Postural instability/gait disturbance in Parkinson's disease has distinct subtypes: an exploratory analysis.
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.
Factor
Stewart A
SA
Emory University School of Medicine, Department of Neurology, 1841 Clifton Road NE, Atlanta, GA 30329, USA. sfactor@emory.edu
Steenland
N Kyle
NK
Higgins
Donald S
DS
Molho
Eric S
ES
Kay
Denise M
DM
Montimurro
Jennifer
J
Rosen
Ami R
AR
Zabetian
Cyrus P
CP
Payami
Haydeh
H
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
D001057:Apolipoproteins E; C054369:MAPT protein, human; C497604:SNCA protein, human; D051844:alpha-Synuclein; D016875:tau Proteins; D019389:Cytochrome P-450 CYP2D6