Comparative and Cost-effectiveness of Personalized Targeted Multi-Factorial Approaches to Reducing Disparities in Alzheimer’s Disease and Related Dementias: The TARDIS-AD Project

About This Grant

As there is no cure for Alzheimer's Diseases and Related Dementias (ADRD), it is imperative to invest in ways to prevent them before they occur. Prior studies have found disparities in ADRD prevalence based on socioeconomic status (SES), race/ethnicity, and sex, with the highest prevalence observed in those who are Black, Hispanic, women, or living in low-SES households. However, few studies have examined the impact of biological factors such as inflammation, Hemoglobin A1c and none have quantified their impact on SES, race/ethnicity and sex disparities in dementia. Furthermore, few studies have considered whether psychosocial factors modify the association between lifestyle/metabolic factors and dementia risk, or whether these associations differ based on SES, race/ethnicity or sex. A deeper understanding of the complex interrelationships between lifestyle, metabolic and psychosocial factors on dementia risk is needed to develop effective interventions to reduce disparities in dementia. Lastly, when designing interventions to prevent ADRD, policymakers must consider inherent trade-offs between interventions that maximize health in the general population and those that minimize health disparities. For dementia, the potential benefits, cost-effectiveness and tradeoffs among these health approaches in reducing disparities are as yet untested. The proposed study, Personalized Targeted Multi-Factorial Approaches to Reducing DIS-parities in ADRD (TARDIS-AD project), will leverage our team’s expertise in causal mediation, machine learning, and simulation modeling to identify personalized intervention strategies that would most effectively and cost effectively reduce disparities in dementia risk. Specifically, the proposed study aims to: Aim 1: Determine the extent to which (a) lifestyle and (b) metabolic factors mediate the relationships of SES, race/ethnicity, sex, with dementia. We hypothesize that SES-, race/ethnicity-, and sex disparities in dementia risk are partially explained by differences in lifestyle (e.g. diet) and metabolic factors (e.g. Hemoglobin A1c) and thus targeting these lifestyle and metabolic factors could help reduce disparities in dementia. Aim 2: Identify early- and midlife psychosocial factors (e.g., early-life trauma) that modify the effect of lifestyle and metabolic factors on dementia risk in vulnerable subpopulations (e.g. low-SES). We hypothesize that negative psychosocial experiences (e.g. early-life trauma) suppress the effect of protective lifestyle/metabolic factors (e.g. high exercise level) on dementia risk in vulnerable subpopulations, suggesting that interventions will need to identify and address these underlying issues to effectively address dementia risk. Aim 3: Evaluate (a) the potential sustained effects of lifestyle/metabolic interventions on dementia incidence targeting high-risk subpopulations, the general population and vulnerable subpopulations, and (b) the cost-effectiveness of these interventions. We hypothesize that Interventions targeting vulnerable subpopulations can yield greater reduction of dementia disparities and be more cost-effective than the general population or high-risk approach.