Plasma cortisol and progression of dementia in subjects with Alzheimer-type dementia

Abstract

Objective: Studies of subjects with dementia of the Alzheimer type have reported correlations between increases in activity of the hypothalamic-pituitary-adrenal (HPA) axis and hippocampal degeneration. In this study, the authors sought to determine whether increases in plasma cortisol, a marker of HPA activity, were associated with clinical and cognitive measures of the rate of disease progression in subjects with Alzheimer-type dementia.

Method: Thirty-three subjects with very mild and mild Alzheimer-type dementia and 21 subjects without dementia were assessed annually for up to 4 years with the Clinical Dementia Rating scale and a battery of neuropsychological tests. Plasma was obtained at 8 a.m. on a single day and assayed for cortisol. Rates of change over time in the clinical and cognitive measures were derived from growth curve models.

Results: In the subjects with dementia, but not in those without dementia, higher plasma cortisol levels were associated with more rapidly increasing symptoms of dementia and more rapidly decreasing performance on neuropsychological tests associated with temporal lobe function. No associations were observed between plasma cortisol levels and clinical and cognitive assessments obtained at the single assessment closest in time to the plasma collection.

Conclusions: Higher HPA activity, as reflected by increased plasma cortisol levels, is associated with more rapid disease progression in subjects with Alzheimer-type dementia.

Figure 1. Correlations Between Plasma Cortisol Concentrations and Measures of Disease Progression in Subjects with Very Mild to Mild DAT

Relationships between plasma cortisol concentrations and measures of disease progression were examined in a combined group of subjects with very mild (CDR 0.5) and mild (CDR 1) DAT. Panel A shows the scatterplot for the association between cortisol concentrations and rates of change (i.e., slopes) in sum-of-box scores. Panel B shows the scatterplot for the association between 8AM cortisol concentrations and rates of change (i.e., slopes) in Temporal Factor scores. Plasma was collected for cortisol at 8AM after an overnight fast. Rates of change in sum-of-box scores were generated using general linear mixed models and up to 4 annual assessments.