Universität zu Köln

Ohndorf, Anna (2024). Elevated serum cortisol levels are associated with cerebral grey matter atrophy, hippocampal volumes and verbal memory performance in healthy aging and the Alzheimer’s disease continuum. PhD thesis, Universität zu Köln.

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Abstract

Background: Elevated levels of cortisol are commonly observed in Alzheimer's disease (AD) patients. Hypothalamic-pituitary-adrenal axis dysregulation, resulting in elevated cortisol levels, is associated with grey matter atrophy, memory impairment and elevated risk for AD in otherwise healthy individuals. However, in most of the studies patients were not characterized by biomarkers and AD diagnoses were vague. Imaging findings were commonly based on CT imaging and voxel-wise analysis of MR-imaging was used sparsely. Methods: Morning pre-scan serum cortisol levels, structural neuroimaging data and verbal memory performance were evaluated in patients with positive biomarkers (CSF, amyloid/tau-PET) suggestive of AD (n=29), and age-matched cognitively healthy seniors (n=29). Verbal memory performance was evaluated by a composite recall score derived from the verbal learning and memory test. The relationship between serum cortisol levels and grey matter volume (derived by CAT12) were assessed via whole brain voxel-wise analysis (pFWE < 0.05). In addition, a ROI-based approach using hippocampal volumes corrected for age, education and intracranial volume was applied. Results: Cortisol levels were significantly higher in AD patients than in healthy seniors. On the voxel level, cortisol levels were negatively correlated with left-hemispheric grey matter volumes of the hippocampus, fusiform gyrus, temporal pole and angular gyrus across the whole sample and in the diagnostic subgroups. In the ROI-based analysis elevated cortisol levels were negatively correlated with left and right hippocampal volumes in the whole sample and left hippocampal volumes in healthy seniors. Verbal memory performance was negatively correlated with serum cortisol levels across the whole sample and in AD patients. Conclusion: Elevated serum cortisol levels are associated with grey matter atrophy and lower hippocampal volumes not only in AD, but also in cognitively healthy seniors and thereby may increase the risk for cognitive decline. In AD, higher serum cortisol levels are associated with verbal memory impairment. To clarify a causal relationship longitudinal studies are needed. However, serum cortisol levels might serve as an early biomarker and could play a relevant role as a target for preventive measures and therapeutic approaches.