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INTRODUCTION: Manual motor problems have been reported in mild cognitive impairment (MCI) and Alzheimer's disease (AD), but the specific aspects that are affected, their neuropathology, and potential value for classification modeling is unknown. The current study examined if multiple measures of motor strength, dexterity, and speed are affected in MCI and AD, related to AD biomarkers, and are able to classify MCI or AD. METHODS: Fifty-three cognitively normal (CN), 33 amnestic MCI, and 28 AD subjects completed five manual motor measures: grip force, Trail Making Test A, spiral tracing, finger tapping, and a simulated feeding task. Analyses included (1) group differences in manual performance; (2) associations between manual function and AD biomarkers (PET amyloid ß, hippocampal volume, and APOE ε4 alleles); and (3) group classification accuracy of manual motor function using machine learning. RESULTS: Amnestic MCI and AD subjects exhibited slower psychomotor speed and AD subjects had weaker dominant hand grip strength than CN subjects. Performance on these measures was related to amyloid ß deposition (both) and hippocampal volume (psychomotor speed only). Support vector classification well-discriminated control and AD subjects (area under the curve of 0.73 and 0.77, respectively) but poorly discriminated MCI from controls or AD. CONCLUSION: Grip strength and spiral tracing appear preserved, while psychomotor speed is affected in amnestic MCI and AD. The association of motor performance with amyloid ß deposition and atrophy could indicate that this is due to amyloid deposition in and atrophy of motor brain regions, which generally occurs later in the disease process. The promising discriminatory abilities of manual motor measures for AD emphasize their value alongside other cognitive and motor assessment outcomes in classification and prediction models, as well as potential enrichment of outcome variables in AD clinical trials.
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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.
