The predictive value of hypothalamic-pituitary-adrenal axis dysfunction in Alzheimer's disease

Abstract

Up to 58% of Alzheimer's disease (AD) patients are dexamethasone nonsuppressors (McKeith 1984: Ferrier et al 1991). In addition, a significant proportion of AD patients are high basal cortisol secretors (Raskind et al 1982; Davis et al 1986). The glucocorticoid cascade hypothesis proposes that hippocampat degeneration in AD might result in hypercortisolism, while simultaneously this overactive hypothalamic-pituitary-adrenal (HPA) system could act as an etiological factor in further neuronal degeneration (Sapolsky and McEwen 1986). If the glucocorticoid cascade hypothesis is relevant to the pathophysiology of AD, then hypercortisolemia and nonsuppression on the dexamethasone suppression test (DST) might be expected to predict the rate of progression. Although Miller et al (1994) reported significantly greater mortality in DST nonsuppressors, two studies have reported findings that are inconsistent with the glucocorticoid cascade hypothesis. Ferrier et al (1991) reported that DST nonsuppression did not predict clinical outcome. Weiner et al (1993) demonstrated that basal cortisol did correlate with subsequent cognitive decline, but when the data from 1 patient with extreme values were excluded the relationship became insignificant. The aim of this study was to determine if basal cortisol levels or DST response might provide a predictive marker for the rate of progression in AD.