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

Abstract

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.

Salivary 3‐methoxy‐4‐hydroxyphenylglycol and MRI‐based volume change of the precuneus in community‐dwelling elderly people

“…Three‐dimensional T 1 ‐weighted structural images were acquired for each participant using a field echo 3‐dimensional (FE3D) method (TR, 21 ms; TE, 5.5 ms; flip angle, 20°; field of view, 240 × 240 mm; matrix, 256 × 256; slice thickness, 1.5 mm; number of slices, 124) and all acquisitions covered the whole brain. The examination conditions were the same for all participants following a standardized procedure 18,20,22 …”

“…This was a longitudinal study conducted in Kurokawa-cho, Imari, Saga Prefecture, Japan, among people aged 65 years and above, as reported previously. [15][16][17][18][19][20][21][22] Kurokawa-cho town is in north-western Saga Prefecture and is a rural district within the city of Imari, somewhat cut off from the urban centre. The area of Kurokawa-cho is 26.48 km.…”

“…The examination conditions were the same for all participants following a standardized procedure. 18,20,22 Preprocessing of brain MRI and longitudinal voxel-based morphometry (VBM) analysis Brain MRI processing steps and analysis were carried out using voxel-based morphometry (VBM) implemented with statistical parametric mapping (SPM12; Wellcome Department of Cognitive Neurology, London, UK) in MATLAB R2016a (MathWorks, Natick, MA, USA). We outsourced preprocessing of all brain images to Araya Brain Imaging (Tokyo, Japan), and statistical analyses were performed in our laboratory as previously reported.…”

“…We outsourced preprocessing of all brain images to Araya Brain Imaging (Tokyo, Japan), and statistical analyses were performed in our laboratory as previously reported. 18,20,22,[27][28][29] T 1 -weighted MRI were first segmented for grey matter and white matter using the segmentation procedures implemented in SPM12. The diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) described in SPM12 was performed on the segmented grey matter and white matter images to construct a template for co-registration across participants.…”

Rationale for a Multi-Factorial Approach for the Reversal of Cognitive Decline in Alzheimer’s Disease and MCI: A Review

“…The dysregulation of the HPA axis and elevated levels of cortisol are commonly seen in people with AD [ 148 , 151 , 152 , 153 , 154 ]. Stress disrupts the balance between the cortisol receptors (glucocorticoid and mineralocorticoid) that are present in the hippocampal area, leading to atrophy and the degeneration of the hippocampus [ 155 , 156 , 157 , 158 , 159 ]. Stress affects other biological pathways as well, including the brain’s immune system, by producing pro-inflammatory cytokines, thereby promoting inflammation, which underlies AD pathogenesis [ 160 , 161 , 162 ].…”