Early Motor Signs in Pathologically Verified Alzheimer's Disease and Lewy Body Disease

Background: The neuropathologies of Alzheimer's disease (AD) and Lewy body disease (LBD) commonly co-occur. Parkinsonism is the hallmark feature in LBD but it can be difficult to predict the presence of these co-pathologies early in the course of clinical disease. Timely diagnosis has crucial implications, especially with the advent of disease-modifying therapies. Objectives: We sought to define early motor features that predict the ultimate neuropathological diagnoses of normal, AD, AD with concurrent LB pathology, and pure LB. Methods: We examined the associations between individuals' early motor features from their initial visit using the Unified Parkinson's Disease Rating Scale (UPDRS) Part III and their neuropathological diagnoses using the U.S. National Alzheimer's Coordinating Center (NACC) Database. Results: We included data from participants with neuropathologically normal brains (n = 49), AD (n = 502), AD w/LB (n = 167), and pure LB (n = 51). Total UPDRS Part III scores were increasingly higher with purer LB pathology. Decreased facial expression at baseline differentiated those with AD w/LB pathology from those with AD. Participants having pure LB pathology more often had deficits in speech, facial expression, posture, gait, bradykinesia, and upper extremity rigidity relative to those with AD w/LB. Conclusion: Diminished facial expression significantly predicted the presence of LBs among those with concurrent AD pathology. Worse early speech, facial expression, posture, gait, bradykinesia, and upper extremity rigidity were suggestive of more pure LB pathology. These findings emphasize the utility of the neurological exam in the clinical assessment of persons with cognitive complaints as it can guide management.