Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Science

Program

Neuroscience

Supervisor

Bartha, Robert

Abstract

Mild cognitive impairment (MCI) is a transitional stage before dementia. Altered gait in MCI has been associated with progression to dementia. Using magnetic resonance spectroscopy, a relationship between primary motor cortex (M1) neurochemistry and dual task gait speed has been reported in MCI. Interventional research suggests exercise, cognitive training, and vitamin D supplementation may benefit MCI, yet the combined effect of these treatments on gait speed and M1 metabolism is unknown. Participants with MCI (N=75) were assigned to one of five intervention arms and dual task cost on gait speed and M1 metabolism was assessed before and five months after intervention. Cognitive training paired with exercise increased M1 N-acetyl aspartate (NAA)/creatine concentrations compared to physical exercise alone. Additionally, those with greater changes in dual task cost on gait speed showed greater decreases in NAA and choline, further establishing a relationship between gait speed and M1 function in MCI.

Summary for Lay Audience

Mild cognitive impairment (MCI) is considered a transitional state between healthy aging and dementia. Unlike dementia, some patients with MCI are responsive and stabilize after incorporating regular exercise, cognitive training, and vitamin D supplementation. Therefore, our understanding of how to delay the onset of dementia is vital to the outcome of a patient’s disease progression. Slow walking speed in MCI has been associated with a significantly higher risk of progressing to dementia. Further, when patients are asked to perform a secondary cognitive task while walking (dual task), those with slower gait were more likely to have abnormal primary motor cortex (M1) metabolism, the region responsible for initiating leg movements. The current study examined whether five months of combined exercise, cognitive training, and vitamin D supplementation could increase dual task speed and improve M1 metabolism in people with MCI. We also wanted to know whether changes in dual task speed were associated with changes in M1 metabolite levels after five months. Before and after the trial, we used magnetic resonance spectroscopy, a non-invasive imaging tool, to assess M1 metabolite levels. We also measured the cognitive cost of the dual task on gait speed by taking the percentage difference in speed between dual task- and normal walking. Greater dual task cost is associated with greater gait impairment, greater cognitive impairment, and a higher risk of progressing to dementia. Six-month changes in M1 metabolite levels and dual task cost were assessed in 75 participants with MCI that were assigned to one of five treatment arms varying in combinations of physical exercise, cognitive training, and vitamin D regimens. Cognitive training combined with physical exercise showed improved M1 neuron function over time compared to participants who only did physical exercise. Additionally, we found that individuals with increased dual task cost on gait speed over time were also more likely to show declines in M1 neuron function. Our findings provide evidence of metabolic benefits in M1 following combined physical and cognitive training. This study also corroborates previously documented relationships between dual task gait speed and the metabolite profile of M1 in people with MCI.

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