Neuropsychiatric symptoms in Parkinson's disease dementia
Eugenia Mamikonyan and Daniel Weintraub
Dementia affects approximately 30% of Parkinson’s disease (PD) patients at any given time , with a long-term cumulative prevalence rate close to 80% . In addition to clinically significant cognitive impairment that defines the disorder, dementia in PD (PD-D) is often accompanied by a range of neuropsychiatric symptoms (NPS), including psychosis, affective symptoms (e.g. depression and anxiety), apathy, and behavioural disturbances (e.g. aggression and agitation). This chapter provides an overview of the epidemiology and presentation, clinical impact, correlates and risk factors, neuropathophysiology, assessment, and clinical management of NPS in PD-D (see Table 5.1 for an overview).
Prevalence of neuropsychiatric symptoms
The Neuropsychiatric Inventory (NPI)  is the most commonly used instrument to assess the range of NPS that can occur in neurodegenerative diseases. In a placebo-controlled clinical trial of rivastigmine for the treatment of PD-D, 537 patients were assessed with the NPI at baseline and serially during the course of the study . Almost all (about 90%) experienced at least one NPS, and 77% had two or more. In that study five distinct NPI clusters were identified: one group with few and mild symptoms (52%); a mood cluster (11%; high depression, anxiety, and apathy scores); an apathy cluster (24%; high apathy score but low scores on other items); an agitation cluster (5%; high score on agitation and high total NPI score); and a psychosis cluster (8%; high scores on delusions and hallucinations). This study sample, however, may not be fully representative as PD-D patients with severe dementia were excluded.
Five NPI clusters were identified in a community-based study that used the NPI to identify NPS in 100 PD patients with (43%) and without dementia (57%) . The clusters with the highest representation of PD-D patients were a group characterized primarily by hallucinations (79% PD-D) and a group with high scores on several NPI items (57% PD-D).
In a study that used factor analysis to determine patterns of NPI symptoms in PD patients with (36%) and without dementia (64%), the most common NPS in the sample overall (patients with and without dementia were not described separately) were depression (38%) and hallucinations (27%), and the least common were euphoria and disinhibition . Factor analysis showed that hallucinations, delusions, and irritability clustered into one factor and apathy and anxiety constituted another factor.
A study utilizing the 12-item NPI to compare NPS in PD patients with normal cognition (NC), mild cognitive impairment (MCI), and PD-D found that apathy was reported in 50% of PD patients with MCI and PD-D. The presence of apathy was found to be the differentiating factor between PD patients with NC and MCI. Additionally, hallucinations and delusions (psychosis) were much more common in the PD-D group, with 48% of patients reporting symptoms; only 12.9% of PD patients with NC and 16.7% with MCI reported similar symptoms. Notably, evaluating the prevalence of psychosis in PD patients with MCI may prove beneficial in monitoring the conversion from PD-MCI to PD-D .
Comparison with other disease states
Several studies have also used the NPI to compare the frequency and patterns of NPS in PD-D with those in other neurodegenerative diseases. In one study, NPS overall were very common in both PD-D and Alzheimer’s disease (AD), with hallucinations being more severe in PD-D and aberrant motor behaviour, agitation, disinhibition, irritability, euphoria, and apathy more common in AD . In a comparative study of PD patients unselected with regard to their cognitive status and patients with progressive supranuclear palsy (PSP), PD patients had a higher frequency of hallucinations, delusions, and depression, but less apathy and disinhibition than PSP patients .
PD-D and dementia with Lewy bodies (DLB) overlap to a great extent in terms of neuropathophysiology and clinical presentation. Regarding NPS, a comparative study of PD-D and DLB found that delusions and hallucinations were more common in DLB, with little difference between the groups otherwise . Another study found that cognitive fluctuations, visual and auditory hallucinations, depression, and sleep disturbances were equally common in both PD-D and DLB, and all these symptoms were more common in PD-D and DLB than in an AD comparison group .