Is constipation a sign of early Parkinson’s disease?

Originally published in MedPage Today

by Charles Bankhead, MedPage Today Staff Writer

Constipation may represent one of the earliest signs of Parkinson’s disease, preceding the onset of motor symptoms by two decades or more, data from a case-control study suggest.

Patients with Parkinson’s disease were more than twice as likely to report a history of constipation compared with a control population. The association remained significant after controlling for other factors associated with constipation, according to a report in the December issue of Neurology.

Though constipation is not specific for Parkinson’s disease, the findings are consistent with the hypothesis that Parkinson’s disease adversely affects autonomic function early in the course of pathogenesis.

“Our findings may suggest that constipation is an early manifestation of the neurodegenerative process underlying Parkinson’s disease, and that it frequently precedes the classic motor signs of Parkinson’s disease by several decades in both men and women,” Walter A. Rocca, MD, of the Mayo Clinic in Rochester, Minn., and colleagues concluded.

However, they cautioned that “there are alternative explanations for this association.”

Autonomic dysfunction is a recognized component of the pathogenetic process of Parkinson’s disease, and Lewy bodies are consistently found in the autonomic nervous system of patients who have died with Parkinson’s disease.

Constipation is one of the most common manifestations of autonomic dysfunction and often is present at the onset of motor symptoms or progression of Parkinson’s disease, the authors noted.

In some cases, constipation may precede the onset of motor symptoms in Parkinson’s patients. Data from the Honolulu-Asia Aging Study showed that men who reported less frequent bowel movements had an increased risk of Parkinson’s disease during a 24-year follow-up period (Neurology 2001; 57: 456-62, J Neurol 2003; 250(suppl 3): III30-39).

Other reports from the Honolulu study described an association between constipation and incidental Lewy body disease and a reduced neuronal density in the substantia nigra (Mov Disord 2007; 22: 1581-86, Mov Disord 2009; 24: 371-76).

Consistent with clinical and pathologic findings, the Braak staging system of Parkinson’s disease neuropathology predicts early involvement in the disease process (Neurosci Lett 2006; 396: 67-72).

Continuing this line of work, investigators reviewed medical records of participants in the Rochester Epidemiology Project. They identified all patients who developed Parkinson’s disease (by conventional diagnostic criteria) from 1976 through 1995. Each case was matched by age and sex with a member of the general population of participants in the epidemiologic study.

Investigators defined constipation as a diagnosis of constipation in the medical records or use of drugs to treat constipation, even in the absence of a diagnosis.

The analysis revealed 196 patients who developed Parkinson’s disease during the period reviewed. The authors found that 71 (36.2%) patients with Parkinson’s disease had a history of constipation compared with 40 (20.4%) of the control group. The difference translated into an odds ratio of 2.48 for cases versus controls (95% CI 1.49 to 4.11, P=0.0005).

The association between constipation and Parkinson’s disease remained significant after adjusting for smoking and coffee consumption and exclusion of possible drug-induced constipation.

Moreover, the association remained significant in an analysis limited to patients with constipation documented 20 or more years before the onset of motor symptoms of Parkinson’s disease (OR 2.98, 95% CI 1.48 to 6.03, P=0.002).

The association was stronger in women (OR 3.38) than in men (OR 1.92) and in patients with rest tremor versus those without, but the differences did not reach statistical significance.

Although the data supported the biologic plausibility of constipation as an early nonmotor manifestation of Parkinson’s disease, the authors offered several alternative explanations:

* Constipation and Parkinson’s disease could be independent manifestations of an unknown risk factor
* The association might reflect a genetic susceptibility
* Constipation might have an indirect, but causal, role in Parkinson’s disease, such as increased intestinal absorption of substances toxic to the substantia nigra

“However, the evidence in support of these alternative interpretations remains limited,” the authors said.

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