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Do Alzheimer’s and Lewy body disease have discrete pathological signatures of gait?

Lookup NU author(s): Ríona McArdle, Dr Brook Galna, Dr Paul Donaghy, Professor Alan Thomas, Professor Lynn Rochester

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Abstract

OBJECTIVE: We aimed to refine the hypothesis that dementia has a unique signature of gait impairment reflective of underlying pathology by considering two dementia subtypes, Alzheimer’s disease (AD) and Lewy body disease (LBD), and exploring the role of cognition in disease-specific gait impairments. BACKGROUND: Accurately differentiating AD and LBD is important for treatment and disease management. Early evidence suggests gait could be a marker of dementia, due to associations between discrete gait characteristics and cognitive domains.UPDATED HYPOTHESIS: We hypothesise that AD and LBD have unique signatures of gait, reflecting disease-specific cognitive profiles and underlying pathologies. An exploratory study included individuals with mild cognitive impairment or dementia due to LBD (n=45) and AD (n=36), and 29 older adult controls. An instrumented walkway quantified 16 gait characteristics reflecting five independent domains of locomotion (pace, rhythm, variability, asymmetry and postural control). The LBD group demonstrated greater impairments in asymmetry and variability compared to AD; both groups were more impaired in pace and variability domains compared to controls. Executive dysfunction explained 11% of variance for gait variability in LBD, while global cognitive impairment explained 13.5% of variance in AD; therefore, gait impairments may reflect disease-specific cognitive profiles. With a refined hypothesis that AD and LBD-specific signatures of gait reflect discrete pathologies, future studies must examine the relationship between a validated model of gait with neural networks, using recognised biomarkers and post-mortem follow-up.MAJOR CHALLENGES FOR HYPOTHESIS: Differential diagnosis of AD and LBD used appropriate criteria and required consensus from an expert diagnostic panel in order to improve diagnostic accuracy. Future work should follow the framework set out in Parkinson’s disease to establish unique signatures of gait as proxy measures of disease-specific pathology, i.e., use a validated gait model to explore the progressive relationship between gait, cognition and pathology. LINKAGE TO OTHER MAJOR THEORIES: These exploratory findings support the theory of interacting cognitive-motor networks, as the gait-cognition relationship may reflect cognitive control over motor networks. Unique signatures of gait may reflect different temporal patterns of pathological burden in neural areas related to cognitive and motor function.


Publication metadata

Author(s): Mc Ardle R, Galna B, Donaghy P, Thomas A, Rochester L

Publication type: Article

Publication status: Published

Journal: Alzheimer's and Dementia

Year: 2019

Pages: In Press, Corrected Proof

Online publication date: 20/09/2019

Acceptance date: 01/07/2019

Date deposited: 30/09/2019

ISSN (print): 1552-5260

ISSN (electronic): 1552-5279

Publisher: Elsevier Inc.

URL: https://doi.org/10.1016/j.jalz.2019.06.4953

DOI: 10.1016/j.jalz.2019.06.4953


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