SYNchronizing Exercises, Remedies in GaIt and Cognition

The proposed SYNERGIC trial is uniquely designed to evaluate the effect of aerobic and progressive resistance training exercises, combined with cognitive training and Vitamin D3 supplementation, in cognition and mobility in older adults with Mild Cognitive Impairment (MCI).

Exercises, specifically resistance and aerobic training, have been demonstrated to improve cognitive outcomes, along with improved physical capacity and mobility. Both aerobic and resistance training trials of different duration have revealed positive results, with the most consistent findings being observed after combined interventions of 6 months to one year. Although the training benefits of progressive resistance training (PRT) have been well documented, PRT has been studied far less extensively in older adults with Mild Cognitive Impairment (MCI). Exercise training has proven to be beneficial for cognition even in vulnarable populations like in frail older adults, and those with mobility issues. The exact mechanism supporting the benefits of exercise for cognition in humans needs to be further explored, as numerous studies in animals and humans have demonstrated that aerobic exercise may have neuroprotective and neurorestorative effects. The rationale of combining aerobic and PRT as multimodal exercise intervention is supported by research that has revealed potential beneficial effects. In addition, multimodal exercise interventions have shown positive effects on muscle/lean mass, cognition and brain structure, functionality, and brain volume.

Similarly cognitive training, i.e. computer based cognitive process training, has also shown positive results in improving cognition, mobility, and postural control. Several recent systematic reviews on the topic support the benefits of cognitive training. In line with exercise training, recent research on cognitive training has also supported important improvements in brain plasticity post-intervention.

Finally, Vitamin D3 deficiency in older adults has been linked to cognitive dysfunction, dementia, and mobility decline. Besides its very well-known effects on muscle and bone physiology, several studies have shown a potential beneficial role of Vitamin D3 on cognitive function. Robustly designed trials, with longitudinal follow-up, have been recommended in older adults with MCI to investigate the comparative benefits of isolated Vitamin D3 supplementation, and combined with physical and cognitive training.

To date, the effect of adding cognitive training and/or Vitamin D3 to a multimodal progressive exercise training for improving global cognition, executive function, memory, and gait in MCI has not been assessed.

Eligibility Criteria:
Inclusion Criteria:

1. At least 60 years of age
2. Self-reported levels of proficiency in English (French for Montreal site only) for speaking and understanding spoken language.
3. Able to comply with scheduled visits, treatment plan, and other trial procedures
4. Able to ambulate at least 10 meters independently
5. Having MCI operationalized using Albert et al. criteria as:

   * objective cognitive impairment in one of the following four cognitive domains: memory, executive function, attention, and language evaluated by the Montreal Cognitive Assessment (MoCA) test with scores ranging from 13-24/30.
   * Preserved activities of daily living on the disability scale confirmed by clinician interview
6. Having normal or corrected to normal vision in at least one eye so that they can identify symbols and stimuli presented on a computer screen in front of them.
7. Must be in sufficient health to participate in the study's aerobic-based exercise training program, based on medical history, vital signs, physical examination by study physicians, or written recommendation by family physician indicating one's appropriateness to participate in aerobic-based exercise training program.

Exclusion Criteria:

1. Serious underlying disease (such as active cancer, or recent heart attack) which, in the opinion of the investigator, may preclude engagement in interventions or may interfere with the participant's ability to participate fully in the study.
2. Diagnosis of dementia using criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition.
3. Participant with uncontrolled major depression, schizophrenia, severe anxiety and substance abuse.
4. Current parkinsonism or any neurological disorder with residual motor deficits (e.g. stroke with motor deficit), active musculo-skeletal disorders (e.g. severe osteoarthritis of lower limbs) or history of knee/hip replacement affecting gait performance at clinical evaluation.
5. Intention to enroll in other clinical trials during the same time period
6. Pre-existing exercise structured training program involving aerobic or resistance training in previous 6 months.
7. Taking cognitive enhancers, neuroleptics, anticholinergics or Vitamin D3 in doses more than 1000IU/day or equivalent.