Relationship Between Brain Volumes and Objective Balance and Gait Measures in Parkinson’s Disease

Article type: Research Article

Authors: Ragothaman, Anjanibhargavi^a | Miranda-Dominguez, Oscar^{b; c; d} | Brumbach, Barbara H.^f | Giritharan, Andrew^g | Fair, Damien A.^{b; c; d; e} | Nutt, John G.^g | Mancini, Martina^{a; g} | Horak, Fay B.^{a; e; g; *}

Affiliations: [a] Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, USA | [b] Masonic Institute for the Developing Brain (MIDB), University of Minnesota, Minneapolis, MN, USA | [c] Institute of Child Development, College of Education and Human Development, University of Minnesota, Minneapolis, MN, USA | [d] Department of Pediatrics, University of Minnesota Medical School, University of Minnesota, Minneapolis, MN, USA | [e] Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, USA | [f] Biostatistics and Design Program, Oregon Health and Science University, Portland, OR, USA | [g] Department of Neurology, Oregon Health and Science University, Portland, OR, USA

Correspondence: [*] Correspondence to: Fay B. Horak, PhD, 3181 S.W. Sam Jackson Park Rd, OP-32, Portland, OR, 97239-3098, USA. Tel.: +1 503 418 2061; E-mail: [email protected].

Abstract: Background:Instrumented measures of balance and gait measure more specific balance and gait impairments than clinical rating scales. No prior studies have used objective balance/gait measures to examine associations with ventricular and brain volumes in people with Parkinson’s disease (PD). Objective:To test the hypothesis that larger ventricular and smaller cortical and subcortical volumes are associated with impaired balance and gait in people with PD. Methods:Regional volumes from structural brain images were included from 96 PD and 50 control subjects. Wearable inertial sensors quantified gait, anticipatory postural adjustments prior to step initiation (APAs), postural responses to a manual push, and standing postural sway on a foam surface. Multiple linear regression models assessed the relationship between brain volumes and balance/gait and their interactions in PD and controls, controlling for sex, age and corrected for multiple comparisons. Results:Smaller brainstem and subcortical gray matter volumes were associated with larger sway area in people with PD, but not healthy controls. In contrast, larger ventricle volume was associated with smaller APAs in healthy controls, but not in people with PD. A sub-analysis in PD showed significant interactions between freezers and non-freezers, in several subcortical areas with stride time variability, gait speed and step initiation. Conclusion:Our models indicate that smaller subcortical and brainstem volumes may be indicators of standing balance dysfunction in people with PD whereas enlarged ventricles may be related to step initiation difficulties in healthy aging. Also, multiple subcortical region atrophy may be associated with freezing of gait in PD.

Keywords: Balance, brain volume, gait, Parkinson’s disease

DOI: 10.3233/JPD-202403

Journal: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 283-294, 2022