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

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.

Health Disparities in Appalachian and Other Rural Communities

“…It is known that many health conditions, including those that have been mentioned above, contribute to the onset of dementia. The health disparities that contribute include higher levels of comorbid chronic conditions such as obesity, diabetes, and heart disease (Nagar et al, 2022). As discussed above, these disparities are significantly higher in rural communities.…”

Physiological Mechanisms Inherent to Diabetes Involved in the Development of Dementia: Alzheimer’s Disease

“…In this relationship, insulin levels and insulin resistance are best correlated with the severity and progression of VaD [ 92 , 93 ]. Furthermore, it seems that DM promotes vascular damage caused by high levels of glucose in the blood, which is accentuated if it coexists with other pathologies that affect blood vessels, such as arteriosclerosis and hypertension [ 32 , 94 ].…”

“…Thus, individuals with T2D are at an increased risk of developing cardiovascular disease. These risks have been extensively studied in clinical and epidemiological research [ 30 , 31 , 32 , 33 , 34 , 35 ] as well as in basic research [ 36 , 37 , 38 , 39 , 40 ].…”

Investigating the impact of hypertension with and without diabetes on Alzheimer's disease risk: A clinico‐pathological study

“…Approximately 50%–90% of individuals with DM have hypertension, 19 , 20 and DM is 2.5 times more likely to occur in individuals with hypertension compared to those without. 21 As such, investigating the comorbid impact of hypertension and DM on AD risk is important as studies that have investigated each of their impacts individually may not be translatable to individuals who have both CVRFs.…”