| 1. |
- Kang, Xiaoying, et al.
(författare)
-
Association between Microscopic Colitis and Parkinson's Disease in a Swedish Population
- 2021
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 96:15
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Gastrointestinal inflammation has been linked with Parkinson's disease (PD). Microscopic colitis (MC) is an intestinal inflammatory disease with unknown relationship with PD.Objective: This study aimed to examine the association of MC with PD risk.Methods: In this nationwide matched cohort study in Sweden, PD incidence was compared between 12,609 patients with histologically confirmed MC and a matched population cohort of 58,879 MC-free individuals and a sibling cohort comprising all unaffected siblings of the MC patients (N-MC/N-Sibling = 6281/12,351). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models.Results: During a mean follow-up of similar to 7 years, we identified 449 incident PD diagnoses among the MC patients and the population cohort. Overall, MC was associated with an adjusted HR of 1.76 for PD, but the association attenuated substantially during follow-up. In the time-varying effects model, PD hazard was 3.45-fold (95% CI: 2.42, 4.93) higher during the first 2 years after biopsy and 1.80-fold (95% CI: 1.23, 2.64) higher during the following 3 years among MC versus MC-free individuals but was not different beyond 5 years after biopsy (HR: 1.03; 95% CI: 0.68, 1.54). This temporal pattern of MC-PD associations persisted when comparing MC patients to their siblings. In a post hoc case-control analysis, we also detected a strong association between MC and preexisting PD (odds ratio: 3.46; 95% CI: 2.91, 4.12).Conclusions: Our findings suggest that MC may not be a risk factor for PD; instead, it may co-occur with PD as a comorbidity or develop after a diagnosis of PD.
|
|
| 2. |
- Kang, Xiaoying, et al.
(författare)
-
Association between Microscopic Colitis and Parkinson's Disease in a Swedish Population
- 2021
-
Ingår i: Neurology. - : Wolters Kluwer. - 0028-3878 .- 1526-632X. ; 96:15 Suppl.
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objective: To examine the association between microscopic colitis (MC) and Parkinson’s disease (PD) risk.Background: Gastrointestinal inflammation has been linked with PD. MC is a chronic intestinal inflammatory disease; however, its relationship with PD is unknown.Design/Methods: A population-based matched cohort study was conducted to estimate the association between MC and incident PD diagnosis using Cox regression models. An exposed cohort of 12,609 MC patients diagnosed 1990–2017 and aged ≥35 years at diagnosis was identified from the Epidemiology Strengthened by histoPathology Reports in Sweden cohort (ESPRESSO). Two unexposed cohorts were compared to: a population cohort comprising 58,879 MC-free individuals randomly selected from the population and 1:5 matched to each MC patient by age, sex, year of biopsy and county of residence at the time of biopsy; and a sibling cohort (NMC/NSibling=6,281/12,351) including all siblings of the MC patients. Follow-up was from the date of biopsy until December 31st 2016 at latest.Results: During a mean follow-up of ~7 years, we identified 449 incident PD diagnoses among the MC patients and their matched population cohort. The overall PD risk was 76% higher among MC versus MC-free individuals; but the association attenuated substantially during follow-up. In the time-varying effects model, PD risk was 3.45-fold (95% CI: 2.42, 4.93) higher during the first 2 years after biopsy and 1.80-fold (95% CI: 1.23, 2.64) higher during the following 3 years among MC versus MC-free individuals, but was not differential beyond 5 years after biopsy (hazard ratio=1.03; 95% CI: 0.68, 1.54). This temporal pattern of MC-PD associations persisted in sibling analyses. Using a matched case-control design, we also observed a higher prevalence of prior PD diagnosis among MC patients than the matched MC-free individuals (odds ratio=3.46; 95% CI: 2.91, 4.12).Conclusions: Our findings suggest that MC may not be a risk factor, but rather a comorbidity or complication of PD.
|
|
| 3. |
- Kang, Xiaoying, et al.
(författare)
-
Clostridium difficile infection and risk of Parkinson's disease : A Swedish population-based cohort study
- 2020
-
Ingår i: European Journal of Neurology. - : Blackwell Publishing. - 1351-5101 .- 1468-1331. ; 27:11, s. 2134-2141
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gastrointestinal inflammation has been implicated in Parkinson's disease (PD). This study examined whether individuals with a history of Clostridium difficile infection (CDI) are at elevated risk of PD.METHODS: We performed a population-based cohort study using Swedish national register data. Adults aged ≥ 35 years were identified from the Swedish Population and Housing Census 1990 and followed during 1997-2013. Diagnoses of CDI and PD were extracted from the National Patient Register. Associations of CDI history with PD risk were estimated using Cox proportional hazards regression. We also explored whether the association differed by the source of CDI diagnosis (inpatient vs outpatient), presence of recurrent infections, and pre-infection use of antibiotics.RESULTS: Amongst the study population (N = 4,670,423), 34,868 (0.75%) had a history of CDI. A total of 165 and 47,035 incident PD cases were identified from individuals with and without CDI history, respectively. Across the entire follow-up, a 16% elevation of PD risk was observed among CDI group (hazard ratio: 1.16, 95% confidence interval: 1.00-1.36), which was mainly driven by increased PD risk within the first 2 years since CDI diagnosis (hazard ratio: 1.38, 95% confidence interval: 1.12-1.69). In longer follow-up, CDI was not associated with subsequent PD occurrence. This temporal pattern of CDI-PD associations was generally observed across all CDI subgroups.CONCLUSIONS: CDI may be associated with an increased short-term PD risk, but this might be explained by reverse causation and/or surveillance bias. Our results do not imply that CDI history affects long-term PD risk.
|
|
| 4. |
- Kang, Xiaoying
(författare)
-
The gut-brain axis in Parkinson’s disease : epidemiological studies on causes, underlying mechanisms and novel treatments
- 2022
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Parkinson’s disease (PD) is an age-related neurodegenerative disease with highly heterogeneous symptomatology. Little is known about why PD occurs. The gastrointestinal tract has been postulated as an origin of PD pathology, which then spreads along the gut- brain axis to enter the brain. This so-called “Braak hypothesis” well explains the gastrointestinal symptoms that are experienced by nearly 80% of PD patients during the prodromal stage of disease and the detectable α-synuclein (the pathogenic protein in PD) in multiple sites outside the brain. It has also been supported by subsequent evidence emerging from various settings. Hence, this thesis aimed to expand our knowledge about PD etiology and to inform therapeutic innovation from the perspective of the gut-brain axis. In Study I, we tested whether Clostridium difficile infection (CDI), an infectious diarrhea caused by a Gram-positive bacillus, is a risk factor for PD in a cohort study. By following 4.7 million Swedish adults between 1997 and 2013 for incident PD diagnosis, we found that CDI was associated with a short-term PD risk increase, which may be spurious due to reverse causation or surveillance bias, but was not associated with long-term PD risk. In Study II, we examined the relationship between microscopic colitis (MC), a chronic intestinal inflammatory disease, and PD. Using a matched cohort design, we showed that PD incidence was only associated with MC during the first five years since MC diagnosis, but not in longer follow-up. A post-hoc matched case-control analysis also found that PD prevalence was higher among MC versus MC-free individuals. Collectively, these findings imply that MC is more likely to be a comorbidity than a risk factor for PD. In Study III, we performed a Mendelian randomization study to estimate the causal effect of tumor necrosis factor (TNF) inhibition, an anti-inflammatory therapy for inflammatory bowel disease (IBD), on PD. Pharmacologic blockade of the pro-inflammatory signaling mediated by TNF receptor 1 (TNFR1) was genetically instrumented by four variants in the vicinity of the TNFR1-encoding gene. Results from different models consistently showed no benefits of TNF/TNFR1 antagonism for the prevention or delay of PD onset for the general population. In Study IV, genetic overlap between IBD and PD was explored via the conditional false discovery rate framework. We detected robust evidence for a genetic link between PD and each subtype of IBD, underpinned by many shared genomic loci. The genetic findings suggested the presence of both common etiology and antagonistic pleiotropy between PD and IBD risk genes, and further highlighted host immunity and/or autoimmunity in explaining the biological connection between the two seemingly unrelated diseases. In summary, findings from this thesis shed new light on the relationship between several intestinal diseases and PD, and from a public health perspective, provide novel data about the potential of anti-inflammatory treatment for intestinal disorders to prevent PD. Future work is warranted to replicate and follow-up with our findings and to translate the knowledge into clinical practice.
|
|
| 5. |
- Tang, Xiaojie, et al.
(författare)
-
Orbital hydroclimate variability revealed by grain-size evidence in the tropical Pacific Islands since 140 ka
- 2024
-
Ingår i: Global and Planetary Change. - 0921-8181. ; 236
-
Tidskriftsartikel (refereegranskat)abstract
- The past evolution of precipitation and atmospheric convection in the Western Pacific Warm Pool (WPWP) is critical for global climate changes but is under debate because of its forcing mechanisms. Here, we present a high temporal resolution (∼156 years) grain-size record of core MD01–2385 over the last 140 kyr, in offshore northern New Guinea to reveal sediment dynamics as a proxy for precipitation changes. End-member analysis revealed that a two-endmember model was optimal. The end-member 1/end-member 2 (EM1/EM2) ratio could represent the variation in grain size and exhibited significant precessional cycles changes in phase with modelled Niño 3 SST anomaly from a global climate model transient simulation. From these data, we inferred orbital fluctuations in precipitation from tropical western Pacific islands, with general precipitation peaks during the time of perihelion at the boreal autumnal equinox (midpoint from a low to high precession index), corresponding to La Niña-like conditions and vice versa. Comparisons of our new record with published precipitation records showed that orbital precipitation changes in the WPWP are mainly dominated by El Niño-Southern Oscillation-like (ENSO-like) oscillations in the precession band, while the Intertropical Convergence Zone (ITCZ) mainly controls the distribution of precipitation over a larger spatial area.
|
|
