Gastrointestinal Dysfunction in Parkinson's Disease

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease. Patients show deposits of pathological, aggregated α-synuclein not only in the brain but throughout almost the entire length of the digestive tract. This gives rise to non-motor symptoms particularly within the gastrointestinal tract and patients experience a wide range of frequent and burdensome symptoms such as dysphagia, bloating, and constipation. Recent evidence suggests that progressive accumulation of gastrointestinal pathology is underway several years before a clinical diagnosis of PD. Notably, constipation has been shown to increase the risk of developing PD and in contrast, truncal vagotomy seems to decrease the risk of PD. Animal models have demonstrated gut-to-brain spreading of pathological α-synuclein and it is currently being intensely studied whether PD begins in the gut of some patients. Gastrointestinal symptoms in PD have been investigated by the use of several different questionnaires. However, there is limited correspondence between subjective gastrointestinal symptoms and objective dysfunction along the gastrointestinal tract, and often the magnitude of dysfunction is underestimated by the use of questionnaires. Therefore, objective measures are important tools to clarify the degree of dysfunction in future studies of PD. Here, we summarize the types and prevalence of subjective gastrointestinal symptoms and objective dysfunction in PD. The potential importance of the gastrointestinal tract in the etiopathogenesis of PD is briefly discussed.

Keywords: Parkinson’s disease; alpha-synuclein; autonomic; constipation; gastrointestinal; parasympathetic.

Figure 1

Gastric scintigraphy images at 0, 30 and 120 min after ingestion of a radioactive solid meal. (A). Healthy control with normal gastric emptying time. (B). Parkinson’s disease (PD) patient with severely delayed gastric emptying time compatible with gastroparesis. (C). PD patient with rapid gastric emptying suggestive of ”gastric dumping” (compare the image taken at 30 min. to the image from A taken at 120 min.).

Figure 2

Abdominal x-ray topograms visualizing the retention of radio-opaque markers in the gastrointestinal tract as an objective measure of colonic transit time (CTT). (A). Healthy control with an estimated CTT within the normal range. (B). Parkinson’s disease (PD) patient with an estimated CTT near the mean for PD patients. (C). PD patient with severely prolonged CTT.

Figure 3

¹¹C-Donepezil PET illustrating the summed signal of gastrointestinal organs (L liver, P pancreas, S small intestine).