Postural instability/gait disturbance in Parkinson's disease has distinct subtypes: an exploratory analysis

• Type of Material: Article
• Authors: Stewart Factor, Emory University; Nelson Steenland, Emory University; Donald S. Higgins, Albany Medical Center; Eric S. Molho, Albany Medical Center; Denise M. Kay, New York State Department of Health; Jennifer Montimurro, New York State Department of Health; Ami Rosen, Emory University; Cyrus P. Zabetian, University of Washington; Haydeh Payami, New York State Department of Health
• Language: English
• Date: 2011-05-01
• Publisher: BMJ Publishing Group
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011, Published by the BMJ Publishing Group Limited.
• Final Published Version (URL): http://dx.doi.org/10.1136/jnnp.2010.222042
• Title of Journal or Parent Work: Journal of Neurology, Neurosurgery and Psychiatry
• ISSN: 0022-3050
• Volume: 82
• Issue: 5
• Start Page: 564
• End Page: 568
• Grant/Funding Information: Michael J. Fox Foundation: Edmond J. Safra Global Genetics Consortia Grant; Close to a Cure Foundation: A Fund for Parkinson's Research of Foundation for the Carolinas; NIH: R01-NS36960, Department of Veterans Affairs Merit Review Award; New York State Department of Health Wadsworth Center; The Sartain Lanier Family Foundation.
• Keywords: FALLS; ALPHA-SYNUCLEIN; Surgery; AGE; RISK; DATATOP COHORT; QUALITY-OF-LIFE; Psychiatry; Neurosciences & Neurology; FREQUENCY; Science & Technology; Life Sciences & Biomedicine; DEMENTIA; Clinical Neurology; GAIT; ASSOCIATION
• Research Categories: Biology, Neuroscience; Health Sciences, Pathology

Abstract

Objective To test the hypothesis that postural instability with falling (PIF) and freezing of gait (FOG) are distinct subtypes of the postural instability/gait disturbance (PIGD) form of Parkinson's disease (PD). Methods 499 PD subjects from the NeuroGenetics Research Consortium were studied using logistic regression to examine, in a cross sectional analysis, predictors of FOG and PIF. Potential predictors were from four spheres; demographic, clinical motor, clinical nonmotor and genetic. Results FOG and PIF were both associated with greater gait subscores and lower tremor subscores on the Unified Parkinson's Disease Rating Scale (p≤0.02). However, they differed with regard to demographic, non-motor and genetic predictors. FOG was associated with greater duration of disease, with ORs of 3.01 (95% CI 1.35 to 6.72) and 4.91 (95% CI 2.29 to 10.54) for third and fourth quartiles of duration, respectively, versus the lowest half of duration. The risk of having psychotic symptoms was also significantly increased (OR 3.02, 95% CI 1.41 to 6.49; p=0.004). FOG was inversely associated with the presence of the CYP2D6*4 allele (OR 0.41, 95% CI 0.21 to 0.80; p=0.009) suggesting a protective effect. PIF was associated with depression (OR 1.08, 95% CI 1.01 to 1.15; p<0.02) and was inversely associated with APOE 34 (OR 0.21, 95% CI 0.05 to 0.87; p=0.03), again suggesting a protective effect. Conclusion FOG and PIF have different demographic, non-motor and genetic predictors suggesting that they may be pathophysiologically distinct subtypes of PIGD.These findings have implications in the discovery of therapeutic targets for these disabling features as well as for predicting outcomes of PD.