ABSTRACT
Introduction
Non-motor symptoms (NMS) affect patients with Parkinson’s disease (PD) from the prodromal to the advanced stages. NMS phenotypes greatly vary and have a huge impact on patients’ and caregivers’ quality of life (QoL). The management of cognitive and neuropsychiatric NMS remains an unmet need.
Areas covered
The authors, herein, review the dopaminergic and non-dopaminergic pathogenesis, clinical features, assessment, and pharmacological and non-pharmacological treatments of cognitive and neuropsychiatric NMS in PD. They discuss the current evidence and report the findings of an overview of ongoing trials on pharmacological and selected non-pharmacological strategies.
Expert opinion
The treatment of cognitive and neuropsychiatric NMS in PD is poorly explored, and therapeutic options are unsatisfactory. Pharmacological treatment of cognitive NMS is based on symptomatic active principles used in Alzheimer’s disease. Dopamine agonists, selective serotonin, and serotonin-norepinephrine reuptake inhibitors have some evidence on PD-related depression. Clozapine, quetiapine, and pimavanserin may be considered for psychosis in PD. Evidence on the treatment of other neuropsychiatric NMS is limited or lacking. Addressing pathophysiological and clinical issues, which hamper solid evidence on the treatment of cognitive and neuropsychiatric NMS, may reduce the impact on QoL for PD patients and their caregivers.
Article highlights
Non-motor symptoms (NMS) in Parkinson’s disease (PD) encompass cognitive, neuropsychiatric, sleep, sensory, autonomic, gastrointestinal symptoms, and other manifestations, which are highly prevalent from the prodromal to the advanced stages and have a huge impact on patients’ and caregivers’ quality of life.
The pathophysiology of cognitive and neuropsychiatric NMS in PD may be related to dopaminergic, non-dopaminergic pathogenesis, or a combination of both.
The treatment of cognitive and neuropsychiatric NMS in PD is poorly explored, and pharmacological and non-pharmacological therapeutic options are unsatisfactory; ongoing trials may help address some open questions.
Pharmacological treatment of cognitive NMS is based on symptomatic drugs used in Alzheimer’s disease; dopamine agonists, selective serotonin, and serotonin-norepinephrine reuptake inhibitors have some evidence in PD-related depression; clozapine, quetiapine, and pimavanserin may be considered for psychosis in PD.
Some pathophysiological and clinical knowledge gaps hamper the collection of solid evidence on the treatment of cognitive and neuropsychiatric NMS in PD.
Declaration of Interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership, or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer Disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
List of abbreviations
5-HT 5-hydroxy-tryptamine
AD Alzheimer’s disease
ADL Activities of daily living
BPSD Behavioral and psychological symptoms of dementia
CBT Cognitive behavioral therapy
ChEIs Cholinesterase inhibitors
CR Cognitive rehabilitation
CS Cognitive stimulation
CT Cognitive training
DLPFC Dorsolateral prefrontal cortex
DRT Dopamine replacement therapy
FDA Food and Drug Administration
ICDs Impulse control disorders
M1 Primary motor cortex
MAO-B Monoamine oxidase-B
α Alpha
MCI Mild cognitive impairment
MDS Movement Disorder Society
NIBS Non-invasive brain stimulation
NMDA N-methyl-D-aspartate receptor
NMS Non-motor symptoms
PD Parkinson’s disease
PDD Parkinson’s disease-related dementia
QoL Quality of life
RCTs Randomized clinical trials
rTMS Repetitive transcranial magnetic stimulation
SCD/SCI Subjective cognitive decline/impairment
SNRI Selective serotonin-norepinephrine reuptake inhibitors
SSRI Selective serotonin reuptake inhibitors
TCA Tricyclic antidepressant
tDCS Transcranial direct current stimulation