Investigation of hypertension and type 2 diabetes as risk factors for dementia in the All of Us cohort

• Type of Material: Article
• Authors: Shashwat Deepali Nagar, Georgia Institute of Technology; Priscilla Pemu, Morehouse School of Medicine; Jun Qian, National Institutes of Health; Eric Boerwinkle, National Institutes of Health; Mine Cicek, National Institutes of Health; Cheryl R. Clark, National Institutes of Health; Elizabeth Cohn, National Institutes of Health; Kelly Gebo, National Institutes of Health; Roxana Loperena, National Institutes of Health; Kelsey Mayo, National Institutes of Health; Stephen Mockrin, National Institutes of Health; Lucila Ohno-Machado, National Institutes of Health; Andrea H. Ramirez, National Institutes of Health; Sheri Schully, National Institutes of Health; Ashley Able, National Institutes of Health; Ashley Green, National Institutes of Health; Stephan Zuchner, Vanderbilt University Medical Center; I. King Jordan, Georgia Institute of Technology; Robert Meller, Morehouse School of Medicine; Alvaro Alonso, Emory University; Theodore Johnson II, Emory University; Gregory Martin, Emory University; Arshed Quyyumi, Emory University; Michael Zwick, Emory University
• Language: English
• Date: 2022-12-01
• Publisher: Nature Research
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2022
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41598-022-23353-z
• Title of Journal or Parent Work: Scientific Reports
• Volume: 12
• Issue: 1
• Start Page: 19797
• End Page: 19797
• Grant/Funding Information: On behalf of the All of Us Research Program Investigators. This project was supported by NIH grant for the South Eastern Coordinating Center (SEEC) (NIH 3OT2OD026551-01S2). Funding also from a supplemental award to NIH U54MD007602-33S1. “The All of Us Research Program is supported by the National Institutes of Health, Office of the Director: Regional Medical Centers: 1 OT2 OD026549; 1 OT2 OD026554; 1 OT2 OD026557; 1 OT2 OD026556; 1 OT2 OD026550; 1 OT2 OD 026552; 1 OT2 OD026553; 1 OT2 OD026548; 1 OT2 OD026551; 1 OT2 OD026555; IAA #: AOD 16037; Federally Qualified Health Centers: HHSN 263201600085U; Data and Research Center: 5 U2C OD023196; Biobank: 1 U24 OD023121; The Participant Center: U24a OD023176; Participant Technology Systems Center: 1 U24 OD023163; Communications and Engagement: 3 OT2 OD023205; 3 OT2 OD023206; and Community Partners: 1 OT2 OD025277; 3 OT2 OD025315; 1 OT2 OD025337; 1 OT2 OD025276. In addition, the All of Us Research Program would not be possible without the partnership of its participants”.
• Keywords: Hypertension; Humans; United States; Risk Factors; Cross-Sectional Studies; Cohort Studies; Diabetes Mellitus, Type 2; Child, Preschool; Population Health
• Research Categories: Health Sciences, Human Development

Abstract

The World Health Organization recently defined hypertension and type 2 diabetes (T2D) as modifiable comorbidities leading to dementia and Alzheimer’s disease. In the United States (US), hypertension and T2D are health disparities, with higher prevalence seen for Black and Hispanic minority groups compared to the majority White population. We hypothesized that elevated prevalence of hypertension and T2D risk factors in Black and Hispanic groups may be associated with dementia disparities. We interrogated this hypothesis using a cross-sectional analysis of participant data from the All of Us (AoU) Research Program, a large observational cohort study of US residents. The specific objectives of our study were: (1) to compare the prevalence of dementia, hypertension, and T2D in the AoU cohort to previously reported prevalence values for the US population, (2) to investigate the association of hypertension, T2D, and race/ethnicity with dementia, and (3) to investigate whether race/ethnicity modify the association of hypertension and T2D with dementia. AoU participants were recruited from 2018 to 2019 as part of the initial project cohort (R2019Q4R3). Participants aged 40–80 with electronic health records and demographic data (age, sex, race, and ethnicity) were included for analysis, yielding a final cohort of 125,637 individuals. AoU participants show similar prevalence of hypertension (32.1%) and T2D (13.9%) compared to the US population (32.0% and 10.5%, respectively); however, the prevalence of dementia for AoU participants (0.44%) is an order of magnitude lower than seen for the US population (5%). AoU participants with dementia show a higher prevalence of hypertension (81.6% vs. 31.9%) and T2D (45.9% vs. 11.4%) compared to non-dementia participants. Dominance analysis of a multivariable logistic regression model with dementia as the outcome shows that hypertension, age, and T2D have the strongest associations with dementia. Hispanic was the only race/ethnicity group that showed a significant association with dementia, and the association of sex with dementia was non-significant. The association of T2D with dementia is likely explained by concurrent hypertension, since > 90% of participants with T2D also had hypertension. Black race and Hispanic ethnicity interact with hypertension, but not T2D, to increase the odds of dementia. This study underscores the utility of the AoU participant cohort to study disease prevalence and risk factors. We do notice a lower participation of aged minorities and participants with dementia, revealing an opportunity for targeted engagement. Our results indicate that targeting hypertension should be a priority for risk factor modifications to reduce dementia incidence.