Treatment for cognitive and neuropsychiatric non-motor symptoms in Parkinson’s disease: current evidence and future perspectives

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.

KEYWORDS:

• Assessment
• non-motor symptoms
• non-pharmacological treatment
• parkinson’s disease
• pathophysiology
• pharmacological treatment

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

Additional information

Funding

This paper was not funded.