The etiology of Parkinson’s disease (PD) is not well understood but likely to involve both genetic and environmental factors. Incidence and prevalence estimates vary to a large extent—at least partly due to methodological differences between studies—but are consistently higher in men than in women. Several genes that cause familial as well as sporadic PD have been identified and familial aggregation studies support a genetic component. Despite a vast literature on lifestyle and environmental possible risk or protection factors, consistent findings are few. There is compelling evidence for protective effects of smoking and coffee, but the biologic mechanisms for these possibly causal relations are poorly understood. Uric acid also seems to be associated with lower PD risk. Evidence that one or several pesticides increase PD risk is suggestive but further research is needed to identify specific compounds that may play a causal role. Evidence is limited on the role of metals, other chemicals and magnetic fields. Important methodological limitations include crude classification of exposure, low frequency and intensity of exposure, inadequate sample size, potential for confounding, retrospective study designs and lack of consistent diagnostic criteria for PD. Studies that assessed possible shared etiological components between PD and other diseases show that REM sleep behavior disorder and mental illness increase PD risk and that PD patients have lower cancer risk, but methodological concerns exist. Future epidemiologic studies of PD should be large, include detailed quantifications of exposure, and collect information on environmental exposures as well as genetic polymorphisms.

/pdf/epidemiology-and-etiology-of-parkinson-s-disease-a-review-of-4l04xld1q9.pdf

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

The autonomic nervous system.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/wps.20204

Effects of antipsychotics, antidepressants and mood stabilizers on risk for physical diseases in people with schizophrenia, depression and bipolar disorder

Objective- The aim of this study was to evaluate whether type 2 diabetes at baseline is a risk factor for Parkinson's disease.

Abstract Research design and methods- We prospectively followed 51 552 Finnish men and women of 25 to 74 years of age without a history of Parkinson's disease at baseline. History of diabetes and other study parameters were determined at baseline using standardized measurements. Ascertainment of the Parkinson's disease status was based on the nationwide Social Insurance Institution's Drug Register data. Hazards ratios of incident Parkinson's disease associated with the history of type 2 diabetes were estimated.

Abstract Result- During a mean follow up period of 18.0 years, 324 men and 309 women developed incident Parkinson's disease. Age-and study year-adjusted hazard ratios of incident Parkinson's disease among subjects with type 2 diabetes, compared to those without it, were 1.80 (95% CI 1.03-3.15) in men, 1.93 (95% CI 1.05-3.53) in women, and 1.85 (95% CI 1.23-2.80) in men and women combined (adjusted also for sex), respectively. Further adjustment for body mass index, systolic blood pressure, total cholesterol, education, leisure time physical activity, smoking, alcohol drinking, coffee and tea consumption affected the results only slightly. The multivariate adjusted association between type 2 diabetes and the risk of Parkinson's disease was also confirmed in stratified subgroup analysis.

Abstract Conclusion- These data suggest that type 2 diabetes is associated with an increased risk of Parkinson's disease. Surveillance bias might account for higher rates in diabetes. The mechanism behind this association between diabetes and Parkinson's disease is not known.

https://care.diabetesjournals.org/content/diacare/30/4/842.full.pdf

Type 2 Diabetes and the Risk of Parkinson's Disease

OBJECTIVE To investigate the relationship between diabetes and future risk of Parkinson’s disease (PD) among older U.S. adults. RESEARCH DESIGN AND METHODS A prospective study of self-reported diabetes in 1995 and 1996 in relation to PD diagnosed after 1995 among 288,662 participants of the National Institutes of Health-AARP Diet and Health Study. Multivariate odds ratio (OR) and 95% CI were derived from logistic regression models. RESULTS A total of 1,565 participants with PD diagnosed after 1995 were included in the analysis. After adjustment for potential confounders, PD risk was ∼40% higher (OR = 1.41 [95% CI 1.20–1.66]) among diabetic patients than among participants without diabetes. Further analysis showed that the risk elevation was largely limited to individuals who had diabetes for more than 10 years at the time of baseline survey (1.75 [1.36–2.25]). The association with diabetes was seen for both participants with PD diagnosed between 1995 and 1999 and participants with PD diagnosed after 2000. In addition, similar results were obtained after excluding participants with stroke, heart disease, cancers, or poor or fair health status and in subgroup analyses by age, sex, smoking status, and coffee consumption. CONCLUSIONS This large study showed that diabetes was associated with a higher future risk of PD and the nature of this association warrants further investigation.

https://care.diabetesjournals.org/content/diacare/34/4/910.full.pdf

Diabetes and Risk of Parkinson’s Disease

Background and Purpose— Sympathetic hyperactivity is a contributing cause of vascular disorders because it increases blood pressure, blood sugar, and blood lipids. Pervasive compromise of the central and peripheral autonomic nervous systems is common in idiopathic Parkinson disease (IPD) resulting in reduced sympathetic and parasympathetic function. We hypothesized that IPD was associated with reduced prevalence of cardiovascular disease risk factors as a result of reduced sympathetic activity. Methods— We performed a retrospective case-control study on 178 newly diagnosed consecutive IPD patients, and 533 age- (±3 years) and sex-matched controls with other neurological diseases seen over the same period at the same hospital. For each case and control the following were noted on admission: smoking, diabetes, hypertension, body mass index, serum glucose, plasma cholesterol, triglycerides and total lipid levels, and blood pressure. Results— Diabetes, history of smoking, high blood pressure, high blood gluco...

Reduced Risk Factors for Vascular Disorders in Parkinson Disease Patients A Case-Control Study

The use of antipsychotics is hindered by the frequent occurrence of metabolic and cardiovascular side effects, resulting in worsened quality of life and greater mortality as a result of cardiovascular and cerebrovascular disorders in schizophrenia patients than the comparable general population. The various antipsychotics induce extrapyramidal symptoms, impaired glucose and lipid metabolism, weight gain, hypertension and arrhythmias, with variable frequency. Second-generation antipsychotics appear to have several advantages over first-generation antipsychotics, including a claimed better action on cognitive function and the negative symptoms of schizophrenia, and lower frequency of extrapyramidal side effects; however, their use is associated with a greater frequency of metabolic and cardiovascular disturbances. The mechanisms of these important side effects are not well understood, and generic approaches (psychoeducational programmes and symptomatic therapies) have been proposed to limit their severity. Extensive data from the literature indicate that autonomic nervous system dysfunction—intrinsic to schizophrenia and strongly exacerbated by antipsychotic treatment—is the cause of the pervasive metabolic and vascular dysfunctions associated with schizophrenia. In this article, we marshal further literature data to argue that the metabolic and cardiovascular side effects of antipsychotics are primarily mediated by their ability to block peripheral dopamine receptors, which physiologically modulate sympathetic activity. We also propose that these effects might be overcome by providing peripheral dopaminergic stimulation.

/pdf/antipsychotic-induced-metabolic-and-cardiovascular-side-4avre8ho9o.pdf

Antipsychotic-induced metabolic and cardiovascular side effects in schizophrenia: a novel mechanistic hypothesis

Sympathetic modulation by levodopa reduces vascular risk factors in Parkinson disease.

Background: The prognosis of cerebral metastases (MTS) is linked to progression of both systemic and local disease. The importance of MTS resection has been already pointed out. The observation of a high mortality for not-neurological causes confirms that the modern treatments allow a significant control of the disease within the nervous system. Nevertheless, management difficulties increase with multiple lesions and in these cases the role of surgery has still to be defined. Materials and Methods: We collected the clinical data of patients operated in two centers for cerebral MTS from lung carcinoma during 8 years. Patient selection for surgery followed definite criteria; the limit for multiple MTS was three. We analyzed the functional and survival outcomes of the cohort. Results and Conclusions: Our series included 242 patients: 105 had multiple MTS. Statistical analysis did not show significant differences in mean survival and outcomes between patients with single and multiple lesions. The decease occurred for neurological causes in 15.7% of cases. The selection of candidates for surgery requires several considerations and entails the success rate of this treatment. In patients with the multiple lesions who fulfilled the selection criteria we observed a nevertheless satisfying success after the operation. Our results imply that surgery may be applied also in selected patients with more diffuse intracranial disease. A pre-operative accurate patient selection is related to acceptable quality-of-life following the operation even in cases of multiple MTS.

Surgery in cerebral metastases: are numbers so important?

Alterations of the cardiovascular system and of the glucose and lipid metabolism can represent important factors of vascular risk. The autonomic nervous system, through its two efferent branches, the parasympatheticcholinergic and the sympathetic-adrenergic, plays an important role in the control of the cardiovascular activity and of the glucose and lipid metabolism, and its impaired working can interfere with these functions. An increased sympathetic activity and an increased frequency of diabetes, dyslipidemia, hypertension and obesity have been reported in untreated schizophrenic patients, and a further worsening of these vascular risk factors has been signalled as a side effect of treatment with neuroleptic drugs. The opposite is observed in Parkinson’s disease, where the reduced autonomic activity induced by the illness is associated with a decreased frequency of vascular risk factors, and their occurrence is further reduced by the treatment with dopaminergic drugs.

Gabriele Ronchetti

Papers

Reduced Risk Factors for Vascular Disorders in Parkinson Disease Patients A Case-Control Study

Antipsychotic-induced metabolic and cardiovascular side effects in schizophrenia: a novel mechanistic hypothesis

Sympathetic modulation by levodopa reduces vascular risk factors in Parkinson disease.

Surgery in cerebral metastases: are numbers so important?

Autonomic nervous system and risk factors for vascular disease. Effects of autonomic unbalance in schizophrenia and Parkinson's disease.