Although constipation is common in PD and can precede its motor symptoms by 12 years or more years1
, the pathologic association between impaired gastrointestinal motility and PD is poorly understood. The motility impairment might be caused by the same processes that produce the motor symptoms of PD, but in different regions of the nervous system. This would suggest a pathologic process preceding the sequence of CNS injuries proposed by Braak.34
Evidence for this includes findings of dopaminergic neuron depletion in the colon and LB in the myenteric plexus in decedents who had PD.6,17
It is interesting that an association between bowel movements and neuron density was absent in decedents who smoked cigarettes during mid-life. Cigarette smoking, is known to be associated with a low frequency of PD. In our data, cigarette smoking was also associated with higher neuron densities in all quadrants of the SN and across all bowel movement frequencies as compared to non-smokers (see ). It may be that an association between bowel movement frequency and neuron density is more subtle in cigarette smokers where neuron density seems uniformly high.34
The mechanism by which cigarette smoking changes the relationship between bowel movement frequency and neuron density in the SN is clearly in need of further study.
Data from the HAAS autopsy study demonstrate that low counts in the SN can occur with or without LB being present.35
Among non-smokers, our data suggest that nigral neuron counts are lower in individuals with a history of infrequent bowel movements. The relationship is strongest in the ventrolateral quadrant where there is a preponderance of SN injury in PD36
but was also present in the dorsomedial and ventromedial quadrants. This relationship appears to be independent of the presence of LB in the SN or LC or clinical diagnosis of PD.
In addition to statistically adjusting for LB, we repeated our analyses after removal of all cases of PD and incidental LB. Although our sample has been reduced and our statistical methods become less precise, decedents with >1 bowel movement/day continued to have a significant excess of neuron counts in the dorsomedial and ventrolateral quadrants relative to those with <1 bowel movement/day (p=0.018 and p=0.019). This is also true after adjustment for all other factors.
There were 29 men with no LB in the SN or LC who also had exams that included the Unified Parkinson’s Disease Rating Scale (UPDRS) at the time of assessment of bowel movement frequency. Unfortunately, this sample size is too limited to provide a careful assessment with additional adjustment for the UPDRS. Among the 29 men, however, 2 had <1 bowel movement per day, 19 had 1 bowel movement per day, and 8 had >1 bowel movement per day. The 2 men with <1 bowel movement per day fell in the highest tertile of UPDRS scores. They also had average neuron densities in all quadrants that were lower than any other combination of bowel movement frequency and UPDRS score.
Although the cause of constipation in PD remains unknown, data presented here suggest that constipation in non-smoking men is associated with low neuron counts in the SN and can occur without LB in the SN. Current initiatives in the HAAS are now investigating whether individuals with constipation and low nigral neuron density have synuclein deposition in the nervous system of the gut or the dorsal motor vagal nucleus.