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 (approximate to 73% females, age of approximate to 70 +/- 1 years) were randomly divided into three groups: aerobic-based training (AT-group, n = 27), aerobic-based training plus cognitive games (ACT-group, n = 25), and a control group engaged in reading (CG, n = 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. Results: Aerobic and combined training induced a positive effect on all cognitive functions tested at W4 (except problemsolving) andW8(all p < 0.001) with greater improvements inworking-memory and problem-solving inACT-group (p < 0.05). Depression levels also decreased significantly, and quality of life improved at W8 (p < 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. Conclusions: 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.