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L-dopa responsiveness in early Parkinson's disease is associated with the rate of motor progression

Malek, Naveed, Kanavou, Sofia, Lawton, Michael A., Pitz, Vanessa, Grosset, Katherine A., Bajaj, Nin, Barker, Roger A., Ben-Shlomo, Yoav, Burn, David J., Foltynie, Tom, Hardy, John, Williams, Nigel M., Wood, Nicholas, Morris, Huw R. and Grosset, Donald G. 2019. L-dopa responsiveness in early Parkinson's disease is associated with the rate of motor progression. Parkinsonism and Related Disorders 65 , pp. 55-61. 10.1016/j.parkreldis.2019.05.022
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Abstract

Background L-dopa responsiveness in Parkinson's disease (PD) varies, but the clinical correlates and significance of this are ill-defined. Methods Patients were assessed before and after their usual morning L-dopa dose, using the MDS Unified PD Rating Scale Part 3 (MDS UPDRS 3), and rated as definite responders (≥24.5% improvement) or limited responders (<24.5%). Results 1007 cases, mean age 66.1 years (SD 9.1) at diagnosis, were assessed 3.4 (SD 0.9) years after diagnosis. The L-dopa response was definite in 614 cases (61.0%), median reduction in MDS UPDRS 3 scores was 42.0%, (IQR 33.3, 53.1), and was limited in 393 cases (39.0%), median reduction in MDS UPDRS 3 scores 11.5% (IQR 4.3, 18.2). Definite responders were younger (66.3 years at study entry, SD 9.3) than limited responders (69.2 years, SD 8.4, p < 0.001). The MDS UPDRS 3 score at study entry in definite responders (21.0, SD 10.5) was significantly lower than in limited responders (24.7, SD 13.4, p < 0.001). The MDS UPDRS 3 increase over 18 months was less in definite responders at 3.0 (SD 10.4), compared to limited responders (6.4, SD 11.0, p < 0.001). The levodopa equivalent daily dose (LEDD) was not significantly different at study entry (definite responders 317 mg, SD 199, vs limited responders 305 mg, SD 191, p = 0.53). However, LEDD was significantly higher at the time of the L-dopa challenge test in definite responders (541 mg, SD 293) compared to limited responders (485 mg, SD 215, p = 0.01). Responsiveness to L-dopa was unaffected by the challenge test dose (p = 0.54). Conclusions The main determinants of variation in the L-dopa response in early PD are age and motor severity. A limited L-dopa response is associated with faster motor progression.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Elsevier
ISSN: 1353-8020
Date of First Compliant Deposit: 6 June 2019
Date of Acceptance: 12 May 2019
Last Modified: 30 Oct 2019 15:20
URI: http://orca-mwe.cf.ac.uk/id/eprint/123235

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