Associations between neuropsychiatric symptoms, white matter microstructural integrity, and diagnostic status in the spectrum of Alzheimer’s disease

Abstract

AbstractBackgroundRecent studies have found that individuals who have undergone psychological stress and/or are affected by a chronic stress‐related disorder have an increased risk of developing Alzheimer’s Disease (AD). However, currently the biological mechanism underlying this relationship remains elusive. We hypothesized that white matter integrity loss may be a potential mediator between psychological stress and the development of AD. The goal of this study was to examine the relationship between neuropsychiatric symptoms as a proxy of stress responses, white matter microstructural integrity, and diagnostic status along the spectrum of AD.MethodWe evaluated the relationship between neuropsychiatric symptoms, white matter microstructural integrity, and diagnostic status along the spectrum of AD in 133 participants (ages 55.2‐90.4 years) selected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI‐2). Total scores in a brief Neuropsychiatric Inventory Questionnaire (NPI‐Q) were used to represent individuals’ psychological stress responses. We quantified white matter integrity measures using diffusion tensor imaging scans processed by the FMRIB's Diffusion Toolbox followed by the FSL Tract‐Based Spatial Statistics toolbox.ResultNPI‐Q scores representing stress responses significantly differed across diagnostic groups. Specifically, patients with AD (N=40, mean age=74.39) showed significantly higher NPI‐Q scores compared with cognitively normal (CN) older adults (N=44, mean age=73.39) and patients with Mild Cognitive Impairment (MCI)(N=49, mean age=75.64). Whole brain voxel‐wise analyses with white matter integrity measures as quantified as fractional anisotropy (FA) and mean diffusivity (MD) showed significant FA and MD differences (p ≤ 0.01) in the splenium, cingulum, superior longitudinal fasciculus, posterior thalamic radiation and the corpus callosum regions when controlling for age and sex. These differences were greater for AD patients compared with CN participants than those with MCI. NPI‐Q scores, however, were not related to a degree of white matter integrity in this sample.ConclusionSignificant group differences are shown in stress responses and white matter integrity across the diagnostic groups in the AD spectrum, which is consistent with the literature. Future studies are warranted to integrate reliable biological markers of stress responses to assess the impact of stress responses on microstructural changes and AD pathologies.