Effectiveness of Simultaneous Combined Intervention for Enhancing Cognitive Function in Patients with Moderate Alzheimer's Disease.

Background: The evidence supporting the effectiveness of combined interventions in Alzheimer's disease (AD) patients remains inconclusive.

Objective: The aim of this study was to evaluate the mid- and long-term effectiveness of physical training, alone or combined with cognitive games, on cognitive performance in patients with moderate AD.

Methods: Seventy-nine AD patients (≈73% females, age of ≈70±1 years) were randomly divided into three groups: aerobic-based training (AT-group,  = 27), aerobic-based training plus cognitive games (ACT-group,  = 25), and a control group engaged in reading (CG,  = 26), two sessions per week. Cognitive performance was evaluated at the start, 4th week (W4), end of the 8th week (W8), and after a 4-week detraining period (W12), using problem-solving (Tower-of-Hanoi), selective attention (Stroop-test), and working memory (Digit-Span-test) assessments. Stress levels and quality of life were also evaluated. Aerobic and combined training induced a positive effect on all cognitive functions tested at W4 (except problem-solving) and W8 (all  < 0.001) with greater improvements in working-memory and problem-solving in ACT-group ( < 0.05). Depression levels also decreased significantly, and quality of life improved at W8 ( < 0.001) in both groups. After 4 weeks of detraining, the beneficial effect of AT and ACT was still observed. The CG did not show any significant improvements at all time points. Physical and cognitive interventions appear effective for improving cognitive-functions, quality-of-life, and reducing depression in AD patients. Combined training emerges as a more effective strategy to mitigate AD progression. Further research is necessary to validate these results and explore their potential for preventing early cognitive decline.