Helicobacter pylori has been implicated in the pathogenesis of Parkinson's disease (PD). Its eradication, in a randomized placebo-controlled trial, improved PD hypokinesia. Helicobacter species zoonosis might explain excess mortality from PD and non-Hodgkin lymphoma in livestock, but not arable, farmers. Indeed, Helicobacter is causally-associated with gastric lymphoma. We have previously shown that the relative-frequency, H. suis to H. pylori , was 10-times greater in 60 PD-patients than in 256 controls. We now go on to evaluate the pathological significance of H. suis , detected in gastric-biopsy DNA-extracts by ureA -based species-specific qPCR, validated by amplicon sequencing. The methodology had been cross-validated by a carR -based PCR. The pathological significance is put in context of H. pylori detection [urea-breath-test (UBT) with biopsy-culture, and, if negative, PCR], and the potential reservoir in pigs. Here, we explore, in these 60 PD-patients, associations of H. suis status with all-cause-mortality, and with orthostatic cardiovascular and blood profiling. H. suis had been detected in 19 of the 60 PD-patients on one or more occasion, only two (with co-existent H. pylori ) being UBT positive. We found that the hazard-of-death (age-at-diagnosis- and gender-adjusted) was 12 (95% CI 1,103) times greater (likelihood-ratio test, P = 0.005) with H. suis -positivity (6/19) than with negativity (2/40: one lost to follow-up). UBT-values did not influence the hazard. H. suis -positivity was associated with lower standing mean-arterial-pressure [6 (1, 11) mmHg], H. pylori -positivity having no effect. The lower total lymphocyte count with H. pylori -positivity [−8 (−1, −14) %] was not seen with H. suis , where T-cell counts were higher [24 (2, 52) %]. Regarding the potential zoonotic reservoir in the UK, Helicobacter -like-organism frequency was determined in freshly-slaughtered pigs, nature ascertained by sequencing. Organisms immunostaining for Helicobacter , with corkscrew morphology typical of non- H. pylori Helicobacter , were seen in 47% of 111 pig-antra. We conclude that H. suis is associated with all-cause-mortality in PD and has a potential zoonotic reservoir.
Depression is associated with constipation within and outside Parkinson’s disease (PD). Since inefficient cognitive-processing (bradyphrenia) features in PD and an enterokinetic agent improved cognitive performance in healthy individuals, bradyphrenia may be associated with constipation. We aim to define the archetypical bowel function of PD, and its association with cognition, mood, and motor features within and outside PD. We assessed colonic transit time (oral radio-opaque markers over 6 days), bowel function and psychometric questionnaires and measures of PD facets, including bradyphrenia, in 58 participants with diagnosed PD, and 71 without (controls). The best abdominal X-ray (day 7) predictors of PD status were total retained marker count and transverse colon segmental delay. However, Rome functional constipation status complemented segmental delay better, giving good specificity (85%) but low sensitivity (56%). Transverse colon marker count appeared to be age-associated only in PD. In PD, those correctly classified by bowel dysfunction had higher depression scores (p = 0.02) and longer cognitive-processing times than the misclassified (p = 0.05). Controls misclassified as PD by bowel dysfunction had higher depression and anxiety scores than the correctly classified (p = 0.002 and 0.003, respectively), but not slower cognitive processing. Measures of motor features were independent of sub-classification by bowel function in PD and in controls. In conclusion, constipation in PD has distinct localized pathophysiology, and is associated with bradyphrenia.
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