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Harnessing combination therapy: Current treatments, recent advancements, and future directions in Alzheimer's disease
Article de revue

Harnessing combination therapy: Current treatments, recent advancements, and future directions in Alzheimer's disease

Howard Fillit, Jacques Touchon, Bruno Vellas, Laura Nisenbaum et Aaron Burstein
The Journal of prevention of Alzheimer's disease, Vol.12(10)
12/2025
PMCID: PMC12627881
PMID: 41145343

Résumé

Abstract Background We aimed to investigate the effect of daily supplemental vitamin D, omega‐3s, and a thrice‐weekly home exercise program, alone or in combination, on change of appendicular lean muscle mass index (ALMI) and incident sarcopenia in older adults. Methods This is a secondary endpoint analysis of a 3‐year randomized, double‐blind, placebo‐controlled trial with a 2 × 2 × 2 factorial design among 2157 community‐dwelling, healthy adults aged 70 + years, from 2012 to 2018 (DO‐HEALTH). Participants were randomized to 2000 IU/d vitamin D and/or 1 g/d marine omega‐3s and/or exercise. Change in ALMI over 3 years was calculated in all participants who underwent dual energy X‐ray absorptiometry (DXA) ( n = 1495) using mixed effect models. Incident sarcopenia was analyzed based on the Sarcopenia Definitions and Outcomes Consortium in all non‐sarcopenic participants ( n = 1940). Results Among 1495 participants (mean age 74.9 (sd 4.4); 63.3% were women; 80.5% were at least moderately physically active at baseline) mean gait speed at baseline was 1.2 m/s (sd 0.3), mean ALMI at baseline was 6.65 (SD 0.95) in women, and 8.01 (SD 0.88) kg/m 2 in men. At year 3, average change of ALMI was −0.09 (sd 0.34) kg/m 2 (−1.35%) in women and − 0.17 (sd 0.33) kg/m 2 (−2.0%) in men. None of the treatments individually or in combination had a benefit on ALMI change compared to control over 3 years, with omega‐3s showing a small protective effect on ALMI at year 1 only (−0.021 vs. no‐omega‐3s −0.066 kg/m 2 , p = 0.001). Of 1940 non‐sarcopenic participants at baseline, 88 (4.5%) developed incident sarcopenia over 3 years. None of the treatments individually or in combination reduced the odds of incident sarcopenia compared with placebo. Conclusion Among healthy, physically active older adults, ALMI and incidence of sarcopenia were not improved by treatment of daily 2000 IU vitamin D, daily 1 g omega‐3s, or a simple home exercise program compared with control over 3 years.

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