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 non-motor 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 ɛ4 (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.
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Statistical Analysis was completed by NKS, School of Public Health Emory University.
Funding Michael J Fox Foundation: Edmond J Safra Global Genetics Consortia Grant, New York, NY USA. Close to a Cure Foundation: A Fund for Parkinson's Research of Foundation for the Carolinas, North Carolina USA. NIH: R01-NS36960, Washington, DC USA. Department of Veterans Affairs Merit Review Award. New York State Department of Health Wadsworth Center, Albany, NY, USA. The Sartain Lanier Family Foundation, Atlanta, GA, USA. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. The funding agencies had no role in design of this study. The authors had full access to all of the data in the study and SAF takes responsibility for the integrity of the data and accuracy of the data analysis
Competing interests SAF has research grants from TEVA Neurosciences, Ipsen and Schering Plough. He is also a consultant for Boehringer–Ingelheim, Allergan, UCB and Lundbeck. ESM has the following disclosures: TEVA—speakers bureau, research grant support; Allergan—research grant support, speakers bureau, consulting fee; Merz—research grant, consulting fee; Ipsen—research grant, consulting fee; Boehringer–Ingelheim—speakers bureau.
Ethics approval The study was conducted with the approval of the Emory University, Albany Medical Center, New York State Department of Health and University of Washington.
Provenance and peer review Not commissioned; externally peer reviewed.