Gait function and locus coeruleus Lewy body pathology in 51 Parkinson's disease patients.
Gait impairment in Parkinson's Disease (PD) is often severely disabling, yet frequently remains refractory to treatment. The locus coeruleus (LC) has diffuse noradrenergic projections that are thought to play a role in gait function. Enhancement of norepinephrine transmission may improve gait in some PD patients. We hypothesized that the severity of PD pathology, and more specifically, Lewy bodies and neuronal loss in the LC, would correlate with the severity of gait dysfunction in PD.



Autopsy data from 51 patients, collected through the Morris K. Udall Parkinson's Disease Research Center, were correlated with clinical gait-related measures, including individual Unified Parkinson's Disease Rating Scale (UPDRS) Part II and III questions, total UPDRS Part III scores, and timed up-and-go speed (TUG).



Neither the presence nor degree of Lewy body pathology in the LC on autopsy was associated with a higher UPDRS part III gait score. LC tau deposition and frontal Lewy body deposition were not correlated with any of the assessed gait measures. The degree of Lewy body pathology, independent of Braak stage, was positively associated with the severity of motor symptoms overall (UPDRS Part III total score).



Neither the degree of Lewy body nor tau pathology in the LC is associated with severity of gait disorders in PD. This finding may have implications for targeted noradrenergic therapies in patients with refractory gait disorders.
Movement Disorders Division, Dept. of Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Meyer 6-181, Baltimore, MD, 21287, United States; Morris K. Udall Parkinson's Disease Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States. Electronic address: kmills16@jhmi.edu.
Kelly A
KA
Mills
Movement Disorders Division, Dept. of Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Meyer 6-181, Baltimore, MD, 21287, United States; Morris K. Udall Parkinson's Disease Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Zoltan
Z
Mari
Morris K. Udall Parkinson's Disease Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Catherine
C
Bakker
Morris K. Udall Parkinson's Disease Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Vanessa
V
Johnson
Movement Disorders Division, Dept. of Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Meyer 6-181, Baltimore, MD, 21287, United States; Morris K. Udall Parkinson's Disease Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Gregory M
GM
Pontone
Movement Disorders Division, Dept. of Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Meyer 6-181, Baltimore, MD, 21287, United States; Morris K. Udall Parkinson's Disease Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Alexander
A
Pantelyat
Morris K. Udall Parkinson's Disease Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Clinical and Neuropathology Core, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Juan C
JC
Troncoso
Morris K. Udall Parkinson's Disease Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Clinical and Neuropathology Core, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Olga
O
Pletnikova
Movement Disorders Division, Dept. of Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Meyer 6-181, Baltimore, MD, 21287, United States; Morris K. Udall Parkinson's Disease Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, United States; Solomon H. Snyder Department of Neuroscience, United States; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, 21205, United States.
Ted M
TM
Dawson
Movement Disorders Division, Dept. of Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Meyer 6-181, Baltimore, MD, 21287, United States; Morris K. Udall Parkinson's Disease Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Liana S
LS
Rosenthal
D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D005260:Female; D020233:Gait Disorders, Neurologic / Q000209:etiology*; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology*; D008125:Locus Coeruleus / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications* / Q000473:pathology*; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
Autopsy; Gait; Locus coeruleus; Parkinson's disease; Pathology
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