Chapter 23: The Neuropsychiatry of Parkinson’s Disease and Dementia with Lewy Bodies

INTRODUCTION

The focus of the first section of this chapter is the epidemiology and pathophysiology of non-motor features of Parkinson’s disease (PD), as well as the clinical presentation and approaches to diagnosis and treatment of PD. The second section emphasizes parallel features of dementia with Lewy bodies (DLB).

Parkinson’s disease (also called Parkinson’s disease) is a progressive, neurodegenerative disorder attributable to dopaminergic neuronal deterioration and loss in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) of the midbrain. Although James Parkinson, a physician working in London in 1817, described “the absence of any injury to the senses and to the intellect,” in An Essay on the Shaking Palsy, the core clinical attributes of PD are now widely acknowledged to include both motor and non-motor signs and symptoms.¹ Motor clinical features—asymmetric resting tremor, rigidity, akinesia or bradykinesia, and later, postural instability—result largely from disruption of nigrostriatal pathways, which extend from the midbrain’s pigmented SNc to the dorsal “motor” striatum (caudate and putamen; see Figure 23-1). The term striatum refers to the striped appearance of gray and white matter. These motor features manifest due to decreased dopaminergic input to the basal ganglia and resultant thalamic inhibition and reduced excitatory input to the motor cortex. The role of direct and indirect striatal output circuitry on promoting and inhibiting movement, respectively, are outside the scope of this chapter; for details, please see a review by Calabresi and colleagues.²

The non-motor features of PD include mood dysregulation, anxiety, psychosis, sleep disturbances, personality changes, and cognitive impairment, among others. Other non-motor manifestations of PD, including olfactory, autonomic, and gastrointestinal dysfunction, are not reviewed here. Cognitive impairment and neuropsychiatric manifestations result, at least partially, from the respective disruption of the dopaminergic mesocortical and mesolimbic pathways—this disruption is mediated by deterioration of dopaminergic neurons in the VTA. Although SNc neurons are the most susceptible dopaminergic neurons to degeneration in PD (with average degeneration in PD of approximately 80% of SNc neurons), about 50% of dopaminergic neurons within the VTA deteriorate as well.³ Mesocortical pathways, implicated in cognitive impairment in PD, extend from the VTA to the prefrontal cortex. Emotional dysregulation in PD occurs due to disruption of mesolimbic “reward” pathways, which project from the VTA to the ventral striatum (primarily to the nucleus accumbens, or NAc) in the basal forebrain anterior to the hypothalamus (Figure 23-2).