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Background and purposeClinicians use reference values to contextualize physical performance scores, but data are sparse in individuals 90 years and older and racial/ethnic diversity is limited in existing studies. Gait speed provides valuable information about an individual's health status. Slow gait speed is associated with falls, cognitive decline, and mortality. Here, we report gait speed reference values in a racially/ethnically diverse oldest-old cohort.MethodsLifeAfter90 is a multiethnic cohort study of individuals 90 years and older. Participants are long-term members of an integrated healthcare delivery system without a dementia diagnosis at enrollment. We assessed gait speed using the 4-m walk test and calculated means, standard deviations, and percentiles by age, sex, assistive device use, and device type. We used linear regression to compare means by sex, age, device use and type, living situation and arrangement, and race/ethnicity.Results and discussionThe mean age of the 502 participants was 92.9 (range 90.1-102.8) years. Of these, 62.6% were women, 34.7% were college educated, 90.8% lived in a private residence, 20.9% self-reported as Asian, 22.5% as Black, 11.8% as Hispanic, 35.7% as White, and 9.2% as multiple, "other," or declined to state. The overall mean gait speed was 0.54 m/s (women = 0.51 m/s, men = 0.58 m/s). Mean gait speeds were 0.58 m/s, 0.53 m/s, and 0.48 m/s in the 90 to 91, 92 to 93, and 94+ age categories, respectively. In those without a device, mean gait speed was 0.63 m/s compared to 0.40 m/s in those with a device (cane = 0.44 m/s, walker = 0.37 m/s). Mean gait speed was significantly slower in women compared to men, age category 94+ compared to 90 to 91, participants with a device compared to those without, participants with a walker compared to a cane, and Black participants compared to Asian and White participants. However, differences by race/ethnicity were attenuated when chronic health conditions were considered.ConclusionsReference values developed from this multiethnic 90+ cohort will help clinicians interpret gait speed measures and tailor recommendations toward a 90+ population that is growing in number and in racial/ethnic diversity.

IntroductionFew studies have examined the relationship between education and cognition among the oldest-old.MethodsCognitive assessments were conducted biannually for 803 participants (62.6% women) of LifeAfter90, a longitudinal study of individuals ≥ 90 years old. Gender differences in associations between education (

IntroductionSchool-based social support for Black students may mediate or modify the association between school segregation and late-life cognition.MethodsStudy 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.ResultsSegregated 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 (β = -0.18 [-0.34, -0.02]) and semantic memory z-scores (β = -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.DiscussionEarly-childhood school segregation was associated with poorer cognitive function. Sources of resilience within racialized educational experiences should be further evaluated to bridge inequities.HighlightsSchool 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.

BackgroundIntersectionality has rarely been considered in research studies of cognitive ageing. We investigated whether life-course financial mobility is differentially associated with later-life memory function and decline across intersectional identities defined by gender, and race and ethnicity.MethodsData were from two harmonised multiethnic cohorts (the Kaiser Healthy Aging and Diverse Life Experiences cohort and the Study of Healthy Aging in African Americans cohort) in northern California, USA (n=2340). Life-course financial mobility, measured using a combination of self-reported financial capital measures in childhood (from birth to age 16 years) and later adulthood (at the cohort baseline) was defined as consistently high, upwardly mobile, downwardly mobile, or consistently low. We clustered individuals into 32 strata representing intersectional identities defined by life-course financial mobility combined with gender, and race and ethnicity. Verbal episodic memory was assessed using the Spanish and English Neuropsychological Assessment Scales over four waves from 2017 to 2023. Adjusted mixed-effects linear regression models were estimated with and without fixed effects of gender, race and ethnicity, and financial mobility, to evaluate whether the random effects of the intersectional identity strata contributed variance to memory beyond individual fixed effects.FindingsMean age was 73·6 years (SD 8·1). Of 2340 individuals, 1460 (62·4%) were women, 880 (37·6%) were men, 388 (16·6%) were Asian, 1136 (48·5%) were Black, 334 (14·3%) were Latinx, and 482 (20·6%) were White. Consistently low and downwardly mobile financial capital were strongly negatively associated with later-life memory at baseline (-0·162 SD units [95% CI -0·273 to -0·051] for consistently low and -0·171 [-0·250 to -0·092] for downwardly mobile), but not rate of change over time. Intersectional identities contributed 0·2% of memory variance after accounting for the fixed effects of gender, race and ethnicity, and financial mobility.InterpretationConsistently low and downward life-course financial mobility are associated with lower later-life memory function. Intersectional identities defined by financial mobility in addition to gender, and race and ethnicity, contribute negligible additional variance to later-life memory in this study setting.FundingUS National Institute on Aging, US National Institutes of Health.

INTRODUCTION: Although poor glycemic control is associated with dementia, it is unknown if variability in glycemic control, even in those with optimal glycosylated hemoglobin A1c (HbA1c) levels, increases dementia risk. METHODS: Among 171,964 people with type 2 diabetes, we evaluated the hazard of dementia association with long-term HbA1c variability using five operationalizations, including standard deviation (SD), adjusting for demographics and comorbidities. RESULTS: The mean baseline age was 61 years (48% women). Greater HbA1c SD was associated with greater dementia hazard (adjusted hazard ratio = 1.15 [95% confidence interval: 1.12, 1.17]). In stratified analyses, higher HbA1c SD quintiles were associated with greater dementia hazard among those with a mean HbA1c

BACKGROUND: Cardiometabolic diseases (CMDs) including type 2 diabetes, heart disease, and stroke have been linked to a higher risk of dementia. We examined whether high levels of cognitive reserve (CR) can attenuate the increased dementia risk and brain pathologies associated with CMDs. METHODS: Within the UK Biobank, 216,178 dementia-free participants aged ≥ 60 were followed for up to 15 years. Baseline CMDs and incident dementia were ascertained from medical records, medication use, and medical history. Latent class analysis was used to generate an indicator of CR (low, moderate, and high) based on education, occupational attainment, confiding in others, social contact, leisure activities, and television watching time. A subsample (n = 13,663) underwent brain MRI scans during follow-up. Volumes of total gray matter (GMV), hippocampus (HV), and white matter hyperintensities (WMHV) were ascertained, as well as mean diffusivity (MD) and fractional anisotropy (FA) in white matter tracts. RESULTS: At baseline, 43,402 (20.1%) participants had at least one CMD. Over a mean follow-up of 11.7 years, 6,600 (3.1%) developed dementia. The presence of CMDs was associated with 57% increased risk of dementia (HR 1.57 [95% CI 1.48, 1.67]). In joint effect analysis, the HRs of dementia for people with CMDs and moderate-to-high CR and low CR were 1.78 [1.66, 1.91] and 2.13 [1.97, 2.30]), respectively (reference: CMD-free, moderate-to-high CR). Dementia risk was 17% lower (HR 0.83 [0.77, 0.91], p

Elucidating the mechanisms by which late-life neurodegeneration causes cognitive decline requires understanding why some individuals are more resilient than others to the effects of brain change on cognition (cognitive reserve). Currently, there is no way of measuring cognitive reserve that is valid (e.g. capable of moderating brain-cognition associations), widely accessible (e.g. does not require neuroimaging and large sample sizes), and able to provide insight into resilience-promoting mechanisms. To address these limitations, this study sought to determine whether a machine learning approach to combining standard clinical variables could (i) predict a residual-based cognitive reserve criterion standard and (ii) prospectively moderate brain-cognition associations. In a training sample combining data from the University of California (UC) Davis and the Alzheimer's Disease Neuroimaging Initiative-2 (ADNI-2) cohort (N = 1665), we operationalized cognitive reserve using an MRI-based residual approach. An eXtreme Gradient Boosting machine learning algorithm was trained to predict this residual reserve index (RRI) using three models: Minimal (basic clinical data, such as age, education, anthropometrics, and blood pressure), Extended (Minimal model plus cognitive screening, word reading, and depression measures), and Full [Extended model plus Clinical Dementia Rating (CDR) and Everyday Cognition (ECog) scale]. External validation was performed in an independent sample of ADNI 1/3/GO participants (N = 1640), which examined whether the effects of brain change on cognitive change were moderated by the machine learning models' cognitive reserve estimates. The three machine learning models differed in their accuracy and validity. The Minimal model did not correlate strongly with the criterion standard (r = 0.23) and did not moderate the effects of brain change on cognitive change. In contrast, the Extended and Full models were modestly correlated with the criterion standard (r = 0.49 and 0.54, respectively) and prospectively moderated longitudinal brain-cognition associations, outperforming other cognitive reserve proxies (education, word reading). The primary difference between the Minimal model-which did not perform well as a measure of cognitive reserve-and the Extended and Full models-which demonstrated good accuracy and validity-is the lack of cognitive performance and informant-report data in the Minimal model. This suggests that basic clinical variables like anthropometrics, vital signs, and demographics are not sufficient for estimating cognitive reserve. Rather, the most accurate and valid estimates of cognitive reserve were obtained when cognitive performance data-ideally augmented by informant-reported functioning-was used. These results indicate that a dynamic and accessible proxy for cognitive reserve can be generated for individuals without neuroimaging data and gives some insight into factors that may promote resilience.

IntroductionThere is a dearth of research on cognitive aging and dementia in Asian Americans, particularly in Vietnamese Americans, the fourth largest Asian subgroup in the United States.MethodsThe Vietnamese Insights into Cognitive Aging Program (VIP) investigates early life adversity and war-related trauma and their associations with cognitive health in a community-based sample of older Vietnamese Americans in Northern California (i.e., Sacramento and Santa Clara counties). Baseline measurements include a comprehensive neuropsychological battery, including measures of global cognition along with executive function, semantic memory, and episodic memory. Data also include measures of functioning, early life adversity and trauma exposure, and psychosocial and traditional cardiovascular disease risk factors. Cognitive assessments will be repeated twice over the course of the data collection period, approximately 12- and 24- months post-baseline. Blood samples collected during Wave 2 will be assayed for biochemical risk factors.ResultsBaseline assessments were conducted from January 2022 to November 2023, with N = 548 Vietnamese Americans; mean age ± SD was 73 ± 5.31 years and 55% of participants were women. There were significant differences in social factors by site, with Santa Clara participants having higher education (some college or higher: Sacramento, ≈25%; Santa Clara: ≈48%) and marginally higher incomes compared to Sacramento participants. A higher percentage of Santa Clara participants reported speaking English well or very well (24%) compared to Sacramento participants (13%), although the majority of the entire sample (81%) reported speaking some to no English (response options: not at all; some/a little bit; well/very well).DiscussionThis longitudinal study providea a unique opportunity to more fully delineate psychosocial factors that contribute to dementia disparities in diverse and under-engaged populations. Future work will examine cognition, the prevalence of mild cognitive impairment and dementia, and other health outcomes, while controlling for site differences in all analyses.HighlightsVietnamese Insights into Cognitive Aging Program (VIP) is a new study.VIP has detailed early life and health data on 548 older Vietnamese Americans.History of war and trauma may contribute to Alzheimer's disease and related dementias (ADRD)-related burden.VIP may provide insight into ADRD burden in other understudied groups.

BACKGROUND: With the availability of disease-modifying therapies for Alzheimers 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 (Aβ)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.

IntroductionDepressive symptoms are associated with higher risk of dementia, but how they impact cognition in diverse populations is unclear.MethodsAsian, 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.ResultsHigher 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.DiscussionDepressive symptoms were associated with worse cognitive outcomes, with some evidence of heterogeneity across racial/ethnic groups.HighlightsWe 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.

Dementia research lacks appropriate representation of diverse groups who often face substantial adversity and greater risk of dementia. Current research participants are primarily well-resourced, non-Hispanic White, cisgender adults who live close to academic medical centers where much of the research is based. Consequently, the field faces a knowledge gap about Alzheimer's-related risk factors in those other groups. The Alzheimer's Association hosted a virtual conference on June 14-16, 2021, supported in part by the National Institute on Aging (R13 AG072859-01), focused on health disparities. The conference was held entirely online and consisted of 2 days of core programming and a day of focused meetings centered on American Indian and Alaska Natives and on LGBTQIA+ populations. Over 1300 registrants attended discussions focused on the structural and systemic inequities experienced across diverse groups, as well as ways to investigate and address these inequities.

IntroductionThe prevalence of poor sleep quality and sleep apnea differs by race and ethnicity and may contribute to racial disparities in cognitive aging. We investigated whether sleep quality and sleep apnea risk were associated with cognitive function and decline and whether the associations differed by race/ethnicity.MethodsParticipants from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE; N = 1690; mean age: 75.7 years) study, a cohort of Asian, Black, Latino, and White participants, completed a modified Pittsburgh Sleep Quality Index assessing subjective sleep quality, latency, duration, disturbances, sleep medication use, and daytime dysfunction. Sleep apnea risk was measured by questions about snoring, tiredness, and whether apnea was observed. Executive function and verbal episodic memory were assessed at three time points over an average of 2.7 years with the Spanish and English Neuropsychological Assessment Scale. We fit linear mixed-effect models and stratified analyses by race/ethnicity.ResultsHigher sleep apnea risk was associated with faster declines in verbal episodic memory (β^ sleep apnea = -0.02, 95% confidence interval [CI], -0.04, -0.001) but not in executive function. Poorer sleep quality was associated with lower levels of and faster decline in executive function but not in verbal episodic memory. Race/ethnicity modified these associations: compared to estimated effects among White participants, poorer global sleep quality (β^ sleep*time = -0.02, 95% CI, -0.02, -0.01) was associated with larger effects on decline in executive function among Black participants. Estimated effects of some individual sleep quality components were also modified by race/ethnicity; for example, sleep medication use was associated with faster declines in executive function (β^ sleep*time = -0.05, 95% CI, -0.07, -0.03) and verbal episodic memory β^ sleep*time = -0.04, 95% CI, -0.07, -0.02) among Black participants compared to White participants.DiscussionObservational evidence indicates sleep quality is a promising target for addressing racial/ethnic disparities in cognitive aging, especially among Black older adults.HighlightsSleep apnea risk was associated with faster declines in verbal episodic memory but not executive function among all participants.Global sleep quality was associated with lower levels of and faster decline in executive function but not verbal episodic memory among all participants.Black older adults were particularly susceptible to the estimated adverse cognitive impacts of global sleep quality, particularly the use of sleep medication.

Abstract: Background: The oldest‐old are the fastest growing segment of the elderly population but very little is known about cognition in this age group; particularly in diverse populations. Our goal was to evaluate if domain specific cognitive change was different across different ethnoracial groups in those aged 90+. Method: LifeAfter90 (LA90) is an ongoing cohort of participants aged 90+ who are long‐term members of Kaiser Permanente Northern California participants. Participants (n = 984) were interviewed every 6 months for up to 3.5 years (1‐7 visits). Executive Function (EF) and Verbal Episodic Memory (VEM) were measured every six months using z‐standardized Spanish English Neuropsychological Assessment Scale. Racial/ethnic identify (Asian, Black, Latino, or White participants) was used in linear mixed models with random slopes and intercepts adjusting for baseline age, gender, education, interview mode, and practice effects. Result: Participants were 20% Latino, 23% Black, 24% Asian, 27% White, and 7% other individuals with a mean age of 92.4 (SD = 2.3) and a mean follow up time 1.1 years (Table 1). 39% of the cohort were men, 35% were college educated, and 29% were high school or less educated. Average annual change in EF was ‐0.06 (95% CI: ‐0.12, ‐0.00). Stratified models with Latino as the reference group showed White participants had significantly greater decline in EF (β = ‐0.13; 95%CI:‐0.20,‐0.06), followed by Asian participants (β = ‐0.09; 95%CI:‐0.17,‐0.01). EF scores among Black participants and participants who identified as other declined at a similar rate as Latino participants (β = ‐0.03; 95%CI:‐0.11,‐0.05; β = 0.00; 95%CI:‐0.10, 0.11; respectively) (Table 2: model 2). VEM had an annual change of ‐0.26 (95%CI: ‐0.40, ‐0.13), but there were no significant differences across ethnoracial groups in rate of decline. Conclusion: In this population of individuals aged 90+, decline in EF over the study period varied across ethnoracial group with White participants experiencing the fastest decline and Black, Latino, and other participants experiencing the slowest decline. Continued follow up will identify if there are differences in risk of cognitive impairment in this diverse population of oldest‐old. The results suggest the disparities in cognitive aging for those aged 90+ don’t mirror disparities seen in younger‐elderly ages.

Abstract: Background: Neuropathology studies of the oldest‐old have significantly advanced our understanding of the multiple etiologies late in very late life. Most studies, however, have limited ethnoracial diversity with almost exclusively White decedents. Our goal was to characterize neuropathology in a cohort of ethnically and racially diverse oldest‐old decedents. Method: The LifeAfter90 study is an ongoing cohort study of Kaiser Permanente Northern California members, aged 90+ with targeted recruitment of individuals across different racial/ethnic groups with no prior diagnosis of dementia in their medical record. Interviews and cognitive assessments occur approximately every 6 months. Brain donation was available to all interested consenting participants. Neuropathology was assessed using the National Alzheimer’s Coordinating Center Neuropathology form v.10 and used NIA‐AA guidelines for Alzheimer’s diagnoses. As of January 2023, 304 participants (40%) were enrolled in autopsy (20% Asian, 18% African American, 17% Latino, 9% Multiracial/Other, and 36% White). Result: Of the 304 participants, 59 had died and neuropathological evaluations were completed. The median age of death was 93 years (range 90‐105), 33 (56%) were female, 8 Asian, 5 Black, 10 Latino, 31 White, and 5 Multiracial/Other. At final clinical exam, 17 participants had dementia (29%), 25 questionable/mild cognitive impairment (42%), and 16 were cognitively normal (27%). Alzheimer disease (AD) and vascular pathologies were the most frequent findings (Figure). Twenty two percent of participants did not have AD, one lacked neurofibrillary tangles (NFT). The most severe distributions/densities of NFTs and plaques were infrequent, with high likelihood of AD in two participants. For vascular pathologies, 98% had some level of arteriolosclerosis, 97% had atherosclerosis, 70% had amyloid angiopathy, and 26% had at least one old microinfarct. Other pathologies were less common: 27% had Lewy bodies, 18% had TDP‐43 deposits, and only one had Hippocampal sclerosis. Although data is sparse to test for associations, the proportion of individuals with dementia tended to increase with increasing pathology severity especially for AD pathologies. Conclusion: This diverse cohort of oldest‐old individuals reveal numerous brain pathologies are present with advanced age, with AD and select vascular pathologies being the most common. Future analyses will investigate their role with cognitive impairment.

Abstract: Background: Whether subjective evaluations of cognition can accurately predict cognitive decline is not well understood in ethnically diverse populations nor oldest‐old. In a multi‐ethnic cohort of adults aged 90+, we aim to investigate the association between self‐perceived memory concerns and objectively measured cognitive change. Method: LifeAfter90 is an active longitudinal cohort study of Kaiser Permanente Northern California members ages 90+ with no prior dementia diagnosis. Verbal episodic memory (VEM) and executive function (EF) were assessed every 6 months between July 2018 and March 2022 using the Spanish and English Neuropsychological Assessment Scales (SENAS). At baseline, participants answered the question “Are you concerned that you have a memory or other thinking problem?” We evaluated associations between memory concerns and domain‐specific cognition at baseline and over time using linear mixed models with random intercepts and slopes, adjusted for baseline age, sex, race/ethnicity, education, interview mode (in‐person or phone), and practice effects. Sensitivity analyses stratified by 1) gender and 2) age (+/‐ 95 years). Result: At baseline, participants (n = 975) had a mean age of 92.4 (SD = 2.3) years, 61% were women, 73% were racial/ethnic minorities, and 36% reported memory concerns (Table 1). Memory concerns were associated with worse baseline VEM (b = ‐0.17, 95% CI ‐0.27,‐0.07; Table 2) and EF (b = ‐0.08, 95% CI ‐0.15,‐0.01; Table 3), but not associated with rate of change for either domain. When stratified by gender, both men and women with memory concerns had worse baseline VEM (b = ‐0.21, 95% CI ‐0.36,‐0.06 and b = ‐0.15, 95% CI ‐0.27,‐0.02, respectively; Table 2). Additionally, men with memory concerns had worse baseline EF (b = ‐0.19; 95% CI ‐0.30,‐0.08; Table 3). Among participants younger than 95 years, memory concerns were associated with worse baseline VEM (b = ‐0.15, 95% CI ‐0.25,‐0.04; Table 2) and EF (b = ‐0.10, 95% CI ‐0.17,‐0.02; Table 3). Conclusion: In this diverse cohort of oldest‐old, those with subjective memory concerns had worse baseline VEM and EF. Although memory concern may suggest objective cognitive impairment, it is not associated with decline over the short term; (an average follow up time of 1.05 years). Additional follow up will identify how changes in memory concerns may be associated with cognitive change.

ObjectivesAdverse 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).DesignLinear 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.SettingsKaiser Permanente Northern California members living in the Bay Area.ParticipantsSTAR 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).ResultsTwenty-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 (β=0.117; 95% CI 0.052 to 0.182), three ACEs (β=0.075; 95% CI 0.007 to 0.143) and four or more ACEs (β=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.ConclusionIn 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.

ObjectivesEarly-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.MethodsOur 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.ResultsChild 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.ConclusionsEarly-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.

IntroductionHigher occupational complexity has been linked to favorable cognitive outcomes, but rarely examined in racially and ethnically diverse populations.MethodsIn 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.ResultsFor occupational complexity with data, highest tertile (vs. lowest) was associated with higher baseline executive function (β = 0.11; 95% confidence interval [CI] 0.00-0.22) and slower annual rate of decline (β = 0.03; 95% CI 0.01-0.06), and higher baseline semantic memory (β = 0.14; 95% CI 0.04-0.25). Highest tertile of occupational complexity with people was associated with higher baseline executive function (β = 0.29; 95% CI 0.18-0.40), verbal episodic memory (β = 0.12; 95% CI 0.00-0.24), and semantic memory (β = 0.23; 95% CI 0.12-0.34).DiscussionIn a diverse cohort, higher occupational complexity is associated with better cognition. Findings should be verified in larger cohorts.HighlightFew 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.

IntroductionCurrent efforts to reduce dementia focus on prevention and risk reduction by targeting modifiable risk factors. As dementia and cardiometabolic non-communicable diseases (NCDs) share risk factors, a single risk-estimating tool for dementia and multiple NCDs could be cost-effective and facilitate concurrent assessments as compared with a conventional single approach. The aim of this study is to develop and validate a new risk tool that estimates an individual's risk of developing dementia and other NCDs including diabetes mellitus, stroke and myocardial infarction. Once validated, it could be used by the public and general practitioners.Methods and analysisTen high-quality cohort studies from multiple countries were identified, which met eligibility criteria, including large representative samples, long-term follow-up, data on clinical diagnoses of dementia and NCDs, recognised modifiable risk factors for the four NCDs and mortality data. Pooled harmonised data from the cohorts will be used, with 65% randomly allocated for development of the predictive model and 35% for testing. Predictors include sociodemographic characteristics, general health risk factors and lifestyle/behavioural risk factors. A subdistribution hazard model will assess the risk factors' contribution to the outcome, adjusting for competing mortality risks. Point-based scoring algorithms will be built using predictor weights, internally validated and the discriminative ability and calibration of the model will be assessed for the outcomes. Sensitivity analyses will include recalculating risk scores using logistic regression.Ethics and disseminationEthics approval is provided by the University of New South Wales Human Research Ethics Committee (UNSW HREC; protocol numbers HC200515, HC3413). All data are deidentified and securely stored on servers at Neuroscience Research Australia. Study findings will be presented at conferences and published in peer-reviewed journals. The tool will be accessible as a public health resource. Knowledge translation and implementation work will explore strategies to apply the tool in clinical practice.

IntroductionThe 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.MethodsIn 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.ResultsAPM-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.DiscussionConstraining PEs based on a preliminary model is a flexible, pragmatic approach allowing for meaningful interpretation of cognitive change.HighlightsThe 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.

IntroductionBlack 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.MethodsBlack 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.ResultsHBCU (vs. PWI) attendees averaged better EF (β = 0.05 [-0.22, 0.32]) and VEM (β = 0.21 [-0.06, 0.46]) at age 70 though neither association was statistically significant. HBCU attendance was associated with slightly faster VEM decline (β = -0.03 [-0.05, 0.00]).DiscussionHarmonized analyses with larger studies are needed to estimate important effects of HBCU attendance.HighlightsHigher 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.

Abstract: Background: SuperAgers are individuals who maintain superior cognitive performance despite advanced age. Most studies define SuperAgers as superior performers only in episodic memory. Our aim was to assess in a diverse oldest‐old cohort if superior performance in one domain indicates superior performance in other domains and explore demographic characteristics. Methods: The LifeAfter90 study is a multi‐ethnic cohort of members of Kaiser Permanente Northern California aged 90 or older. Baseline verbal episodic memory (VEM), semantic memory (SM), and executive function (EF) were evaluated using the Spanish and English Neuropsychological Assessment Scale (SENAS). SuperAgers were individuals who scored above the mean of domain and race‐specific SENAS scores from a reference cohort aged 65‐70 years. The reference group were similar participants from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study. To assess the association between age, sex, education, and being a SuperAger, odds ratios (OR) and 95% confidence interval (CI) were calculated using multiple logistic regression. Results: The 617 study participants (236 men and 381 women) had a mean age of 92.9 years (Table1). 53.6% of individuals were SuperAgers in one domain, 22.8% in any two domains, and 7.7% in all three domains. 7.0% of individuals were SuperAgers in SM and EF, 4.5% in VEM and EF, and 3.5% in VEM and SM (Figure1). SuperAgers were younger than non‐SuperAgers. Women were more likely to be SuperAgers in VEM (OR = 2.13; 95%CI: 1.43,3.18) and EF (OR = 2.18; 95%CI: 1.44,3.30) and less likely in SM (OR = 0.49; 95%CI: 0.34,0.71) compared to men. Higher education was related to being a SuperAger in SM (OR = 1.85; 95%CI: 1.28,2.67) and EF (OR = 2.56; 95%CI: 1.74,3.78) but not VEM (Table2). Conclusion: In this diverse cohort of oldest‐old SuperAgers we found that exceptional episodic memory performance does not indicate exceptional performance in other cognitive domains. Education was not a predictor of exceptional performance in all domains. Future work should investigate predictors of exceptional cognitive aging after age 90.

AimsAlthough 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 resultsA 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.ConclusionDyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies.

BackgroundThough dementia rates vary by racial or ethnic groups, it is unknown if these disparities remain among those aged 90 or older.AimsTo 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.MethodsParticipants 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.ResultsThe 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

There is a dearth of research on cognitive aging and dementia in Asian Americans, particularly Vietnamese Americans, who are the fourth largest Asian subgroup in the United States. The National Institutes of Health is mandated to make certain that racially and ethnically diverse populations are included in clinical research. Despite the widespread recognition to ensure that research findings can be generalizable to all groups, there are no estimates of the prevalence or incidence of mild cognitive impairment and Alzheimer's disease and related dementias (ADRD) in Vietnamese Americans, nor do we understand ADRD risk and protective factors in this group. In this article, we posit that studying Vietnamese Americans contributes to a better understanding of ADRD in general and offers unique opportunities for elucidating life course and sociocultural factors that contribute to cognitive aging disparities. That is, the unique context of Vietnamese Americans may provide understanding in terms of within-group heterogeneity and key factors in ADRD and cognitive aging. Here, we provide a brief history of Vietnamese American immigration and describe the large but often ignored heterogeneity of Asian Americans in the United States, elucidate how early life adversity and stress might influence late-life cognitive aging, and provide a basis for the role of sociocultural and health factors in the study of Vietnamese cognitive aging disparities. Research with older Vietnamese Americans provides a unique and timely opportunity to more fully delineate the factors that contribute to ADRD disparities for all populations.

ObjectiveThis 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.MethodParticipants 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.Resultsϵ4 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).ConclusionCalculated 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.

IntroductionSome evidence suggests that neighborhood socioeconomic disadvantage is associated with dementia-related outcomes. However, prior research is predominantly among non-Latino Whites.MethodsWe 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.ResultsAmong 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).DiscussionADI 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.

ObjectivesWe examined the association of generational status and age at immigration with later life cognitive outcomes in a diverse sample of Latinos and Asian Americans.DesignBaseline data were obtained from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study, and a prospective cohort is initiated in 2017.SettingOlder adults in Northern California.ParticipantsOur cohort consisted of Asians (n = 411) and Latinos (n = 340) who were on average 76 years old (SD = 6.8).MeasurementsWe 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.ResultsGenerational 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 (β = -0.96; 95% CI: -1.12, -0.81) than immigration in adolescence (β = -0.68; 95% CI: -0.96, -0.41) or childhood (β = -0.28; 95% CI: -0.49, -0.06). Moreover, immigration in adulthood was associated with lower executive function (β = -0.63; 95% CI: -0.78, -0.48) than immigration in adolescence (β = -0.49; 95% CI: -0.75, -0.23). Similarly, compared to third-generation individuals, first-generation immigrants had lower executive functioning scores.ConclusionsOur 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.

BackgroundModifiable 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.MethodsThe 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.ResultsAfter adjusting for time-varying SES, the estimated marginal effect of rural residence in childhood was harmful for both executive function (β = -0.19, 95% confidence interval [CI] = -0.32, -0.06) and verbal episodic memory (β = -0.22, 95% CI = -0.35, -0.08). Effects of adult rural residence were imprecisely estimated with beneficial point estimates for both executive function (β = 0.19; 95% CI = -0.07, 0.44) and verbal episodic memory (β = 0.24, 95% CI = -0.07, 0.55).ConclusionsChildhood rurality is associated with poorer late-life cognition independent of SES.

IntroductionFew longitudinal studies have examined the joint impact of neighborhood segregation and neighborhood socioeconomic status (NSES) in cognitive decline over time.MethodsThis study included non-Hispanic White (NHW, n = 209) and Black participants (n = 118) whose cognition was evaluated as part of an ongoing longitudinal study. Four distinct categories of segregation and NSES were evaluated for their association with cognitive outcomes (episodic memory, semantic memory, executive function, and spatial ability) using race-specific mixed-effects models.ResultsCompared to Black participants living in higher segregation-lower NSES areas, Black participants living in lower segregation-lower NSES areas or higher segregation-higher NSES areas experienced slower decline in episodic memory over time. Compared to NHW participants living in higher segregation-lower NSES areas, NHWs living in lower segregation-higher NSES areas experienced faster decline in spatial ability.DiscussionSegregation and NSES are differentially associated with cognition depending on participant race. Further research is needed to replicate study results.

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  β = 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.

IntroductionMost dementia studies are not population-representative; statistical tools can be applied to samples to obtain critically-needed population-representative estimates, but are not yet widely used.MethodsWe pooled data from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study and the California Behavioral Risk Factor Surveillance System (CA-BRFSS), a population-representative study. Using weights accounting for sociodemographic/health differences between KHANDLE and CA-BRFSS, we estimated cognitive impairment prevalence and age- and sex-adjusted racial/ethnic inequalities in California adults 65+ without prior dementia diagnosis.ResultsAfter weighting KHANDLE, the estimated cognitive impairment prevalence in California was 20.3% (95% confidence interval 17.8-23.0); unweighted prevalence was 24.8% (23.1%-26.6%). Inequalities (larger prevalences) were observed among Black and Asian groups versus whites.DiscussionWe used a novel statistical approach to estimate population-representative cognitive impairment prevalence and inequalities. Such statistical tools can help obtain population-representative estimates from existing studies and inform efforts to reduce racial/ethnic disparities.

IntroductionLiterature shows lower dementia incidence in Asian American groups versus whites, varying by Asian ethnicity. One hypothesized driver is nativity differences (eg, healthy immigrant effect).MethodsWe followed a cohort of 6243 Chinese, 4879 Filipino, 3256 Japanese, and 141,158 white Kaiser Permanente Northern California members for incident dementia (2002 to 2020), estimating age-adjusted dementia incidence rates by ethnicity and nativity, and hazard ratios (HR) for nativity on dementia incidence using ethnicity-stratified age- and sex-adjusted Cox proportional hazards models.ResultsDementia incidence appeared higher in foreign- versus US-born Filipinos (HR, 95% confidence interval: 1.39, 1.02 to 1.89); differences were small in Japanese (1.07, 0.88 to 1.30) and Chinese (1.07, 0.92 to 1.24). No nativity differences were observed among whites (1.00, 0.95 to 1.04).DiscussionNativity does not explain lower dementia incidence in Asian Americans versus whites, but may contribute to heterogeneity across Asian ethnicities. Future research should explore differential impacts of social and cardiometabolic factors.

ObjectiveCognitive functioning is associated with instrumental activity of daily living (IADL) performance among older adults. The present study examines potential differences in the prevalence of IADL difficulty and association with cognition across diverse groups.MethodParticipants included 455 non-Hispanic Whites, 395 Blacks, 370 Asians, and 296 Latinos aged 65 years and older without a current dementia diagnosis from the Kaiser Healthy Aging and Diverse Life Experience cohort. Participants' self-reported IADL functioning and cognition was measured across episodic memory and executive functioning.ResultsOlder age, male gender, and being Black were associated with more IADL difficulties. Executive functioning showed a stronger association with IADLs than memory, and it was independent of health status, whereas memory was not. In joint models including both cognitive domains, executive functioning remained a significant predictor of IADL difficulty, but memory did not. Results for both cognitive domains were attenuated with self-rated health added to the joint model. These relationships did not significantly differ across racial/ethnic groups.ConclusionsOur study supports previous work suggesting that Black older adults are at increased risk for IADL disability. This is the first study we are aware of that examined the association between specific cognitive domains and IADL performance across multiple racial/ethnic groups. Findings indicate that cognitive functioning has similar associations with self-reported IADL disability across diverse groups, and that executive functioning plays a particularly important role in IADL disability among older adults without dementia; however, health status largely attenuates the relationship between IADL difficulty and cognition.

IntroductionThe incidence of both type 1 diabetes (T1D) and type 2 diabetes (T2D) is increasing. Life expectancy is improving in T1D, resulting in a growing population of elderly adults with diabetes. While it is well established that older adults with T2D are at increased risk of cognitive impairment, little is known regarding cognitive aging in T1D and how their cognitive profiles may differ from T2D.Research design and methodsWe compared baseline cognitive function and low cognitive function by diabetes status (n=734 T1D, n=232 T2D, n=247 without diabetes) among individuals from the Study of Longevity in Diabetes (mean age=68). We used factor analysis to group cognition into five domains and a composite measure of total cognition. Using linear and logistic regression models, we examined the associations between diabetes type and cognitive function, adjusting for demographics, comorbidities, depression, and sleep quality.ResultsT1D was associated with lower scores on total cognition, language, executive function/psychomotor processing speed, and verbal episodic memory, and greater odds of low executive function/psychomotor processing speed (OR=2.99, 95% CI 1.66 to 5.37) and verbal episodic memory (OR=1.92, 95% CI 1.07 to 3.46), compared with those without diabetes. T2D was associated with lower scores on visual episodic memory. Compared with T2D, T1D was associated with lower scores on verbal episodic memory and executive function/psychomotor processing speed and greater odds of low executive function/psychomotor processing speed (OR=1.74, 95% CI 1.03 to 2.92).ConclusionsOlder adults with T1D had significantly poorer cognition compared with those with T2D and those without diabetes even after accounting for a range of comorbidities. Future studies should delineate how to reduce risk in this vulnerable population who are newly surviving to old age.

ObjectivesUnderstanding racial/ethnic disparities in late-life cognitive health is a public health imperative. We used baseline data from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study to examine how age, education, gender, and clinical diagnosis, a proxy for brain health, are associated with cross-sectional measures of cognition in diverse racial/ethnic groups.MethodsComprehensive measures of cognition were obtained using the Spanish and English Neuropsychological Assessment Scales and the National Institutes of Health Toolbox Cognitive Health Battery in a sample of 1,695 KHANDLE participants (Asians 24%, Blacks 26%, Latinos 20%, Whites 29%). A 25% random subsample was clinically evaluated and diagnosed with normal cognition, mild cognitive impairment (MCI), or dementia. Cognitive test scores were regressed on core demographic variables and diagnosis in the combined sample and in multiple group analyses stratified by racial/ethnic group.ResultsRace/ethnicity and education were variably associated with test scores with strongest associations with tests of vocabulary and semantic memory. Older age was associated with poorer performance on all measures, and gender differences varied across cognitive tests. Clinical diagnosis of MCI or dementia was associated with average decrements in test scores that ranged from -0.41 to -0.84 SD, with largest differences on tests of executive function and episodic memory. With few exceptions, associations of demographic variables and clinical diagnosis did not differ across racial/ethnic groups.DiscussionThe robust associations of cognitive test results with clinical diagnosis independent of core demographic variables and race/ethnicity support the validity of cognitive tests as indicators for brain health in diverse older adults.

BackgroundDespite growing research on the association between discrimination and disparities in cognitive aging, an evidence gap remains on how the association varies by racial/ethnic group. This study evaluates the associations of experiences of discrimination with cognitive function and whether these associations varied by race/ethnicity and nativity.MethodUsing the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) cohort (N = 1 712) with approximately equal groups of Black, White, Latino, and Asian community-dwelling older adults aged 65 years and older, we evaluated the associations between self-reported experiences of everyday and major lifetime discrimination with overall cognitive performance and domain-specific cognition (verbal episodic memory, semantic memory, and executive functioning) across race/ethnicity and nativity. Linear regression models examined the cross-sectional association between self-reported experiences of everyday and major lifetime discrimination with z-standardized coefficients for cognition. We tested for effect modification by race and nativity. All models controlled for age, sex, and education.ResultsAmong KHANDLE participants (mean age: 76 years; SD: 6.8), everyday discrimination was not associated with cognitive scores. Major lifetime discrimination was associated with better average cognitive scores among Black participants but not among other racial/ethnic groups. Major lifetime discrimination was associated with better average cognitive scores among U.S.-born but not among non-U.S.-born individuals.ConclusionOur findings do not imply that discrimination improves cognition, but rather suggest that future research should include more detailed measures on discrimination and unfair treatment that could help disentangle the extent to which relationships are causal or reflect some other underlying factor.

Neuropathology studies of the oldest-old have significantly advanced our understandingof the multiple etiologies late in very late life; however, this hasbeen limited to studies of non-Hispanic white (NHW) decedents. The LifeAfter90study is an ongoing cohort study of integrated healthcare deliverysystem members in Northern California, aged 90+ with targeted recruitmentof persons across different racial/ethnic backgrounds with no prior diagnosisof dementia in their medical record. Brain donation is available to all interestedconsenting participants. As of January 2022, 216 participants (26% ofsample) were enrolled in autopsy (autopsy enrollees: 20% Asian, 15% AfricanAmerican, 17% Latino, 9% Multiracial/Other, and 39% NHW) with 25deceased and neuropathological evaluations completed. Average age ofdeath was 95 years (range 91-106), 13 (62.5%) were female, 14 NHW, 6 Latino,3 Multiracial, 1 Asian, and 1 African American. At final clinical exam,14 participants were cognitively normal (56%), 8 had questionable/mild cognitiveimpairment (32%), and 3 were dementia (12%). With respect to Alzheimer'sdisease (AD) neuropathologic diagnosis, no cases had high ADlikelihood, 8 met criteria for intermediate (32%), 11 low (44%), and 6 did nothave AD (24%). All participants had some level of neurofibrillary tangles(NFTs); median Braak NFT stage was II (range I-V). Six participants lackedplaques, and highest Thal phase was 4. Eleven participants (44%) had Lewybodies. TDP-43 inclusions were detected in 5 participants (20%). The mostcommon assessed pathologies were ARTAG in 19 participants (76%) andsome degree of arteriolosclerosis in 24 participants (96%) although only 4were considered to have severe arteriolosclerosis. This diverse cohort ofoldest-old individuals indicate numerous brain pathologies are present withadvanced age, albeit most participants having mild severity and distributionsof pathologies providing further evidence of the complex and multifactorialnature of clinic-pathological correlations.

The Alzheimer's Association International Conference held its sixth Satellite Symposium in Sydney, Australia in 2019, highlighting the leadership of Australian researchers in advancing the understanding of and treatment developments for Alzheimer's disease (AD) and other dementias. This leadership includes the Australian Imaging, Biomarker, and Lifestyle Flagship Study of Ageing (AIBL), which has fueled the identification and development of many biomarkers and novel therapeutics. Two multimodal lifestyle intervention studies have been launched in Australia; and Australian researchers have played leadership roles in other global studies in diverse populations. Australian researchers have also played an instrumental role in efforts to understand mechanisms underlying vascular contributions to cognitive impairment and dementia; and through the Women's Healthy Aging Project have elucidated hormonal and other factors that contribute to the increased risk of AD in women. Alleviating the behavioral and psychological symptoms of dementia has also been a strong research and clinical focus in Australia.

Alzheimer's disease (AD) and vascular dementia are two of the most prevalent dementias that afflict the aging population in the United States (US). Studies have made great strides in understanding the neuropathology of these diseases; however, many studies are conducted in the context of non-Hispanic whites (NHWs), and few include the rapidly growing underrepresented populations that reside in the US. We sought to characterize current knowledge of the neuropathologic landscape of AD and vascular dementia of the largest growing US minority groups, namely Latinos/Hispanics, Black Americans, and Asian Americans, compared with NHWs being the majority group. It is vital to note these historic categories are social constructs and cultural and social associations may underlie differences.  We conducted a literature search utilizing specific criteria to yield neuropathology papers that addressed the demographics and neuropathologies of relevance, then collated the findings into this review. We reveal that while there has been much progress in neuropathological research involving Latinos/Hispanics and Black Americans in the past decade, no cohesive conclusions could be extrapolated from the existing data due to the dearth of minority participants and even smaller amount of information related to the heterogeneity within each minority group, especially Latinos/Hispanics. Furthermore, we reveal an even greater scarcity in neuropathological studies involving Asian Americans, also a very heterogeneous group. We hope the presented findings will illuminate the paucity of minority representation in not just neuropathological research but the field of clinical research overall and serve to inspire clinicians and researchers to help reduce the health disparities underrepresented groups in the US face.

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.

PurposeWe examined the association of Stroke Belt birth state with late-life cognition in The Study of Healthy Aging in African Americans (STAR).MethodsSTAR 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.ResultsTwenty-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 (β [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}]).ConclusionsBlack 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.

BackgroundLow 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.MethodsIn 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.ResultsParticipants with low childhood/high late-life financial capital had better semantic memory (β = 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 (β = 0.32; 95% CI: 0.01, 0.63), but lower verbal episodic memory if they had high childhood/low late-life cultural capital (β = - 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 (β = 0.34; 95% CI: 0.14, 0.55), but lower verbal episodic memory among those with a foreign childhood (β = - 0.10; 95% CI: - 0.51, 0.31).ConclusionsHigh financial and cultural capital in late life is associated with better cognition, regardless of early childhood SES or childhood residence.

Persons over the age of 90 are the fastest growing segment of the population in the US, yet there is a dearth of studies investigating the underlying neuropathology of cognitive impairment and dementias, in ethnically diverse, non-white decedents. The Life after 90 study began enrollment in July 2018 and is an ongoing cohort study of members of Kaiser Permanente Northern California aged 90+ with targeted recruitment of individuals across different racial/ethnic groups with no prior diagnosis of dementia in their medical record. Participants are examined every 6 months. Brain donation was available to all interested consenting participants. Neuropathology was assessed using the National Alzheimer's Coordinating Center Neuropathology form v. 10. As of January 2021, 173 (26%) participants enrolled in autopsy (18% Asian, 12% African American, 12% Latino, and 10% as multiracial) with 8 deceased and neuropathological evaluations completed. Average age of death was 96 years (range 91 to 105), 5 (62.5%) were female, 3 Latino, 3 Caucasian, and 2 multiracial. At the final clinical exam, which was on average 4 months before death (range: 2-8), 2 participant had dementia (25%), 3 questionable/mild cognitive impairment (37.5%), and 3 cognitively normal (37.5%). With respect to a neuropathologic diagnosis of Alzheimer's disease (AD), 2 met criteria for intermediate likelihood (25%), 4 low (50%), and 2 were considered not to have AD (25%). Notably, none had high likelihood of AD. All participants had some level of neurofibrillary tangles with Braak stages between II and IV. Two participants lacked plaques (Amyloid-Beta or neuritic types), and the highest Thal phase was 4. Four participants (50%) had Lewy bodies (LBs), 1 in olfactory bulb/tract only, 2 Transitional, and 1 with Diffuse. Hippocampal sclerosis was not seen in any whereas TDP-43 inclusions were detected in 2 participants (25%). Diffuse LB, TDP-43 inclusions, and intermediate AD co-occurred in one (50%) of the dementia participants while all lacking in the other. Preliminary results of the first 8 deaths in this multiethnic cohort of oldest-old individuals indicate that numerous brain pathologies are present with advanced age. Further work with this study will examine the clinical impact of this pathological heterogeneity.