Motor sequence learning as a potential behavioral correlate of Alzheimer's disease: Evaluating associations with current biomarkers

While amnestic Mild Cognitive Impairment (aMCI) and Alzheimer’s disease (AD) are primarily defined by cognitive deficits, studies have demonstrated that motor impairments can precede cognitive symptoms by several years in these conditions. However, it is uncertain if the ability to learn sequences of movements is also impaired in this population. Therefore, this study investigated whether aMCI and AD affect motor sequence learning abilities, and how such abilities are related to AD biomarkers. The sample included 33 individuals with aMCI, 28 with AD, and 52 healthy controls (HCs). All groups completed a motor task consisting of performing a sequence of button presses, alternated with random blocks. Reaction time, coefficient of variation, and learning rates were obtained from the task. Participants also completed a series of cognitive tests to assess memory, visuospatial abilities, processing speed, language, and attention. Additionally, the following biomarkers for AD were assessed...Show moreWhile amnestic Mild Cognitive Impairment (aMCI) and Alzheimer’s disease (AD) are primarily defined by cognitive deficits, studies have demonstrated that motor impairments can precede cognitive symptoms by several years in these conditions. However, it is uncertain if the ability to learn sequences of movements is also impaired in this population. Therefore, this study investigated whether aMCI and AD affect motor sequence learning abilities, and how such abilities are related to AD biomarkers. The sample included 33 individuals with aMCI, 28 with AD, and 52 healthy controls (HCs). All groups completed a motor task consisting of performing a sequence of button presses, alternated with random blocks. Reaction time, coefficient of variation, and learning rates were obtained from the task. Participants also completed a series of cognitive tests to assess memory, visuospatial abilities, processing speed, language, and attention. Additionally, the following biomarkers for AD were assessed: amyloid beta via PET imaging, hippocampal volume via structural MRI, and number of e4 alleles via APOE genotyping. ANOVAs showed that AD participants had longer and more variable reaction times, followed by aMCI individuals, and with HCs having the shorter and more consistent reaction times. No significant differences in sequence learning rate were observed between groups. Exploratory analyses revealed that aMCI/AD had significantly slower initial learning rate than HCs. Linear regressions showed associations of slower reaction times with smaller hippocampal volume, and of higher coefficients with higher amyloid deposition. Poisson regressions revealed no significant correlations between motor sequence learning and APOEe4 allele count. Akaike Information Criterion (AIC) results indicated that combining cognitive test with motor measures improves the prediction of AD biomarkers. Overall, AD and aMCI individuals showed impairments in general motor performance but relatively preserved motor sequence learning abilities, with some deficits in initial rate of learning. Moreover, statistical model comparison suggested that adding motor sequence learning measures to neuropsychological assessment tools enhanced the prediction of AD biomarkers. As such, future studies should explore the value of integrating motor sequence learning measures in the assessment and tracking of AD/aMCI.Show less

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Motor sequence learning as a potential behavioral correlate of Alzheimer's disease: Evaluating associations with current biomarkers