Association between cortisol and aging-related hippocampus volume changes in community-dwelling older adults: a 7-year follow-up study

Background Identifying peripheral biomarkers related to modifiable risk factors to prevent dementia at an early stage will be extremely beneficial. We have been studying how older adults can maintain their mental health and continue to live in a familiar community. The aim of this study is to investigate the association between serum cortisol levels and brain volume among older adults in rural Japan. Methods This was a longitudinal study conducted in Kurokawa-cho, Imari, Saga Prefecture, Japan, among people aged 65 years and above, as reported previously. We conducted a survey twice. The first survey was conducted from October 2009 to March 2011 (Timepoint 1) and the second was conducted from November 2016 to September 2017 (Timepoint 2). Blood samples for serum cortisol levels analysis were collected from participants at Timepoint 1. Serum cortisol levels were measured using the enzyme-linked immunosorbent assay. The participants underwent brain MRI examinations, and Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) for cognitive function assessment at Timepoint 1 and Timepoint 2. We obtained 70 participants (16 men, mean age 72.69 ± 3.18 years; 54 women, mean age 72.69 ± 4.60 years, at Timepoint 1) for analysis. Correlation analysis was performed between serum cortisol levels at baseline (Timepoint 1) and brain volume (Timepoint 1, Timepoint 2, and Timepoint 1–Timepoint 2 difference) using voxel-based morphometry method. Results There was no significant difference in serum cortisol levels between men (72.32 ± 17.30 ng/ml) and women (76.60 ± 21.12 ng/ml) at baseline. Additionally, no effect of blood collection time on cortisol levels was observed in these participants. Small volume correction analysis at the cluster level by applying multiple comparison corrections (family-wise error; P < 0.05) showed a negative correlation between serum cortisol levels (Timepoint 1) and brain volume (Timepoint 2) within the region containing the left hippocampus. Conclusions Serum cortisol levels may serve as a peripheral biomarker of age-related volume changes involving the hippocampus in older adults aged 65 years and above.