Severe Constipation at Parkinson's Diagnosis Predicts Faster Disease Progression

Daniel M. Keller, PhD    October 10, 2018

HONG KONG — Although constipation affects only one third of patients with idiopathic Parkinson's disease (PD) at the time of diagnosis, constipation severity at baseline predicts faster disease progression, a new study suggests. Constipation is also often present before diagnosis.

Although constipation is not ubiquitous in PD, its predictive nature prompts "the suggestion that it might be heterogeneous and might be a marker for different PD subtypes with different progression rates," Marta Camacho, PhD candidate at the University of Cambridge, United Kingdom, told a poster tour group here at the International Congress of Parkinson's Disease and Movement Disorders 2018.

Camacho and colleagues therefore performed a study to see whether constipation may predict motor and cognitive progression in PD. Patients entered the study very soon after diagnosis, at an average of 0.4 years.

Using the Parkinsonism: Incidence and Cognitive Heterogeneity in Cambridgeshire (PICNICS) incident community-based cohort of 281 patients with PD, researchers followed them every 18 months with standardized clinical assessments including the Movement Disorders Society-Unified PD Rating Scale (MDS-UPDRS) and Mini-Mental State Examination (MMSE) out to 108 months. Mean follow-up was 4.15 years.

Patients were stratified at baseline according to the severity of constipation on the MDS-UPDRS constipation item scores. Of the 281 patients, 43 were classified as having mild constipation and 35 were classified as moderate-to-severe. Kaplan-Meier analyses compared rates of progression to key milestones of dementia, postural instability, and death.

There were no differences in several demographic or clinical variables (for example, age, gender, smoking status, Hoehn and Yahr stage, MDS-UPDRS part III, or levodopa equivalent doses) among patients classified as having no constipation, mild constipation, or moderate-to-severe constipation.

The only difference was a slight but significantly lower MMSE score in the moderate-to-severe constipation group than the no-constipation and mild groups (27.34 vs 28.54 vs 28.36; P = .01).

Based on Kaplan-Meier analyses, the group with moderate-to-severe constipation at baseline had an earlier onset of PD-related dementia (P < .05) and progressed to Hoehn and Yahr stage 3 or higher more rapidly compared with the other groups (P < .05).

"We observed that there's no difference in mortality between the three groups. However, the patients who develop dementia develop it earlier, and they develop postural instability," Camacho reported.

When performing a Cox regression analysis to control for the potential confounding factor of low MMSE scores among the moderate-to-severe constipation group, she said, "We lost the significance for the earlier onset of postural instability as assessed by the Hoehn and Yahr of 3 or more, but we still had an earlier onset of dementia."

Table 1. Moderate-to-Severe Constipation and Dementia Risk After Correcting for Baseline MMSE  

Variable	Time to Hoehn and Yahr 3+ HR (P value)	Time to Dementia HR (P value)
Moderate-to-severe constipation	1.57 (.09)	2.1 (.05)
MMSE	0.70 (< .001)	0.71 (.003)

HR: hazard ratio, MMSE: Mini-Mental State Examination

She concluded that constipation affects about a third of the cohort, but "it's the severity that could be an important predictor of cognitive function and disease onset."

However, she said that the UPDRS with only four Likert scores may not be sensitive enough, and the researchers plan to address the issue. They also plan to follow the patients until death.

Poster tour moderator K. Ray Chaudhuri, MD, DSc, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom, wondered how long before patients had constipation in the prodromal phase.

"It's very important because otherwise it becomes heterogeneous. There are lots of other prodromal features [that] can do the same," he said. He cited, for example, REM sleep behavior disorder (RBD) that can predict dementia. Camacho said those data have been collected but are yet to be analyzed.

Chaudhuri also "strongly encouraged" her to look at constipation in relation to nonmotor phenotypes. He said motor phenotypes are unstable and really not very relevant.

"What you need to look at, particularly if you have constipation and it's predicting RBD [or] postural instability, this could be a cholinergic dysfunction...a cholinergic subtype of Parkinson's," he said.

Camacho said of the 50 people who developed dementia, only 13 had constipation at baseline. "It's not a linear effect [and] not causing it," she noted. She speculated that if a patient was destined to have dementia, "then constipation may be associated with faster development of it, but it's not a driving factor...maybe."

There was no commercial funding for the study. Camacho has reported no conflicts of interest. Chaudhuri has consulted and served on advisory boards for Britannia, AbbVie, NeuroNova, Mundipharma, and UCB, and has served on advisory boards for Synapsus and Medtronic. He has received honoraria from Boehringer Ingelheim, GlaxoSmithKline, AbbVie, Britannia, UCB, Mundipharma, Otsuka, and Zambon, and grants from Boehringer Ingelheim, GlaxoSmithKline, Britannia, AbbVie, UCB, and NeuroNova. He holds intellectual property rights for the KPP scale and PDSS, and receives royalties for two books on PD. 

International Congress of Parkinson's Disease and Movement Disorders (MDS) 2018. Abstract 1554, presented October 8, 2018.

https://www.medscape.com/viewarticle/903227#vp_1