Recent advances in the detection and management of motor dysfunction in Alzheimer's disease.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder primarily characterized by cognitive decline. However, there is growing recognition of the significant impact of motor dysfunction in individuals affected by AD. These motor impairments contribute substantially to functional decline, reduced quality of life, and increased caregiver burden in AD patients.1 Current research efforts are increasingly focused on identifying motor dysfunction as a potential early marker in the progression of AD. The temporal relationship between motor and cognitive decline is under intense investigation, with studies suggesting that subtle motor changes, such as gait and balance disturbances or slowed walking speed, may precede detectable cognitive impairment by several years.2 Specifically, research indicates that gait speed predicts a decline in processing speed and visuospatial abilities, and in ApoE4 carriers, it also predicts a memory decline.3 One study found that increased amyloid-beta (Aβ) deposition is associated with reduced gait speed, muscle strength, and balance in cognitively impaired older adults.4 Emerging evidence strongly supports the inclusion of motor function assessments, particularly gait analysis, in the early detection and risk stratification of AD. This could enable earlier interventions and potentially lead to improved disease management. Technological advancements provide increasingly sophisticated non-invasive methods for detecting motor impairments in AD, potentially enabling earlier and more accurate diagnoses. Digital tools and applications-including smartphone-based assessments and virtual reality platforms-are being explored for objective and quantitative evaluation of mobility. These digital measures offer the potential for longitudinal data collection and the detection of subtle changes in motor function over time.5 Digital biomarkers provide the advantage of frequent, objective monitoring in real-world settings, potentially capturing early motor changes that may be missed by traditional clinical evaluations.6 Nonetheless, challenges remain regarding validation, standardization, and the influence of variables such as demographics and disease stage. Wearable devices offer the potential for continuous, non-invasive monitoring of motor behavior, revealing subtle changes indicative of early AD. However, interpreting data from these devices requires careful consideration and further validation in larger studies. Additionally, recent applications of MRI, PET, and other neuroimaging techniques are being examined to detect brain changes related to motor dysfunction in AD. Advanced MRI techniques, such as diffusion tensor imaging (DTI), are used to assess white matter integrity along motor pathways, while molecular PET imaging can visualize amyloid and tau pathology in brain regions associated with motor control.7 Of note, tau pathology in higher motor regions has been significantly associated with cognitive decline. Advanced neuroimaging is essential for visualizing structural and functional brain changes linked to AD, including those that impact motor control.8 These methods may assist in early diagnosis, differential diagnosis from other dementias, and monitoring disease progression. Current therapeutic approaches to managing motor dysfunction in AD include both pharmacological and non-pharmacological interventions. Clinical trials specifically targeting motor symptoms in AD with pharmacological treatments are limited. Management typically relies on drugs primarily aimed at cognitive symptoms, which may have secondary benefits on motor function. Cholinesterase inhibitors (donepezil, rivastigmine) and memantine, which are approved for cognitive symptoms, have shown mild effects on motor function (e.g., donepezil restores mitochondrial respiratory function in skeletal muscles).9 Emerging disease-modifying therapies targeting amyloid and tau, and their potential indirect effects on motor function, are under investigation. Non-pharmacological interventions, particularly physical therapy tailored to improve balance, gait, and muscle strength, play a key role in managing motor symptoms and enhancing functional independence and safety. Physical activity can improve brain function and memory and may delay functional decline. Combined training that integrates motor and cognitive exercises (dual-task training) may provide additional benefits. Music therapy has also been shown to positively influence cognitive status, emotional well-being, and quality of life in older adults with early-stage dementia.10 Motor impairments are increasingly recognized as early markers of disease progression and critical targets in the comprehensive care of AD. Improving mobility, balance, and functional independence may result in greater patients' autonomy and reduced physical and emotional strain on caregivers.