Objective

To assess whether being able to quit smoking is an early marker of Parkinson disease (PD) onset rather than tobacco being "neuroprotective," we analyzed information about ease of quitting and nicotine substitute use.

Methods

For this case-control study, we identified 1,808 patients with PD diagnosed between 1996 and 2009 from Danish registries, matched 1,876 population controls on sex and year of birth, and collected lifestyle information. We estimated odds ratios and 95% confidence intervals with logistic regression adjusting for matching factors and confounders.

Results

Fewer patients with PD than controls ever established a smoking habit. Among former smokers, those with greater difficulty quitting or using nicotine substitutes were less likely to develop PD, with the risk being lowest among those reporting "extremely difficult to quit" compared with "easy to quit." Nicotine substitute usage was strongly associated with quitting difficulty and duration of smoking, i.e., most strongly among current smokers, followed by former smokers who had used nicotine substitutes, and less strongly among former smokers who never used substitutes.

Conclusions

Our data support the notion that patients with PD are able to quit smoking more easily than controls. These findings are compatible with a decreased responsiveness to nicotine during the prodromal phase of PD. We propose that ease of smoking cessation is an aspect of premanifest PD similar to olfactory dysfunction, REM sleep disorders, or constipation and suggests that the apparent "neuroprotective" effect of smoking observed in epidemiologic studies is due to reverse causation.

OBJECTIVE: To assess whether being able to quit smoking is an early marker of Parkinson disease (PD) onset rather than tobacco being neuroprotective, we analyzed information about ease of quitting and nicotine substitute use. METHODS: For this case-control study, we identified 1,808 patients with PD diagnosed between 1996 and 2009 from Danish registries, matched 1,876 population controls on sex and year of birth, and collected lifestyle information. We estimated odds ratios and 95% confidence intervals with logistic regression adjusting for matching factors and confounders. RESULTS: Fewer patients with PD than controls ever established a smoking habit. Among former smokers, those with greater difficulty quitting or using nicotine substitutes were less likely to develop PD, with the risk being lowest among those reporting extremely difficult to quit compared with easy to quit. Nicotine substitute usage was strongly associated with quitting difficulty and duration of smoking, i.e., most strongly among current smokers, followed by former smokers who had used nicotine substitutes, and less strongly among former smokers who never used substitutes. CONCLUSIONS: Our data support the notion that patients with PD are able to quit smoking more easily than controls. These findings are compatible with a decreased responsiveness to nicotine during the prodromal phase of PD. We propose that ease of smoking cessation is an aspect of premanifest PD similar to olfactory dysfunction, REM sleep disorders, or constipation and suggests that the apparent neuroprotective effect of smoking observed in epidemiologic studies is due to reverse causation.

Objective

To examine the association between head injuries throughout life and the risk for Parkinson disease (PD) in an interview-based case-control study.

Methods

We identified 1,705 patients diagnosed with PD at 10 neurologic centers in Denmark in 1996-2009 and verified their diagnoses in medical records. Patients were matched to 1,785 controls randomly selected from the Danish Central Population Register on sex and year of birth. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression.

Results

We observed no association between any head injury before first cardinal symptom and PD (OR 1.02; 95% CI 0.88, 1.19). Examination of number of head injuries (1: OR 1.02; 95% CI 0.87, 1.20; ≥2: OR 1.03; 95% CI 0.72, 1.47) or hospitalization for a head injury (OR 0.89; 95% CI 0.70, 1.12) did not show an association with PD. For 954 study subjects with at least one head injury, there was no evidence of an association between loss of consciousness (OR 0.89; 95% CI 0.67, 1.17), duration of loss of consciousness (≤1 minute: OR 0.93; 95% CI 0.58, 1.49; 1-5 minutes: OR 0.74; 95% CI 0.51, 1.08; ≥5 minutes: OR 0.81; 95% CI 0.53, 1.24), or amnesia (OR 1.31; 95% CI 0.88, 1.95) and risk for PD. Application of a lag time of 10 years between head injury and first cardinal symptom resulted in similar risk estimates.

Conclusions

The results do not support the hypothesis that head injury increases the risk for PD.

Previous studies have suggested that dopamine agonists have an antidepressant effect in Parkinson's disease (PD) patients. We examined whether fewer PD patients used antidepressant medication, when they were first treated with a dopamine agonist compared to other PD medications. PD patients diagnosed in Denmark were identified, and the diagnosis was confirmed by a review of the medical record. Antidepressant medication was assessed using the Danish National Prescription Registry. We used Cox proportional hazards regression to model the association between PD medications and time to antidepressant prescription. The type of PD medication first prescribed did not affect the subsequent use of antidepressants.

Background and purpose

Drinking caffeinated coffee has been reported to provide protection against Parkinson's disease (PD). Caffeine is an adenosine A2A receptor (encoded by the gene ADORA2A) antagonist that increases dopaminergic neurotransmission and Cytochrome P450 1A2 (gene: CYP1A2) metabolizes caffeine; thus, gene polymorphisms in ADORA2A and CYP1A2 may influence the effect coffee consumption has on PD risk.

Methods

In a population-based case-control study (PASIDA) in Denmark (1,556 PD patients and 1,606 birth year- and gender-matched controls), we assessed interactions between lifetime coffee consumption and 3 polymorphisms in ADORA2A and CYP1A2 for all subjects, and incident and prevalent PD cases separately using logistic regression models. We also conducted a meta-analysis combining our results with those from previous studies.

Results

We estimated statistically significant interactions for ADORA2A rs5760423 and heavy vs. light coffee consumption in incident (OR interaction = 0.66 [95% CI 0.46-0.94], p = 0.02) but not prevalent PD. We did not observe interactions for CYP1A2 rs762551 and rs2472304 in incident or prevalent PD. In meta-analyses, PD associations with daily coffee consumption were strongest among carriers of variant alleles in both ADORA2A and CYP1A2.

Conclusion

We corroborated results from a previous report that described interactions between ADORA2A and CYP1A2 polymorphisms and coffee consumption. Our results also suggest that survivor bias may affect results of studies that enroll prevalent PD cases.

The relationship between Parkinson disease (PD) and smoking has been examined in several studies, but little is known about smoking in conjunction with other behaviors and a family history of PD. Using unconditional logistic regression analysis, we studied individual and joint associations of these factors with idiopathic PD among 1,808 Danish patients who were diagnosed in 1996-2009 and matched to 1,876 randomly selected population controls. Although there was a downward trend in duration of smoking, this was not observed for daily tobacco consumption. A moderate intake of caffeine (3.1-5 cups/day) was associated with a lower odds ratio for PD (0.45, 95% confidence interval: 0.34, 0.62), as was a moderate intake of alcohol (3.1-7 units/week) (odds ratio = 0.60, 95% confidence interval: 0.58, 0.84); a higher daily intake did not reduce the odds further. When these behaviors were studied in combination with smoking, the odds ratios were lower than those for each one alone. Compared with never smokers with no family history of PD, never smokers who did have a family history had an odds ratio of 2.81 (95% confidence interval: 1.91, 4.13); for smokers with a family history, the odds ratio was 1.60 (95% confidence interval: 1.15, 2.23). In conclusion, duration of smoking seems to be more important than intensity in the relationship between smoking and idiopathic PD. The finding of lower risk estimates for smoking in combination with caffeine or alcohol requires further confirmation.