Περίληψη:
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. © 2018 Elsevier B.V.
Συγγραφείς:
Vavougios, G.D.
Doskas, T.
Kormas, C.
Krogfelt, K.A.
Zarogiannis, S.G.
Stefanis, L.
Λέξεις-κλειδιά:
alpha synuclein; biological marker; somatomedin C; biological marker, aged; Article; cerebrospinal fluid; clinical assessment; cluster analysis; decision making; disease course; female; Hopkins verbal learning test; human; major clinical study; male; motor progression; neuroimaging; neuropsychological test; Parkinson disease; phenotype; priority journal; semantics; serum; bibliographic database; blood; cerebrospinal fluid; diagnostic imaging; disease exacerbation; middle aged; nonparametric test; nuclear magnetic resonance imaging; Parkinson disease; pathophysiology; statistical model; statistics and numerical data, Aged; Biomarkers; Cluster Analysis; Databases, Bibliographic; Disease Progression; Female; Humans; Logistic Models; Magnetic Resonance Imaging; Male; Middle Aged; Parkinson Disease; Phenotype; Statistics, Nonparametric
