TY - JOUR
T1 - Identification of a prospective early motor progression cluster of Parkinson's disease
T2 - Data from the PPMI study
AU - Vavougios, George D
AU - Doskas, Triantafyllos
AU - Kormas, Constantinos
AU - Krogfelt, Karen A
AU - Zarogiannis, Sotirios G
AU - Stefanis, Leonidas
PY - 2018
Y1 - 2018
N2 - Aim
The aim of our study is to phenotype PD motor progression, and to detect whether serum, cerebrospinal fluid (CSF), neuroimaging biomarkers and neuropsychological measures characterize PD motor progression phenotypes.
Methods
We defined motor progression as a difference of at least one point in the Hoehn & Yahr (H&Y) scale between the baseline (Visit 0, V0), 12 months (Visit 04, V04) and 36 months (Visit 08, V08) milestones of the Progression Markers Initiative (PPMI) study. H&Y progression events were recorded at each milestone in order to be used as cluster analysis variables, in order to produce progression phenotypes. Subsequently, cross-cluster comparisons prior to and following (pairwise) propensity score matching were performed in order to assess phenotype – defining characteristics.
Results
Four progression clusters where identified: SPPD: Secondarily Progressive PD, H&Y progression between V04 and V08; EPPD: Early Progressive PD. H&Y progression between V0 and V04; NPPD: Non Progressive PD, no H&Y progression; MIPD: Minimally Improving PD, i.e. Minimal H&Y improvement H&Y progression between V04 and V08;. Independent Samples Mann Whitney U tests determined CSF aSyn (p = 0.006, adj p-value = 0.036. I) and Semantic Animal fluency T-score (SFT, p = 0.003, adjusted p-value = 0.016.) as statistically significant cross-cluster characteristics. Following Propensity Score Matching, SFT, Hopkins Verbal Learning Test (Retention/Recall), Serum IGF1, CSF aSyn, DaT-SPECT binding ratios (SBRs) and the Benton Judgement of Line Orientation Test (BJLOT) were determined as statistically significant predictors of cluster differentiation (p < 0.05).
Discussion
SFT, Serum IGF1, CSF aSyn and DaT-SPECT-derived, basal ganglia Striatal Binding Ratios warrant further investigation as possible motor progression biomarkers.
AB - Aim
The aim of our study is to phenotype PD motor progression, and to detect whether serum, cerebrospinal fluid (CSF), neuroimaging biomarkers and neuropsychological measures characterize PD motor progression phenotypes.
Methods
We defined motor progression as a difference of at least one point in the Hoehn & Yahr (H&Y) scale between the baseline (Visit 0, V0), 12 months (Visit 04, V04) and 36 months (Visit 08, V08) milestones of the Progression Markers Initiative (PPMI) study. H&Y progression events were recorded at each milestone in order to be used as cluster analysis variables, in order to produce progression phenotypes. Subsequently, cross-cluster comparisons prior to and following (pairwise) propensity score matching were performed in order to assess phenotype – defining characteristics.
Results
Four progression clusters where identified: SPPD: Secondarily Progressive PD, H&Y progression between V04 and V08; EPPD: Early Progressive PD. H&Y progression between V0 and V04; NPPD: Non Progressive PD, no H&Y progression; MIPD: Minimally Improving PD, i.e. Minimal H&Y improvement H&Y progression between V04 and V08;. Independent Samples Mann Whitney U tests determined CSF aSyn (p = 0.006, adj p-value = 0.036. I) and Semantic Animal fluency T-score (SFT, p = 0.003, adjusted p-value = 0.016.) as statistically significant cross-cluster characteristics. Following Propensity Score Matching, SFT, Hopkins Verbal Learning Test (Retention/Recall), Serum IGF1, CSF aSyn, DaT-SPECT binding ratios (SBRs) and the Benton Judgement of Line Orientation Test (BJLOT) were determined as statistically significant predictors of cluster differentiation (p < 0.05).
Discussion
SFT, Serum IGF1, CSF aSyn and DaT-SPECT-derived, basal ganglia Striatal Binding Ratios warrant further investigation as possible motor progression biomarkers.
KW - Parkinson's disease
KW - Progression
KW - Biomarkers
KW - Cluster analysis
KW - Phenotypes
U2 - 10.1016/j.jns.2018.01.025
DO - 10.1016/j.jns.2018.01.025
M3 - Journal article
VL - 387
SP - 103
EP - 108
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
SN - 0022-510X
ER -