Neural Mechanisms of Motor Dysfunction in Mild Cognitive Impairment and Alzheimer's Disease: A Systematic Review

Background: Despite the prevalence of motor symptoms in mild cognitive impairment (MCI) and Alzheimer's disease (AD), their underlying neural mechanisms have not been thoroughly studied. Objective: This review summarizes the neural underpinnings of motor deficits in MCI and AD. Methods: We searched PubMed up until August of 2021 and identified 37 articles on neuroimaging of motor function in MCI and AD. Study bias was evaluated based on sample size, availability of control samples, and definition of the study population in terms of diagnosis. Results: The majority of studies investigated gait, showing that slower gait was associated with smaller hippocampal volume and prefrontal deactivation. Less prefrontal activation was also observed during cognitive-motor dual tasking, while more activation in cerebellar, cingulate, cuneal, somatosensory, and fusiform brain regions was observed when performing a hand squeezing task. Excessive subcortical white matter lesions in AD were associated with more signs of parkinsonism, poorer performance during a cognitive and motor dual task, and poorer functional mobility. Gait and cognitive dual-tasking was furthermore associated with cortical thickness of temporal lobe regions. Most non-gait motor measures were only reported in one study in relation to neural measures. Conclusion: Cross-sectional designs, lack of control groups, mixing amnestic- and non-amnestic MCI, disregard of sex differences, and small sample sizes limited the interpretation of several studies, which needs to be addressed in future research to progress the field.