Combining exercise with cognitive training and vitamin D to improve functional brain connectivity (FBC) in older adults with mild cognitive impairment (MCI). Results from the SYNERGIC trial.

Nick W Bray, Frederico Pieruccini-Faria, Suzanne T Witt, Robert Bartha, Timothy J Doherty, Lindsay S Nagamatsu, Quincy J Almeida, Teresa Liu-Ambrose, Laura E Middleton, Louis Bherer, Manuel Montero-Odasso

Journal: GeroScience 2023;45(3):1967-1985

PMID: 37162700

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Plain Language Summary

Brain health deteriorates with ageing, but it occurs much more rapidly in those with mild cognitive impairment (MCI), a prodromal state between healthy cognitive ageing and dementia syndromes, including Alzheimer’s disease. The aim of this study to evaluate the effect of combined physical exercise (PE) modalities (aerobic and resistance training) separately and synergistically with cognitive training (CT) and/or vitamin D (VD) supplementation on functional brain connectivity (FBC) in older adults with MCI. This study was a multi-site, randomised, phase II, fractional-factorial, double-blind controlled study. Participants were randomly assigned to one of the five arms. Regardless of the intervention arm, all participants completed group-training sessions three times per week for 20-weeks. Results showed that PE increased FBC between the hippocampus and the angular gyrus, representing regions of the Default-Mode Network. CT with and without VD appeared to add very little to PE-induced FBC. None of the intervention or control arms demonstrated a significant correlation between FBC change and change in behavioural outcomes of physical and cognitive performance. Authors concluded that their findings support previous research suggesting that PE is efficacious in altering connectivity of the Default-Mode Network, one of the initial networks compromised in MCI.

Abstract

Changes in functional brain connectivity (FBC) may indicate how lifestyle modifications can prevent the progression to dementia; FBC identifies areas that are spatially separate but temporally synchronized in their activation and is altered in those with mild cognitive impairment (MCI), a prodromal state between healthy cognitive aging and dementia. Participants with MCI were randomly assigned to one of five study arms. Three times per week for 20-weeks, participants performed 30-min of (control) cognitive training, followed by 60-min of (control) physical exercise. Additionally, a vitamin D (10,000 IU/pill) or a placebo capsule was ingested three times per week for 20-weeks. Using the CONN toolbox, we measured FBC change (Post-Pre) across four statistical models that collapsed for and/or included some or all study arms. We conducted Pearson correlations between FBC change and changes in physical and cognitive functioning. Our sample included 120 participants (mean age: 73.89 ± 6.50). Compared to the pure control, physical exercise (model one; p-False Discovery Rate (FDR) < 0.01 & < 0.05) with cognitive training (model two; p-FDR = < 0.001), and all three interventions combined (model four; p-FDR = < 0.01) demonstrated an increase in FBC between regions of the Default-Mode Network (i.e., hippocampus and angular gyrus). After controlling for false discovery rate, there were no significant correlations between change in connectivity and change in cognitive or physical function. Physical exercise alone appears to be as efficacious as combined interventional strategies in altering FBC, but implications for behavioral outcomes remain unclear.

Address: Cumming School of Medicine, Department of Physiology & Pharmacology, University of Calgary, Calgary, AB, T2N 1N4, Canada. [email protected].; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, T2N 1N4, Canada. [email protected].; Gait and Brain Lab, Parkwood Institute, Lawson Health Research Institute, 550 Wellington Road, Room A3-116, London, ON, N6C-0A7, Canada. [email protected].; Gait and Brain Lab, Parkwood Institute, Lawson Health Research Institute, 550 Wellington Road, Room A3-116, London, ON, N6C-0A7, Canada.; Department of Medicine, Division of Geriatric Medicine, Schulich School of Medicine & Dentistry, Western University, London, ON, N6A-5C1, Canada.; BrainsCAN, Western University, London, ON, N6A-3K7, Canada.; Department of Medical Biophysics, Schulich School of Medicine and Dentistry, Western University, London, ON, N6A-5C1, Canada.; Robarts Research Institute, Western University, London, ON, N6A-5B7, Canada.; Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, London, ON, N6A-5C1, Canada.; Department of Physical Medicine and Rehabilitation, Schulich School of Medicine and Dentistry, Western University, London, ON, N6A-5C1, Canada.; Faculty of Health Sciences, School of Kinesiology, Western University, London, ON, N6G-2V4, Canada.; Faculty of Science, Department of Kinesiology and Physical Education, Wilfrid Laurier University, Waterloo, ON, N2L-3C5, Canada.; Department of Physical Therapy, University of British Columbia, Vancouver, BC, V6T-1Z3, Canada.; Centre for Aging SMART at Vancouver Coastal Health, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada.; Department of Kinesiology and Health Sciences, University of Waterloo, Waterloo, ON, N2L-3G1, Canada.; Department of Medicine, University of Montréal, Montréal, QC, H3T-1J4, Canada.; Research Centre, Montreal Heart Institute, Montréal, QC, H1T-1C8, Canada.; Gait and Brain Lab, Parkwood Institute, Lawson Health Research Institute, 550 Wellington Road, Room A3-116, London, ON, N6C-0A7, Canada. [email protected].; Department of Medicine, Division of Geriatric Medicine, Schulich School of Medicine & Dentistry, Western University, London, ON, N6A-5C1, Canada. [email protected].; Department of Epidemiology and Biostatistics, Schulich School of Medicine & Dentistry, Western University, London, ON, N6A-5C1, Canada. [email protected].

DOI: 10.1007/s11357-023-00805-6