@article{69c5662fa00f4ee999a2a0b446691864,
title = "Cognition as a mediator for gait and balance impairments in GBA-related Parkinson{\textquoteright}s disease",
abstract = "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.",
author = "Rosie Morris and Martini, {Douglas N.} and Katrina Ramsey and Kelly, {Valerie E.} and Katrijn Smulders and Amie Hiller and Chung, {Kathryn A.} and Hu, {Shu Ching} and Zabetian, {Cyrus P.} and Poston, {Kathleen L.} and Mata, {Ignacio F.} and Edwards, {Karen L.} and Jodi Lapidus and Brenna Cholerton and Montine, {Thomas J.} and Quinn, {Joseph F.} and Fay Horak",
note = "Funding Information: The authors declare no competing non-financial interests but the following competing financial interests; V.E.K. has received grant support from the report{\textquoteright}s grants from NIH, Department of Veterans Affairs, and University of Washington and is an external advisor for projects by Sage Bionetworks. B.C. is supported by grants from the NIH. C.P.Z. is supported by grants from the NIH, Department of Veterans Affairs, and the American Parkinson Disease Association. K.P. has received grants from the NIH, clinical trial funded by Sanofi, and consulting for Allergan. K.L.E. has received grants from the NIH. T.J.M. has received grants from the NIH and Farmer Family Foundation. J.F.Q. receives compensation for conducting clinical trials for Roche, Sanofi, Abbvie, and member of DSMB for Retrophin pharmaceuticals. F.H. has a significant financial interest in APDM, a division of Clario Int, a company that may have a commercial interest in the results of this research and technology. This potential institutional and individual conflict has been reviewed and managed by OHSU. R.M., D.N.M., K.R., K.S., A.H., K.A.C., S.C.H., I.M., and J.L. have nothing to declare. 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{\textquoteright}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. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41531-022-00344-5",
language = "English (US)",
volume = "8",
journal = "npj Parkinson's Disease",
issn = "2373-8057",
publisher = "Springer Nature",
number = "1",
}