Introduction:To generalize safety and efficacy findings, it is essential that diverse populations are well represented in Alzheimer's disease (AD) drug trials. In this review, we aimed to investigate participant diversity in disease-modifying AD trials over time, and the frequencies of participant eligibility criteria.Methods: A systematic review was performed using Medline, Embase, the Cochrane Library, and Clinicaltrials.gov, identifying 2247 records. Results:In the 101 included AD trials, participants were predominantly White (median percentage: 94.7%, interquartile range: 81.0-96.7%); and this percentage showed no significant increase or decrease over time (2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018)(2019). Eligibility criteria such as exclusion of persons with psychiatric illness (78.2%), cardiovascular disease (71.3%) and cerebrovascular disease (68.3%), obligated caregiver attendance (80.2%), and specific Mini-Mental State Examination scores (90.1%; no significant increase/decrease over time) may have led to a disproportionate exclusion of ethnoracially diverse individuals.Discussion: Ethnoracially diverse participants continue to be underrepresented in AD clinical trials. Several recommendations are provided to broaden eligibility criteria.

CONFLICTS OF INTERESTRLvB-V, JES, ELA, GMB, JMP, EvdB have nothing to disclose (aside from the funding reported elsewhere). SF received support to attend meetings/conferences from Alzheimer Nederland and the Erasmus Trustfonds. She served as the executive committee member of the Cultural Diversity & Psychology commission of the Dutch Association of Psychologists and serves as executive committee member to the Diversity and Disparities PIA of ISTAART. NDP is consultant to Boehringer Ingelheim, Amylyx, and Aribio (payments made to his institution). He is co-PI of studies with EIP Pharma and Fuji Film Toyama Chemical. He serves on the DSMB of Abbvie's M15-566 trial (payment to his institution). He is CEO and co-owner of the Brain Research Center, the Netherlands. He is also on the scientific program committee of the Alzheimer's Association. LSS reports grants/contracts by Eisai, Eli Lilly, Roche/ Genentech, Biogen, Biohaven, Novartis, and Washington University/NIA-DIAN-TU paid to the institution. In addition, he reports

BackgroundTo generalize safety and efficacy findings, it is essential that diverse populations are well represented in global Alzheimer’s disease (AD) drug trials. In this review, we aimed to 1) investigate participant diversity in disease‐modifying AD trials over time, 2) identify which eligibility criteria were used and how they were defined, and 3) how the eligibility criteria may have affected participant diversity levels.MethodA systematic review of amyloid and tau trials in Alzheimer’s disease was performed using Medline, Embase, the Cochrane Library, and Clinicaltrials.gov, identifying 2247 records.ResultIn the 101 included AD trials, participants were predominantly white (median percentage: 94.7%, IQR: 81.0%‐96.7%); and this percentage showed no significant increase or decrease over time (2001‐2019). Eligibility criteria such as exclusion of persons with psychiatric illness (78.2%), cardiovascular disease (71.3%) and cerebrovascular disease (68.3%), obligated caregiver attendance (80.2%), and specific MMSE‐scores (90.1%; no significant increase/decrease over time, Fig. 1) may have led to a disproportionate exclusion of ethnoracially diverse individuals. Furthermore, many eligibility criteria—such as those describing diabetes, hepatic disease, and renal conditions—often were not well defined, or the cut‐offs varied considerably across studies.ConclusionEthnoracially diverse participants continue to be underrepresented in AD clinical trials. Several recommendations will be provided, such as the use of internationally recognized clinical classifications and cut‐offs, inclusion of participants with specific medical conditions as long as they are medically stable, and flexibility in requirements regarding caregiver attendance. Furthermore, changes need to be considered to 1) the instruments used in trials (e.g. overreliance on MMSE) and 2) requirements regarding education, literacy, and language.