Ritalin, Memory and Attention in MCI: a Behaviour-EEG Study

Can Methylphenidate (Ritalin) Improve Memory and Attention in Mild Cognitive Impairment? A Combined Behaviour-EEG Study

Traditionally, memory impairments in the elderly population are treated using cholinesterase inhibitors, although impairments remain after treatment. Dopamine (DA) is also involved in cognition and is especially of interest in healthy ageing because of the role in processing speed and cognitive control. To what extent dopamine treatment improves memory and attention in older impaired individuals is unknown. However, such an effect is conceivable because of the close relationship between memory and attention in aging and since improved processing speed and cognitive control may lead to improved memory.

The investigators aim to examine, in the impaired older population, whether a treatment using methylphenidate, a DA re-uptake inhibitor that enhances DA, improves attention and memory. The study will be conducted according to a cross-sectional, double-blind, placebo-controlled, 2-way cross-over design. 20 male and female patients with Mild Cognitive Impairment (MCI), amnestic type, aged above 60 years of age; 20 male and female patients with MCI, non-amnestic type, will be recruited from the Orbis Medical Centre. Participants will be treated once with 20 mg methylphenidate (MPH) and once with placebo. All medications will be administered orally with a capsule. The treatment order will be established by counterbalancing.

Study Overview

• Status: Unknown
• Conditions: Mild Cognitive Impairment
• Intervention / Treatment: Drug: Methylphenidate

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Anke Sambeth, Dr.; Phone Number: 0031 43 3881757; Email: anke.sambeth@maastrichtuniversity.nl
• Study Contact Backup: Name: Walther Sipers, M.D.; Phone Number: 0031 88 4597783; Email: w.sipers@orbisconcern.nl

Study Locations

• Netherlands
  • Limburg
    • Sittard-Geleen, Limburg, Netherlands, 6162BG
      • Recruiting
      • Orbis Medical Centre
      • Contact: Walther Sipers, M.D.; Phone Number: 0031 884597783; Email: w.sipers@orbisconcern.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The participant has been diagnosed with Mild Cognitive Impairment, either of the amnestic or the non-amnestic type.
• In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
• The participant signs and dates a written informed consent form.
• The volunteer is male or female.
• The participant is aged 60 to 80 years, inclusive, at the time of informed consent.
• The participant has a body mass index of 18.5-30, inclusive, at medical screening.
• The volunteer is healthy, i.e. absence of all exclusion criteria and has normal static binocular acuity (corrected or uncorrected) as well as normal hearing (using a whisper test during medical screening).

Exclusion Criteria:

• The subject has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, or endocrine disease or other abnormality which may impact the ability of the subject to participate or potentially confound the study results.
• The volunteer has uncontrolled existing major psychiatric symptoms.
• The subject has uncontrolled hypertension.
• The volunteer has hyperthyroidism.
• The participant has known hypersensitivity to any component of the formulation of MPH or related compounds.
• The participant has glaucoma.
• The subject has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to the first visit or is unwilling to agree to abstrain from alcohol from 24 hours prior to each test day and/or drugs throughout the study.
• The participant has any sensory or motor deficits which could reasonably be expected to affect test performance.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ritalin; Methylphenidate, capsule, 20 mg, single oral administration	Drug: Methylphenidate; single oral administration of 20 mg tablet; Other Names: Ritalin
Placebo Comparator: Placebo; Placebo, capsule, single oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Verbal Learning Test Immediate Recall		140 min after drug intake
Verbal Learning Test Delayed Recall		175 min after drug intake
Verbal Learning Test Recognition	Accuracy and reaction time	180 min after drug intake
Amplitude of the N400 and P600 event-related potential (ERP) components	during encoding and recognition of words of VLT, measured with EEG	140-190 min after drug intake

Secondary Outcome Measures

Outcome Measure	Time Frame
Performance on visual and auditory N-back test	150 minutes after drug intake
Performance on a sustained attention to response task (SART)	165 minutes after drug intake
Performance on a motor task	170 minutes after drug intake
Amplitude of ERP components during the visual and auditory N-back test	150-165 minutes after drug intake
Amplitude of ERP components during SART	165 - 170 minutes after drug intake

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: Orbis Medical Centre
• Investigators: Principal Investigator: Anke Sambeth, Dr., Maastricht University

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: December 22, 2014
• First Submitted That Met QC Criteria: December 24, 2014
• First Posted (Estimate): December 25, 2014

Study Record Updates

• Last Update Posted (Estimate): December 25, 2014
• Last Update Submitted That Met QC Criteria: December 24, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: MCI; Attention; Memory; Ritalin
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Methylphenidate
• Other Study ID Numbers: 14T111; 2014-003117-28 (EudraCT Number)