ADNI aims to increase diversity in clinical trials

The Alzheimer's Disease Neuroimaging Initiative (ADNI) has launched its latest study – ADNI-4 – with an increased commitment to enroll a more diverse population in clinical trials.

ADNI investigators led by Michael Weiner, MD, of the University of California, San Francisco, recently reviewed the initiative's sponsored trials from 2021 to 2022, with the analysis revealing significant advances in the field, but also an Achilles heel.

"Generalizability of ADNI results is limited by lack of cohort diversity, an issue ADNI-4 aims to address by enrolling a diverse cohort," the group noted in an article published September 12 in Alzheimer's and Dementia.

The ADNI was launched in 2004 with $40 million in initial funding from the National Institutes of Health (NIH). Its primary aim is to improve Alzheimer's disease (AD) clinical trials, with this expected to translate into improved patient care.

Since 2006, the ADNI has shared clinical, neuroimaging, and cognitive data for researchers to explore new avenues of understanding and treating the disease, with ADNI-3 recently drawing to a close. In a review, the authors identified 1,459 publications from 2021 to 2022 that used ADNI data/samples and then reviewed the impact of 291 of these studies.

Among the significant advances during the period, the group noted that ADNI samples contributed to the development of plasma biomarkers such as phosphorylated tau for clinical use and described prognostic abilities of amyloid beta, tau, neurodegeneration, and inflammation biomarkers, primarily based on PET imaging.

In addition, ADNI most studies supported the "amyloid cascade hypothesis," the group wrote. This theory postulates that neurodegeneration in Alzheimer's disease is caused by the abnormal accumulation of beta-amyloid plaques in various areas of the brain, followed by a gradual spread of tau protein neurofibrillary tangles as clinical symptoms emerge.

Moreover, studies detailed how genetic and vascular risk, copathologies, resilience, and sex contribute to heterogeneity and biological subtypes of the disease.

However, the results may not be generalizable due to the limited cohort diversity, the group wrote.

Specifically, compared to U.S. census data, the ADNI cohort underrepresents the Asian (2% vs. 4.7%), Black/African American (5% vs. 10%), and Hispanic/Latinx (4% vs. 9.2%) populations, and overrepresents the non-Hispanic white population (87% vs. 74.6%), according to the findings.

"The ADNI-4 cohort, currently enrolling, will be more diverse to ensure generalizability of results," the authors wrote.

Ultimately, by enrolling a cohort more representative of the general population, the five-year study is hoped to result in a greater understanding of differences in disease progression among individuals and their response to therapeutic interventions, the group concluded.

The full article is available here.

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