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.

The Effect of Visit-to-Visit Blood Pressure Variability on Renal Function in Geriatric Chronic Kidney Disease.

OBJECTIVE: The visit-to-visit variability (VVV) of blood pressure (BP) has been recognized as a risk factor for cardiovascular events and chronic kidney disease (CKD). The objective of this study is to valuate the association between the VVV of BP and changes in estimated glomerular filtration rate (eGFR) in elderly CKD patients at different stages of renal function. MATERIALS AND METHODS: For 60 months, we analyzed the medical records of 105 patients with and without diabetes and hypertension. Systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) were examined. A multivariable linear regression model was used to analyze the correlation between eGFR and the VVV of BP. RESULTS: No differences were demonstrated between the groups in the clinical characteristics. Mean SBP and DBP were not significant between the groups, and we observed no decrease in renal function. A significant negative correlation between PP and eGFR was observed in the total CKD population with a P of .010 (95% CI: -0.20, -0.03) and a correlation coefficient of -0.11. CONCLUSION: Our study shows no statistical significances in terms of the VVVs of BP in any of the geriatric groups, with no significant decreases in renal function. However, we observed a significant negative correlation between PP and eGFR. We demonstrated that if a VVV of BP does not occur, there is no decrease in eGFR.

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.

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.

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.

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.

Precision health diagnostic and surveillance network uses S gene target failure (SGTF) combined with sequencing technologies to track emerging SARS-CoV-2 variants.

INTRODUCTION: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic revealed a worldwide lack of effective molecular surveillance networks at local, state, and national levels, which are essential to identify, monitor, and limit viral community spread. SARS-CoV-2 variants of concern (VOCs) such as Alpha and Omicron, which show increased transmissibility and immune evasion, rapidly became dominant VOCs worldwide. Our objective was to develop an evidenced-based genomic surveillance algorithm, combining reverse transcription polymerase chain reaction (RT-PCR) and sequencing technologies to quickly identify highly contagious VOCs, before cases accumulate exponentially. METHODS: Deidentified data were obtained from 508,969 patients tested for coronavirus disease 2019 (COVID-19) with the TaqPath COVID-19 RT-PCR Combo Kit (ThermoFisher) in four CLIA-certified clinical laboratories in Puerto Rico (n = 86,639) and in three CLIA-certified clinical laboratories in the United States (n = 422,330). RESULTS: TaqPath data revealed a frequency of S Gene Target Failure (SGTF) > 47% for the last week of March 2021 in both, Puerto Rico and US laboratories. The monthly frequency of SGTF in Puerto Rico steadily increased exponentially from 4% in November 2020 to 47% in March 2021. The weekly SGTF rate in US samples was high (>8%) from late December to early January and then also increased exponentially through April (48%). The exponential increase in SGFT prevalence in Puerto Rico was concurrent with a sharp increase in VOCs among all SARS-CoV-2 sequences from Puerto Rico uploaded to Global Influenza Surveillance and Response System (GISAID) (n = 461). Alpha variant frequency increased from <1% in the last week of January 2021 to 51.5% of viral sequences from Puerto Rico collected in the last week of March 2021. CONCLUSIONS: According to the proposed evidence-based algorithm, approximately 50% of all SGTF patients should be managed with VOCs self-quarantine and contact tracing protocols, while WGS confirms their lineage in genomic surveillance laboratories. Our results suggest this workflow is useful for tracking VOCs with SGTF.