Written by Alex Baumgartner, MD
In a recent issue of the journal Movement Disorders, colleagues and I published a study examining the relationship between two of the most common ‘non-motor’ symptoms of Parkinson’s disease (PD): decreased sense of smell (olfactory dysfunction) and constipation. It has been known for some time that these symptoms often start several years or even decades before the typical ‘motor’ symptoms of PD, which include tremor, stiffness, and slow movement. Going along with this, accumulation of the abnormal protein alpha-synuclein, which is thought to play a critical role in the development of PD, have been found in the nasal passages and GI tracts of PD patients before it is found in the brain. This has led many to hypothesize that PD may actually begin in the nose or in the gut and spread from there to the brain.
We wanted to explore whether we could find evidence that for some people, PD begins in the nasal passages while in other people, it begins in the gut. We hypothesized that if people had PD originating in the nasal passages only, they would have only loss of smell and not constipation. On the other hand, if PD originated in the GI tract only, they would have constipation but not loss of smell. We looked at data from the Parkinson’s Progression Markers Initiative (PPMI), which collects information from patients who have recently been diagnosed with PD.
We found that at the time people are diagnosed with PD, they tend to have problems with smelling and constipation to similar degrees. That is, people with worse sense of smell also tend to have worse constipation, and those with minimal loss of smell tend to have mild constipation. This finding actually went against our hypothesis. There may be a few reasons for this. The first is that the time of diagnosis of PD (based on tremor, slowness, and stiffness) may be too late to detect a difference in smell and constipation. Even if PD begins in either the nose or the gut, symptoms in the other location may have already ‘caught up’ with the first. The second possible explanation is that PD may begin in both locations at about the same time. This is called the dual-hit hypothesis, and has gained popularity in recent years. In the future, we hope to expand our research to help elucidate where and when the earliest signs of Parkinson’s occur.