Patients with Inflammatory Bowel Disease Are at an Increased Risk of Parkinson’s Disease: A South Korean Nationwide Population-Based Study
Abstract
:1. Introduction
2. Material and Methods
2.1. Data Source
2.2. Study Population
2.3. Data Collection
2.4. Study Endpoint
2.5. Statistical Analysis
3. Results
3.1. Baseline Characteristics of the Study Population
3.2. Incidence and Risk of Parkinson’s Disease in Patients with Inflammatory Bowel Disease
3.3. Incidence and Risk of Parkinson’s Disease According to Medication Use
3.4. Subgroup Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Conflicts of Interest
Abbreviations
CD | Crohn’s disease; |
CI | confidence interval; |
DM | diabetes mellitus; |
HR | hazard ratio; |
IBD | inflammatory bowel disease; |
IL | interleukin; |
ICD-10 | International Classification of Diseases, tenth revision; |
NHIS | National Health Insurance Service; |
PD | Parkinson’s disease; |
RID | rare intractable disease; |
TNF | tumor necrosis factor; |
UC | ulcerative colitis; |
UK | United Kingdom. |
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IBD | CD | UC | |||||||
---|---|---|---|---|---|---|---|---|---|
Non-IBD Control (n = 116,583) | IBD Cohort (n = 38,861) | P Value | Non-CD Control (n = 37,893) | CD Cohort (n = 12,631) | P Value | Non-UC Control (n = 78,690) | UC Cohort (n = 26,230) | P Value | |
Age, years * | 39.91 ± 16.62 | 39.91 ± 16.62 | - | 30.74 ± 14.56 | 30.74 ± 14.56 | - | 44.33 ± 15.72 | 44.33 ± 15.72 | - |
≥60 ‡ | 16,335 (14.0) | 5445 (14.0) | - | 2130 (5.6) | 710 (5.6) | - | 14,205 (18.1) | 4735 (18.1) | - |
Male gender ‡ | 71,292 (61.2) | 23,764 (61.2) | - | 26,580 (70.1) | 8860 (70.1) | - | 44,712 (56.8) | 14,904 (56.8) | - |
Rural residence ‡ | 62,113 (53.3) | 19,328 (49.7) | <0.001 | 20,117 (53.1) | 6186 (49.0) | <0.001 | 41,996 (53.4) | 13,142 (50.1) | <0.001 |
Lowest income 20% †,‡ | 27,195 (23.3) | 7687 (19.8) | <0.001 | 8785 (23.2) | 2668 (21.1) | <0.001 | 18,410 (23.4) | 5019 (19.1) | <0.001 |
Comorbidities | |||||||||
DM ‡ | 5786 (5.0) | 1610 (4.1) | <0.001 | 867 (2.3) | 280 (2.2) | 0.642 | 4919 (6.3) | 1330 (5.1) | <0.001 |
Hypertension ‡ | 14,911 (12.8) | 4503 (11.6) | <0.001 | 2312 (6.1) | 684 (5.4) | 0.005 | 12,599 (16.0) | 3819 (14.6) | <0.001 |
Dyslipidemia ‡ | 8621 (7.4) | 2744 (7.1) | 0.029 | 1388 (3.7) | 389 (3.1) | 0.002 | 7233 (9.2) | 2355 (9.0) | 0.299 |
Depression ‡ | 3535 (3.0) | 2336 (6.0) | <0.001 | 760 (2.0) | 690 (5.5) | <0.001 | 2775 (3.5) | 1646 (6.3) | <0.001 |
Ischemic heart disease ‡ | 4028(3.5) | 1764 (4.6) | <0.001 | 631 (1.7) | 392 (3.1) | <0.001 | 3397 (4.3) | 1372 (5.2) | <0.001 |
History of myocardial infarction ‡ | 458 (0.4) | 235 (0.6) | < 0.001 | 73 (0.2) | 68 (0.5) | <0.001 | 385 (0.5) | 167 (0.6) | 0.004 |
History of stroke ‡ | 1752 (1.5) | 648 (1.8) | 0.023 | 241 (0.6) | 129 (1.0) | <0.001 | 1,511 (1.9) | 519 (2.0) | 0.552 |
Medications for IBD | |||||||||
Corticosteroids ‡ | 37,450 (32.1) | 22,321 (57.4) | < 0.001 | 10,793 (28.5) | 7417 (58.7) | <0.001 | 26,657 (33.9) | 14,904 (56.8) | <0.001 |
Immunomodulators ‡ | 373 (0.3) | 10,405 (26.8) | < 0.001 | 92 (0.2) | 7008 (55.5) | <0.001 | 281 (0.4) | 3397 (13.0) | <0.001 |
Anti-TNF ‡ | 28 (0.0) | 2110 (5.4) | < 0.001 | 11 (0.0) | 1665 (13.2) | <0.001 | 17 (0.0) | 445 (1.7) | <0.001 |
Follow-up period, years * | 4.88 ± 1.27 | 4.87 ± 1.29 | 0.201 | 4.90 ± 1.27 | 4.86 ± 1.31 | 0.005 | 4.88 ± 1.28 | 4.88 ± 1.28 | 0.704 |
Health care visits * | 11.86 ± 17.84 | 20.0 ± 20.7 | < 0.001 | 8.43 ± 13.73 | 17.56 ± 18.23 | <0.001 | 13.51 ± 19.3 | 21.17 ± 21.69 | <0.001 |
Total No. | PD Cases | Person-Years (y) | PD Incidence (/100,000 Person-Years) | Age at PD Diagnosis, Years * | Model 1 † HR (95% CI) | P Value | Model 2 ‡ HR (95% CI) | P Value | Model 3 § HR (95% CI) | P Value | |
---|---|---|---|---|---|---|---|---|---|---|---|
Total IBD | <0.001 | <0.001 | <0.001 | ||||||||
Control | 116,583 | 134 | 569,360 | 24 | 64.1 ± 10.2 | 1 (Ref.) | 1 (Ref.) | 1 (Ref.) | |||
Case | 38,861 | 92 | 189,415 | 49 | 60.9 ± 12.1 | 2.07 (1.59–2.70) | 1.95 (1.49–2.54) | 1.87 (1.43–2.44) | |||
IBD subgroup | |||||||||||
Incident | 16,620 | 25 | 65,692 | 38 | 61.8 ± 11.7 | 1.93 (1.26–2.96) | 0.003 | 1.65 (1.07–2.55) | 0.023 | 1.58 (1.02–2.44) | 0.039 |
Prevalent | 22,241 | 67 | 123,722 | 54 | 60.6 ± 12.3 | 2.13 (1.59–2.86) | <0.001 | 2.08 (1.55–2.8) | <0.001 | 2.00 (1.49–2.70) | <0.001 |
Total CD | 0.008 | 0.012 | 0.023 | ||||||||
Control | 37,893 | 19 | 185,637 | 10 | 64.9 ± 8.2 | 1 (Ref.) | 1 (Ref.) | 1 (Ref.) | |||
Case | 12,631 | 15 | 61,416 | 24 | 53.7 ± 16.3 | 2.52 (1.28–4.95) | 2.44 (1.22–4.86) | 2.23 (1.12–4.45) | |||
CD subgroup | |||||||||||
Incident | 5607 | 4 | 21,928 | 18 | 57.8 ± 16.2 | 1.71 (0.58–5.05) | 0.332 | 1.52 (0.51–4.55) | 0.457 | 1.36 (0.45–4.07) | 0.587 |
Prevalent | 7024 | 11 | 39,488 | 28 | 52.3 ± 16.9 | 3.05 (1.44–6.43) | 0.004 | 3.12 (1.46–6.69) | 0.004 | 2.91 (1.36–6.24) | 0.006 |
Total UC | <0.001 | <0.001 | <0.001 | ||||||||
Control | 78,690 | 115 | 383,722 | 30 | 63.9 ± 10.5 | 1 (Ref.) | 1 (Ref.) | 1 (Ref.) | |||
Case | 26,230 | 77 | 127,998 | 60 | 62.3 ± 10.6 | 2.00 (1.50–2.67) | 1.92 (1.43–2.56) | 1.85 (1.38–2.48) | |||
UC subgroup | |||||||||||
Incident | 11,013 | 21 | 43,765 | 48 | 62.6 ± 11.0 | 1.97 (1.23–3.15) | 0.005 | 1.75 (1.09–2.8) | 0.020 | 1.68 (1.05–2.69) | 0.031 |
Prevalent | 15,217 | 56 | 84,234 | 66 | 62.2 ± 10.6 | 2.01 (1.46–2.77) | <0.001 | 1.99 (1.44–2.75) | <0.001 | 1.93 (1.40–2.67) | <0.001 |
Total No. | PD Cases | Person-Years (y) | PD Incidence (/100,000 Person-Years) | Model 1 * HR (95% CI) | P Value | Model 2 † HR (95% CI) | P Value | |
---|---|---|---|---|---|---|---|---|
CD | ||||||||
Corticosteroids | 0.006 | <0.001 | ||||||
No | 5214 | 11 | 26,582 | 41 | 1 (Ref.) | 1 (Ref.) | ||
Yes | 7417 | 4 | 34,834 | 11 | 0.19 (0.06–0.63) | 0.08 (0.02–0.33) | ||
Immunomodulators | 0.193 | 0.227 | ||||||
No | 5623 | 13 | 27,465 | 47 | 1 (Ref.) | 1 (Ref.) | ||
Yes | 7008 | 2 | 33,951 | 6 | 0.35 (0.07–1.67) | 0.38 (0.08–1.83) | ||
Anti-TNF | - | - | ||||||
No | 10,966 | 15 | 53,347 | 28 | 1 (Ref.) | 1 (Ref.) | ||
Yes | 1665 | 0 | 8069 | 0 | - | - | ||
UC | ||||||||
Corticosteroids | 0.386 | 0.213 | ||||||
No | 11,326 | 35 | 56,378 | 62 | 1 (Ref.) | 1 (Ref.) | ||
Yes | 14,904 | 42 | 71,621 | 59 | 0.82 (0.52–1.29) | 0.75 (0.47–1.18) | ||
Immunomodulators | 0.541 | 0.521 | ||||||
No | 22,833 | 71 | 111,139 | 64 | 1 (Ref.) | 1 (Ref.) | ||
Yes | 3397 | 6 | 16,860 | 36 | 0.77 (0.33–1.78) | 0.76 (0.33–1.76) | ||
Anti-TNF | - | - | ||||||
No | 25,785 | 77 | 126,117 | 61 | 1 (Ref.) | 1 (Ref.) | ||
Yes | 445 | 0 | 1881 | 0 | - | - | ||
Non-IBD controls | ||||||||
Corticosteroids | 0.353 | 0.585 | ||||||
No | 79,133 | 73 | 388,691 | 19 | 1 (Ref.) | 1 (Ref.) | ||
Yes | 37,450 | 61 | 180,669 | 34 | 1.18 (0.83–1.66) | 1.10 (0.78–1.57) | ||
Immunomodulators | 0.108 | 0.116 | ||||||
No | 116,210 | 132 | 567,574 | 23 | 1 (Ref.) | 1 (Ref.) | ||
Yes | 373 | 2 | 1786 | 112 | 3.16 (0.78–12.84) | 3.08 (0.76–12.52) | ||
Anti-TNF | - | |||||||
No | 116,555 | 134 | 569,235 | 24 | 1 (Ref.) | 1 (Ref.) | ||
Yes | 28 | 0 | 125 | 0 | - | - |
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Share and Cite
Park, S.; Kim, J.; Chun, J.; Han, K.; Soh, H.; Kang, E.A.; Lee, H.J.; Im, J.P.; Kim, J.S. Patients with Inflammatory Bowel Disease Are at an Increased Risk of Parkinson’s Disease: A South Korean Nationwide Population-Based Study. J. Clin. Med. 2019, 8, 1191. https://doi.org/10.3390/jcm8081191
Park S, Kim J, Chun J, Han K, Soh H, Kang EA, Lee HJ, Im JP, Kim JS. Patients with Inflammatory Bowel Disease Are at an Increased Risk of Parkinson’s Disease: A South Korean Nationwide Population-Based Study. Journal of Clinical Medicine. 2019; 8(8):1191. https://doi.org/10.3390/jcm8081191
Chicago/Turabian StylePark, Seona, Jihye Kim, Jaeyoung Chun, Kyungdo Han, Hosim Soh, Eun Ae Kang, Hyun Jung Lee, Jong Pil Im, and Joo Sung Kim. 2019. "Patients with Inflammatory Bowel Disease Are at an Increased Risk of Parkinson’s Disease: A South Korean Nationwide Population-Based Study" Journal of Clinical Medicine 8, no. 8: 1191. https://doi.org/10.3390/jcm8081191