P4-399: The somatotrophics, memory and aging research trial (SMART): Study of mental activity & resistance training for the prevention of cognitive impairment in at-risk older individuals

Abstract

Background: Epidemiological, basic science and clinical evidence suggests that cognitive and physical exercise may benefit brain function in late life. Potentially protective neurobiological effects include adaptations in cortical volume, neuropeptides, functional activation, cytokines, body composition and insulin sensitivity. Delaying the onset of dementia and age-related cognitive impairment through cognitive and physical activity may therefore be a realistic goal, however this has yet to be fully tested in a RCT. In particular, the possibility of synergistic effects between cognitive and physical activity has not been robustly evaluated. Methods: A fully factorial, double-blind, placebo controlled and longitudinal randomized clinical trial. 182 initially non-demented older individuals at-risk for dementia by virtue of borderline cognitive function will be recruited and randomly assigned to one of four intervention conditions in equal numbers. Eligible individuals will be older than 65 years without dementia or depression, physically and linguistically capable of completing supervised cognitive and physical exercise, and at-risk defined as corrected MMSE 23-27. Interventions: 1. Cognitive exercise: 6 months of thrice weekly 1 hour sessions of computer-based multi-modal cognitive exercise plus sham physical exercise (stretching). 2. Physical exercise: 6 months of thrice weekly 1 hour sessions of progressive resistance exercise plus sham cognitive exercise (lectures). 3. Combined exercise: both active cognitive and physical exercise. 4. Double Sham Control group: both sham cognitive and physical exercise. Results: Will occur at 0 (baseline), 6 months (immediately after the intervention: proximal follow-up) and 18 months (longitudinal follow- up). These will include: Neuropsychological battery including ADASCog; Neuropsychiatric evaluation; Magnetic Resonance Imaging (MRI) brain scans; Mood and well-being; Physical fitness and functional performance; and Systemic inflammation, metabolism, nutritional biochemistry. Conclusions: Primary: To determine whether active interventions lead to a differential rate of cognitive decline at longitudinal follow-up compared to the placebo group, and whether combined mental and physical exercise is more effective than either modality alone. Secondary: To determine whether active intervention effects are mediated by specific changes in brain structure and function, or via alterations in metabolism, body composition or systemic inflammation. To determine whether active intervention effects are associated with improved mood and well-being.