Effects and mechanisms of exercise timing on cognitive function in older type 2 diabetes mellitus patients with mild cognitive impairment: A magnetic resonance imaging-based randomized controlled trial protocol.

Mild cognitive impairment (MCI) is a prevalent complication of type 2 diabetes mellitus (T2DM). Cognitive impairment progressively impairs self-care abilities, thereby triggering a vicious cycle of poor glycemic control and further cognitive decline. Exercise has been widely recognized as an effective strategy to improve both glycemic control and cognitive function; however, an optimal time of day for exercise to mitigate this neurodegenerative trajectory has not been determined. This trial aims to determine the most effective exercise timing to maximize cognitive benefits in older T2DM patients with MCI (T2DM-MCI) and to investigate the underlying neurobiological mechanisms using multimodal magnetic resonance imaging.

In this randomized controlled trial, patients 60-75 years of age with T2DM-MCI will be assigned to a morning exercise group (09:00-10:10), an evening exercise group (19:00-20:10), or a health education group. The exercise groups will complete a 12-week, home-based, remotely supervised exercise program comprising aerobic and resistance exercises. The health education group will receive a 12-week health education program. Cognitive function will be evaluated at baseline and post-intervention using the Montreal Cognitive Assessment, Color-Word Stroop Test, N-back task, Trail making Test, Attention Network Test, and Digit Symbol Substitution Test. Additionally, brain structure and function based on imaging, blood biomarkers, and physical fitness will also be assessed.

In this study, we aim to identify the optimal time of day for exercise to maximize cognitive benefits in patients with T2DM-MCI and to elucidate underlying neurocognitive mechanisms. We will examine whether glycemic control mediates the relationship between exercise and cognitive function improvement. This research is expected to provide "time-specific" evidence for exercise prescription to maximize the neurocognitive benefits and mitigate dementia risk in this population.

Chinese Clinical Trial Registry: [http://www.chictr.org.cn], identifier [ChiCTR2300073737].