Dopaminergic Mechanism of Memory Impairment in Parkinson's Disease

Dopaminergic Mechanism of Temporal Working Memory Impairment in Parkinson's Disease

The cognitive impairment of Parkinson's disease is non amnestic, which is characterized by working memory impairment and executive dysfunction. The current drug therapy (such as levodopa, dopamine receptor agonists) and surgical treatment (such as deep brain electrical stimulation, thalamic lesion) not only can not effectively alleviate cognitive impairment, but also may aggravate cognitive and speech behavior abnormalities. This project will explore how dopamine regulates temporal working memory in human research by combining drug intervention, neuroimaging and cognitive tasks.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease; Memory Impairment
• Intervention / Treatment: Drug: Madopar monotherapy; Drug: senfrol monotherapy; Drug: placebo monotherapy

Detailed Description

Parkinson's disease (PD) is a common neurodegenerative disease in the elderly. The incidence rate of China's disease is 1.7% in the population over 65 years old. The latest research shows that Parkinson's disease is not a simple motor disorder, but a multi organ dysfunction disorder with both motor symptoms and non motor symptoms. With the development of the disease, more than 80% of the PD patients will develop dementia. Different from the amnestic cognitive impairment of Alzheimer's disease, the cognitive impairment of Parkinson's disease is non amnestic, characterized by working memory impairment and executive dysfunction. The current mainstream drug therapy (such as levodopa, dopamine receptor agonists) and surgical treatment (such as deep brain electrical stimulation, thalamic lesion) can not effectively alleviate cognitive impairment, and may even aggravate cognitive and speech behavior abnormalities, We should first understand the neurochemical (molecular) mechanisms of working memory impairment and executive dysfunction in Parkinson's disease. A prospective single blind randomized controlled design was used. Newly diagnosed PD patients were randomly assigned to three treatment groups: Madopar monotherapy group (n = 50), senfrol monotherapy group (n = 50) and placebo group (n = 50). Objective to study the performance of temporal working memory in PD patients and reveal the dopaminergic mechanism of temporal working memory.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking University Third Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Inclusion criteria for PD patients: age 50-80 years old; Junior high school or above, able to read and sign informed consent; Primary PD has just been diagnosed, Hoehn Yahr grade 1-2.5, and has not received any drug or non drug treatment.

The inclusion criteria of healthy control group: age 50-80 years old; Junior high school or above, able to read and sign informed consent.

Exclusion Criteria:

• The exclusion criteria of PD patients group were confirmed as secondary PD; Mental retardation, dementia or depression; Other neuropsychiatric diseases (such as epilepsy, schizophrenia), cerebrovascular diseases (such as stroke) or brain trauma; Antidepressants were used; History of alcohol dependence or drug abuse; Head MRI examination (such as claustrophobia, implantable medical device) is not allowed.

Exclusion criteria of healthy control group: Parkinson's disease symptoms (such as static tremor, bradykinesia, limb stiffness); Mental retardation, dementia or depression; REM sleep behavior disorder; There were symptoms of hypoosmia; Other neuropsychiatric diseases, cerebrovascular diseases or brain trauma; Antidepressants were used; History of alcohol dependence or drug abuse; No head MRI.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Madopar monotherapy group; Patients in this group received Madopar monotherapy	Drug: Madopar monotherapy; In addition to basic treatment, the patient also received Madopar treatment
Active Comparator: senfrol monotherapy group; Patients in this group were treated with senfrol (D2 receptor agonist) alone	Drug: senfrol monotherapy; In addition to the basic treatment, the patient also received the rofosson treatment
Placebo Comparator: placebo group; Patients in this group were treated with selegiline alone	Drug: placebo monotherapy; In addition to basic treatment, the patient also received selegiline treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of cognition function	The score of MontrealCognitiveAssessment(MoCA),ranging from 0-30,with higher socre means better outcome	12 months after the trail

Secondary Outcome Measures

Outcome Measure	Time Frame
Task state fMRI scanning	Before drug treatment
Task state fMRI scanning	4 weeks after receiving drug treatment

Collaborators and Investigators

• Sponsor: Peking University Third Hospital
• Collaborators: Chinese Academy of Sciences

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: June 27, 2021
• First Submitted That Met QC Criteria: July 8, 2021
• First Posted (Actual): July 20, 2021

Study Record Updates

• Last Update Posted (Actual): July 20, 2021
• Last Update Submitted That Met QC Criteria: July 8, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Memory Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Dopamine Agents; Benserazide, levodopa drug combination
• Other Study ID Numbers: M2017368

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No