Journal
PARKINSONISM & RELATED DISORDERS
Volume 33, Issue -, Pages 102-106Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.parkreldis.2016.09.024
Keywords
Parkinson's disease; Gait; Locus coeruleus; Pathology; Autopsy
Categories
Funding
- NIH/NINDS [NS38377, U01 NS082133, P50 NS38377, R37NS067525, P50 DA00266]
- NTH NCATS [KL2TR001077]
- Northwestern University
- Adamas Pharmaceuticals
- National Parkinson's Foundation
- Center of Excellence Grant
- NIH/NIA as part of a K23 award [AG044441-01A1]
- NIH through NIA [U19AG033655, P50AG005146]
- NIH through NINDS [P50NS38377, R25NS079185]
- NIH [R01MH096636, R01NS086074, R01NS086888, R01HL091541]
- NIH
- Emory University [U01AG046161]
- BrightFocus Foundation
- Sanofi-Aventis Recherce and Development
- JPB Foundation
- MDSCRF [2013-MSCRFII-0105-00, 2015-MSCRFE-1782]
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Introduction: 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. Methods: 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). Results: 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). Conclusion: 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. (C) 2016 Elsevier Ltd. All rights reserved.
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