Ríona Mc Ardle1, Brook Galna2, Paul Donaghy1, Alan Thomas1, Lynn Rochester3. 1. Institute of Neuroscience, Newcastle University Institute of Ageing, Newcastle Upon Tyne, UK. 2. Institute of Neuroscience, Newcastle University Institute of Ageing, Newcastle Upon Tyne, UK; School of Biomedical Sciences, Newcastle University, Newcastle Upon Tyne, UK. 3. Institute of Neuroscience, Newcastle University Institute of Ageing, Newcastle Upon Tyne, UK; Newcastle Upon Tyne Hospital NHS Foundation Trust, Newcastle Upon Tyne, UK. Electronic address: lynn.rochester@ncl.ac.uk.
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 hypothesize 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 with AD; both groups were more impaired in pace and variability domains than controls. Executive dysfunction explained 11% of variance for gait variability in LBD, whereas 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 recognized biomarkers and postmortem follow-up. MAJOR CHALLENGES FOR HYPOTHESIS: Differential diagnosis of AD and LBD used appropriate criteria and required consensus from an expert diagnostic panel 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; that is, 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.
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 hypothesize 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 with AD; both groups were more impaired in pace and variability domains than controls. Executive dysfunction explained 11% of variance for gait variability in LBD, whereas 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 recognized biomarkers and postmortem follow-up. MAJOR CHALLENGES FOR HYPOTHESIS: Differential diagnosis of AD and LBD used appropriate criteria and required consensus from an expert diagnostic panel 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; that is, 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.
Authors: Ríona Mc Ardle; Stephanie Pratt; Christopher Buckley; Silvia Del Din; Brook Galna; Alan Thomas; Lynn Rochester; Lisa Alcock Journal: Front Bioeng Biotechnol Date: 2021-03-11
Authors: Maria Angeles Prats-Sedano; George Savulich; Ajenthan Surendranathan; Paul C Donaghy; Alan J Thomas; James B Rowe; Li Su; John T O'Brien Journal: Int J Geriatr Psychiatry Date: 2020-12-14 Impact factor: 3.850
Authors: David Renggli; Christina Graf; Nikolaos Tachatos; Navrag Singh; Mirko Meboldt; William R Taylor; Lennart Stieglitz; Marianne Schmid Daners Journal: Front Physiol Date: 2020-02-20 Impact factor: 4.566