Cognition as a mediator for gait and balance impairments in GBA-related Parkinson’s disease

Morris, Rosie, Martini, Douglas N., Ramsey, Katrina, Kelly, Valerie E., Smulders, Katrijn, Hiller, Amie, Chung, Kathryn A., Hu, Shu-Ching, Zabetian, Cyrus P., Poston, Kathleen L., Mata, Ignacio F., Edwards, Karen L., Lapidus, Jodi, Cholerton, Brenna, Montine, Thomas J., Quinn, Joseph F. and Horak, Fay (2022) Cognition as a mediator for gait and balance impairments in GBA-related Parkinson’s disease. npj Parkinson's Disease, 8 (1). p. 78. ISSN 2373-8057

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The extent to which the heterogeneity of gait and balance problems in PD may be explained by genetic variation is unknown. Variants in the glucocerebrosidase (GBA) gene are the strongest known genetic risk factor for PD and are associated with greater motor and cognitive severity. However, the impact of GBA variants on comprehensive measures of gait and balance and their relationship to cognition remains unknown. We aimed to determine differences in gait and balance impairments in those with and without GBA variants (mutation carriers and E326K polymorphism) and explore direct and indirect effects of GBA status on gait, balance, and cognition. 332 participants, 43 of whom had GBA variants, were recruited. Participants completed a comprehensive, objective assessment of gait and standing balance using body-worn inertial sensors. Group differences in gait and balance between PD with and without GBA variants were assessed with linear regression, adjusting for age, gender, clinical testing site, disease duration, and apolipoprotein E (APOE) ɛ4 status. Structural equation modeling (SEM) explored direct relationships between GBA status and gait and balance and indirect relationships between GBA status and gait and balance via cognition. The GBA variant group had more impaired gait (pace and variability) and balance (sway area/jerk and sway velocity), than the non-GBA variant group. SEM demonstrated cognition as a mediator of GBA status on gait and balance. The close relationships among GBA, gait/balance, and cognition suggest potential for novel therapeutics to target the GBA pathway and/or cognition to improve mobility in PD GBA variants.

Item Type: Article
Additional Information: Funding information: This work was supported by grants from the National Institutes of Health (NIH) (Pacific Udall Center; P50 NS062684) and the Department of Veterans Affairs (101 CX001702), and by infrastructure provided by the Veterans Affairs Northwest Parkinson’s Disease Research, Education, and Clinical Center. This publication was made possible with support from the Oregon Clinical and Translational Research Institute (OCTRI), grant number UL1TR002369 from the National Center for Advancing Translational Sciences (NCATS), a component of the NIH, and NIH Roadmap for Medical Research.
Subjects: A300 Clinical Medicine
C600 Sports Science
Department: Faculties > Health and Life Sciences > Sport, Exercise and Rehabilitation
Depositing User: John Coen
Date Deposited: 06 Jul 2022 10:05
Last Modified: 06 Jul 2022 10:15

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