Glucagon-Like Peptide-1 Receptor Agonists and Incidence of Dementia Among Older Adults With Type 2 Diabetes: A Target Trial Emulation: Annals of Internal Medicine: Vol 178, No 9

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to decrease blood glucose levels, promote weight loss, and prevent cardiovascular events. However, evidence is limited regarding their effect on dementia, although emerging observational studies, some with serious methodological limitations, have suggested large reductions in dementia associated with GLP-1RAs that may not be entirely causally related. Objective: To compare the effect of GLP-1RAs versus dipeptidyl peptidase-4 inhibitors (DPP4is) as second-line therapy for type 2 diabetes on risk for dementia among older adults. Design: Target trial emulation. Setting: United States from January 2016 to December 2020. Participants: Medicare fee-for-service beneficiaries aged 66 years or older with diabetes who used metformin and did not have dementia at baseline and initiated GLP-1RAs or DPP4is between January 2017 and December 2018. Measurements: Onset of dementia was defined as 1 year before the date of a new dementia diagnosis. Risks were calculated at 30 months in GLP-1RA and DPP4i groups matched in a 1:2 ratio on an estimated propensity score and compared via ratios and differences. Results: Among 2418 patients initiating GLP-1RAs and 4836 matched patients initiating DPP4is, the mean age was 71 years, and 55% were female. Over a median follow-up of 1.9 years, the outcome occurred in 96 patients in the GLP-1RA group and 217 in the DPP4i group. The estimated risk difference at 30 months was −0.93 (95% CI, −2.33 to 0.23) percentage points, and the estimated risk ratio was 0.83 (95% CI, 0.61 to 1.05). The estimated risk ratios were 0.64 (95% CI, 0.46 to 0.93) and 1.22 (95% CI, 0.74 to 1.66) among those younger than 75 years and aged 75 years or older, respectively. Limitations: Potential residual confounding (no data on body mass index, glycemic control, or duration of diabetes), outcome misclassification, and short follow-up. Conclusion: Among older adults with diabetes, no clear evidence was found that the incidence of dementia differed overall between patients using GLP-1RAs versus DPP4is. Under conventional statistical criteria, an effect of GLP-1RAs between a 39% decrease and a 5% increase in risk for dementia was highly compatible with the data, although estimates differed by age. Randomized trials are needed to quantify the effect of GLP-1RAs on dementia. Primary Funding Source: Gregory Annenberg Weingarten, GRoW @ Annenberg.

How Would You Manage HIV Pre-exposure Prophylaxis in This Patient With Medical Comorbidities?

Implications of the European Association for the Study of Obesity’s New Framework Definition of Obesity: Prevalence and Association With All-Cause Mortality

Background: The European Association for the Study of Obesity (EASO) recently introduced a new framework to define obesity that incorporates anthropometric measures beyond body mass index (BMI) and clinical comorbidities. However, this framework has not been validated. Objective: To describe the distribution of overweight and obesity and determine the prevalence of complications and association of obesity with all-cause mortality using BMI categories and the new EASO framework. Design: Cross-sectional and longitudinal analysis. Setting: NHANES (National Health and Nutrition Examination Survey) from 1999 to 2018 linked to mortality data. Participants: A representative sample of the adult population in the United States aged 18 to 79 years. Measurements: Obesity defined using BMI categories was compared with the new EASO definition. Results: The study population included 44 030 adults. On the basis of the new EASO definition, 18.8% of adults who were previously defined as overweight based on BMI alone were now considered persons with obesity (PWO). Similar mortality risk was found among the newly identified PWO and persons with normal weight (hazard ratio [HR], 0.98 [95% CI, 0.87 to 1.10]), whereas higher risk was seen among persons with BMI of 30 kg/m2 or greater (HR, 1.19 [CI, 1.08 to 1.32]). However, when compared with persons with normal weight who did not have major morbidities, a higher risk was seen among the newly identified PWO (HR, 1.50 [CI, 1.20 to 1.88]), although this higher risk was no greater than the higher risk seen among persons with normal weight and comorbidities (HR, 1.74 [CI, 1.34 to 2.22]). Excess risk was seen among PWO compared with persons with overweight according to both the new EASO framework and the traditional BMI definition. The most prevalent complications among the newly identified PWO were hypertension (79.9%), arthritis (33.2%), diabetes (15.6%), and cardiovascular disease (10.5%). Limitation: Residual confounding; body weight assessed at a single time point. Conclusion: The new EASO framework may provide a more sensitive tool to diagnose obesity than the traditional BMI definition, but whether these newly identified adults with obesity would benefit comparably to obesity treatment as those traditionally included in treatment trials is uncertain. Primary Funding Source: Ariel University and the Holon Institute of Technology, Israel.

Dementia

Dementia, or major neurocognitive disorder, is defined as a decline in 1 or more cognitive domains that causes impairment in everyday function. Alzheimer disease is the most common type of dementia in the United States, with an estimated 6.9 million adults who have Alzheimer disease and are 65 years or older. This article discusses the latest findings in preventing cognitive decline. It also discusses dementia screening, diagnosis, treatment, and the quality of life for persons with dementia and their caregivers.

Trends in Alcohol Use After the COVID-19 Pandemic: A National Cross-Sectional Study

Prescription for Change: Health Care Professionals and Advocacy for Farm Bill Reform

The Nuances of Performance Measurement and Clinical Guidelines

Perceptions of Culturally Responsive Care Among People With Disabilities

Long-Term Autoimmune Inflammatory Rheumatic Outcomes of COVID-19

Assessment and Management of Patients at Risk for Suicide: Synopsis of the 2024 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guidelines

Description: The U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DOD) updated the 2019 joint clinical practice guideline (CPG) for assessing and managing patients who are at risk for suicide. This synopsis provides primary care physicians with a summary of the updated 2024 recommendations regarding evaluation and management of military members and veterans at risk for suicide. Methods: In 2023, the VA/DOD Evidence-Based Practice Work Group convened to develop a joint VA/DOD guideline, including clinical stakeholders, which conformed to the National Academy of Medicine's tenets for trustworthy CPGs. The Work Group drafted 12 key questions, reviewed systematically identified literature (1 April 2018 to 15 March 2023), evaluated the evidence, created algorithms, and advanced 24 recommendations in accordance with the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Recommendations: Despite insufficient evidence to recommend for or against suicide risk screening programs as a means for reducing suicide attempts or deaths, the VA/DOD Work Group identified validated tools that could be used to identify populations at higher risk for suicide-related behaviors. Cognitive behavioral therapy was also recommended for reducing the risk for suicide attempts and decreasing suicidal ideation among those with a history of suicidal behavior or a history of self-directed violence. Periodic communications after previous suicide attempts were also recommended as a prevention strategy. Pharmacologic treatments, such as clozapine or ketamine infusion, also have a role in the management of suicide risk among those with schizophrenia or major depressive disorder, respectively.