Constipation distinguishes different clinical-biochemical patterns in de novo Parkinson's disease

Introduction: Prodromal constipation (PC) at Parkinson's disease (PD) onset may mark a distinct neurodegen-erative trajectory; accordingly, presenting phenotype, biochemical signature, and progression of PD patients with PC (PD + PC) might differ from those without (PDwoPC). We compared the clinical-biochemical profile of de novo PD patients with and without PC, and the respective mid-term progression, to establish the grouping effect of PC. Methods: Motor and non-motor scores were collected at diagnosis in n = 57 PD + PC patients and n = 73 PDwoPC. Paired CSF biomarkers (alpha-synuclein, amyloid and tau peptides, lactate, CSF/serum albumin ratio or AR) were assessed into a smaller sample and n = 46 controls. Clinical progression was estimated as Hoehn and Yahr stage (HY) and levodopa equivalent daily dose (LEDD) change 2.06 +/- 1.35 years after diagnosis. Results: At onset, PD + PC patients had higher HY and MDS-UPDRS-part III scores, and higher CSF AR. PDwoPC had higher Non-Motor Symptoms Scale domain-2 score, and lower CSF alpha-synuclein level. At follow-up, PD + PC had greater LEDD. Conclusions: PC identifies a group of de novo patients with more severe motor impairment, possible blood brain barrier disruption, and greater dopaminergic requirement at mid-term; conversely, de novo PDwoPC patients had prominent fatigue, and pronounced central synucleinopathy.