Chapter 12 - Nucleus basalis of Meynert degeneration predicts cognitive impairment in Parkinson's disease

Abstract

Cognitive impairment affects approximately 20%-50% of patients with Parkinson's disease (PD), with a higher prevalence as the disease advances. The nucleus basalis of Meynert (NBM) provides the majority of cholinergic innervations to the cerebral cortex. Dysfunction of the cholinergic system and degeneration of the NBM have been implicated in the pathophysiology of cognitive impairment in neurodegenerative disorders including PD. Several studies have aimed to identify risk factors associated with cognitive decline in order to construct models to predict future cognitive impairment in PD. Given the link between cholinergic dysfunction and the pathogenesis of cognitive decline in PD, a number of studies have focused on the role of the NBM underlying cognitive performance. Recently, microstructural alterations within the NBM, detected using diffusion tensor imaging, have been identified as a strong predictor for the development of cognitive impairment in patients with PD. These microstructural changes in NBM have been shown to precede structural gray matter volumetric loss and may present with an early marker to predict cognitive decline in patients with PD. Longitudinal studies are warranted to provide insights into the potential utility of cholinergic positron emission tomography imaging to predict the development of cognitive impairment in PD and other neurodegenerative disorders. Provided the urgent need for disease modifying therapies aiming to slow and ultimately halt the progression of cognitive impairment, neuromodulation of NBM, and treatments targeting the cholinergic system may hold a promising potential. In this review, we discuss the link between NBM pathology and clinical symptomatology of cognitive impairment in PD with a focus on the use of in vivo imaging techniques and potential therapeutic interventions.