TY - JOUR
T1 - L-dopa responsiveness in early Parkinson's disease is associated with the rate of motor progression
AU - Malek, Naveed
AU - Kanavou, Sofia
AU - Lawton, Michael
AU - Pitz, Vanessa
AU - Grosset, Katherine
AU - Bajaj, Nin
AU - Barker, Roger A
AU - Ben-Shlomo, Yoav
AU - Burn, David J
AU - Foltynie, Tom
AU - Hardy, John
AU - Williams, Nigel M
AU - Wood, Nicholas W
AU - Morris, Huw R
AU - Grosset, Donald G
AU - PRoBaND Clinical Consortium
PY - 2019/5/14
Y1 - 2019/5/14
N2 - 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.
AB - 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.
KW - Parkinson's disease
KW - L-dopa
KW - Therapy
UR - http://www.scopus.com/inward/record.url?scp=85065610468&partnerID=8YFLogxK
U2 - 10.1016/j.parkreldis.2019.05.022
DO - 10.1016/j.parkreldis.2019.05.022
M3 - Article (Academic Journal)
C2 - 31105012
JO - Parkinsonism & Related Disorders
JF - Parkinsonism & Related Disorders
ER -