The Role of Basal Cortisol Elevations in Alzheimer’s Disease: Presence and Prediction of Associated Pathology
Saelzler, Ursula Grace
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Elevations in the glucocorticoid steroid hormone cortisol have long been suspected to be characteristic of Alzheimer’s disease, and there is a renewed interest in the contribution of cortisol to the progression of the disease. However, to date, no systematic examination of basal cortisol levels in AD has been conducted. Further, although cortisol elevations are hypothesized to facilitate cerebral amyloid-beta accumulation, direct examinations of this relationship have been restricted to samples already showing evidence of amyloid accumulation. The two studies included in this dissertation directly addressed these issues. First, a comprehensive meta-analysis was conducted to compare basal cortisol levels between cognitively normal and demented older adults. The cortisol levels in the demented samples were significantly higher than those of the cognitively normal samples (d = 0.39, QM = 34.73, p < 0.001) and this difference was not moderated by the age, sex, or cognitive performance of the included samples. The second study applied a Cox regression analysis to data collected from the Baltimore Longitudinal Study of Aging to test whether basal cortisol measures collected prior to imaging evidence of amyloid-beta deposition would predict the risk of subsequent amyloid-beta accumulation. Both the cortisol slope and the cortisol level measured nearest to the estimated event time were significantly positively associated with the risk of amyloid-beta accumulation (HR = 1.31, p = 0.04 and HR = 1.03, p = 0.01 respectively). Taken together these studies suggest that basal cortisol elevations are often observed in Alzheimer’s disease and that the influence of cortisol on disease progression may begin even before detection by neuroimaging markers.