Objective: To investigate if constipation predicts the development of cognitive impairment (CI) and dementia in de novo Parkinson’s disease (PD).

Background: Constipation is one of the commonest features of PD, occurring from prodromal to palliative stages [1]. Recent evidence supports the role of the gut-brain axis in the pathogenesis of PD, and gastrointestinal dysfunction has been linked to CI in PD [2].

Method: Data on de novo PD patients were obtained from the Non-Motor Longitudinal International Study (NILS) (N=196) and the Parkinson’s Progression Markers Initiative (PPMI) (N=423) databases. Non-Motor Symptoms Scale (NMSS) item 21 (NILS) and SCales for Outcomes in PArkinson’s disease (SCOPA) autonomic items 5 and 6 (PPMI) were used to stratify patients based on presence (PD-C) or absence (PD-NC) of constipation. We performed the following analyses: 1. assessment of baseline group differences in the two cohorts; 2. Kaplan-Meier survival analyses to estimate group differences in cumulative proportion of patients with incident cognitive decline over 3 years (CI defined as Mini-Mental State Examination (MMSE)<24 (NILS) and Montreal Cognitive Assessment (MoCA)<26 (PPMI); 3. in PPMI, multivariate Cox survival analysis with constipation scores as univariate and previously validated predictors of CI as covariates [3]. Patients were categorised at follow-up (up to 6 years) as having normal cognition or dementia (as per PPMI protocol) [4]. Occurrence of dementia at follow-up was used as the time-to-event.

Results: 1. No significant differences in MMSE and MoCA scores between PD-NC and PD-C were found in either cohort at baseline, although PD-C reported more cognitive issues (p<0.05). Significant group differences were shown for both motor (p<0.05) and non-motor features (p<0.001) [table1-3]. 2. Kaplan-Meier plots showed an accelerated conversion to CI in the PD-C groups (Log Rank, NILS: p=0.034; PPMI: p=0.002) [figure1]. 3. During a median follow-up of 5.0 years, 37 subjects developed dementia. Constipation was an independent predictor of dementia onset in Cox regression (hazard ratio 1.313[1.048-1.645]; p=0.01). Other predictors of dementia are shown in table 4.

Conclusion: Our findings suggest that constipation may predict the onset of dementia in PD with possible clinical implications for the management of patients.

References: 1. Stocchi F and Torti M. Constipation in Parkinson’s Disease. Int Rev Neurobiol. 2017;134:811-826. 2. Jones JD, Rahmani E, Garcia E, Jacobs JP. Gastrointestinal symptoms are predictive of trajectories of cognitive functioning in de novo Parkinson’s disease. Parkinsonism Relat Disord. 2020 Jan 25; 72:7-12. 3. Schrag A, Siddiqui UF, Anastasiou Z, Weintraub D, Schott JM. Clinical variables and biomarkers in prediction of cognitive impairment in patients with newly diagnosed Parkinson’s disease: a cohort study. Lancet Neurol 2017; 16: 66–75. 4. Parkinson Progression Marker Initiative. The Parkinson Progression Marker Initiative (PPMI). Prog Neurobiol 2011; 95: 629–35.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/does-constipation-predict-cognitive-impairment-and-dementia-in-de-novo-parkinsons-disease-patients-a-multi-cohort-longitudinal-data-analysis/