1 Department of Medicine, Division of Geriatric Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
2 Parkwood Institute, Gait and Brain Laboratory, London, Ontario, Canada.
3 Western University, Schulich School of Medicine and Dentistry, Department of Epidemiology and Biostatistics, London, Ontario, Canada.
4 Alimentiv Inc., London, Ontario, Canada.
5 Carespace Health and Wellness Neurodegeneration Clinics, Waterloo, Ontario, Canada.
6 Department of Kinesiology and Health Sciences, University of Waterloo, Waterloo, Ontario, Canada.
7 Schlegel-UW Research Institute for Aging, Waterloo, Ontario, Canada.
8 Recovery and Performance Laboratory, Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
9 Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal, Université de Montréal, Montreal, Quebec, Canada.
10 École de Réadaptation, Faculté de Médecine, Université de Montréal, Montreal, Québec, Canada.
11 School of Kinesiology, University of Western Ontario, London, Ontario, Canada.
12 Department of Epidemiology and Biostatistics, and Schulich Interfaculty Program in Public Health, Western University, London, Ontario, Canada.
13 Department of Physical Therapy, University of British Columbia, Vancouver, British Columbia, Canada.
14 Djavad Mowafaghian Centre for Brain Health, Vancouver Coastal Health Research Institute, Vancouver, British Columbia, Canada.
15 Centre for Aging SMART at Vancouver Coastal Health, Vancouver Coastal Health Research Institute, Vancouver, British Columbia, Canada.
16 Ontario Shores Centre for Mental Health Sciences, Whitby, Ontario, Canada.
17 Department of Psychiatry, Temerity Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
18 Department of Medicine and Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada.
19 Department of Psychology, Concordia University, Montréal, Québec, Canada.
20 Interdisciplinary School of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada.
21 Département des Sciences de l'Activité Physique, Université du Québec à Montréal, Montréal, Québec, Canada.
22 Institut national du sport du Québec, Montréal, Québec, Canada.
23 Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal, Montréal, Québec, Canada.
24 Centre de Recherche, Institut de Cardiologie de Montréal, Montréal, Québec, Canada.
25 Département de Médecine, Université de Montréal, Montréal, Québec, Canada.

Background: Older adults with mild cognitive impairment (MCI) have a higher risk of gait impairments and falls; yet, the effects of multimodal interventions, including combinations of exercises with cognitive training, on improving their mobility remain unclear.

Objectives: To investigate the synergistic effects of aerobic-resistance exercise combined with cognitive training, with or without vitamin D supplementation, on gait performance and falls risk in older adults with MCI.

Methods: The effect of 20 weeks of aerobic-resistance exercise, cognitive training, and Vitamin D supplementation (10 000 IU 3×/week) on gait and falls in older adults with MCI was evaluated in the SYNERGIC trial, using a fractional factorial design. Assessments were conducted at baseline, 6-month endpoint (after intervention) and 12-month endpoint (follow-up). Eligible participants were between the ages of 65 and 84 years with MCI enrolled from 19 September 2016 to 7 April 2020. Main outcomes of interest for gait performance were gait speed and gait variability changes, whilst for falls were incidental falls and incidental injurious falls.

Results: Amongst 161 participants, the four exercise-based arms improved gait speed (+7.5 cm/s, P < .001) and reduced falls (incidence rate ratios (IRR) = 0.65, 95% confidence interval (CI): 0.32-1.42, P = .25) and injurious falls (IRR = 0.38, 95% CI: 0.15-1.05, P = .05) at 6-month endpoint. Falls reduction reached statistical significance (IRR = 0.28, 95% CI: 0.13-0.64, P = .002) at 12-month endpoint. Exercises combined with cognitive training showed the greatest gains in gait speed at 6-month endpoint (P < .001) and in reducing falls at 12-month endpoint (IRR = 0.24, 95% CI: 0.05-0.77, P = .02) compared to the control. Vitamin D did not enhance outcomes and increased gait variability, a marker of instability.

Conclusion: Aerobic-resistance exercise combined with sequential computerised cognitive training improved gait performance at 6 months and decreased the risk of falls and injuries at 12 months in older adults with MCI. The addition of vitamin D did not produce benefits.