Relationships between psychosocial stress, cerebrospinal fluid markers of Alzheimer’s disease, and cognitive function in middle‐aged and older adults

Abstract

AbstractBackgroundExposure to psychosocial stress empirically associates with risk of cognitive impairment and dementia. Plausible mechanisms include (I) direct influence on AD pathology, and (II) indirect influence through cognitive reserve processes. Current evidence for modifiable determinants of amyloid and tau deposition is mixed, and stress has rarely been studied in this context. In richly characterized cognitive aging samples, we explored preliminary associations between (i) stress measures and amyloid (A), tau (T) and neurodegeneration (N) biomarkers in cerebrospinal fluid (CSF), and (ii) synergistic effects of stress and ATN in cognition.MethodParticipants were enrolled in the Wisconsin Registry for Alzheimer’s Prevention (WRAP) or Wisconsin Alzheimer’s Disease Research Center (ADRC), were cognitively intact, had stress and cognition data from at least one timepoint, and had available CSF data assayed using the NeuroToolKit panel of robust prototype assays (Roche Diagnostics International Ltd). Predictors included Perceived Stress T‐scores from the NIH Toolbox Emotion Battery, and self‐reported recent (past‐year) stressors. ATN outcomes included CSF measures of amyloid positivity, tau positivity, and neurofilament light protein (NfL). Cognitive outcomes included performance in domains of (a) processing speed and mental flexibility and (b) episodic memory. Multivariable regression models assessed cross‐sectional predictor‐outcome relationships.ResultCharacteristics of the predominantly white, middle‐aged and older samples are in Table 1. Stress scores associated with poorer performance on tests of speed and mental flexibility but not memory. There were no significant associations between measures of stress and any AD biomarker (Table 2). Estimate precision was limited by sample sizes, but there were observable interactions between stress measures and tau positivity and NfL, specifically in domains of speed and flexibility (Table 3; eg Figure 1); higher stress predicted poorer performance in the presence of accumulated pathology.ConclusionThere was no evidence for direct relationships between stress exposure and ATN pathology. However, the presence of elevated AD biomarkers exacerbated cognitive detriment associated with psychosocial stress, particularly in a key domain of executive function. Our findings must be replicated in a larger and more diverse sample. However, this study provides preliminary evidence suggesting high stress may act on dementia risk indirectly, through reduced resilience to pathological changes in the brain.