Most patients with Parkinson disease (PD) have non-motor symptoms (NMS), and on average these can range from four to 19 different symptoms. NMS dominate the prodromal phase of PD and some may serv...

Background: Constipation is regarded as one of the prodromal features of Parkinson’s disease (PD) and there is emerging evidence linking gastrointestinal dysfunction and cognitive impairment (CI) in PD. Objective: We explored whether constipation is associated with development of CI in two independent cohorts of de novo PD patients (n = 196 from the Non-motor International Longitudinal Study [NILS] and n = 423 from the Parkinson’s Progression Markers Initiative [PPMI] study). Methods: Constipation was clinically defined using the Non-Motor Symptoms Scale (NMSS) item-21 [NILS] and Scales for Outcomes in PD-Autonomic (SCOPA-AUT) item-5 [PPMI]. We assessed baseline group differences (PD with or without constipation) in CI, global non-motor symptoms burden, motor dysfunction, and striatal dopaminergic denervation. Kaplan-Meier method estimated group differences in cumulative proportion of patients with incident CI over three years. In PPMI, we subsequently performed univariate and multivariate Cox survival analyses to evaluate whether constipation predicts incident mild cognitive impairment or dementia over a 6-year period, including constipation and other known predictors of CI as covariates. Results: Patients with constipation had greater motor and global non-motor burden in both cohorts at baseline (p < 0.05). Kaplan-Meier plots showed faster conversion to CI in patients with constipation in both cohorts (p < 0.05). In PPMI, 37 subjects developed dementia during a mean follow-up of 4.9 years, and constipation was an independent predictor of dementia onset (hazard ratio = 2.311; p = 0.02). Conclusion: Constipation in de novo PD patients is associated with development of cognitive decline and may serve as a clinical biomarker for identification of patients at risk for cognitive impairment.

Device-aided therapies, including levodopa-carbidopa intestinal gel infusion, apomorphine subcutaneous infusion, and deep brain stimulation, are available in many countries for the management of the advanced stage of Parkinson’s disease (PD). Currently, selection of device-aided therapies is mainly focused on patients’ motor profile while non-motor symptoms play a role limited to being regarded as possible exclusion criteria in the decision-making process for the delivery and sustenance of a successful treatment. Differential beneficial effects on specific non-motor symptoms of the currently available device-aided therapies for PD are emerging and these could hold relevant clinical implications. In this viewpoint, we suggest that specific non-motor symptoms could be used as an additional anchor to motor symptoms and not merely as exclusion criteria to deliver bespoke and patient-specific personalised therapy for advanced PD.

‘Levodopa Phobia’ is under-recognised in Parkinson’s disease but can cause profound detrimental clinical complications if left to continue. Several types can be encountered in clinical practice and can be driven by a misplaced fear of levodopa-induced dyskinesias, other gastrointestinal side effects and also the theoretical notion that levodopa may be toxic to dopaminergic neurons in the brain. The condition can be underpinned by a sense of strong influence from the physicians or carers who are unwilling to prescribe or consider levodopa, and also high levels of anxiety or even impulsive compulsive traits in patients who have been influenced by available literature or social media-based information. If unrecognised, the clinical issue may lead to motor deterioration and related muscle contractures leading to social isolation as well as a range of non-motor symptoms. In some, there may be emergence of intrusive impulse control disorders because of reliance on only dopamine agonists related to the fear of taking levodopa. Four cases illustrate the different patterns of ‘Levodopa Phobia’ in this study. Management of levodopa phobia is complex and includes recognition and skilled neuropsychological interventions to break the misperceptions about the complications of levodopa therapy.