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Alzheimer disease (AD) is a progressive disorder common among older adults and culminating in profound cognitive impairments and high mortality risk. The US Food and Drug Administration (FDA) recently provided accelerated approval for Aduhelm, a medication for AD treatment. Aduhelm (Biogen Inc., Cambridge, Massachusetts) has been described as the first disease-modifying treatment for AD but has not been demonstrated to improve patients' cognitive or functional outcomes. In this commentary, we describe why Aduhelm approval was controversial and aspects of the current evidence of special pertinence to epidemiologists. The FDA decision was based primarily on 2 randomized controlled trials (RCTs), both terminated early, with conflicting findings about the cognitive benefits of Aduhelm. Both RCTs showed important adverse effects of the medication. The FDA cited the documented reduction in brain amyloid, an AD biomarker hypothesized as a surrogate outcome, to justify accelerated approval. Despite lack of racial/ethnic diversity in the RCT participants, concerns about health disparities have been invoked to argue for public funding of this expensive medication. The Centers for Medicare and Medicaid Services recently made a "Coverage with Evidence Development" determination for Aduhelm and similar medications. We end by describing how innovative study designs could accelerate postapproval research and evaluate the proposed surrogate outcomes., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To determine changes in the incidence of dementia between 1988 and 2015., Methods: This analysis was performed in aggregated data from individuals >65 years of age in 7 population-based cohort studies in the United States and Europe from the Alzheimer Cohort Consortium. First, we calculated age- and sex-specific incidence rates for all-cause dementia, and then defined nonoverlapping 5-year epochs within each study to determine trends in incidence. Estimates of change per 10-year interval were pooled and results are presented combined and stratified by sex., Results: Of 49,202 individuals, 4,253 (8.6%) developed dementia. The incidence rate of dementia increased with age, similarly for women and men, ranging from about 4 per 1,000 person-years in individuals aged 65-69 years to 65 per 1,000 person-years for those aged 85-89 years. The incidence rate of dementia declined by 13% per calendar decade (95% confidence interval [CI], 7%-19%), consistently across studies, and somewhat more pronouncedly in men than in women (24% [95% CI 14%-32%] vs 8% [0%-15%])., Conclusion: The incidence rate of dementia in Europe and North America has declined by 13% per decade over the past 25 years, consistently across studies. Incidence is similar for men and women, although declines were somewhat more profound in men. These observations call for sustained efforts to finding the causes for this decline, as well as determining their validity in geographically and ethnically diverse populations., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

We used differences in state school policies as natural experiments to evaluate the joint influence of educational quantity and quality on late-life physical and mental health. Using US Census microsample data, historical measures of state compulsory schooling and school quality (term length, student-teacher ratio, and attendance rates) were combined via regression modeling on a scale corresponding to years of education (policy-predicted years of education (PPYEd)). PPYEd values were linked to individual-level records for 8,920 black and 14,605 white participants aged ≥45 years in the Reasons for Geographic and Racial Differences in Stroke study (2003-2007). Linear and quantile regression models estimated the association between PPYEd and Physical Component Summary (PCS) and Mental Component Summary (MCS) from the Short Form Health Survey. We examined interactions by race and adjusted for sex, birth year, state of residence at age 6 years, and year of study enrollment. Higher PPYEd was associated with better median PCS (β = 1.28, 95% confidence interval (CI): 0.40, 1.49) and possibly better median MCS (β = 0.46, 95% CI: -0.01, 0.94). Effect estimates were higher among black (vs. white) persons (PCS × race interaction, β = 0.22, 95% CI: -0.62, 1.05, and MCS × race interaction, β = 0.18; 95% CI: -0.08, 0.44). When incorporating both school quality and duration, this quasiexperimental analysis found mixed evidence for a causal effect of education on health decades later., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)