Per Borghammer, March 2017.

An estimated 7-10 million people worldwide are living with PD. For decades, PD was considered to be primarily a brain disorder. However, recent evidence suggests that PD may actually be initiated in nerve endings of the enteric nervous system in the gut, and spread via the autonomic nerves to the brain and spinal cord. The parasympathetic nervous system seems to be of singular importance in PD. Many patients suffer constipation decades prior to the diagnosis of PD, signifying the involvement of parasympathetic nerves at the earliest stages of the disease.

At the PET Centre, Aarhus University Hospital, we recently validated the world’s first PET tracer for imaging the parasympathetic nervous system and showed that PD patients display a marked decrease of parasympathetic nerves in the gut (Figure 1). We are currently studying newly diagnosed PD patients and pro-dromal PD patients (ie. prior to diagnosis) to establish whether the loss of parasympathetic innervation undergoes years prior to the diagnosis of PD.

Currently, little is known about pathophysiological cause of constipation and other parasympathetic symptoms of PD. To better understand the complicated interplay between autonomic innervation of the gut and the physiological consequences, we employ a range of other techniques. Volumes of the intestine and other internal organs are measured on CT scans. Colonic transit time is estimated using radio-opaque markers. Gastric emptying time is measured using gastric scintigraphies, and intestinal motility is studied using a recently invented endo-capsule method (Motilis GI motility monitoring system). Using this multi-facetted approach, we aim to improve our understanding of the cause for constipation and other debilitating symptoms of PD, and also determine which of these methods can be used for diagnosing PD in the pre-clinical phase of the disease.

Figure 1. Left. Whole-body PET scans using 11C-donepezil. Right. 11C-donepezil PET scans of a healthy volunteer (top), and a patient with Parkinson’s disease (bottom). Notice the decreased signal in the small intestine of the patient.