title: Postural instability/gait disturbance in Parkinson's disease has distinct subtypes: an exploratory analysis.
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 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 ε4 (OR 0.21, 95% CI 0.05 to 0.87; p=0.03), again suggesting a protective effect.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Emory University School of Medicine, Department of Neurology, 1841 Clifton Road NE, Atlanta, GA 30329, USA. sfactor@emory.edu
authors.forename: Stewart A
authors.initials: SA
authors.lastname: Factor
authors.forename: N Kyle
authors.initials: NK
authors.lastname: Steenland
authors.forename: Donald S
authors.initials: DS
authors.lastname: Higgins
authors.forename: Eric S
authors.initials: ES
authors.lastname: Molho
authors.forename: Denise M
authors.initials: DM
authors.lastname: Kay
authors.forename: Jennifer
authors.initials: J
authors.lastname: Montimurro
authors.forename: Ami R
authors.initials: AR
authors.lastname: Rosen
authors.forename: Cyrus P
authors.initials: CP
authors.lastname: Zabetian
authors.forename: Haydeh
authors.initials: H
authors.lastname: Payami
mesh_terms: D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D005260:Female; D005684:Gait; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D011110:Polymorphism, Genetic / Q000235:genetics; D004856:Postural Balance; D012307:Risk Factors; D051844:alpha-Synuclein / Q000235:genetics; D016875:tau Proteins / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; C054369:MAPT protein, human; C497604:SNCA protein, human; D051844:alpha-Synuclein; D016875:tau Proteins; D019389:Cytochrome P-450 CYP2D6