Naam Frederique van den Bos
Datum proefschrift 28-09-2017
(Co) promotoren prof.dr.ir. Y.T. van der Schouw, dr. M.H. Emmelot-Vonk
Titel proefschrift Comorbidities in Parkinson's disease, cause or consequence?

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Samenvatting proefschrift
Parkinson’s disease (PD) is a common neurodegenerative disease, affecting approximately 1.8% of the population over the age of 65. The prevalence of PD and comorbidities increase with age and therefore many patients with PD suffer from other diseases related to old age. The presence of comorbid diseases has consequences for disability, substantially adding to disease burden. In this thesis, we have shown that comorbidities like osteoporosis, T2D and hypertension are common in PD. The high prevalence of these conditions may be explained by several reasons. First, the risk of developing most chronic diseases increases progressively with age. Second, we proved that T2D and hypertension are both risk factors for developing PD (complicating- (or causal-) comorbidity). And third, we showed that T2D, hypertension and PD share inflammation as an important common pathway, thus explaining the clustering of comorbidities in PD (concurrent comorbidity). We also showed that besides inflammation other disease-specific risk factors connect osteoporosis and PD, i.e. hyperhomocysteinemia, BMI, and vitamin D, whereas insulin sensitivity and oxidative stress connectT2D and PD, and the renine-angiotensine system and oxidative stress link hypertension and PD. These findings have made us question the relevance of a disease management model in the care of patients with PD. Although disease-specific guidelines are usually evidence-based, this does not mean that they are applicable in all situations. In addition, disease specific guidelines often do not take into consideration the simultaneous occurrence of other diseases. Guideline development must systematically approach the most common disease combinations and, in case of an absence of evidence, outline high-priority research questions. It is increasingly clear that chronic disease research must be approached holistically rather than on a disease-by-disease basis. Hence, further research is needed to examine biological pathways and systems (including causality) for understanding specific combinations of comorbidities in PD. Using modern advanced epidemiological techniques, such as Mendelian randomisation, can provide insight in causality. In particular, the use of Mendelian randomisation for providing compelling final evidence on the causal association between inflammation, vitamin D, hypertension and diabetes on PD will answer some of the remaining question in this thesis.