Association of anthropometry and weight change with risk of dementia and its major subtypes : A meta-analysis consisting 2.8 million adults with 57 294 cases of dementia

Uncertainty exists regarding the relation of body size and weight change with dementia risk. As populations continue to age and the global obesity epidemic shows no sign of waning, reliable quantification of such associations is important. We examined the relationship of body mass index, waist circumference, and annual percent weight change with risk of dementia and its subtypes by pooling data from 19 prospective cohort studies and four clinical trials using meta-analysis. Compared with body mass index-defined lower-normal weight (18.5-22.4 kg/m(2)), the risk of all-cause dementia was higher among underweight individuals but lower among those with upper-normal (22.5-24.9 kg/m(2)) levels. Obesity was associated with higher risk in vascular dementia. Similarly, relative to the lowest fifth of waist circumference, those in the highest fifth had nonsignificant higher vascular dementia risk. Weight loss was associated with higher all-cause dementia risk relative to weight maintenance. Weight gain was weakly associated with higher vascular dementia risk. The relationship between body size, weight change, and dementia is complex and exhibits non-linear associations depending on dementia subtype under scrutiny. Weight loss was associated with an elevated risk most likely due to reverse causality and/or pathophysiological changes in the brain, although the latter remains speculative.Peer reviewe

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

A Taxonomy of Data Synthesis: A Tutorial

As more data is shared and concerns over the replicability, reproducibility, and generalizability of psychological and other social sciences continue, more researchers aim to conduct multi-study or multi-sample research and synthesize findings via data synthesis, using different parameterizations of individual participant meta-analysis. However, there is no overarching framework organizing different parameterizations and a relatively small number of simulation-based or empirical examples testing or comparing these parameterizations. Thus, this tutorial paper has three main goals. First, we provide an overview of six parameterizations of individual participant meta-analysis, which we organize into a taxonomy based on different features of each parameterization (e.g., sample-specific parameters, meta-analytic parameters, number of models required). Second, using empirical data from 26,205 participants across 11 longitudinal studies, we provide a tutorial estimating each parameterization by investigating prospective meta-analytic and sample-specific associations between the Big Five personality traits and crystallized abilities along with four moderators of these associations. Finally, we compare convergence and divergence of findings across methods. We found that Openness is a robust predictor of crystallized abilities across samples and methods and that there were few moderators of personality trait-crystallized ability associations. Across methods, we largely see convergence in model estimates, with some exceptions. We conclude by making recommendations and providing a flow chart for choosing the most appropriate parameterization of data synthesis given a particular team’s research goals, questions, data availability, and model features

Association of anthropometry and weight change with risk of dementia and its major subtypes: A meta-analysis consisting 2.8 million adults with 57 294 cases of dementia.

Uncertainty exists regarding the relation of body size and weight change with dementia risk. As populations continue to age and the global obesity epidemic shows no sign of waning, reliable quantification of such associations is important. We examined the relationship of body mass index, waist circumference, and annual percent weight change with risk of dementia and its subtypes by pooling data from 19 prospective cohort studies and four clinical trials using meta-analysis. Compared with body mass index-defined lower-normal weight (18.5-22.4 kg/m2 ), the risk of all-cause dementia was higher among underweight individuals but lower among those with upper-normal (22.5-24.9 kg/m2 ) levels. Obesity was associated with higher risk in vascular dementia. Similarly, relative to the lowest fifth of waist circumference, those in the highest fifth had nonsignificant higher vascular dementia risk. Weight loss was associated with higher all-cause dementia risk relative to weight maintenance. Weight gain was weakly associated with higher vascular dementia risk. The relationship between body size, weight change, and dementia is complex and exhibits non-linear associations depending on dementia subtype under scrutiny. Weight loss was associated with an elevated risk most likely due to reverse causality and/or pathophysiological changes in the brain, although the latter remains speculative

Association of anthropometry and weight change with risk of dementia and its major subtypes: A meta-analysis consisting 2.8 million adults with 57 294 cases of dementia.

Uncertainty exists regarding the relation of body size and weight change with dementia risk. As populations continue to age and the global obesity epidemic shows no sign of waning, reliable quantification of such associations is important. We examined the relationship of body mass index, waist circumference, and annual percent weight change with risk of dementia and its subtypes by pooling data from 19 prospective cohort studies and four clinical trials using meta-analysis. Compared with body mass index-defined lower-normal weight (18.5-22.4 kg/m2 ), the risk of all-cause dementia was higher among underweight individuals but lower among those with upper-normal (22.5-24.9 kg/m2 ) levels. Obesity was associated with higher risk in vascular dementia. Similarly, relative to the lowest fifth of waist circumference, those in the highest fifth had nonsignificant higher vascular dementia risk. Weight loss was associated with higher all-cause dementia risk relative to weight maintenance. Weight gain was weakly associated with higher vascular dementia risk. The relationship between body size, weight change, and dementia is complex and exhibits non-linear associations depending on dementia subtype under scrutiny. Weight loss was associated with an elevated risk most likely due to reverse causality and/or pathophysiological changes in the brain, although the latter remains speculative.Adult Changes in Thought Study was funded by a National Institutes of Health Grant U01 AG0006781. The Cache County Memory Study was funded by NIA grants R01 AG011380 and R01 AG018712; Dr Hayden’s effort on this project was supported by NIA R01 AG042633. JKaprio acknowledges support for the Finnish Twin Cohort by the Academy of Finland (grants 265240, 263278, 308248, 312073). This work was supported by the dedication of the Framingham Heart Study participants. This work and the investigators received grant support from the National Heart, Lung, and Blood Institute’s Framingham Heart Study (contracts no. N01-HC-25195 and HHSN268201500001I) and grants from the National Institute of Neurological Disorders and Stroke (NS17950 and UH2 NS100605), the National Institute on Aging (R01 AG054076, R01 AG049607, R01 AG033193, U01 AG049505 and U01 AG052409). The Study of Osteoporotic Fractures (SOF) is supported by National Institutes of Health funding. The National Institute on Aging (NIA) provides support under the following grant numbers: R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, and R01 AG027576. The Three-City Study is conducted under a partnership agreement between the INSERM, the ISPED of the University of Bordeaux, and Sanofi-Aventis. The Foundation pour la Recherche Médicale funded the preparation and initiation of the study. TheThree-City Study is also supported by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, Mutuelle Générale de l’Education Nationale, Institut de la Longévité, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research-INSERM Programme « Cohortes et collections de données biologiques », French National Research Agency COGINUT ANR-06-PNRA-005, COGICARE ANR Longvie (LVIE-003-01), the Fondation Plan Alzheimer (FCS 2009–2012), and the Caisse Nationale pour la Solidarité et l’Autonomie. This research has been conducted using the UK Biobank Resource under Application number 7439. SBell and EDA are supported by core funding from: NIHR Blood and Transplant Research Unit in Donor Health and Genomics (NIHR BTRU-2014-10024), UK Medical Research Council (MR/L003120/1), British Heart Foundation (RG/13/13/30194), and the NIHR Cambridge BRC. GDB is supported by the UK Medical Research Council (MR/P023444/1) and the US National Institute on Aging (1R56AG052519-01; 1R01AG052519-01A1). Whitehall II was supported by the Medical Research Council (MR/R024227/1), the NIH National Institute on Aging (R01AG056477) and British Heart Foundation (32334). EVuoksimaa was supported by the Academy of Finland (grants 314639 & 320109)