Dementia Attributable Healthcare Utilizations in the Caribbean versus United States.

BACKGROUND: Despite the high burden of Alzheimer's disease and other dementias among the Hispanic population worldwide, little is known about how dementia affects healthcare utilizations among this population outside of the US, in particular among those in the Caribbean region. OBJECTIVE: This study examines healthcare utilization associated with Alzheimer's disease and other dementias among older adults in the Caribbean as compared to the US. METHODS: We conducted harmonized analyses of two population-based surveys, the 10/66 Dementia Group Research data collected in Dominican Republic, Cuba, and Puerto Rico, and the US-based Health and Retirement Study. We examined changes in hospital nights and physician visits in response to incident and ongoing dementias. RESULTS: Incident dementia significantly increased the risk of hospitalization and number of hospital nights in both populations. Ongoing dementia increased the risk of hospitalization and hospital nights in the US, with imprecise estimates for the Caribbean. The number of physician visits was elevated in the US but not in the Caribbean. CONCLUSIONS: The concentration of increased healthcare utilization on hospital care and among patients with incident dementia suggests an opportunity for improved outpatient management of new and existing dementia patients in the Caribbean.

Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS): Study design and harmonization.

INTRODUCTION: Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS) is the first non-pharmacological multicenter randomized clinical trial (RCT) to prevent cognitive impairment in Latin America (LA). Our aim is to present the study design and discuss the strategies used for multicultural harmonization. METHODS: This 1-year RCT (working on a 1-year extension) investigates the feasibility of a multi-domain lifestyle intervention in LA and the efficacy of the intervention, primarily on cognitive function. An external harmonization process was carried out to follow the FINGER model, and an internal harmonization was performed to ensure this study was feasible and comparable across the 12 participating LA countries. RESULTS: Currently, 1549 participants have been screened, and 815 randomized. Participants are ethnically diverse (56% are Nestizo) and have high cardiovascular risk (39% have metabolic syndrome). DISCUSSION: LatAm-FINGERS overcame a significant challenge to combine the region's diversity into a multi-domain risk reduction intervention feasible across LA while preserving the original FINGER design.

Longitudinal head-to-head comparison of 11C-PiB and 18F-florbetapir PET in a Phase 2/3 clinical trial of anti-amyloid-ß monoclonal antibodies in dominantly inherited Alzheimer's disease.

PURPOSE: Pittsburgh Compound-B (11C-PiB) and 18F-florbetapir are amyloid-ß (Aß) positron emission tomography (PET) radiotracers that have been used as endpoints in Alzheimer's disease (AD) clinical trials to evaluate the efficacy of anti-Aß monoclonal antibodies. However, comparing drug effects between and within trials may become complicated if different Aß radiotracers were used. To study the consequences of using different Aß radiotracers to measure Aß clearance, we performed a head-to-head comparison of 11C-PiB and 18F-florbetapir in a Phase 2/3 clinical trial of anti-Aß monoclonal antibodies. METHODS: Sixty-six mutation-positive participants enrolled in the gantenerumab and placebo arms of the first Dominantly Inherited Alzheimer Network Trials Unit clinical trial (DIAN-TU-001) underwent both 11C-PiB and 18F-florbetapir PET imaging at baseline and during at least one follow-up visit. For each PET scan, regional standardized uptake value ratios (SUVRs), regional Centiloids, a global cortical SUVR, and a global cortical Centiloid value were calculated. Longitudinal changes in SUVRs and Centiloids were estimated using linear mixed models. Differences in longitudinal change between PET radiotracers and between drug arms were estimated using paired and Welch two sample t-tests, respectively. Simulated clinical trials were conducted to evaluate the consequences of some research sites using 11C-PiB while other sites use 18F-florbetapir for Aß PET imaging. RESULTS: In the placebo arm, the absolute rate of longitudinal change measured by global cortical 11C-PiB SUVRs did not differ from that of global cortical 18F-florbetapir SUVRs. In the gantenerumab arm, global cortical 11C-PiB SUVRs decreased more rapidly than global cortical 18F-florbetapir SUVRs. Drug effects were statistically significant across both Aß radiotracers. In contrast, the rates of longitudinal change measured in global cortical Centiloids did not differ between Aß radiotracers in either the placebo or gantenerumab arms, and drug effects remained statistically significant. Regional analyses largely recapitulated these global cortical analyses. Across simulated clinical trials, type I error was higher in trials where both Aß radiotracers were used versus trials where only one Aß radiotracer was used. Power was lower in trials where 18F-florbetapir was primarily used versus trials where 11C-PiB was primarily used. CONCLUSION: Gantenerumab treatment induces longitudinal changes in Aß PET, and the absolute rates of these longitudinal changes differ significantly between Aß radiotracers. These differences were not seen in the placebo arm, suggesting that Aß-clearing treatments may pose unique challenges when attempting to compare longitudinal results across different Aß radiotracers. Our results suggest converting Aß PET SUVR measurements to Centiloids (both globally and regionally) can harmonize these differences without losing sensitivity to drug effects. Nonetheless, until consensus is achieved on how to harmonize drug effects across radiotracers, and since using multiple radiotracers in the same trial may increase type I error, multisite studies should consider potential variability due to different radiotracers when interpreting Aß PET biomarker data and, if feasible, use a single radiotracer for the best results. TRIAL REGISTRATION: ClinicalTrials.gov NCT01760005. Registered 31 December 2012. Retrospectively registered.

Apolipoprotein E (APOE) genotype, dementia, and memory performance among Caribbean Hispanic versus US populations.

INTRODUCTION: Apolipoprotein E (APOE) is considered the major susceptibility gene for developing Alzheimer's disease. However, the strength of this risk factor is not well established across diverse Hispanic populations. METHODS: We investigated the associations among APOE genotype, dementia prevalence, and memory performance (immediate and delayed recall scores) in Caribbean Hispanics (CH), African Americans (AA), Hispanic Americans (HA) and non-Hispanic White Americans (NHW). Multivariable logistic regressions and negative binomial regressions were used to examine these associations by subsample. RESULTS: Our final dataset included 13,516 participants (5198 men, 8318 women) across all subsamples, with a mean age of 74.8 years. Prevalence of APOE ε4 allele was similar in CHs, HAs, and NHWs (21.8%-25.4%), but was substantially higher in AAs (33.6%; P < 0.001). APOE ε4 carriers had higher dementia prevalence across all groups. DISCUSSION: APOE ε4 was similarly associated with increased relative risk of dementia and lower memory performance in all subsamples.

Amyloid-Related Imaging Abnormalities in the DIAN-TU-001 Trial of Gantenerumab and Solanezumab: Lessons from a Trial in Dominantly Inherited Alzheimer Disease.

OBJECTIVE: To determine the characteristics of participants with amyloid-related imaging abnormalities (ARIA) in a trial of gantenerumab or solanezumab in dominantly inherited Alzheimer disease (DIAD). METHODS: 142 DIAD mutation carriers received either gantenerumab SC (n = 52), solanezumab IV (n = 50), or placebo (n = 40). Participants underwent assessments with the Clinical Dementia Rating® (CDR®), neuropsychological testing, CSF biomarkers, ß-amyloid positron emission tomography (PET), and magnetic resonance imaging (MRI) to monitor ARIA. Cross-sectional and longitudinal analyses evaluated potential ARIA-related risk factors. RESULTS: Eleven participants developed ARIA-E, including 3 with mild symptoms. No ARIA-E was reported under solanezumab while gantenerumab was associated with ARIA-E compared to placebo (odds ratio [OR] = 9.1, confidence interval [CI][1.2, 412.3]; p = 0.021). Under gantenerumab, APOE-ɛ4 carriers were more likely to develop ARIA-E (OR = 5.0, CI[1.0, 30.4]; p = 0.055), as were individuals with microhemorrhage at baseline (OR = 13.7, CI[1.2, 163.2]; p = 0.039). No ARIA-E was observed at the initial 225 mg/month gantenerumab dose, and most cases were observed at doses >675 mg. At first ARIA-E occurrence, all ARIA-E participants were amyloid-PET+, 60% were CDR >0, 60% were past their estimated year to symptom onset, and 60% had also incident ARIA-H. Most ARIA-E radiologically resolved after dose adjustment and developing ARIA-E did not significantly increase odds of trial discontinuation. ARIA-E was more frequently observed in the occipital lobe (90%). ARIA-E severity was associated with age at time of ARIA-E. INTERPRETATION: In DIAD, solanezumab was not associated with ARIA. Gantenerumab dose over 225 mg increased ARIA-E risk, with additional risk for individuals APOE-ɛ4(+) or with microhemorrhage. ARIA-E was reversible on MRI in most cases, generally asymptomatic, without additional risk for trial discontinuation. ANN NEUROL 2022;92:729-744.

Multilevel barriers to using assistive technology devices among older hispanics from poor and disadvantaged communities: the relevance of a gender analysis.

PURPOSE: To get a rich description of the barriers to using assistive technology (AT) among men and women ≥65 years living in poor and disadvantaged communities in Puerto Rico, an issue not well described among older people. METHODS: We conducted qualitative interviews assisted by videos of AT and guided by the Matching Person and Technology Model and the Gender Analysis Framework with a purposive sample of 23 men and women. Participants were asked questions regarding reasons for not using AT, willingness for using AT, their identified gender roles and gender-related activities, and bargaining positions. They were also asked about their access to resources to acquire AT, bargaining positions, the stigma associated with AT use, and the characteristics of AT. Directed content analysis with input from a Community Advisory Board was used for the interpretation of the results. RESULTS: The predominant barrier (for both men and women) to using AT devices were: lack of information about AT s and access to money for their purchase, lack of availability and cost of such devices, and (self)-stigma. More women than men experienced limited access to AT services, limited access to and control of money, limited skills for using AT, and less bargaining power for making independent decisions. More men than women expressed a lack of functional need and personal preferences other than using AT devices for managing difficulties in activities. CONCLUSION: There are gender differences concerning the multilevel barriers to using AT devices among older Hispanics residing in low-income communities.IMPLICATIONS FOR REHABILITATIONOlder Hispanic men and women in this study experienced different obstacles to using assistive technology (AT) they need for compensating their functional disabilities in daily living activities.Women in this study reported having less access to money and AT services, diminished skills for using AT devices, and less power to make independent decisions to access AT devices compared to men.To ensure the equitable provision of AT, cultural as well as gender-related factors concerning AT use need to be considered.Future research should focus on women's functional health, also should focus on the development of gender-sensitive and culturally competent AT interventions to improve older Hispanics from poor communities function and opportunities for ageing at their homes and in their communities.

Color disparities in cognitive aging among Puerto Ricans on the archipelago.

This research seeks to contribute new understanding of color disparities and gender in cognitive aging among older adults residing in Puerto Rico. We use the island-representative Puerto Rican Elderly Health Conditions (PREHCO) longitudinal study that measures cognitive health at baseline and cognitive decline between waves. In pooled models, we discern little or no color disparities in cognition at baseline. Sex-stratified models of baseline cognition indicate that Trigueño men slightly outperform white men. In contrast, color disparities in cognitive decline are apparent. In just four years between the two waves of PREHCO, on a 20-point cognitive test scale, Black men experienced 0.78 more points of cognitive decline, while Trigueño men experienced 0.44 more points of cognitive decline than white men in Puerto Rico. Mestiza women experience 0.80 less points of cognitive decline relative to white women. Nearly all of the color/race association with cognitive decline appears to be independent from health behaviors and conditions, individual human capital attainment, and family background. While lower-status color groups more frequently report discrimination, discrimination does not mediate the impact of color/skin tone and cognitive performance, suggesting the importance of further research on the role of broader dimensions of life course structural racism.

FMNL2 regulates gliovascular interactions and is associated with vascular risk factors and cerebrovascular pathology in Alzheimer's disease.

Alzheimer's disease (AD) has been associated with cardiovascular and cerebrovascular risk factors (CVRFs) during middle age and later and is frequently accompanied by cerebrovascular pathology at death. An interaction between CVRFs and genetic variants might explain the pathogenesis. Genome-wide, gene by CVRF interaction analyses for AD, in 6568 patients and 8101 controls identified FMNL2 (p = 6.6 × 10-7). A significant increase in FMNL2 expression was observed in the brains of patients with brain infarcts and AD pathology and was associated with amyloid and phosphorylated tau deposition. FMNL2 was also prominent in astroglia in AD among those with cerebrovascular pathology. Amyloid toxicity in zebrafish increased fmnl2a expression in astroglia with detachment of astroglial end feet from blood vessels. Knockdown of fmnl2a prevented gliovascular remodeling, reduced microglial activity and enhanced amyloidosis. APP/PS1dE9 AD mice also displayed increased Fmnl2 expression and reduced the gliovascular contacts independent of the gliotic response. Based on this work, we propose that FMNL2 regulates pathology-dependent plasticity of the blood-brain-barrier by controlling gliovascular interactions and stimulating the clearance of extracellular aggregates. Therefore, in AD cerebrovascular risk factors promote cerebrovascular pathology which in turn, interacts with FMNL2 altering the normal astroglial-vascular mechanisms underlying the clearance of amyloid and tau increasing their deposition in brain.

Admixture Mapping of Alzheimer's disease in Caribbean Hispanics identifies a new locus on 22q13.1.

Late-onset Alzheimer's disease (LOAD) is significantly more frequent in Hispanics than in non-Hispanic Whites. Ancestry may explain these differences across ethnic groups. To this end, we studied a large cohort of Caribbean Hispanics (CH, N = 8813) and tested the association between Local Ancestry (LA) and LOAD ("admixture mapping") to identify LOAD-associated ancestral blocks, separately for ancestral components (European [EUR], African [AFR], Native American[NA]) and jointly (AFR + NA). Ancestral blocks significant after permutation were fine-mapped employing multi-ethnic whole-exome sequencing (WES) to identify rare variants associated with LOAD (SKAT-O) and replicated in the UK Biobank WES dataset. Candidate genes were validated studying (A) protein expression in human LOAD and control brains; (B) two animal AD models, Drosophila and Zebrafish. In the joint AFR + NA model, we identified four significant ancestral blocks located on chromosomes 1 (p value = 8.94E-05), 6 (p value = 8.63E-05), 21 (p value = 4.64E-05) and 22 (p value = 1.77E-05). Fine-mapping prioritized the GCAT gene on chromosome 22 (SKAT-O p value = 3.45E-05) and replicated in the UK Biobank (SKAT-O p value = 0.05). In LOAD brains, a decrease of 28% in GCAT protein expression was observed (p value = 0.038), and GCAT knockdown in Amyloid-ß42 Drosophila exacerbated rough eye phenotype (68% increase, p value = 4.84E-09). In zebrafish, gcat expression increased after acute amyloidosis (34%, p value = 0.0049), and decreased upon anti-inflammatory Interleukin-4 (39%, p value = 2.3E-05). Admixture mapping uncovered genomic regions harboring new LOAD-associated loci that might explain the observed different frequency of LOAD across ethnic groups. Our results suggest that the inflammation-related activity of GCAT is a response to amyloid toxicity, and reduced GCAT expression exacerbates AD pathology.

Prevalence of parkinsonism and Parkinson disease in urban and rural populations from Latin America: A community based study.

Background: Age and gender specific prevalence rates for parkinsonism and Parkinson's disease (PD) are important to guide research, clinical practice, and public health planning; however, prevalence estimates in Latin America (LatAm) are limited. We aimed to estimate the prevalence of parkinsonism and PD and examine related risk factors in a cohort of elderly individuals from Latin America (LatAm). Methods: Data from 11,613 adults (65+ years) who participated in a baseline assessment of the 10/66 study and lived in six LatAm countries were analyzed to estimate parkinsonism and PD prevalence. Crude and age-adjusted prevalence were determined by sex and country. Diagnosis of PD was established using the UK Parkinson's Disease Society Brain Bank's clinical criteria. Findings: In this cohort, the prevalence of parkinsonism was 8.0% (95% CI 7.6%-8.5%), and the prevalence of PD was 2.0% (95% CI 1.7%-2.3%). PD prevalence increased with age from 1.0 to 3.5 (65-69vs. 80 years or older, p < 0.001). Age-adjusted prevalence rates were lower for women than for men. No significant differences were found across countries, except for lower prevalence in urban areas of Peru. PD was positively associated with depression (adjusted prevalence ratio [aPR] 2.06, 95% CI 1.40-3.01, I 2 = 56.0%), dementia (aPR 1.57, 95% CI 1.07- 2.32, I 2 = 0.0%) and educational level (aPR 1.14, 95% CI 1.01- 1.29, I 2 = 58.6%). Interpretation: The reported prevalence of PD in LatAm is similar to reports from high-income countries (HIC). A significant proportion of cases with PD did not have a previous diagnosis, nor did they seek any medical or neurological attention. These findings underscore the need to improve public health programs for populations currently undergoing rapid demographic aging and epidemiological transition. Funding: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Progranulin mutations in clinical and neuropathological Alzheimer's disease.

INTRODUCTION: Progranulin (GRN) mutations occur in frontotemporal lobar degeneration (FTLD) and in Alzheimer's disease (AD), often with TDP-43 pathology. METHODS: We determined the frequency of rs5848 and rare, pathogenic GRN mutations in two autopsy and one family cohort. We compared Braak stage, ß-amyloid load, hyperphosphorylated tau (PHFtau) tangle density and TDP-43 pathology in GRN carriers and non-carriers. RESULTS: Pathogenic GRN mutations were more frequent in all cohorts compared to the Genome Aggregation Database (gnomAD), but there was no evidence for association with AD. Pathogenic GRN carriers had significantly higher PHFtau tangle density adjusting for age, sex and APOE ε4 genotype. AD patients with rs5848 had higher frequencies of hippocampal sclerosis and TDP-43 deposits. Twenty-two rare, pathogenic GRN variants were observed in the family cohort. DISCUSSION: GRN mutations in clinical and neuropathological AD increase the burden of tau-related brain pathology but show no specific association with ß-amyloid load or AD.

Race/Ethnic Differences, Skin Tone, and Memory Among Older Latinos in the United States.

OBJECTIVES: U.S. Latino populations are diverse. Research on racial identity, skin tone, and Latino health is imperative for understanding and combating racism and colorism. We examined differences in memory performance: among non-Latinos and Latinos who identified as Black, other, and White in the United States and then among Puerto Ricans in Boston whose skin tones ranged from dark, medium, light to "white." METHODS: We used 2010 Health and Retirement Study and 2004 Boston Puerto Rican Health Survey data, respectively, to examine racial and color differences in memory performance among 50 and older adults in the United States and Puerto Rican older adults in Boston. We applied ordinary least squares regression to immediate and delayed word recall test scores and adjusted for education, health conditions, and health behaviors. RESULTS: In adjusted models, White non-Latinos had better memory performance than White Latinos. Black Latinos, other Latinos, and Black non-Latinos had lower delayed word recall scores than White Latinos. Black Latinos and Black non-Latinos had similar scores. Intra-Latino racial disparities endured despite the inclusion of education and other covariates. Among Puerto Ricans in Boston, medium-toned individuals had higher scores than "white"-toned individuals. DISCUSSION: Findings support the importance of examining self-identified race and skin tone in Latino aging research. Further investigation is needed to understand the stubborn intra-Latino racial disparities in memory performance and surprising adverse cognitive performance among "white"-toned relative to darker-toned Puerto Ricans in Boston.

Addressing the disparities in dementia risk, early detection and care in Latino populations: Highlights from the second Latinos & Alzheimer's Symposium.

The Alzheimer's Association hosted the second Latinos & Alzheimer's Symposium in May 2021. Due to the COVID-19 pandemic, the meeting was held online over 2 days, with virtual presentations, discussions, mentoring sessions, and posters. The Latino population in the United States is projected to have the steepest increase in Alzheimer's disease (AD) in the next 40 years, compared to other ethnic groups. Latinos have increased risk for AD and other dementias, limited access to quality care, and are severely underrepresented in AD and dementia research and clinical trials. The symposium highlighted developments in AD research with Latino populations, including advances in AD biomarkers, and novel cognitive assessments for Spanish-speaking populations, as well as the need to effectively recruit and retain Latinos in clinical research, and how best to deliver health-care services and to aid caregivers of Latinos living with AD.

Loneliness Among Older Adults in Latin America, China, and India: Prevalence, Correlates and Association With Mortality.

Objectives: This study was designed to explore prevalence and correlates of self-reported loneliness and to investigate whether loneliness predicts mortality among older adults (aged 65 or above) in Latin America, China and India. Methods: The study investigated population-based cross-sectional (2003-2007) and longitudinal surveys (follow-up 2007-2010) from the 10/66 Dementia Research Group project. Poisson regression and Cox regression analyses were conducted to analyse correlates of loneliness and its association with mortality. Results: The standardised prevalence of loneliness varied between 25.3 and 32.4% in Latin America and was 18.3% in India. China showed a low prevalence of loneliness (3.8%). In pooled meta-analyses, there was robust evidence to support an association between loneliness and mortality across Latin American countries (HR = 1.13, 95% CI 1.01-1.26, I2 = 10.1%) and China (HR = 1.58, 95% CI 1.03-2.41), but there were no associations in India. Conclusion: Our findings suggest potential cultural variances may exist in the concept of loneliness in older age. The effect of loneliness upon mortality is consistent across different cultural settings excluding India. Loneliness should therefore be considered as a potential dimension of public health among older populations.

Intrinsic capacity and its associations with incident dependence and mortality in 10/66 Dementia Research Group studies in Latin America, India, and China: A population-based cohort study.

BACKGROUND: The World Health Organization (WHO) has reframed health and healthcare for older people around achieving the goal of healthy ageing. The recent WHO Integrated Care for Older People (ICOPE) guidelines focus on maintaining intrinsic capacity, i.e., addressing declines in neuromusculoskeletal, vitality, sensory, cognitive, psychological, and continence domains, aiming to prevent or delay the onset of dependence. The target group with 1 or more declines in intrinsic capacity (DICs) is broad, and implementation may be challenging in less-resourced settings. We aimed to inform planning by assessing intrinsic capacity prevalence, by characterising the target group, and by validating the general approach-testing hypotheses that DIC was consistently associated with higher risks of incident dependence and death. METHODS AND FINDINGS: We conducted population-based cohort studies (baseline, 2003-2007) in urban sites in Cuba, Dominican Republic, Puerto Rico, and Venezuela, and rural and urban sites in Peru, Mexico, India, and China. Door-knocking identified eligible participants, aged 65 years and over and normally resident in each geographically defined catchment area. Sociodemographic, behaviour and lifestyle, health, and healthcare utilisation and cost questionnaires, and physical assessments were administered to all participants, with incident dependence and mortality ascertained 3 to 5 years later (2008-2010). In 12 sites in 8 countries, 17,031 participants were surveyed at baseline. Overall mean age was 74.2 years, range of means by site 71.3-76.3 years; 62.4% were female, range 53.4%-67.3%. At baseline, only 30% retained full capacity across all domains. The proportion retaining capacity fell sharply with increasing age, and declines affecting multiple domains were more common. Poverty, morbidity (particularly dementia, depression, and stroke), and disability were concentrated among those with DIC, although only 10% were frail, and a further 9% had needs for care. Hypertension and lifestyle risk factors for chronic disease, and healthcare utilisation and costs, were more evenly distributed in the population. In total, 15,901 participants were included in the mortality cohort (2,602 deaths/53,911 person-years of follow-up), and 12,939 participants in the dependence cohort (1,896 incident cases/38,320 person-years). One or more DICs strongly and independently predicted incident dependence (pooled adjusted subhazard ratio 1.91, 95% CI 1.69-2.17) and death (pooled adjusted hazard ratio 1.66, 95% CI 1.49-1.85). Relative risks were higher for those who were frail, but were also substantially elevated for the much larger sub-groups yet to become frail. Mortality was mainly concentrated in the frail and dependent sub-groups. The main limitations were potential for DIC exposure misclassification and attrition bias. CONCLUSIONS: In this study we observed a high prevalence of DICs, particularly in older age groups. Those affected had substantially increased risks of dependence and death. Most needs for care arose in those with DIC yet to become frail. Our findings provide some support for the strategy of optimising intrinsic capacity in pursuit of healthy ageing. Implementation at scale requires community-based screening and assessment, and a stepped-care intervention approach, with redefined roles for community healthcare workers and efforts to engage, train, and support them in these tasks. ICOPE might be usefully integrated into community programmes for detecting and case managing chronic diseases including hypertension and diabetes.

Associations between education and dementia in the Caribbean and the United States: An international comparison.

INTRODUCTION: Despite high dementia prevalence in Hispanic populations globally, especially Caribbean Hispanics, no study has comparatively examined the association between education and dementia among Hispanics living in the Caribbean Islands and older adults in the United States. METHODS: We used data on 6107 respondents aged 65 and older in the baseline wave of the population-based and harmonized 10/66 survey from Cuba, the Dominican Republic, and Puerto Rico, collected between 2003 and 2008, and 11,032 respondents aged 65 and older from the U.S.-based Health and Retirement Study data in 2014, a total of 17,139 individuals. We estimated multivariable logistic regression models examining the association between education and dementia, adjusted for age, income, assets, and occupation. The models were estimated separately for the Caribbean population (pooled and by setting) and the U.S. population by race/ethnicity (Hispanic, Black, and White), followed by pooled models across all populations. RESULTS: In the Caribbean population, the relative risk of dementia among low versus high educated adults was 1.45 for women (95% confidence interval [CI] 1.17, 1.74) and 1.92 (95% CI 1.35, 2.49) for men, smaller compared to those in the United States, especially among non-Hispanic Whites (women: 2.78, 95% CI 1.94, 3.61; men: 5.98, 95% CI 4.02, 7.95). DISCUSSION: The differential associations between education and dementia across the Caribbean and US settings may be explained by greater disparities in social conditions in the United States compared to the Caribbean, such as access to health care, healthy behaviors, and social stressors, which serve as potentially important mediators.

Sex disparities in the prevalence of physical function disabilities: a population-based study in a low-income community.

BACKGROUND: Functional disability continues to be a significant public health problem that increases older adults' vulnerability to experience a diminished quality of life, loss of independence, higher healthcare costs and health services utilization, and increased risks of mortality. Thus, we aimed to study the prevalence of functional disabilities by sex according to the types of daily living activities, controlling for specific sociodemographic variables among older Hispanics from low-income communities. METHODS: We used a cross-sectional epidemiological research design, considering a complex sampling design of households to interview adults ≥65 years living in low-income communities in Puerto Rico. Functional disability was measured by the PROMIS® Physical Function Short Form-20 T-score. The selected community was reported to have 5980 adult residents ≥65 years, according to the USA Census. The prevalence of functional disability was estimated using the logistic regression model, weighting by the effect of the sampling. Our estimated prevalence was compared between sexes using the prevalence ratio (PR), which was estimated with logistic regression models, controlling for age, income, number of chronic conditions, high and low impact of chronic conditions in functional disabilities, marital status, and sampling design. RESULTS: We recruited 211 older Hispanics from a randomly selected sample. Their mean age was 74.4 ± 7.1 years, with female predominance (57.3%). The overall estimated prevalence of physical function disability using T-score among females was 2.70 (95% CI: 1.4, 5.1) times the estimated prevalence of physical function disability among males. Women were more likely to report functional disabilities in instrumental activities of daily living, self-care activities, and functional mobility compared to males. However, sex differences were largely explained by the presence of musculoskeletal conditions of high impact in functional disability. CONCLUSIONS: The females in our study bear the greater burden of physical function disability in their adult age. Health policies, as well as future studies, should be targeted at reducing the burden of physical function disabilities in different types of daily activities through gender-sensitive disability self-management programs.

A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer's disease.

Dominantly inherited Alzheimer's disease (DIAD) causes predictable biological changes decades before the onset of clinical symptoms, enabling testing of interventions in the asymptomatic and symptomatic stages to delay or slow disease progression. We conducted a randomized, placebo-controlled, multi-arm trial of gantenerumab or solanezumab in participants with DIAD across asymptomatic and symptomatic disease stages. Mutation carriers were assigned 3:1 to either drug or placebo and received treatment for 4-7 years. The primary outcome was a cognitive end point; secondary outcomes included clinical, cognitive, imaging and fluid biomarker measures. Fifty-two participants carrying a mutation were assigned to receive gantenerumab, 52 solanezumab and 40 placebo. Both drugs engaged their Aß targets but neither demonstrated a beneficial effect on cognitive measures compared to controls. The solanezumab-treated group showed a greater cognitive decline on some measures and did not show benefits on downstream biomarkers. Gantenerumab significantly reduced amyloid plaques, cerebrospinal fluid total tau, and phospho-tau181 and attenuated increases of neurofilament light chain. Amyloid-related imaging abnormalities edema was observed in 19.2% (3 out of 11 were mildly symptomatic) of the gantenerumab group, 2.5% of the placebo group and 0% of the solanezumab group. Gantenerumab and solanezumab did not slow cognitive decline in symptomatic DIAD. The asymptomatic groups showed no cognitive decline; symptomatic participants had declined before reaching the target doses.

The impact of COVID-19 on the well-being and cognition of older adults living in the United States and Latin America.

BACKGROUND: In the COVID-19 pandemic, older adults from vulnerable ethnoracial groups are at high risk of infection, hospitalization, and death. We aimed to explore the pandemic's impact on the well-being and cognition of older adults living in the United States (US), Argentina, Chile, Mexico, and Peru. METHODS: 1,608 (646 White, 852 Latino, 77 Black, 33 Asian; 72% female) individuals from the US and four Latin American countries aged ≥ 55 years completed an online survey regarding well-being and cognition during the pandemic between May and September 2020. Outcome variables (pandemic impact, discrimination, loneliness, purpose of life, subjective cognitive concerns) were compared across four US ethnoracial groups and older adults living in Argentina, Chile, Mexico, and Peru. FINDINGS: Mean age for all participants was 66.7 (SD = 7.7) years and mean education was 15.4 (SD = 2.7) years. Compared to Whites, Latinos living in the US reported greater economic impact (p < .001, ηp 2  = 0.031); while Blacks reported experiencing discrimination more often (p < .001, ηp 2  = 0.050). Blacks and Latinos reported more positive coping (p < .001, ηp 2  = 0.040). Compared to Latinos living in the US, Latinos in Chile, Mexico, and Peru reported greater pandemic impact, Latinos in Mexico and Peru reported more positive coping, Latinos in Argentina, Mexico, and Peru had greater economic impact, and Latinos in Argentina, Chile, and Peru reported less discrimination. INTERPRETATION: The COVID-19 pandemic has differentially impacted the well-being of older ethnically diverse individuals in the US and Latin America. Future studies should examine how mediators like income and coping skills modify the pandemic's impact. FUNDING: Massachusetts General Hospital Department of Psychiatry.

Polygenic Risk Score for Alzheimer's Disease in Caribbean Hispanics.

OBJECTIVE: Polygenic risk scores (PRSs) assess the individual genetic propensity to a condition by combining sparse information scattered across genetic loci, often displaying small effect sizes. Most PRSs are constructed in European-ancestry populations, limiting their use in other ethnicities. Here we constructed and validated a PRS for late-onset Alzheimer's Disease (LOAD) in Caribbean Hispanics (CH). METHODS: We used a CH discovery (n = 4,312) and independent validation sample (n = 1,850) to construct an ancestry-specific PRS ("CH-PRS") and evaluated its performance alone and with other predictors using the area under curve (AUC) and logistic regression (strength of association with LOAD and statistical significance). We tested if CH-PRS predicted conversion to LOAD in a subsample with longitudinal data (n = 1,239). We also tested the CH-PRS in an independent replication CH cohort (n = 200) and brain autopsy cohort (n = 33). Finally, we tested the effect of ancestry on PRS by using European and African American discovery cohorts to construct alternative PRSs ("EUR-PRS", "AA-PRS"). RESULTS: The full model (LOAD ~ CH-PRS + sex + age + APOE-ɛ4), achieved an AUC = 74% (ORCH-PRS  = 1.51 95%CI = 1.36-1.68), raising to >75% in APOE-ɛ4 non-carriers. CH-PRS alone achieved an AUC = 72% in the autopsy cohort, raising to AUC = 83% in full model. Higher CH-PRS was significantly associated with clinical LOAD in the replication CH cohort (OR = 1.61, 95%CI = 1.19-2.17) and significantly predicted conversion to LOAD (HR = 1.93, CI = 1.70-2.20) in the longitudinal subsample. EUR-PRS and AA-PRS reached lower prediction accuracy (AUC = 58% and 53%, respectively). INTERPRETATION: Enriching diversity in genetic studies is critical to provide an effective PRS in profiling LOAD risk across populations. ANN NEUROL 2021;90:366-376.