Gait speed in Parkinson disease correlates with cholinergic degeneration.
ABSTRACT We investigated dopaminergic and cholinergic correlates of gait speed in Parkinson disease (PD) and non-PD control subjects to test the hypothesis that gait dysfunction in PD may result from multisystem degeneration.
This was a cross-sectional study. Subjects with PD but without dementia (n = 125, age 65.6 ± 7.3 years) and elderly subjects without PD (n = 32, age 66.0 ± 10.6 years) underwent [(11)C]dihydrotetrabenazine dopaminergic and [(11)C]methyl-4-piperidinyl propionate acetylcholinesterase PET imaging, and cognitive and clinical testing, including an 8.5-m walk in the dopaminergic "off" state. The fifth percentile of cortical cholinergic activity in the elderly without PD was used to define normal-range activity in the subjects with PD.
Normal-range cortical cholinergic activity was present in 87 subjects with PD (69.6%). Analysis of covariance using gait speed as the dependent variable demonstrated a significant model (F = 6.70, p < 0.0001) with a significant group effect (F = 3.36, p = 0.037) and significant slower gait speed in the low cholinergic PD subgroup (0.97 ± 0.22 m/s) with no significant difference between the normal-range cholinergic PD subgroup (1.12 ± 0.20 m/s) and control subjects (1.17 ± 0.18 m/s). Covariate effects were significant for cognition (F = 6.58, p = 0.011), but not for striatal dopaminergic innervation, sex, or age.
Comorbid cortical cholinergic denervation is a more robust marker of slowing of gait in PD than nigrostriatal denervation alone. Gait speed is not significantly slower than normal in subjects with PD with relatively isolated nigrostriatal denervation.
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ABSTRACT: Freezing of gait is a disabling symptom of Parkinson's disease that causes a paroxysmal cessation of normal footsteps while walking. Despite a great deal of empirical research, the pathophysiological mechanisms underlying the symptom remain unclear. In this targeted review, we synthesize recent insights from research into freezing in an effort to clarify the neurobiological basis of this phenomenon. We conclude that freezing manifests via a common neural pathway in which transient increases in inhibitory basal ganglia output lead to decreased activity within the brainstem structures that coordinate gait. This cascade may be triggered through dopaminergic depletion in the striatum and over-activity within the subthalamic nucleus. These insights may benefit both the diagnostic and therapeutic management of freezing in Parkinson's disease.The Neuroscientist 11/2014; · 7.62 Impact Factor
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ABSTRACT: Reports outlining the association between gait and cognition in Parkinson's disease (PD) are limited because of methodological issues and a bias toward studying advanced disease. This study examines the association between gait and cognition in 121 early PD who were characterized according to motor phenotype, and 184 healthy older adults. Quantitative gait was captured using a 7 m GAITrite walkway while walking for 2 min under single-task conditions and described by five domains (pace, rhythm, variability, asymmetry, and postural control). Cognitive outcomes were summarized by six domains (attention, working memory, visual memory, executive function, visuospatial function, and global cognition). Partial correlations and multivariate linear regression were used to determine independent associations for all participants and for PD tremor-dominant (TD) and postural instability and gait disorder (PIGD) phenotypes, controlling for age, sex, and premorbid intelligence using the national adult reading test. Cognitive and gait outcomes were significantly worse for PD. Gait, but not cognitive outcomes, was selectively worse for the PIGD phenotype compared with TD. Significant associations emerged for two gait domains for controls (pace and postural control) and four gait domains for PD (pace, rhythm, variability, and postural control). The strongest correlation was for pace and attention for PD and controls. Associations were not significant for participants with the TD phenotype. In early PD, the cognitive correlates of gait are predominantly with fronto-executive functions, and are characterized by the PIGD PD phenotype. These associations provide a basis for understanding the complex role of cognition in parkinsonian gait.Frontiers in Aging Neuroscience 10/2014; 6:249. · 2.84 Impact Factor
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ABSTRACT: The progression of mild parkinsonian signs in the absence of idiopathic Parkinson's disease in aging is unclear. This study aims to identify predictors of the evolution of mild parkinsonian signs in non-demented older adults. Two hundred ten participants (76.25 ± 7.10 years, 57 % women) were assessed at baseline and 1-year follow-up. Mild parkinsonian signs were defined as the presence of bradykinesia, rigidity and/or rest tremor. Depending upon the presence of these features at baseline and follow-up, participants were divided into one of four groups (no, transient, persistent or new-onset mild parkinsonian signs). Physical function was assessed using gait velocity. Ninety-five participants presented with mild parkinsonian signs at baseline. At 1-year follow-up, 59 demonstrated persistent mild parkinsonian signs, while 36 recovered (i.e., transient). Participants with persistent mild parkinsonian signs were older (79.66 ± 7.15 vs. 75.81 ± 7.37 years, p = 0.01) and evidenced slower gait velocity (90.41 ± 21.46 vs. 109.92 ± 24.32 cm/s, p < 0.01) compared to those with transient mild parkinsonian signs. Gait velocity predicted persistence of mild parkinsonian signs, even after adjustments (OR: 0.96, 95 % CI: 0.94-0.98). Fifty-five participants demonstrated new-onset of mild parkinsonian signs. In comparison to participants without mild parkinsonian signs, presence of cardiovascular but not cerebrovascular disease at baseline was associated with new-onset mild parkinsonian signs. Our study reveals that gait velocity was the main predictor of persistent mild parkinsonian signs, whereas cardiovascular disease was associated with new-onset mild parkinsonian signs. These findings suggest a vascular mechanism for the onset of mild parkinsonian signs and a different mechanism, possibly neurodegenerative, for the persistence of mild parkinsonian signs.Journal of Neurology 07/2014; · 3.84 Impact Factor