18F-flutemetamol/FLUTE). Each image undergoes spatial normalization based on weighted PET templates and data-driven differential smoothing, then allowing users to perform their quantification of choice. Prior to normalization, users can choose whether to automatically reset the origin of the image to the center of mass or proceed with the pipeline with the image as it is. We validate rPOP with n = 740 (514 FBP, 182 FBB, 44 FLUTE) amyloid-PET scans from the Imaging Dementia-Evidence for Amyloid Scanning - Brain Health Registry sub-study (IDEAS-BHR) and n = 1,518 scans from the Alzheimer's Disease Neuroimaging Initiative (n = 1,249 FBP, n = 269 FBB), including heterogeneous acquisition and reconstruction protocols. After running rPOP, a standard quantification to extract Standardized Uptake Value ratios and the respective Centiloids conversion was performed. rPOP-based amyloid status (using an independent pathology-based threshold of ≥24.4 Centiloid units) was compared with either local visual reads (IDEAS-BHR, n = 663 with complete valid data and reads available) or with amyloid status derived from an MRI-based PET processing pipeline (ADNI, thresholds of >20/>18 Centiloids for FBP/FBB). Finally, within the ADNI dataset, we tested the linear associations between rPOP- and MRI-based Centiloid values. rPOP achieved accurate warping for N = 2,233/2,258 (98.9%) in the first pass. Of the N = 25 warping failures, 24 were rescued with manual reorientation and origin reset prior to warping. We observed high concordance between rPOP-based amyloid status and both visual reads (IDEAS-BHR, Cohen's k = 0.72 [0.7-0.74], ∼86% concordance) or MRI-pipeline based amyloid status (ADNI, k = 0.88 [0.87-0.89], ∼94% concordance). rPOP- and MRI-pipeline based Centiloids were strongly linearly related (R2:0.95, p<0.001), with this association being significantly modulated by estimated PET resolution (ß= -0.016, p<0.001). rPOP provides reliable MRI-free amyloid-PET warping and quantification, leveraging widely available software and only requiring an attenuation-corrected amyloid-PET image as input. The rPOP pipeline enables the comparison and merging of heterogeneous datasets and is publicly available at https://github.com/leoiacca/rPOP.

Caring for the Caregivers: An Alzheimer Disease Research Center Call to Action.

Currently, over 16 million dementia caregivers in the US provide over 18 billion hours of care. As the number of persons living with dementia increases, so too will the number of family caregivers. Given the projected steady growth in caregivers and their health-related needs in caring for persons living with Alzheimer disease and related dementias, several initiatives are underway that focus on caregivers. One overlooked mechanism to meet caregiver needs is the National Institute on Aging's Alzheimer's Disease Research Centers (ADRCs). Through secondary analysis, we present a picture of dementia caregiving from the National Alzheimer's Coordinating Center's database and discuss a call to action for ADRCs to engage caregivers and further support the mission of the ADRC to advance the field of dementia research.

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.