The Link Between Serum Levels of Dehydroepiandrosterone and Alzheimer’s Disease: A Pilot Study in the Serbian Population

Background and aim Alzheimer's disease (AD) is the most prevalent type of dementia and a major health concern among the elderly population. Considering the role of neurosteroids in neurodegenerative processes, this pilot study aimed to investigate the association between serum dehydroepiandrosterone sulfate (DHEA-S) and cortisol concentrations, as well as their ratio, in patients with AD compared with cognitively intact individuals. Methods An observational case-control study was conducted involving 45 patients with clinically probable AD, diagnosed according to the 2011 National Institute on Aging-Alzheimer's Association criteria, and 40 healthy control participants matched for age and sex. Fasting morning serum concentrations of DHEA-S and cortisol were measured after a 12-hour overnight fast in all participants, and the cortisol/DHEA-S ratio was calculated. Cognitive status was assessed using the Montreal Cognitive Assessment and Clinical Dementia Rating scales. Results No statistically significant difference in serum DHEA-S concentrations was found between patients with AD and controls. However, patients with AD had significantly higher cortisol levels (398.85 vs. 337.40 nmol/L; p = 0.026) and a higher cortisol/DHEA-S ratio, showing a trend toward statistical significance (p = 0.078). Among participants aged 65-75 years, the cortisol/DHEA-S ratio was significantly higher in patients with AD than in controls (p = 0.031). In the control group, males had significantly higher DHEA-S levels than females (p = 0.020), whereas no sex difference was observed in the AD group. Conclusions The findings of this pilot study suggest that elevated cortisol levels and an imbalance in the cortisol/DHEA-S ratio may contribute to AD pathophysiology. DHEA-S alone did not show a significant association with disease presence, but the observed age- and sex-related differences indicate that this neurosteroid may play a differential role in the development and progression of AD.