Metabolic pathways associated with multi‐morbidity among Black caregivers of persons living with dementia

Abstract

AbstractBackgroundBlack adults have the highest prevalence of obesity and hypertension, and these multiple chronic conditions increase their risk of morbidity and mortality. Black adults also represent the second largest group of caregivers of persons living with dementia. Gaps exist in our understanding of the physiologic changes associated with multiple chronic conditions in Black caregivers. This study used metabolomics to compare the metabolic profiles of Black caregivers with obesity, with or without hypertension. Our goal was to identify physiologic pathways for targeted interventions to improve morbidity/mortality in this group.MethodHigh‐resolution, untargeted metabolomics assays were run on stored serum samples from Black caregivers (n = 26) with obesity (BMI > = 30kg/m2), among whom 18 also had a diagnosis of hypertension. Linear regression using the xmsPANDA package was employed to identify metabolites differentiating multi‐morbidity. Two‐way hierarchical clustering analysis was used to visualize metabolome‐wide associations with multi‐morbidity. Additionally, metabolic pathways differentially impacted in multi‐morbidity were identified using mummichog.ResultOn average, caregivers were 62.9 (±6.5) years. 88.5% were female and 43% were married. Caregivers had been providing care for about 4.33 (±4) years. A total of 129 metabolites differentiated multi‐morbidity status at a p value < .05. Among these, key metabolic pathways associated with obesity and hypertension were butanoate metabolism and fatty acid activation. Among caregivers with only obesity, metabolites in the butanoate pathway were downregulated, compared to caregivers with both obesity and hypertension. Two exceptions were butyric acid and 2‐hydroxybutyric acid, which were both upregulated in caregivers without multi‐morbidity. In the fatty acid activation pathway, caregivers with only obesity had upregulated metabolites with the exception of icosatrienoic acid and dihomo‐gamma‐linolenic acid, which were down‐regulated.ConclusionIn caregivers with obesity, pathways associated with butanoate metabolism and fatty acid activation significantly differentiated hypertensive status. Healthcare interventions targeting caregiver education on diet/exercise may help optimize fatty acid activation in Black caregivers, thereby helping to reduce their risk of developing multi‐morbidities with hypertension. In addition, expanded health assessment of Black caregivers should be considered, as they may be at high risk for metabolic syndrome due to perturbed fatty acid and butanoate pathway functioning.