Hippocampal perfusion and pituitary-adrenal axis in Alzheimer's disease

The hippocampus is involved in Alzheimer's disease (AD) and regulates the h ypothalamus-pituitary-adrenal axis (HPAA). Enhanced cortisol secretion has been reported in AD. Increased cortisol levels affect hippocampal neuron su rvival and potentiate beta-amyloid toxicity. Conversely, dehydroepiandroste rone (DHEA) and its sulfate (DHEAS) are believed to antagonize noxious gluc ocorticoid effects and exert a neuroprotective activity. The present study was aimed at investigating possible correlations between hippocampus perfus ion - evaluated by SPECT - and HPAA function in AD. Fourteen patients with AD and 12 healthy age-matched controls were studied by Tc-99m-HMPAO high-re solution brain SPECT. Plasma adrenocorticotropin, cortisol, and DHEAS level s were determined at 2.00, 8.00, 14.00, 20.00 h in all subjects and their m ean values were computed. Cortisol/DHEAS ratios (C/Dr) were also calculated . Bilateral impairment of SPECT hippocampal perfusion was observed in AD pa tients as compared to controls. Mean cortisol levels were significantly inc reased and DHEAS titers were lowered in patients with AD, as compared with controls. C/Dr was also significantly higher in patients. Using a stepwise procedure for dependent SPECT variables, the variance of hippocampal perfus ional data was accounted for by mean basal DHEAS levels. Moreover, hippocam pal SPECT data correlated directly with mean DHEAS levels, and inversely wi th C/Dr. These data show a relationship between hippocampal perfusion and H PAA function in AD. Decreased DHEAS, rather than enhanced cortisol levels, appears to be correlated with changes of hippocampal perfusion in dementia. Copyright (C) 2000 S. Karger AG, Basel.