Does a multidomain intervention of aerobic-resistance exercises with cognitive training and vitamin D improve cognition in older adults with mild cognitive impairment?

In a recent study published in the journal JAMA Network Open, researchers used a SYNERGIC Trial to evaluate the efficacy of a combination of cognitive training, progressive exercise, and vitamin D supplementation on reversing the effects of mild cognitive impairment in adults. Their results suggest that while vitamin D supplementation has no observable benefit, sequential computerized cognitive training paired with physical exercise may reverse cognition loss.

Study: Effects of Exercise Alone or Combined With Cognitive Training and Vitamin D Supplementation to Improve Cognition in Adults With Mild Cognitive Impairment A Randomized Clinical Trial. Image Credit: Africa Studio/

Lifestyle interventions to combat cognitive degeneration

Dementia is an umbrella term for conditions that cause loss of cognitive functioning, usually associated with age. It is estimated to affect over 50 million people worldwide and remains without a cure. Recent clinical research has begun evaluating lifestyle and other nonpharmacological interventions to delay dementia onset and progression, especially during the mild cognitive impairment (MCI) stage.

MCI is a stage intermediate between normal cognitive degeneration and the onset of dementia. It has been identified as the optimal time to introduce preventive interventions and early treatments. Previous research has suggested the independent benefits of aerobic- and resistance training in improving cognition in older people, though their combined effects remain unexplored.

Computerized cognitive training (CCT) is a novel digital health application wherein patients can partake in gamified, engaging mental exercises from their smart devices. It has been shown to improve brain function in older people, albeit these results are yet again in isolation from any other nonpharmacological therapies. Vitamin D supplementation, when clubbed with exercise or cognitive training, has been assumed to slow the onset of dementia due to the established neuroprotective effects of the vitamin.

Studies employing a multidomain approach – combining multiple health interventions into one treatment regime – are rare and have shown confounding results, especially for MCI patients. Some studies have even suggested that combining exercise and cognitive training might have poorer outcomes than exercise alone. The long-term effects of these interventions have also remained hitherto understudied.

About the study

In the present study, researchers employed the Synchronizing Exercises, Remedies in Gait and Cognition (SYNERGIC) trail to evaluate the combined effects of exercise, cognitive training, and vitamin D supplementation on delaying dementia onset in MCI patients. The study was 20 months long, with follow-up assessments 6- and 12 months following trial completion.

Researchers began by identifying willing participants between the ages of 60 to 85 who fulfilled the MCI criteria – they had cognitive concerns, tests revealed impairment in attention, memory, function, or language, they retained the ability to perform daily activities adequately, and they were not diagnosed with dementia. Individuals with severe mental health conditions (depression, schizophrenia), a history of substance abuse, or those with prescribed vitamin D doses exceeding 1,000 IU per day were excluded.

Participants were randomly divided into five cohorts, representing different combinations of exercise, cognitive training, and vitamin D administration. This allocation was blind, so participants were unaware of which cohort they belonged to.

All participants underwent training sessions thrice weekly for 20 weeks. These sessions comprised 30 minutes of cognitive training (case or control), after which exercise training (aerobic-resistance or control) was carried out. Capsules containing 10,000 IU of vitamin D (case) or placebo (control) were administered to patients at the matching frequency as the training sessions.

Researchers used the Alzheimer Disease Assessment Scale Cognitive 13 (ADAS-Cog-13) to assess the baseline cognitive function of individual patients and their progress throughout the experiment. The study considered improvements in ADAS-Cog-13 scores at the 6-month mark proof of program efficacy.

Statistical analyses to compare differences within and between the five cohorts were carried out using linear mixed models adjusted for education, age, sex, and comorbidities.

Study findings

Researchers screened 853 volunteers for the study, of which 175 were selected. Participants had an average age of 73.1 years, were slightly biased in sex (50.9% male), and were predominantly White (82=3.2%).

Results of the group training and assessment tests revealed that compared to the control cohort, the remaining four cohorts depicted marked improvements in their ADAS-Cog-13 scores following six months of training. Contrary to previous research, cohorts receiving both exercise and cognitive training showed statistically significant improvements over those receiving only aerobic-resistance exercise.

Contrary to current clinical belief, vitamin D supplementation did not improve cognition scores when combined with exercise and cognitive training. However, the study noted several secondary outcomes – multidomain therapy significantly improved patients’ delayed recall, orientation, word recognition, and the Trail Marking Test (TAT-A) scores.


In the present study, researchers evaluated the efficacy of nonpharmacological multidomain therapy in delaying or reversing the onset of dementia in older adults displaying mild cognitive impairment symptoms.

The 20-month-long study comprised a group training of 30 minutes of mental training followed by 60 minutes of physical exercise, supplemented with 1,000 IU of vitamin D. This was repeated thrice weekly for the study duration, with cognitive progress checked at the 6- and 12-month marks.

Study results revealed that, while vitamin D was ineffective at maintaining or improving cognitive ability, the combination of progressive exercise with cognitive training significantly improved cognition in older adults. This implies that simple lifestyle changes could supplement or replace pharmacological interventions as safer therapeutic options in the future.

Our findings suggest that this multidomain intervention could induce a clinically meaningful cognitive improvement in individuals with MCI, which may have important implications for their quality of life.”

Journal reference:
  • Montero-Odasso, M. et al. (2023) "Effects of Exercise Alone or Combined With Cognitive Training and Vitamin D Supplementation to Improve Cognition in Adults With Mild Cognitive Impairment", JAMA Network Open, 6(7), p. e2324465. doi: 10.1001/jamanetworkopen.2023.24465.

Posted in: Miscellaneous News | Healthcare News

Tags: Brain, Clinical Trial, Cognitive Function, Dementia, Depression, Education, Efficacy, Exercise, Frequency, Language, Mental Health, Placebo, Research, Schizophrenia, Substance Abuse, Vitamin D

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Hugo Francisco de Souza

Hugo Francisco de Souza is a scientific writer based in Bangalore, Karnataka, India. His academic passions lie in biogeography, evolutionary biology, and herpetology. He is currently pursuing his Ph.D. from the Centre for Ecological Sciences, Indian Institute of Science, where he studies the origins, dispersal, and speciation of wetland-associated snakes. Hugo has received, amongst others, the DST-INSPIRE fellowship for his doctoral research and the Gold Medal from Pondicherry University for academic excellence during his Masters. His research has been published in high-impact peer-reviewed journals, including PLOS Neglected Tropical Diseases and Systematic Biology. When not working or writing, Hugo can be found consuming copious amounts of anime and manga, composing and making music with his bass guitar, shredding trails on his MTB, playing video games (he prefers the term ‘gaming’), or tinkering with all things tech.

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