Early Benefits with Potential Long-Term Risks of a Comprehensive Intervention on Serum Cortisol Levels and Cognitive Performance in Patients with Alzheimer's Disease

Abstract

Background: Elevated cortisol levels represent a risk factor for Alzheimer's disease (AD), prompting treatments to lower hormone concentrations for preventive or therapeutic purposes.

Objective: To assess the efficacy of a comprehensive intervention (CI) in modulating serum cortisol levels in patients with AD.

Methods: CI consisted in a 2-month protocol involving cognitive stimulation, psychological support, lifestyle guidance, leisure activities, and socialization. AD subjects were randomly assigned to experimental (EG, n = 45) and control (CG, n = 45) groups. A wide range of sociodemographic, cognitive, psychosocial, and functional conditions were evaluated before, at the conclusion, and 24 months after CI. Data about lifestyle and drug prescription were also recorded.

Results: Baseline evaluations revealed that higher cortisol levels correlated with worse cognitive status (higher CDR and ADAS-Cog values and lower MMSE scores), increased depressive symptoms, and reduced physical and social engagement. Following CI, EG exhibited reduced cortisol levels, improved overall cognitive status, and enhanced verbal working memory and executive functions compared to CG. However, at the 24-month follow-up, EG displayed a rebound effect, characterized by elevated cortisol levels and cognitive decline compared to CG.

Conclusions: These findings strengthen the adverse relationship between excessive cortisol and deficits in cognition/behavior in AD, demonstrate the short-term benefits of CI, and emphasize the potential long-term risks, which may be attributed to the fragile nature of the AD brain. Comprehensive interventions can yield positive results, but careful calibration of type and duration is necessary, considering disease progression and the potential need for re-administration.

Keywords: Alzheimer’s disease; cognitive performance; comprehensive intervention; cortisol.

Fig. 1

Serum cortisol level significantly correlates with cognitive performances and lifestyle in patients with Alzheimer’s disease. The higher the cortisol level, the worse the MMSE (A), the ADAS-Cog (B), and the Corsi supraspan (C) scores. The higher the serum cortisol level, the lower the physical activity (D), the lower the social network (E), and the higher the depressive mood (F). MMSE, Mini-Mental State Examination; ADAS-Cog, Alzheimer’s Disease Assessment Scale-Cognitive; PASE, Physical Activity Scale for Elderly; LSNS, Lubben Social Network Scale; GDS, Geriatric Depression Scale.

Fig. 2

The 2-month comprehensive intervention resulted in a significant reduction in serum cortisol levels and improvement in cognitive performance. EG exhibited a significantly greater reduction in serum cortisol level (A), a significantly greater improvement in general cognitive status (reflected by a reduction in ADAS-Cog (B) and an increase in MMSE (C) scores), and significantly better performance in the reverse digit span (D) and semantic fluency (E) tests compared to the CG. CG, control group; EG, experimental group; ADAS-Cog, Alzheimer’s Disease Assessment Scale-Cognitive; MMSE, Mini-Mental State Examination (MMSE). *p < 0.05, **p < 0.01, ***p < 0.001.

Fig. 3

After 24 months, EG showed an increase in serum cortisol level and a greatest cognitive decline compared to CG. Percent change versus baseline of serum cortisol level was significantly higher in EG to CG (A). Percent change versus baseline of ADAS-Cog scores was significantly higher in EG compared to CG (B). Percent change versus baseline of MMSE values was significantly lower in EG compared to CG (C). Percent change versus baseline of CDR values was significantly higher in EG compared to CG (D). CG, control group; EG, experimental group; ADAS-Cog, Alzheimer’s Disease Assessment Scale-Cognitive; MMSE, Mini-Mental State Examination; CDR, Clinical Dementia Rate. *p < 0.05, ***p < 0.001.