Biological and Clinical Implications of Comorbidities in Parkinson's Disease

Abstract

A wide spectrum of comorbidities has been associated with Parkinson's disease (PD), a progressive neurodegenerative disease that affects more than seven million people worldwide. Emerging evidence indicates that chronic diseases including diabetes, depression, anemia and cancer may be implicated in the pathogenesis and progression of PD. Recent epidemiological studies suggest that some of these comorbidities may increase the risk of PD and precede the onset of motor symptoms. Further, drugs to treat diabetes and cancer have elicited neuroprotective effects in PD models. Nonetheless, the mechanisms underlying the occurrence of these comorbidities remain elusive. Herein, we discuss the biological and clinical implications of comorbidities in the pathogenesis, progression, and clinical management, with an emphasis on personalized medicine applications for PD.

Keywords: Parkinson’s disease; anemia; cancer; comorbidities; depression; diabetes; personalized medicine.

Figure 1

Non-motor conditions and comorbidities associated with Parkinson’s disease (PD). Non-motor conditions and comorbidities have a detrimental impact in the quality of life and clinical status of PD patients. Some of these conditions may precede the onset of PD. Drugs to treat type 2 diabetes, depression, anemia and cancer are currently being tested in clinical trials for PD (orange ovals).

Figure 2

Integrating PD comorbidities in personalized medicine. Understanding disease comorbidities in PD is expected to advance individualized treatment for PD patients. For example, PD patients with comorbid diabetes may respond better to antidiabetic drugs currently under investigation in clinical trials for PD (GLP-1 mimetics and thiazolidinediones). Similarly, disease-modifying effects may be observed in PD patients with other comorbidites recruited for clinical trials testing other potential drugs including monoamine oxidase inhibitors (MAOI), monoamine oxidase type B inhibitors (MAOB, Rasagline), erythropoietin and c-Abl inhibitors (Nilotinib). In the context of biomarkers, some biomarkers may be more useful to diagnose PD patients with comorbid depression, diabetes, cancer or anemia, than other patients with different clinical subtypes of PD. Network-based approaches can be exploited to investigate the molecular mechanisms linking PD with comorbidities and to identify biologically relevant biomarkers and potential therapeutic targets.