Serum cortisol, cerebral amyloidosis, and neurodegeneration: A longitudinal study

Abstract

AbstractBackgroundAlthough elevated blood cortisol has been repeatedly associated with Alzheimer`s disease (AD) and related cognitive decline, the pathological links underlying the association remain poorly understood. In this context, we aimed to investigate the relationship between serum cortisol and AD neuroimaging markers including amyloid beta protein (Aβ) deposition, tau deposition, AD‐signature region cerebral glucose metabolism (AD‐CM), AD‐signature region cortical thickness (AD‐CT), and adjusted hippocampal volume (HVa).MethodThis study was part of the of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE), an ongoing prospective cohort study. A total of 503 middle‐aged and elderly adults, including cognitively normal adults and individuals with mild cognitive impairment and AD dementia, underwent comprehensive clinical and neuropsychological assessments, 11C‐Pittsburgh compound B (PiB)‐PET, 18F‐deoxyglucose (FDG)‐PET, MRI, and serum cortisol level quantification at baseline and 2 years later. A subset of subjects also received 18F‐AV‐1451 PET during the follow‐up evaluation.ResultAt baseline, a significant positive association was found between serum cortisol level and global cerebral Aβ deposition after controlling for the effects of potential confounders (i.e., age, sex, APOE4 status, cognitive status, vascular risk, and depression). In addition, cortisol level showed significant inverse association with AD‐CM even after controlling for global Aβ retention as well as the confounders. There was no significant relationship between cortisol and cerebral tau deposition. In regard of longitudinal changes of AD markers, baseline cortisol level also had significant positive association with increase of cerebral Aβ deposition over 2 years, but not with changes of any neurodegeneration markers.ConclusionThe findings indicate that high serum cortisol contribute to AD processes through pathological cerebral Aβ deposition. Additionally, cortisol appears to directly affect neurodegeneration in AD‐signature brain regions via Aβ‐independent mechanisms.