Parkinson’s disease (PD) is the second most common neurodegenerative disease
worldwide and afflicts approximately 1% of individuals over age 65. The dementia that
develops in association with PD is devastating to both the patient and their family and
common, with more than 80% of individuals with PD developing dementia by 15 years
after symptom onset. Current treatments for both PD and PD-dementia (PDD) have
unacceptable side effects and there are no disease modifying therapies. An improved
understanding of the pathophysiology of PD and PDD, however, is leading to testing of
therapeutics that are targeted to specific pathways that have been implicated in PD
pathophysiology. This pathophysiology is reviewed in Chapter 1, with an emphasis in the
c-Abl molecule pathways role in PD pathophysiology. A biomarker for both PD and PDD
would greatly improve our diagnosis, prognosis, and potentially the efficacy of these new
treatment trials. Chapter 2 therefore considers whether poly (ADP-ribose), a molecule
downstream in the c-Abl pathway, is a potential biomarker for PDD. Finally, we need to
improve the outcomes for our current patients and Chapter 3 explores the role of a
modifiable risk factor, namely vascular disease and subsequent vascular pathology, in the
development of PDD. Together, these investigations broaden our understanding of PDD
and are a step toward improved treatment for individuals with this devastating disease
