To summarize advances over the past 25 years and the current state of affairs, numerous overarching themes emerge: (1) longitudinal studies have demonstrated that the cumulative prevalence of most psychiatric and cognitive complications is much higher than previously thought, with many disorders having a cumulative frequency well over 50%; (2) ample research has documented that nonmotor complications of PD are associated to varying degrees with excess disability, worse QoL, poorer outcomes, and caregiver burden, which highlight their clinical significance as an independent area of clinical focus and research; (3) there have been significant advances in the number of validated screening instruments and rating scales, as well as consensus diagnostic criteria for many psychiatric and cognitive disorders, which has led to improved clinical management and higher-quality research; (4) although our understanding remains limited, there is mounting evidence that the neural substrate of nonmotor complications in PD is a complex interaction of strategically placed PD and other neuro-degenerative disease pathology, deficits in multiple neurotransmitters, impairments in neural circuitry sub-serving mental functioning, and poorly elucidated genetic influences; (5) core PD treatments, especially DRT and DBS, have a complex and varied effect on psychiatric symptoms and cognitive abilities, in certain instances being an etiological factor and in others offering a treatment option; and (6) despite the advances highlighted above, current treatment options for the range of disorders discussed generally remain limited, and nearly all drugs were developed or first used for similar conditions in non-PD patients.
Additional research is needed to address the incomplete understanding of the epidemiology, phenomenology, risk factors, neuropathophysiology, and optimal management strategies for all the discussed disorders. Despite the advances made in the past 25 years, only 7 of the 107 “citation classics” in PD relate to psychiatric or cognitive complications, with almost all focusing on cognitive deficits.186
High-priority areas for future research include: (1) conducting long-term, longitudinal epidemiological research focused on the predictors, development, course, and impact of cognitive decline and psychiatric disorders; (2) using sophisticated statistical techniques to reconceptualize the classification of psychiatric and cognitive disorders in PD to account for the significant comorbidity, heterogeneity, and variability in symptoms that occur and to generate novel pathophysiological hypotheses; (3) improving recognition and diagnosis through continued development and validation of diagnostic criteria and clinically useful assessment tools that are specific to PD; (4) improving our understanding of the neural substrate of cognitive and psychiatric complications through examination of neuropathology, disease-specific biomarkers, neurotransmitters, brain structure, and neural circuitry; (5) resolving the DLB versus PDD debate, as the overlap between DLB and PDD is extensive, and additional research and expert consensus is needed to determine if separate diagnostic categories for these 2 disorders are viable; and (6) conducting large-scale clinical trials to determine the efficacy of different interventions for different psychiatric and cognitive complications, including the use of disease-modifying agents (when available) to delay or prevent cognitive and psychiatric complications. Ultimately, reducing the impact of PD on patients and families will require improved recognition and the development of better therapies for its nonmotor complications.