Visuomotor Control of Stepping over Obstacles Improves in Early Alzheimer’s Disease after Lecanemab Treatment: A Single Subject Case Series

Abstract

Abstract Background: Alzheimer’s disease (AD), an incurable, progressive neurological disease, is the most common cause of dementia among older adults. While traditionally recognized for cognitive impairments, the emergence of gait disturbances presents a pivotal aspect of disease advancement, necessitating consideration of associated sensorimotor dysfunction. AD affects cortical visuomotor transformations, evidenced by diminished cortical thickness and altered reaction times in reaching tasks. Furthermore, eye-tracking studies have identified cognitive interference during visuomotor tasks, manifesting as increased saccadic movements and prolonged fixations, likely attributable to heightened cognitive demands. Although these findings support AD’s effects on the visuomotor transformation in locomotion, its diagnostic and assessment potential remains unexplored. Moreover, the recent use of monoclonal antibody therapies targeting β-amyloid show cognitive improvements, yet their efficacy in improving motor-related functional outcomes remains largely unexplored. Case Presentation: In this case study, we present a 75-year-old female diagnosed with early AD treated with Lecanemab. We explore gait changes pre- and post-Lecanemab infusions over 9-months. Before treatment, the patient scored 23/30 on the Mini Mental State Examination (MMSE) and 25/30 on the Functional Gait Assessment (FGA). Visuomotor processing was assessed using treadmill locomotion with and without obstacles of different sizes. Response time was measured as the period between the obstacle presentation and the initiation of stepping over that obstacle at preferred walking speed maintained across sessions. Additionally, we assessed for potential disruption of embedded limb representation in planning pathways through psychometric testing of limb speed perception. Measurements were repeated every 3-months for 9-months. At 9-months, the patient scored a 29/30 on the MMSE and a 30/30 on the FGA. During advanced gait assessment, she cleared obstacles, with an overall RT of 1.50 ± .39s. Limb speed perception accuracy remained stable. Conclusion: Our patient demonstrated disrupted visuomotor processing and execution functions during the treadmill obstacle avoidance task. Treatment potentially reversed this early functional metric and helped maintain it throughout the treatment period. At the 6-month mark, the participant showed no difference from her neurotypical cohort, with results enduring at 9-months. Psychometric testing indicated stable limb speed perception accuracy over the 9-month period, suggesting no disruption in the representation of limb dynamics.