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INTRODUCTION: Leveraging the nonmonolithic structure of Latin America, which represents a large variability in social determinants of health (SDoH) and high levels of genetic admixture, we aim to evaluate the relative contributions of SDoH and genetic ancestry in predicting dementia prevalence in Latin American populations. METHODS: Community-dwelling participants aged 65 and older (N = 3808) from Cuba, Dominican Republic, Mexico, and Peru completed the 10/66 protocol assessments. Dementia was diagnosed using the cross-culturally validated 10/66 algorithm. Multivariate linear regression models adjusted for SDoH were used in the main analysis. This study used cross-sectional data from the 1066 population-based study. RESULTS: Individuals with higher proportions of Native American (>70%) and African American (>70%) ancestry were more likely to exhibit factors contributing to worse SDoH, such as lower educational levels (p

BackgroundThe 2017 Alzheimer's disease (AD) Strategic Biomarker Roadmap (SBR) structured the validation of AD diagnostic biomarkers into 5 phases, systematically assessing analytical validity (Phases 1-2), clinical validity (Phases 3-4), and clinical utility (Phase 5) through primary and secondary Aims. This framework allows to map knowledge gaps and research priorities, accelerating the route towards clinical implementation. Within an initiative aimed to assess the development of biomarkers of tau pathology, we revised this methodology consistently with progress in AD research.MethodsWe critically appraised the adequacy of the 2017 Biomarker Roadmap within current diagnostic frameworks, discussed updates at a workshop convening the Alzheimer's Association and 8 leading AD biomarker research groups, and detailed the methods to allow consistent assessment of aims achievement for tau and other AD diagnostic biomarkers.ResultsThe 2020 update applies to all AD diagnostic biomarkers. In Phases 2-3, we admitted a greater variety of study designs (e.g., cross-sectional in addition to longitudinal) and reference standards (e.g., biomarker confirmation in addition to clinical progression) based on construct (in addition to criterion) validity. We structured a systematic data extraction to enable transparent and formal evidence assessment procedures. Finally, we have clarified issues that need to be addressed to generate data eligible to evidence-to-decision procedures.DiscussionThis revision allows for more versatile and precise assessment of existing evidence, keeps up with theoretical developments, and helps clinical researchers in producing evidence suitable for evidence-to-decision procedures. Compliance with this methodology is essential to implement AD biomarkers efficiently in clinical research and diagnostics.

Analysis of the specificity and kinetics of neutralizing antibodies (nAbs) elicited by SARS-CoV-2 infection is crucial for understanding immune protection and identifying targets for vaccine design. In a cohort of 647 SARS-CoV-2-infected subjects, we found that both the magnitude of Ab responses to SARS-CoV-2 spike (S) and nucleoprotein and nAb titers correlate with clinical scores. The receptor-binding domain (RBD) is immunodominant and the target of 90% of the neutralizing activity present in SARS-CoV-2 immune sera. Whereas overall RBD-specific serum IgG titers waned with a half-life of 49 days, nAb titers and avidity increased over time for some individuals, consistent with affinity maturation. We structurally defined an RBD antigenic map and serologically quantified serum Abs specific for distinct RBD epitopes leading to the identification of two major receptor-binding motif antigenic sites. Our results explain the immunodominance of the receptor-binding motif and will guide the design of COVID-19 vaccines and therapeutics.

Background: There is an agreement that the methodological quality of randomized trials should be assessed in systematic reviews, but there is a debate on how this should be done. We conducted a construct validation study of the Physiotherapy Evidence Database (PEDro) scale, which is widely used to assess the quality of trials in physical therapy and rehabilitation. Methods: We analyzed 345 trials that were included in Cochrane reviews and for which a PEDro summary score was available. We used one- and two-parameter logistic item response theory (IRT) models to study the psychometric properties of the PEDro scale and assessed the items' difficulty and discrimination parameters. We ran goodness of fit post estimations and examined the IRT unidimensionality assumption with a multidimensional IRT (MIRT) model. Results: Out of a maximum of 10, the mean PEDro summary score was 5.46 (SD = 1.51). The allocation concealment and intention-to-treat scale items contributed most of the information on the underlying construct (with discriminations of 1.79 and 2.05, respectively) at similar difficulties (0.63 and 0.65, respectively). The other items provided little additional information and did not distinguish trials of different quality. There was substantial evidence of departure from the unidimensionality assumption, suggesting that the PEDro items relate to more than one latent trait. Conclusions: Our findings question the construct validity of the PEDro scale to assess the methodological quality of clinical trials. PEDro summary scores should not be used; rather, the physiotherapy community should consider working with the individual items of the scale.

ObjectiveWe studied the relation of early-life (mean age 25 years) and mid-life (mean age 50 years) cognitive function to early measures of hostile attitudes and effortful coping.MethodsIn 3,126 black and white men and women (born in 1955-1968) from the Coronary Artery Risk Development in Young Adults Study (CARDIA), we used linear regression to examine the association of hostile attitudes (Cook-Medley questionnaire) and effortful coping assessed at baseline (1985-1986) to cognitive ability measured in 1987 and to a composite cognitive Z score of tests of verbal memory, psychomotor speed, and executive function ascertained in midlife (2010-2011).ResultsBaseline hostility and effortful coping were prospectively associated with lower cognitive function 25 years later, controlling for age, sex, race, education, long-term exposure to depression, discrimination, negative life events, and baseline cognitive ability. Compared to the lowest quartile, those in the highest quartile of hostility performed 0.21 SD units lower (95% confidence interval [CI] -0.39, -0.02). Those in the highest quartile of effortful coping performed 0.30 SD units lower (95% CI -0.48, -0.12) compared to those in the lowest quartile. Further adjustment for cumulative exposure to cardiovascular risk factors attenuated the association with the cognitive composite Z score for hostility.ConclusionsWorse cognition in midlife was independently associated with 2 psychological characteristics measured in young adulthood. This suggests that interventions that promote positive social interactions may have a role in reducing risk of late-age cognitive impairment.

ImportanceMarijuana use is increasingly common in the United States. It is unclear whether it has long-term effects on memory and other domains of cognitive function.ObjectiveTo study the association between cumulative lifetime exposure to marijuana use and cognitive performance in middle age.Design, setting, and participantsWe used data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a cohort of 5115 black and white men and women aged 18 to 30 years at baseline from March 25, 1985, to June 7, 1986 (year 0), and followed up over 25 years from June 7, 1986, to August 31, 2011, to estimate cumulative years of exposure to marijuana (1 year = 365 days of marijuana use) using repeated measures and to assess associations with cognitive function at year 25. Linear regression was used to adjust for demographic factors, cardiovascular risk factors, tobacco smoking, use of alcohol and illicit drugs, physical activity, depression, and results of the mirror star tracing test (a measure of cognitive function) at year 2. Data analysis was conducted from June 7, 1986, to August 31, 2011.Main outcomes and measuresThree domains of cognitive function were assessed at year 25 using the Rey Auditory Verbal Learning Test (verbal memory), the Digit Symbol Substitution Test (processing speed), and the Stroop Interference Test (executive function).ResultsAmong 3385 participants with cognitive function measurements at the year 25 visit, 2852 (84.3%) reported past marijuana use, but only 392 (11.6%) continued to use marijuana into middle age. Current use of marijuana was associated with worse verbal memory and processing speed; cumulative lifetime exposure was associated with worse performance in all 3 domains of cognitive function. After excluding current users and adjusting for potential confounders, cumulative lifetime exposure to marijuana remained significantly associated with worse verbal memory. For each 5 years of past exposure, verbal memory was 0.13 standardized units lower (95% CI, -0.24 to -0.02; P = .02), corresponding to a mean of 1 of 2 participants remembering 1 word fewer from a list of 15 words for every 5 years of use. After adjustment, we found no associations with lower executive function (-0.03 [95% CI, -0.12 to 0.07]; P = .56) or processing speed (-0.04 [95% CI, -0.16 to 0.08]; P = .51).Conclusions and relevancePast exposure to marijuana is associated with worse verbal memory but does not appear to affect other domains of cognitive function.

BackgroundThe classic view of blood pressure (BP) reactivity to psychological stress in relation to cardiovascular risks assumes that excess reactivity is worse and lower reactivity is better. Evidence addressing how stress-induced BP reactivity in young adults is associated with midlife cognitive function is sparse.Methods and resultsWe assessed BP reactivity during a star tracing task and a video game in adults aged 20 to 32 years. Twenty-three years later, cognitive function was assessed with use of the Digit Symbol Substitution Test (a psychomotor speed test), the Rey Auditory Verbal Learning Test (a verbal memory test), and the modified Stroop test (an executive function test). At the time of follow-up, participants (n=3021) had a mean age of 50.2 years; 56% were women, and 44% were black. In linear regression models adjusted for demographic and clinical characteristics including baseline and follow-up resting BP, lower systolic BP (SBP) reactivity during the star tracing and video game was associated with worse Digit Symbol Substitution Test scores (β [SE]: 0.11 [0.02] and 0.05 [0.02], respectively) and worse performance on the Stroop test (β [SE]: -0.06 [0.02] and -0.05 [0.02]; all P

Background: The Dementia Severity Rating Scale (DSRS) is an informant report, dementia staging tool that is quick to administer and has previous been shown to differentiate between people with dementia and healthy controls. However, it is not clear how accurate the tool is screening against diagnostic criteria in middle-income settings. Methods: Embedded within the STRiDE programme, older adults (aged ≥65 years) and their informants were randomly recruited from four sites across Indonesia and South Africa. All informants were asked to complete DSRS. We report the tool's psychometric properties and accuracy against the 10/66 short diagnostic algorithm. Results: Between September and December 2021, data was collected from 2110 older adults in Indonesia and 408 in South Africa. Overall, the DSRS scores significantly differed between those with and without dementia, as identified on the 10/66 short algorithm (p <.05). The difference between groups remained significant after controlling for key factors related to older adult and informant demographics. A score >2 on the DSRS had the greatest agreement with the 10/66 short algorithm and had excellent discriminative properties in both Indonesia (Area Under Curve (AUC) =.75, 95% CIs =.72–.77) and South Africa (AUC =.82, 95% CIs =.76–.88). Conclusions: The DSRS has potential as a screening tool for dementia in middle-income countries, with high sensitivity and specificity against a standardized diagnostic algorithm. [ABSTRACT FROM AUTHOR]

Background Seroprevalence and the proportion of people with neutralizing activity (functional immunity) against SARS-CoV-2 variants were high in early 2022. In this prospective, population- based, multi-region cohort study, we assessed the development of functional and hybrid immunity (induced by vaccination and infection) in the general population during this period of high incidence of infections with Omicron variants. Methods We randomly selected and assessed individuals aged ≥16 years from the general population in southern (n  = 739) and north-eastern (n  = 964) Switzerland in March 2022. We assessed them again in June/July 2022, supplemented with a random sample from western (n  = 850) Switzerland. We measured SARS-CoV-2 specific IgG antibodies and SARS-CoV-2 neutralizing antibodies against three variants (ancestral strain, Delta, Omicron). Results Seroprevalence remained stable from March 2022 (97.6%, n  = 1894) to June/July 2022 (98.4%, n  = 2553). In June/July, the percentage of individuals with neutralizing capacity against ancestral strain was 94.2%, against Delta 90.8% and against Omicron 84.9%, and 50.6% developed hybrid immunity. Individuals with hybrid immunity had highest median levels of anti-spike IgG antibodies titres [4518 World Health Organization units per millilitre (WHO U/mL)] compared with those with only vaccine- (4304 WHO U/mL) or infection- (269 WHO U/mL) induced immunity, and highest neutralization capacity against ancestral strain (hybrid: 99.8%, vaccinated: 98%, infected: 47.5%), Delta (hybrid: 99%, vaccinated: 92.2%, infected: 38.7%) and Omicron (hybrid: 96.4%, vaccinated: 79.5%, infected: 47.5%). Conclusions This first study on functional and hybrid immunity in the Swiss general population after Omicron waves showed that SARS-CoV-2 has become endemic. The high levels of antibodies and neutralization support the emerging recommendations of some countries where booster vaccinations are still strongly recommended for vulnerable persons but less so for the general population. [ABSTRACT FROM AUTHOR]