Higher allostatic load is associated with poorer structural integrity in the limbic network in cognitively unimpaired elderly

Abstract

AbstractBackgroundAllostatic load (AL) is a cumulative measure of dysregulations across multiple physiological systems of the body occurring over time. AL was originally developed to explain how chronic stress damages physiologic systems and accelerates aging. Studies exploring the relationship between AL and brain health in older adults using a multimodal approach are limited. Our objective was to provide a comprehensive overview of the brain substrates of AL in cognitively unimpaired elderly using complementary multimodal neuroimaging techniques.MethodBaseline data of 111 cognitively unimpaired older adults (mean age, 68.9years) from the Age‐Well study (NCT02977819) were included. They underwent multimodal neuroimaging (T1‐weighted and diffusion MRI, FDG‐PET and amyloid‐PET). A global measure of brain integrity was obtained for each modality by extracting the averaged signal across the whole gray matter (GM) or white matter (WM) for diffusion. AL was computed based on 19 markers of health. First, we examined the relationships between AL and sex or age. Second, we performed multiple regression and voxel‐wise analyses to predict AL from each neuroimaging modality and to highlight the brain regions involved. Finally, we conducted forward stepwise multiple regressions including the 19 AL‐components to determine the prognostic components of each of these associations; correcting for age, sex and education.ResultAL was associated with sex (men>women) but not with age. Higher AL was associated with lower global GM volume and WM mean diffusivity. Adjusting for alcohol consumption, smoking habits, treatments or comorbidities, these associations remained unchanged. Association with lower GM volume was found in the parahippocampus, hypothalamus, anterior insula and prefrontal gyrus and with WM diffusivity in the corona radiata and corpus callosum. Stepwise regressions revealed that these associations with GM volume and WM diffusivity were mainly explained by the body mass index (BMI) and waist‐hip‐ratio (WHR), respectively.ConclusionHigher AL is associated with poorer structural integrity in regions of the limbic network, which is implicated in memory, emotion and stress processes and known to be particularly vulnerable to Alzheimer’s disease. Our results further suggest that maintenance of a healthy weight (by monitoring BMI and WHR) might help to prevent AL increase, thus promoting brain health.