Motor sequence learning and learning to learn across the Alzheimer's disease continuum: Associations with biomarkers

Abstract

Background While amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) are primarily associated with cognitive impairments, motor dysfunction has also consistently been observed. Less is known, however, about the acquisition of new motor sequences along the AD continuum. Objective This study examined motor sequence learning in individuals with aMCI and AD dementia compared to cognitively normal individuals (CNI), and to what extent such learning is related to AD biomarkers. Methods A total of 28 individuals with AD dementia, 33 with aMCI, and 52 CNI performed a computerized task that assessed general motor performance and motor sequence learning abilities. Participants also completed a neuropsychological test battery to assess their cognitive abilities. APOE genotyping was used to determine the presence of ɛ4 alleles, amyloid PET imaging to quantify amyloid deposition, and structural MRI scanning to obtain hippocampal volume. Results While individuals with aMCI or AD dementia generally performed slower and less consistent than CNI, motor sequence learning occurred regardless of cognitive status. The rate of initial learning was slower in individuals with aMCI or AD dementia than in CNI. No significant associations between motor learning and AD biomarkers were observed. A combination of motor and cognitive measures best predicted amyloid burden, whereas a model with cognitive measures only best predicted hippocampal volume and APOE allele count. Conclusions Overall, individuals with aMCI and AD dementia showed relatively preserved motor sequence learning abilities, despite some decrements in the initial rate of learning. Combining measures of motor and cognitive functioning may enhance the prediction of amyloid burden. Future studies should use more complex sequential movements and further explore the value of integrating motor measures in AD/aMCI assessment and monitoring.

The authors' abstract, as published at the source. Journal of Alzheimer s Disease, 2026 · DOI ↗