Strength together: examining risk and protective factors associated with dementia and cognitive impairment in Aboriginal and Torres Strait Islander peoples through harmonisation of landmark studies.

BACKGROUND: Rates of dementia for Aboriginal and Torres Strait Islander peoples are three to five times greater compared to non-Indigenous Australians, with earlier age of onset. However, the risk and protective factors that drive these higher rates vary across existing cohort studies, with minimal findings on the role of vascular risk factors beyond stroke. Harmonisation of data across studies may offer greater insights through enhanced diversity and strengthened statistical capabilities. This study aims to combine three landmark cohort studies of Aboriginal and Torres Strait Islander participants to better understand the determinants of cognitive health and dementia. METHODS/DESIGN: Three cohort studies - the Kimberley Healthy Adults Project (KHAP, N = 363), Koori Growing Old Well Study (KGOWS, N = 336) and Torres Strait Dementia Prevalence Study (TSDPS, N = 274) - share a similar research methodology with demographic, medical history, psychosocial factors, cognitive tests and consensus clinical diagnoses of cognitive impairment and dementia. Associations between risk and protective factors of interest and the presence of dementia and/or cognitive impairment diagnoses will be evaluated by univariable and multivariable logistic regression in a harmonised cross-sectional cohort of 898 participants. Factors associated with incident dementia and/or cognitive impairment will be assessed in a subset of KHAP (n = 189) and KGOWS participants (n = 165) who were available in longitudinal follow-up, after exclusion of those with baseline dementia or cognitive impairment. Analyses in relation to outcome measure of death or dementia will be conducted to account for the competing risk of death. Logistic regression will be used to evaluate the association between the individual components of the 16-component Kimberley Indigenous Cognitive Assessment (KICA) tool and the presence of dementia and cognitive impairment determined by independent consensus diagnoses. Multivariable binary logistic regression will be used to adjust for the effect of confounding variables. Results will be reported as odds ratios (OR) with 95% confidence intervals (95% CI). DISCUSSION: Greater understanding of risk and protective factors of dementia and cognitive impairment relevant to Aboriginal and Torres Strait Islander peoples may improve approaches across the life course to delay cognitive decline and reduce dementia risk.

Potentially Avoidable Hospitalizations Among Historically Marginalized Nursing Home Residents.

Importance: Nursing home (NH) transfers to hospitals are common and have been associated with cognitive decline; approximately 45% of NH hospital transfers are potentially avoidable hospitalizations (PAHs). Objective: To determine PAH incidence for historically marginalized NH residents with severe cognitive impairment compared with non-Hispanic White residents. Design, Setting, and Participants: This cross-sectional study merged 2018 Centers for Medicaid & Medicare Services datasets and LTCFocus, a public dataset on US NH care, for US NH residents aged 65 years and older who had a hospitalization. Analyses were performed from January to May 2022. Exposure: Race and ethnicity of NH residents. Main Outcomes and Measures: Racial and ethnic differences in resident-level annual rates of PAHs were estimated for residents with and without severe cognitive impairment (measured using the Cognitive Function Scale), controlling for resident characteristics, comorbidities, dual eligibility, and time at risk. PAHs were defined as NH hospital transfers that resulted from neglectful NH care or for which NH treatment would have been appropriate. Results: Of 2 098 385 NH residents nationwide included in the study, 7151 (0.3%) were American Indian or Alaska Native, 39 873 (1.9%) were Asian, 229 112 (10.9%) were Black or African American, 99 304 (4.7%) were Hispanic, 2785 (0.1%) were Native Hawaiian or Pacific Islander, 1 713 670 (81.7%) were White, and 6490 (0.3%) were multiracial; 1 355 143 (64.6%) were female; 128 997 (6.2%) were severely cognitively impaired; and the mean (SD) age was 81.8 (8.7) years. PAH incidence rate ratios (IRRs) were significantly greater for residents with severe cognitive impairment compared with those without. In unadjusted analyses comparing historically marginalized residents with severe cognitive impairment vs non-Hispanic White residents with severe cognitive impairment, American Indian or Alaska Native residents had a 49% higher PAH incidence (IRR, 1.49 [95% CI, 1.10-2.01]), Black or African American residents had a 64% higher incidence (IRR, 1.64 [95% CI, 1.48-1.81]), and Hispanic residents had a 45% higher incidence (IRR, 1.45 [95% CI, 1.29-1.62]). Higher incidences persisted for historically marginalized residents with severe cognitive impairment vs non-Hispanic White residents with severe cognitive impairment in adjusted analyses. Asian residents had a 24% higher PAH incidence (IRR, 1.24 [95% CI, 1.06-1.45]), Black or African American residents had a 48% higher incidence (IRR, 1.48 [95% CI, 1.36-1.60]), and Hispanic residents had a 27% higher incidence (IRR, 1.27 [95% CI, 1.16-1.39]). Conclusions and Relevance: In this cross-sectional study of PAHs, compared with non-Hispanic White NH residents, historically marginalized residents had increased PAH incidence. In the presence of severe cognitive impairment, incidence rates increased significantly compared with rates for residents without severe cognitive impairment. These results suggest that identification of residents with severe cognitive impairment and proper NH care may help prevent further cognitive decline by avoiding PAHs.

Associations of Nativity and the Role of the Hispanic Paradox on the Cognitive Health of Older Latinos Living in the United States.

Background: US-based Latinos have lower education and income combined with higher health risks than non-Latino whites, but often 'paradoxically' evidence better health-related outcomes. Less work has investigated this paradox for cognitive-related outcomes despite nativity diversity. Objective: We evaluated cognitive aging within older Latinos of diverse nativity currently living in the US and participating in Rush Alzheimer's Disease Center studies. Methods: Participants without baseline dementia, who completed annual neuropsychological assessments (in English or Spanish) were grouped by US-born (n = 117), Mexico-born (n = 173), and born in other Latin American regions (LAr-born = 128). Separate regression models examined associations between nativity and levels of (N = 418) or change in (n = 371; maximum follow-up ∼16 years) global and domain-specific cognition. Results: Demographically-adjusted linear regression models indicated that foreign-born nativity was associated with lower levels of global cognition and select cognitive domains compared to US-born Latinos. No associations of nativity with cognitive decline emerged from demographically-adjusted mixed-effects models; however, Mexico-born nativity appeared associated with slower declines in working memory compared to other nativity groups (p-values ≥ 0.051). Mexico-born Latinos had relatively higher vascular burden and lower education levels than other nativity groups; however, this did not alter results. Conclusions: Nativity differences in baseline cognition may be due, in part, to accumulated stressors related to immigration and acculturation experienced by foreign-born Latinos which may hasten meeting criteria for dementia later in life. In contrast, Mexico-born participants' slower working memory declines, taken in the context of other participant characteristics including vascular burden, suggests the Hispanic Paradox may relate to factors with the potential to affect cognition.

Ethnoracial Identity and Cognitive Impairment: A Community Study.

BACKGROUND: Identifying potentially modifiable risk factors associated with MCI in different ethnoracial groups could reduce MCI burden and health inequity in the population. METHODS: Among 2845 adults aged 65+ years, we investigated potential risk exposures including education, physical and mental health, lifestyle, and sensory function, and their cross-sectional associations with MCI. We compared proportions of exposures between Black and White participants and explored relationships among race, MCI, and exposures. Logistic regression modeled MCI as a function of each exposure in the overall sample adjusting for age, sex, educational level, and race, and investigating race*exposure interactions. RESULTS: Compared with White participants, Black participants had greater odds of MCI (OR 1.53; 95% CI, 1.13 to 2.06) and were more likely to report depressive symptoms, diabetes, and stroke, to have high blood pressure and BMI, and to be APOE - 4 carriers. Exposures associated with higher odds of MCI were diabetes, stroke, lifetime smoking, sleep disturbances, social isolation, loneliness, depression and anxiety symptoms, and vision and hearing loss. There were no significant interactions between race and any exposure. CONCLUSIONS: Black participants had 53% higher odds of MCI adjusting for age, sex, and education. The same exposures were associated with MCI in Black and White participants.

Cardiovascular Health, Race, and Decline in Cognitive Function in Midlife Women: The Study of Women's Health Across the Nation.

BACKGROUND: Cognitive decline may progress for decades before dementia onset. Better cardiovascular health (CVH) has been related to less cognitive decline, but it is unclear whether this begins early, for all racial subgroups, and all domains of cognitive function. The purpose of this study was to determine the impact of CVH on decline in the 2 domains of cognition that decline first in White and Black women at midlife. METHODS AND RESULTS: Subjects were 363 Black and 402 White women, similar in baseline age (mean±SD, 46.6±3.0 years) and education (15.7±2.0 years), from the Chicago site of the Study of Women's Health Across the Nation. Cognition, measured as processing speed and working memory, was assessed annually or biennially over a maximum of 20 years (mean±SD, 9.8±6.7 years). CVH was measured as Life's Essential 8 (blood pressure, body mass index, glucose, non-high-density lipoprotein cholesterol, smoking, physical activity, diet, sleep). Hierarchical linear mixed models identified predictors of cognitive decline with progressive levels of adjustment. There was a decline in processing speed that was explained by race, age, and the 3-way interaction of race, CVH, and time (F1,4308=8.8, P=0.003). CVH was unrelated to decline in White women but in Black women poorer CVH was associated with greater decline. Working memory did not decline in the total cohort, by race, or by CVH. CONCLUSIONS: In midlife Black women, CVH promotion may be a target for preventing the beginnings of cognitive decline, thereby enhancing independent living with aging.

Traumatic brain injury, race, ethnicity and cognition in newly diagnosed persons with multiple sclerosis.

We sought to determine whether a history of traumatic brain injury (TBI) could explain the lower symbol digit modalities test (SDMT) scores observed among newly diagnosed multiple sclerosis (MS) and control participants identifying as Black or Hispanic versus white in the MS Sunshine Study (n = 1172). 330 (29.2 %) participants reported a history of ≥1 TBI. Accounting for TBI did not explain the significant independent associations between having MS, being Black or Hispanic and lower SDMT. The pervasive effects of systemic racism in the United States remain the best explanation for the lower SDMT scores observed in Black and Hispanic participants.

Association Between Hypertensive Disorders of Pregnancy and Interval Neurocognitive Decline: An Analysis of the Hispanic Community Health Study/Study of Latinos.

OBJECTIVE: To evaluate whether hypertensive disorders of pregnancy, including gestational hypertension, preeclampsia, and eclampsia, are associated with cognitive decline later in life among U.S. Hispanic/Latina individuals. METHODS: The HCHS/SOL (Hispanic Community Health Study/Study of Latinos) is a prospective population-based study of Hispanic/Latino individuals aged 18-74 years from four U.S. communities. This analysis included parous individuals aged 45 years or older who participated in the HCHS/SOL clinic study visit 1 (2008-2011) neurocognitive assessment and subsequently completed a repeat neurocognitive assessment as part of the Study of Latinos-Investigation of Neurocognitive Aging ancillary study visit 2 (2015-2018). Hypertensive disorders of pregnancy were assessed retrospectively by self-report of any gestational hypertension, preeclampsia, or eclampsia. Cognitive functioning was measured at both study visits with the Brief Spanish-English Verbal Learning Test, Digit Symbol Substitution, and Word Fluency. A regression-based approach was used to define cognitive decline at visit 2 as a function of cognition at visit 1 after adjustment for age, education, and follow-up time. Linear regression models were used to determine whether hypertensive disorders of pregnancy or their component diagnoses were associated with standardized cognitive decline after adjustment for sociodemographic characteristics, clinical and behavioral risk factors, and follow-up time. RESULTS: Among 3,554 individuals included in analysis, the mean age was 56.2 years, and 467 of individuals (13.4%) reported at least one hypertensive disorder of pregnancy. Individuals with hypertensive disorders of pregnancy compared with those without were more likely to have higher mean systolic blood pressure, fasting glucose, and body mass index. After an average of 7 years of follow-up, in fully adjusted models, gestational hypertension was associated with a 0.17-SD relative decline in Digit Symbol Substitution scores (95% CI, -0.31 to -0.04) but not other cognitive domains (Brief Spanish-English Verbal Learning Test or Word Fluency). Neither preeclampsia nor eclampsia was associated with neurocognitive differences. CONCLUSION: The presence of preeclampsia or eclampsia was not associated with interval neurocognitive decline. In this cohort of U.S. Hispanic/Latina individuals, gestational hypertension alone was associated with decreased processing speed and executive functioning later in life.

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.

Hearing Loss and Associated 7-Year Cognitive Outcomes Among Hispanic and Latino Adults.

Importance: Hearing loss appears to have adverse effects on cognition and increases risk for cognitive impairment. These associations have not been thoroughly investigated in the Hispanic and Latino population, which faces hearing health disparities. Objective: To examine associations between hearing loss with 7-year cognitive change and mild cognitive impairment (MCI) prevalence among a diverse cohort of Hispanic/Latino adults. Design, Setting, and Participants: This cohort study used data from a large community health survey of Hispanic Latino adults in 4 major US cities. Eligible participants were aged 50 years or older at their second visit to study field centers. Cognitive data were collected at visit 1 and visit 2, an average of 7 years later. Data were last analyzed between September 2023 and January 2024. Exposure: Hearing loss at visit 1 was defined as a pure-tone average (500, 1000, 2000, and 4000 Hz) greater than 25 dB hearing loss in the better ear. Main outcomes and measures: Cognitive data were collected at visit 1 and visit 2, an average of 7 years later and included measures of episodic learning and memory (the Brief-Spanish English Verbal Learning Test Sum of Trials and Delayed Recall), verbal fluency (word fluency-phonemic fluency), executive functioning (Trails Making Test-Trail B), and processing speed (Digit-Symbol Substitution, Trails Making Test-Trail A). MCI at visit 2 was defined using the National Institute on Aging-Alzheimer Association criteria. Results: A total of 6113 Hispanic Latino adults were included (mean [SD] age, 56.4 [8.1] years; 3919 women [64.1%]). Hearing loss at visit 1 was associated with worse cognitive performance at 7-year follow-up (global cognition: ß = -0.11 [95% CI, -0.18 to -0.05]), equivalent to 4.6 years of aging and greater adverse change (slowing) in processing speed (ß = -0.12 [95% CI, -0.23 to -0.003]) equivalent to 5.4 years of cognitive change due to aging. There were no associations with MCI. Conclusions and relevance: The findings of this cohort study suggest that hearing loss decreases cognitive performance and increases rate of adverse change in processing speed. These findings underscore the need to prevent, assess, and treat hearing loss in the Hispanic and Latino community.

Psychometric reliability, validity, and generalizability of 3MSE scores among American Indian adults: the Strong Heart Study.

OBJECTIVE: Modified Mini-Mental State Examination (3MSE) is often used to screen for dementia, but little is known about psychometric validity in American Indians. METHODS: We recruited 818 American Indians aged 65-95 for 3MSE examinations in 2010-2013; 403 returned for a repeat examination in 2017-2019. Analyses included standard psychometrics inferences for interpretation, generalizability, and extrapolation: factor analysis; internal consistency-reliability; test-retest score stability; multiple indicator multiple cause structural equation models. RESULTS: This cohort was mean age 73, majority female, mean 12 years education, and majority bilingual. The 4-factor and 2nd-order models fit best, with subfactors for orientation and visuo-construction (OVC), language and executive functioning (LEF), psychomotor and working memory (PMWM), verbal and episodic memory (VEM). Factor structure was supported for both research and clinical interpretation, and factor loadings were moderate to high. Scores were generally consistent over mean 7 years. Younger participants performed better in overall scores, but not in individual factors. Males performed better on OVC and LEF, females better on PMWM. Those with more education performed better on LEF and worse on OVC; the converse was true for bilinguals. All differences were significant, but small. CONCLUSION: These findings support use of 3MSE for individual interpretation in clinic and research among American Indians, with moderate consistency, stability, reliability over time. Observed extrapolations across age, sex, education, and bilingual groups suggest some important contextual differences may exist.

Cross-cultural Diagnostic Validity of the Multilingual Naming Test (MINT) in a Sample of Older Adults.

OBJECTIVE: We aimed to evaluate the psychometric properties and diagnostic accuracy of the 32-item version of the Multilingual Naming Test (MINT) in participants from 2 ethnic groups (European Americans [EA; n = 106] and Hispanic Americans [HA; n = 175]) with 3 diagnostic groups (cognitively normal [CN], n = 94, mild cognitive impairment [MCI], n = 148, and dementia, n = 39). METHOD: An Item Response Theory model was used to evaluate items across ethnicity and language groups (Spanish and English), resulting in a 24-item version. We analyzed the MINT discriminant and predictive validity across diagnostic groups. RESULTS: A total of 8 items were differentially difficult between languages in the 32-item version of the MINT. EA scored significantly higher than HA, but the difference was not significant when removing those 8 items (controlling for Education). The Receiver Operating Characteristics showed that the MINT had poor accuracy when identifying CN participants and was acceptable in identifying dementia participants but unacceptable in classifying MCI participants. Finally, we tested the association between MINT scores and magnetic resonance imaging volumetric measures of language-related areas in the temporal and frontal lobes. The 32-item MINT in English and Spanish and the 24-item MINT in Spanish were significantly correlated with the bilateral middle temporal gyrus. The left fusiform gyrus correlated with MINT scores regardless of language and MINT version. We also found differential correlations depending on the language of administration. CONCLUSIONS: Our results highlight the importance of analyzing cross-cultural samples when implementing clinical neuropsychological tests such as the MINT.

Perspectives From Black and White Participants and Care Partners on Return of Amyloid and Tau PET Imaging and Other Research Results.

PURPOSE: Alzheimer disease (AD) biomarker testing is now common in research and approaching clinical translation. Disclosure protocols must be informed by diverse participants' perspectives on if/how the information would be useful. METHODS: This study utilized semistructured interviews assessing interest in receiving positron emission tomography (PET) amyloid and tau results, as well as perceived risks and benefits of hypothetical PET disclosure as a function of race and participant diagnosis. PARTICIPANTS: Participants [39% Black; 61% White; Mage =74.28 (5.98)] included 57 adults diagnosed as either cognitively healthy (58%) or with mild cognitive impairment (42%) and their respective care partners [33% Black; 67% White; Mage =66.93 (10.92)]. RESULTS: Most dyads endorsed strong interest in PET results (82.5% of both participants and partners) regardless of race or diagnosis. Black care partners were less interested in receiving the participant's results than White care partners ( χ2(4) =8.31, P =0.047). Reasons for disclosure were diverse and highly personalized, including access to treatments or clinical trials (23.2% participants; 29.8% partners), advance planning (14.3% participants; 17.5% partners), and improved health knowledge (12.5% participants; 15.8% partners). In contrast, over 80% of respondents denied any risks of disclosure. DISCUSSION: Results suggest that predisclosure education, decisional capacity assessment, and a flexible disclosure approach are needed.

Association Between Acute Myocardial Infarction and Cognition.

Importance: The magnitude of cognitive change after incident myocardial infarction (MI) is unclear. Objective: To assess whether incident MI is associated with changes in cognitive function after adjusting for pre-MI cognitive trajectories. Design, Setting, and Participants: This cohort study included adults without MI, dementia, or stroke and with complete covariates from the following US population-based cohort studies conducted from 1971 to 2019: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, Multi-Ethnic Study of Atherosclerosis, and Northern Manhattan Study. Data were analyzed from July 2021 to January 2022. Exposures: Incident MI. Main Outcomes and Measures: The main outcome was change in global cognition. Secondary outcomes were changes in memory and executive function. Outcomes were standardized as mean (SD) T scores of 50 (10); a 1-point difference represented a 0.1-SD difference in cognition. Linear mixed-effects models estimated changes in cognition at the time of MI (change in the intercept) and the rate of cognitive change over the years after MI (change in the slope), controlling for pre-MI cognitive trajectories and participant factors, with interaction terms for race and sex. Results: The study included 30 465 adults (mean [SD] age, 64 [10] years; 56% female), of whom 1033 had 1 or more MI event, and 29 432 did not have an MI event. Median follow-up was 6.4 years (IQR, 4.9-19.7 years). Overall, incident MI was not associated with an acute decrease in global cognition (-0.18 points; 95% CI, -0.52 to 0.17 points), executive function (-0.17 points; 95% CI, -0.53 to 0.18 points), or memory (0.62 points; 95% CI, -0.07 to 1.31 points). However, individuals with incident MI vs those without MI demonstrated faster declines in global cognition (-0.15 points per year; 95% CI, -0.21 to -0.10 points per year), memory (-0.13 points per year; 95% CI, -0.22 to -0.04 points per year), and executive function (-0.14 points per year; 95% CI, -0.20 to -0.08 points per year) over the years after MI compared with pre-MI slopes. The interaction analysis suggested that race and sex modified the degree of change in the decline in global cognition after MI (race × post-MI slope interaction term, P = .02; sex × post-MI slope interaction term, P = .04), with a smaller change in the decline over the years after MI in Black individuals than in White individuals (difference in slope change, 0.22 points per year; 95% CI, 0.04-0.40 points per year) and in females than in males (difference in slope change, 0.12 points per year; 95% CI, 0.01-0.23 points per year). Conclusions: This cohort study using pooled data from 6 cohort studies found that incident MI was not associated with a decrease in global cognition, memory, or executive function at the time of the event compared with no MI but was associated with faster declines in global cognition, memory, and executive function over time. These findings suggest that prevention of MI may be important for long-term brain health.

Mild Cognitive Impairment in African Americans Is Associated with Differences in EEG Theta/Beta Ratio.

BACKGROUND: Identification of older individuals with increased risk for cognitive decline can contribute not only to personal benefits (e.g., early treatment, evaluation of treatment), but could also benefit clinical trials (e.g., patient selection). We propose that baseline resting-state electroencephalography (rsEEG) could provide markers for early identification of cognitive decline. OBJECTIVE: To determine whether rsEEG theta/beta ratio (TBR) differed between mild cognitively impaired (MCI) and healthy older adults. METHODS: We analyzed rsEEG from a sample of 99 (ages 60-90) consensus-diagnosed, community-dwelling older African Americans (58 cognitively typical and 41 MCI). Eyes closed rsEEGs were acquired before and after participants engaged in a visual motion direction discrimination task. rsEEG TBR was calculated for four midline locations and assessed for differences as a function of MCI status. Hemispheric asymmetry of TBR was also analyzed at equidistant lateral electrode sites. RESULTS: Results showed that MCI participants had a higher TBR than controls (p = 0.04), and that TBR significantly differed across vertex location (p < 0.001) with the highest TBR at parietal site. MCI and cognitively normal controls also differed in hemispheric asymmetries, such that MCI show higher TBR at frontal sites, with TBR greater over right frontal electrodes in the MCI group (p = 0.003) and no asymmetries found in the cognitively normal group. Lastly, we found a significant task aftereffect (post-task compared to pre-task measures) with higher TBR at posterior locations (Oz p = 0.002, Pz p = 0.057). CONCLUSION: TBR and TBR asymmetries differ between MCI and cognitively normal older adults and may reflect neurodegenerative processes underlying MCI symptoms.

Hypermethylation at CREBBP Is Associated with Cognitive Impairment in a Mexican American Cohort.

BACKGROUND: The aging Mexican American (MA) population is the fastest growing ethnic minority group in the US. MAs have a unique metabolic-related risk for Alzheimer's disease (AD) and mild cognitive impairment (MCI), compared to non-Hispanic whites (NHW). This risk for cognitive impairment (CI) is multifactorial involving genetics, environmental, and lifestyle factors. Changes in environment and lifestyle can alter patterns and even possibly reverse derangement of DNA methylation (a form of epigenetic regulation). OBJECTIVE: We sought to identify ethnicity-specific DNA methylation profiles that may be associated with CI in MAs and NHWs. METHODS: DNA obtained from peripheral blood of 551 participants from the Texas Alzheimer's Research and Care Consortium was typed on the Illumina Infinium® MethylationEPIC chip array, which assesses over 850K CpG genomic sites. Within each ethnic group (N = 299 MAs, N = 252 NHWs), participants were stratified by cognitive status (control versus CI). Beta values, representing relative degree of methylation, were normalized using the Beta MIxture Quantile dilation method and assessed for differential methylation using the Chip Analysis Methylation Pipeline (ChAMP), limma and cate packages in R. RESULTS: Two differentially methylated sites were significant: cg13135255 (MAs) and cg27002303 (NHWs) based on an FDR p < 0.05. Three suggestive sites obtained were cg01887506 (MAs) and cg10607142 and cg13529380 (NHWs). Most methylation sites were hypermethylated in CI compared to controls, except cg13529380 which was hypomethylated. CONCLUSION: The strongest association with CI was at cg13135255 (FDR-adjusted p = 0.029 in MAs), within the CREBBP gene. Moving forward, identifying additional ethnicity-specific methylation sites may be useful to discern CI risk in MAs.

The Effect of Self-Reported Visual Impairment and Sleep on Cognitive Decline: Results of the Hispanic Community Health Study/Study of Latinos.

BACKGROUND: Visual impairment could worsen sleep/wake disorders and cognitive decline. OBJECTIVE: To examine interrelations among self-reported visual impairment, sleep, and cognitive decline in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Miami-site. METHOD: HCHS/SOL Miami-site participants ages 45-74 years (n = 665) at Visit-1, who returned for cognitive test 7-years later (SOL-INCA). Participants completed the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ), validated sleep questionnaires and test for obstructive sleep apnea (OSA) at Visit-1. We obtained verbal episodic learning and memory, verbal fluency, processing speed, and executive functioning at Visit-1 and at SOL-INCA. Processing speed/executive functioning were added to SOL-INCA. We examined global cognition and change using a regression-based reliable change index, adjusting for the time lapse between Visit-1 and SOL-INCA. We used regression models to test whether 1) persons with OSA, self-reported sleep duration, insomnia, and sleepiness have an increased risk for visual impairment, 2a) visual impairment is associated with worse cognitive function and/or decline, and 2b) sleep disorders attenuate these associations. RESULT: Sleepiness (ß= 0.04; p < 0.01) and insomnia (ß= 0.04; p < 0.001) were cross-sectionally associated with visual impairment, adjusting for sociodemographic characteristics, behavioral factors, acculturation, and health conditions. Visual impairment was associated with lower global cognitive function at Visit-1 (ß= -0.16; p < 0.001) and on average 7-years later (ß= -0.18; p < 0.001). Visual impairment was also associated with a change in verbal fluency (ß= -0.17; p < 0.01). OSA, self-reported sleep duration, insomnia, and sleepiness did not attenuate any of the associations. CONCLUSION: Self-reported visual impairment was independently associated with worse cognitive function and decline.

Racial, ethnic, and sex disparities in the incidence and cognitive symptomology of long COVID-19.

BACKGROUND: The pandemic has highlighted and exacerbated health inequities in both acute coronavirus disease 2019 (COVID-19) and its longer-term sequelae. Given the heterogeneity in definitions of long COVID and the lack of centralized registries of patients with the disease, little is known about the differential prevalence among racial, ethnic, and sex subgroups. This study examines long COVID among Black, White, Asian, and Hispanic Americans and evaluates differences in the associated cognitive symptomology. METHOD: Data from four releases of the Census Bureau's Household Pulse Survey detailing COVID-19 incidence and the duration and type of symptoms among a nationally representative sample of adults from June 1, 2022, through October 17, 2022, were combined. Binary logistic regression assessed the relative likelihood of long COVID among those who had been diagnosed COVID between racial, ethnic, and sex subgroups. Among those reporting long COVID, differences in the prevalence of difficulty understanding and difficulty remembering were assessed. Empirical models accounted for household, regional, vaccination, and insurance differences between respondents. Two-stage selection models were applied to test the robustness of the results. RESULTS: Among respondents who tested positive for COVID-19, Blacks (OR=1.097, CI=1.034-1.163), females (OR=1.849, CI=1.794-1.907), and Hispanics (OR=1.349, CI=1.286-1.414) were more likely to experience long COVID (symptoms lasting for 3 months or longer) compared to Whites, males, and non-Hispanics respectively. However, those with private health insurance (OR=0.634, CI=0.611-0.658) and who received the COVID vaccine (OR=0.901, CI=0.864-0.94) were less likely to have endured COVID symptoms than their counterparts. Symptoms of long COVID varied significantly between population subgroups. Compared to Whites, Blacks were more likely to have trouble remembering (OR=1.878, CI=1.765-1.808) while Hispanics were more likely to report difficult understanding (OR=1.827, CI=1.413, 2.362). Females, compared to males, were less likely to experience trouble understanding (OR=0.664, CI=0.537, 0.821), but more likely to report trouble remembering (OR=1.34, CI=1.237, 1.451). CONCLUSIONS: Long COVID is more prevalent among Blacks, Hispanics, and females, but each group appears to experience long COVID differently. Therefore, additional research is needed to determine the best method to treat and manage this poorly understood condition.

Increasing Pain Interference Is Associated With Cognitive Decline Over Four Years Among Older Puerto Rican Adults.

BACKGROUND: Pain is associated with cognitive decline among older adults, but few studies have investigated bidirectional associations between pain and cognitive decline, especially in older Hispanic populations. Our objective was to assess the bidirectional association between pain interference and cognitive performance in a sample of older Puerto Rican adults. METHODS: Data came from baseline and 4-year follow-up of the Puerto Rican Elderly: Health Conditions Study, a longitudinal representative study of Puerto Rican older adults aged 60 and older. Pain and cognitive performance were assessed at each wave. A pain interference variable was created using the sum of pain status (yes/no) and pain interference (yes/no; range 0-2). Global cognitive performance was assessed with the Mini-Mental Cabán. We tested bidirectional associations using a path model with concurrent and cross-lagged paths between pain and cognitive performance, adjusting for sociodemographic and health factors (n = 2 349). RESULTS: Baseline pain interference was not associated with baseline cognitive performance (p = .636) or with cognitive performance at follow-up (p = .594). However, increased pain interference at follow-up was associated with greater cognitive decline at follow-up (ß = -0.07, standard error [SE] = 0.02, p = .003). Greater baseline cognitive performance was associated with lower pain interference at follow-up (ß = -0.07, SE = 0.02, p = .007). CONCLUSIONS: These findings highlight the importance of worsening pain interference as a potentially modifiable risk factor for cognitive decline, as pain treatment options exist. Additionally, better baseline cognitive performance may be a protective factor for pain, providing further evidence of the dynamic relationship between pain and cognitive performance.

Subjective Memory Decline Predicts Incident Cognitive Impairment Among White-But Not Black or Hispanic-Older Adults.

BACKGROUND AND OBJECTIVES: This study investigates whether subjective memory decline (SMD) in a racially diverse sample of older adults without cognitive impairment at baseline is associated with incident cognitive impairment during a 12-year follow-up period. RESEARCH DESIGN AND METHODS: With panel data from a national sample (N = 9,244) of cognitively intact Black, White, and Hispanic Americans 65 years or older in 2004, we examine if SMD is associated with the loss of normal cognition by 2016. Cognitive status was assessed every 2 years with a modified version of the Telephone Interview for Cognitive Status to identify the transition from normal cognition to cognitive impairment. RESULTS: Estimates from Weibull accelerated failure-time models reveal that SMD is associated with earlier incident cognitive impairment (time ratio = 0.96, p < .05). In subsequent models stratified by race-ethnicity, this association was evident among White respondents (time ratio = 0.95, p < .01) but not among Black, U.S.-born Hispanic, or foreign-born Hispanic respondents. DISCUSSION AND IMPLICATIONS: Given that the prognostic validity of SMD differs by race and ethnicity, caution is warranted when using it as a screening or clinical tool in diverse populations.

Dementia Incidence, APOE Genotype, and Risk Factors for Cognitive Decline in Aboriginal Australians: A Longitudinal Cohort Study.

BACKGROUND AND OBJECTIVES: Aboriginal Australians are disproportionately affected by dementia, with incidence in remote populations approximately double that of non-Indigenous populations. This study aimed to identify dementia incidence and risk factors in Aboriginal Australians residing in urban areas, which are currently unknown. METHODS: A population-based cohort of Aboriginal Australians ≥60 years of age was assessed at baseline and 6-year follow-up. Life-course risk factors (baseline) were examined for incident dementia or mild cognitive impairment (MCI) through logistic regression analyses; adjustments were made for age. APOE genotyping was available for 86 people. RESULTS: Data were included from 155 participants 60 to 86 years of age (mean 65.70 years, SD 5.65 years; 59 male). There were 16 incident dementia cases (age-standardized rate 35.97/1,000 person-years, 95% confidence interval [CI] 18.34-53.60) and 36 combined incident MCI and dementia cases. Older age (odds ratio [OR] 2.29, 95% CI 1.42-3.70), male sex (OR 4.14, 95% CI 1.60-10.77), unskilled work history (OR 5.09, 95% CI 1.95-13.26), polypharmacy (OR 3.11, 95% CI 1.17-8.28), and past smoking (OR 0.24, 95% CI 0.08-0.75) were associated with incident MCI/dementia in the final model. APOE ε4 allele frequency was 24%; heterozygous or homozygous ε4 was associated with incident MCI/dementia (bivariate OR 3.96, 95% CI 1.25-12.50). DISCUSSION: These findings provide evidence for higher dementia incidence in Aboriginal Australians from urban areas, where the majority of Aboriginal people reside. This study also sheds light on sociodemographic, health, and genetic factors associated with incident MCI/dementia at older ages in this population, which is critical for targeted prevention strategies.