Serum cortisol is negatively related to hippocampal volume, brain structure, and memory performance in healthy aging and Alzheimer’s disease

Elevated cortisol levels have been frequently reported in Alzheimer’s disease (AD) and linked to brain atrophy, especially of the hippocampus. Besides, high cortisol levels have been shown to impair memory performance and increase the risk of developing AD in healthy individuals. We investigated the associations between serum cortisol levels, hippocampal volume, gray matter volume and memory performance in healthy aging and AD.

In our cross-sectional study, we analyzed the relationships between morning serum cortisol levels, verbal memory performance, hippocampal volume, and whole-brain voxel-wise gray matter volume in an independent sample of 29 healthy seniors (HS) and 29 patients along the spectrum of biomarker-based AD.

Cortisol levels were significantly elevated in patients with AD as compared to HS, and higher cortisol levels were correlated with worse memory performance in AD (Fig. 1).

Serum cortisol is negatively related to hippocampal volume, brain structure, and memory performance in healthy aging and Alzheimer’s disease
Figure 1. Cortisol levels and memory performance. Left side depicts unadjusted relationship of serum cortisol levels and memory performance, right side shows serum cortisol levels in the two groups.

Furthermore, higher cortisol levels were significantly associated with smaller left hippocampal volumes in HS and indirectly negatively correlated to memory function through hippocampal volume. Higher cortisol levels were further related to lower gray matter volume in the hippocampus and temporal and parietal areas in the left hemisphere in both groups (Fig. 2). The strength of this association was similar in HS and AD.

Serum cortisol is negatively related to hippocampal volume, brain structure, and memory performance in healthy aging and Alzheimer’s disease
Figure 2. Voxel-wise correlation of serum cortisol levels and gray matter volume. (A) Glass brain showing clusters of significant negative correlation of serum cortisol levels and gray matter (GM) volume across the whole sample, corrected for age, education, and total intracranial volume (TIV) at p < 0.05 FWE-corrected (cluster-forming threshold p < 0.001). Colorbar represents t-values. (B) Scatterplot depicts unadjusted relationship between serum cortisol levels and GM volume (adjusted for TIV and expressed as %TIV) in individual groups.

In AD, cortisol levels are elevated and associated with worse memory performance. Furthermore, in healthy seniors, higher cortisol levels show a detrimental relationship with brain regions typically affected by AD. Thus, increased cortisol levels seem to be indirectly linked to worse memory function even in otherwise healthy individuals. Cortisol may therefore not only serve as a biomarker of increased risk for AD, but maybe even more importantly, as an early target for preventive and therapeutic interventions.

Publication:

Dronse, J., Ohndorf, A., Richter, N., Bischof, G. N., Fassbender, R., Behfar, Q., Gramespacher, H., Dillen, K., Jacobs, H. I. L., Kukolja, J., Fink, G. R., & Onur, O.A. (2023). Serum cortisol is negatively related to hippocampal volume, brain structure, and memory performance in healthy aging and Alzheimer’s disease. Frontiers in Aging Neuroscience, 15, 1154112. doi: 10.3389/fnagi.2023.1154112

Letzte Änderung: 15.06.2023