Objective: To investigate the clinical influence of Alzheimer’s disease (AD) co-pathology on motor features in Lewy Body Dementia (LBD).
Background: There is considerable heterogeneity of motor features in LBD with unclear underlying neuropathological substrate. AD co-pathology is common in LBD and confers more rapid dementia and greater cortical alpha-synuclein pathology. Subgroups of Parkinson’s disease (PD) patients with prominent postural instability and gait difficulty have been linked to worse clinical outcomes and AD biomarkers, but motor function in the LBD spectrum (i.e. PD with dementia, PDD and Dementia with Lewy bodies, DLB) is understudied. We hypothesize AD CSF biomarker profiles will relate to worse postural instability and gait dysfunction in LBD.
Method: We selected LBD patients with early dementia (DLB=22,PDD with motor-dementia interval<5 years= 4; n=26) and available UPDRS Part III data and AD CSF biomarker data (Luminex Platform) at the time of diagnosis. We tested the association of composite scores for tremor and for postural instability/gait with AD biomarker positivity via autopsy-defined cut-point (CSF T-tau/abeta42>0.3) and continuous measure of natural log transformed CSF T-tau/AB ratio using logistic and linear multivariate regression, respectively, including covariates of age and levodopa equivalent daily dosage.
Results: We found an association between a composite score of postural instability and gait dysfunction with both the categorical designation of AD co-pathology (OR= 2.38, CI 1.05-5.14, p=0.03) and continuous measure of the CSF T-tau/AB ratio (beta=0.25, p=0.02). We found a similar association in the subgroup of DLB alone (p<0.05). In contrast, we did not find an association with total tremor score (p>0.1) and groups did not differ on total UPDRS III motor score or H&Y stage (p>0.1).
Conclusion: AD co-pathology may have a selective influence on motor heterogeneity in LBD based on the association of AD CSF biomarkers with non-tremor features of postural instability and gait dysfunction.
To cite this abstract in AMA style:
I. Walker, S. Shaw, S. Vaishnavi, D. Wolk, N. Dahodwala, J. Morley, J. Duda, A. Chen-Plotkin, A. Siderowf, L. Shaw, E. Lee, J. Trojanowski, M. Grossman, D. Weintraub, D. Irwin. Non-Tremor Motor Dysfunction is Associated with AD Biomarkers in Lewy Body Dementias [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/non-tremor-motor-dysfunction-is-associated-with-ad-biomarkers-in-lewy-body-dementias/. Accessed June 15, 2025.« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/non-tremor-motor-dysfunction-is-associated-with-ad-biomarkers-in-lewy-body-dementias/