Mild Cognitive Impairment in Parkinson’s Disease

Abstract

The concept of Mild Cognitive Impairment is a newly defined entity within the context of Parkinson’s Disease (PD-MCI) with recent development of diagnostic criteria, biomarker research programs and therapeutic strategies. However, it is well-established that MCI represents a heterogeneous entity with different clinical phenotypes, rates of progression, and perhaps underlying pathological processes. As such, while the application of the MCI construct has provided a framework for understanding cognitive decline in PD, additional research is required to validate and/or refine the proposed PD-MCI criteria, as well as to better understand its utilization, association with different PD phenotypes, neurobiological basis, and impact within the context of PD. The studies in this thesis set out to investigate these issues, highlighting the heterogeneity, challenges, and unmet needs regarding the utilization of PD-MCI. In particular, the following issues have been investigated: the exploration of specific MCI phenotypes that might be at higher risk of evolving into PDD; the utility of the proposed Movement Disorder Society (MDS) Task Force Level 1 PD-MCI criteria; the relationships between PD-MCI and clinical phenotypes in PD; and the clinical impact of PD-MCI on caregivers. In addition, a description about treatment options for cognitive impairment in PD will be discussed. Findings from the present thesis showed that additional research is required to validate and refine the proposed MDS Level 1 PD-MCI criteria, as well as to identify MCI phenotypes at risk of developing PDD. Specifically, the present thesis highlighted the importance of exploring the relationship between PD-MCI and heterogeneity in PD, in order for the concept of MCI to be utilized within the context of PD. In parallel, greater emphasis also needs to be placed on identifying specific MCI phenotypes that can be utilized within the prodromal stage of PD, where the neurodegenerative pathology and tissue loss are more likely to be modifiable. In this regard, a close examination regarding specific characteristics of MCI patients with RBD may be particularly relevant. As with treatments for PD-MCI patients, findings from this thesis suggest that it is important to take into account heterogeneity in PD when evaluating PD-MCI so as to better direct their specific management by taking into consideration the constellation of clinical symptoms that are likely to coexist and impact on quality of life. In addition, the need to include management of caregiver distress and associated sequelae should be emphasized alongside the management of PD-MCI patients as caring for PD-MCI patients can be associated with elevated levels of distress. Furthermore, the potential in the possibility of improving cognitive functioning with treatment for comorbid condition (e.g. sleep, depression, and hallucinations) should be explored in future studies.