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1.120 A PROSPECTIVE STUDY OF STATIN USE AND RISK OF PARKINSON DISEASE
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Monday, 12 December 2011 / Parkinsonism and Related Disorders 18S2 (2012) S1–S79
1.118 RISKS OF PARKINSON DISEASE IN PATIENTS WITH AUTOIMMUNE DISORDERS: A NATION-WIDE EPIDEMIOLOGICAL STUDY FROM SWEDEN X. Li1 , J. Sundquist1,2 , K. Sundquist1 . 1 Lund University, Malmo, Sweden; 2 Stanford University, San Francisco, CA, USA Objectives: To investigate association between autoimmune disorders and Parkinson disease (PD), and to study whether the risk is associated with follow-up time and age. Methods: Standardized incidence ratios (SIRs) were calculated for PD in patients with autoimmune disorders by comparing them to subjects without autoimmune disorders. Results: Among 310 522 patients with a total of 33 conditions of autoimmune disorders, 932 patients developed subsequent PD, giving an overall SIR of 1.32 and 1.18 for PD diagnosed later than 1 year after follow-up. Six types of autoimmune disorders showed an increased risk. These conditions included: amyotrophic lateral sclerosis, Graves/hyperthyroidism, hashimoto/hypothyroidism, multiple sclerosis, pernicious anemia, and polymyalgia rheumatica. The risks depended on the age at hospitalization for PD. Conclusions: A 32% overall excess risk of PD was noted among patients with an autoimmune disorder, the risk was increased during the first ten years of follow-up after hospitalization of autoimmune disorders. 1.119 THE ASSOCIATION BETWEEN PARKINSON DISEASE AND FACTORS REFLECTING ENDOGENOUS ESTROGEN ACTIVITY IN WOMEN R. Chen1 , B. Zhang2 , B. Ouyang3 , S. Wang4 . 1 Neurology Department, Tianjin Huanhu Hospital, 2 Tianjin Medical University General Hospital, Tianjin, China; 3 Rush University Medical Center, Chicago, IL, USA; 4 Tianjin Huanhu Hospital, Tianjin, China Purpose: To investigate the association between Parkinson disease (PD) and factors reflecting endogenous estrogen activity. Methods: A case-control study was performed among 119 women with PD and 119 age-matched female controls. A structured questionnaire was administered to query detailed reproductive characteristics as well as past histories (mastadenoma or breast cancer, uterine myomas). Height and weight were measured and body mass index (BMI) was calculated. Statistical analyses between variables of interest and risk of PD were carried out using t tests or Wilcoxon rank-sum tests or chi-square tests or logistic regression. Results: Compared to control subjects, PD patients experienced later menarche (14.4±1.7 vs 15.2±2.0 years old, p < 0.05), longer cumulative duration of pregnancies (19.8±9.7 vs 27.7±15.4 months, p < 0.05). shorter fertile life span (OR = 0.92, 95% CI: 0.85, 0.99), and higher parity (OR = 1.55, 95% CI: 1.17, 2.04). An inverse association between PD and mastadenoma or breast cancer history (OR = 0.19, 95% CI: 0.09, 0.42) was found. Conclusion: Our study suggests a possible increased risk of PD in conditions with reduced estrogen activity, whereas high endogenous estrogen may be protective against PD. 1.120 A PROSPECTIVE STUDY OF STATIN USE AND RISK OF PARKINSON DISEASE X. Gao1 , K. Simon1 , M.A. Schwarzschild2 , A. Ascherio1 . 1 Harvard Medical School & Harvard School of Public Health, 2 Department of Neurology, Massachusetts General Hospital, Boston, MA, USA Objective: Statins have been found to have potent antiinflammatory and immunomodulating effects, which led to the hypothesis that statins could be neuroprotective agents. However, the beneficial effects of statins could be offset by their unfavorable effects on lowering plasma coenzyme Q10 and urate. We therefore prospectively examined whether use of statins was associated with altered risk of PD.
Methods: We conducted a prospective study including 38,191 men and 90,874 women participating in two ongoing US cohorts, the Health Professional Follow-up and the Nurses’ Health Study. Information on regular cholesterol lowering drug use (2+ times/week) was collected in 1994 in both cohorts via questionnaire. Relative risks (RR) and 95% confidence intervals (CI) were computed using Cox proportional hazards models adjusting for age, smoking, caffeine intake, duration of hypercholesterolemia, and other covariates. Results: During 12 years of follow-up (1994–2006), we documented 644 incident PD cases (338 women and 306 men). The risk of PD was lower among current statin users (adjusted pooled RR = 0.74; 95% CI: 0.54, 1.00; P = 0.049), relative to non-users. A significant association was observed in participants who were aged <60 years at baseline (adjusted pooled RR = 0.31, 95% CI: 0.11, 0.86; P = 0.02), but not among those who were older (adjusted pooled RR = 0.83, 95% CI: 0.60, 1.14; P = 0.25) (p for interaction = 0.03). Conclusions: We found that regular use of statins was associated with a modest reduction in PD risk. The possibility that some statins may reduce PD risk deserves further consideration. 1.121 CNS INFECTIONS, SEPSIS, AND RISK OF PARKINSON DISEASE H. Chen1 , F. Fang2 , K. Wirdefeldt2 , A. Jacks3 , F. Kamel1 , W. Ye2 . 1 NIEHS/NIH, RTP, NC, USA; 2 Karolinska Institutet, Stockholm, Sweden; 3 National Institute of Health and Welfare, Helsinki, Finland Objectives: To examine whether infection of the central nervous system (CNS) or sepsis was associated with a greater risk of Parkinson disease (PD). Methods: A nested case-control study of 18,648 PD patients identified from the Swedish Patient Register between 2001 and 2007 and 93,240 matched general population controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived from logistic regression models. Results: Overall, PD patients were more likely to have a previous hospitalization for CNS infection (OR = 1.5, 95%CI: 1.2 to 1.9) or sepsis (OR = 1.6, 95%CI: 1.4–1.7) than controls, due largely to hospitalizations in the year prior to PD identification (CNS infections: OR = 3.0, 95%CI: 1.6–5.7; sepsis: OR = 3.5, 95%CI: 3.0–4.0). We conducted further analyses to examine whether the observed results could entirely be explained by reverse causality. For CNS infections, we found that subjects with multiple infections more than 5 years before the index date had a higher risk of PD than those without (OR=3.3, 95%CI: 1.4–8.2). Among subjects younger than age 70 at the index date or subjects with an index date after 2003, hospitalizations with CNS infections 5–9 years before the index date was associated with a significantly higher PD occurrence: the ORs were 2.2 (95%CI: 1.0–4.6) and 2.2 (95%CI: 1.2 to 3.4) respectively. None of these were however observed for hospitalizations due to sepsis. Conclusions: This study provides preliminary evidence for a potential link between CNS infections and higher risk of PD. In contrast, the findings on sepsis and PD are likely due to reverse causality. 1.122 GSK-3b EXPRESSION IN CEREBROSPINAL FLUID IN PARKINSON’S DISEASE 1,2 ´ Sanchez-Ferro J.A. Molina-Arjona1,2,3 , A. ´ , D. Antequera2,4 , F. Bermejo-Pareja1,2 , E. Carro2,4 . 1 Neurology, Hospital 12 de Octubre, 2 Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), 3 Fundaci´ on Neurociencias y Envejecimiento, 4 Neuroscience Group, Research Institute Hospital 12 de Octubre (i+12), Madrid, Spain Introduction: GSK-3b is a critical intermediate in proapoptotic signaling cascades that are associated with different
Monday, 12 December 2011 / Parkinsonism and Related Disorders 18S2 (2012) S1–S79
1.118 RISKS OF PARKINSON DISEASE IN PATIENTS WITH AUTOIMMUNE DISORDERS: A NATION-WIDE EPIDEMIOLOGICAL STUDY FROM SWEDEN X. Li1 , J. Sundquist1,2 , K. Sundquist1 . 1 Lund University, Malmo, Sweden; 2 Stanford University, San Francisco, CA, USA Objectives: To investigate association between autoimmune disorders and Parkinson disease (PD), and to study whether the risk is associated with follow-up time and age. Methods: Standardized incidence ratios (SIRs) were calculated for PD in patients with autoimmune disorders by comparing them to subjects without autoimmune disorders. Results: Among 310 522 patients with a total of 33 conditions of autoimmune disorders, 932 patients developed subsequent PD, giving an overall SIR of 1.32 and 1.18 for PD diagnosed later than 1 year after follow-up. Six types of autoimmune disorders showed an increased risk. These conditions included: amyotrophic lateral sclerosis, Graves/hyperthyroidism, hashimoto/hypothyroidism, multiple sclerosis, pernicious anemia, and polymyalgia rheumatica. The risks depended on the age at hospitalization for PD. Conclusions: A 32% overall excess risk of PD was noted among patients with an autoimmune disorder, the risk was increased during the first ten years of follow-up after hospitalization of autoimmune disorders. 1.119 THE ASSOCIATION BETWEEN PARKINSON DISEASE AND FACTORS REFLECTING ENDOGENOUS ESTROGEN ACTIVITY IN WOMEN R. Chen1 , B. Zhang2 , B. Ouyang3 , S. Wang4 . 1 Neurology Department, Tianjin Huanhu Hospital, 2 Tianjin Medical University General Hospital, Tianjin, China; 3 Rush University Medical Center, Chicago, IL, USA; 4 Tianjin Huanhu Hospital, Tianjin, China Purpose: To investigate the association between Parkinson disease (PD) and factors reflecting endogenous estrogen activity. Methods: A case-control study was performed among 119 women with PD and 119 age-matched female controls. A structured questionnaire was administered to query detailed reproductive characteristics as well as past histories (mastadenoma or breast cancer, uterine myomas). Height and weight were measured and body mass index (BMI) was calculated. Statistical analyses between variables of interest and risk of PD were carried out using t tests or Wilcoxon rank-sum tests or chi-square tests or logistic regression. Results: Compared to control subjects, PD patients experienced later menarche (14.4±1.7 vs 15.2±2.0 years old, p < 0.05), longer cumulative duration of pregnancies (19.8±9.7 vs 27.7±15.4 months, p < 0.05). shorter fertile life span (OR = 0.92, 95% CI: 0.85, 0.99), and higher parity (OR = 1.55, 95% CI: 1.17, 2.04). An inverse association between PD and mastadenoma or breast cancer history (OR = 0.19, 95% CI: 0.09, 0.42) was found. Conclusion: Our study suggests a possible increased risk of PD in conditions with reduced estrogen activity, whereas high endogenous estrogen may be protective against PD. 1.120 A PROSPECTIVE STUDY OF STATIN USE AND RISK OF PARKINSON DISEASE X. Gao1 , K. Simon1 , M.A. Schwarzschild2 , A. Ascherio1 . 1 Harvard Medical School & Harvard School of Public Health, 2 Department of Neurology, Massachusetts General Hospital, Boston, MA, USA Objective: Statins have been found to have potent antiinflammatory and immunomodulating effects, which led to the hypothesis that statins could be neuroprotective agents. However, the beneficial effects of statins could be offset by their unfavorable effects on lowering plasma coenzyme Q10 and urate. We therefore prospectively examined whether use of statins was associated with altered risk of PD.
Methods: We conducted a prospective study including 38,191 men and 90,874 women participating in two ongoing US cohorts, the Health Professional Follow-up and the Nurses’ Health Study. Information on regular cholesterol lowering drug use (2+ times/week) was collected in 1994 in both cohorts via questionnaire. Relative risks (RR) and 95% confidence intervals (CI) were computed using Cox proportional hazards models adjusting for age, smoking, caffeine intake, duration of hypercholesterolemia, and other covariates. Results: During 12 years of follow-up (1994–2006), we documented 644 incident PD cases (338 women and 306 men). The risk of PD was lower among current statin users (adjusted pooled RR = 0.74; 95% CI: 0.54, 1.00; P = 0.049), relative to non-users. A significant association was observed in participants who were aged <60 years at baseline (adjusted pooled RR = 0.31, 95% CI: 0.11, 0.86; P = 0.02), but not among those who were older (adjusted pooled RR = 0.83, 95% CI: 0.60, 1.14; P = 0.25) (p for interaction = 0.03). Conclusions: We found that regular use of statins was associated with a modest reduction in PD risk. The possibility that some statins may reduce PD risk deserves further consideration. 1.121 CNS INFECTIONS, SEPSIS, AND RISK OF PARKINSON DISEASE H. Chen1 , F. Fang2 , K. Wirdefeldt2 , A. Jacks3 , F. Kamel1 , W. Ye2 . 1 NIEHS/NIH, RTP, NC, USA; 2 Karolinska Institutet, Stockholm, Sweden; 3 National Institute of Health and Welfare, Helsinki, Finland Objectives: To examine whether infection of the central nervous system (CNS) or sepsis was associated with a greater risk of Parkinson disease (PD). Methods: A nested case-control study of 18,648 PD patients identified from the Swedish Patient Register between 2001 and 2007 and 93,240 matched general population controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived from logistic regression models. Results: Overall, PD patients were more likely to have a previous hospitalization for CNS infection (OR = 1.5, 95%CI: 1.2 to 1.9) or sepsis (OR = 1.6, 95%CI: 1.4–1.7) than controls, due largely to hospitalizations in the year prior to PD identification (CNS infections: OR = 3.0, 95%CI: 1.6–5.7; sepsis: OR = 3.5, 95%CI: 3.0–4.0). We conducted further analyses to examine whether the observed results could entirely be explained by reverse causality. For CNS infections, we found that subjects with multiple infections more than 5 years before the index date had a higher risk of PD than those without (OR=3.3, 95%CI: 1.4–8.2). Among subjects younger than age 70 at the index date or subjects with an index date after 2003, hospitalizations with CNS infections 5–9 years before the index date was associated with a significantly higher PD occurrence: the ORs were 2.2 (95%CI: 1.0–4.6) and 2.2 (95%CI: 1.2 to 3.4) respectively. None of these were however observed for hospitalizations due to sepsis. Conclusions: This study provides preliminary evidence for a potential link between CNS infections and higher risk of PD. In contrast, the findings on sepsis and PD are likely due to reverse causality. 1.122 GSK-3b EXPRESSION IN CEREBROSPINAL FLUID IN PARKINSON’S DISEASE 1,2 ´ Sanchez-Ferro J.A. Molina-Arjona1,2,3 , A. ´ , D. Antequera2,4 , F. Bermejo-Pareja1,2 , E. Carro2,4 . 1 Neurology, Hospital 12 de Octubre, 2 Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), 3 Fundaci´ on Neurociencias y Envejecimiento, 4 Neuroscience Group, Research Institute Hospital 12 de Octubre (i+12), Madrid, Spain Introduction: GSK-3b is a critical intermediate in proapoptotic signaling cascades that are associated with different