A randomized, double blind, placebo-controlled crossover study to investigate the effects of cholinergic and serotonergic challenges with galantamine and citalopram on resting state FMRI in aging and dementia.

Completed

Conditions: neurodegeneratieve aandoeningen
cognitive deterioration
Dementia

Registration Number: NL-OMON37710

Lead Sponsor: Centre for Human Drug Research

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 60

Inclusion Criteria

Part A: Healthy subjects;• Have a body-mass index (BMI) between 18 and 34 kg/m2.
• All subjects participating in this study are absent on cognitive deficits with a Mini Mental State Examination (MMSE) score between 28 and 30.
• Each subject is familiar with the procedures of the study, and agrees to participate in the study program by giving oral and written informed consent.
• Healthy young subjects: age 18-30.
• Healthy elderly subjects: age 55-75.;Part B-D: Dementia patients
• A body-mass index (BMI) between 18 and 34 kg/m2.
• All patients participating in this study only have mild cognitive deficits with a Mini Mental State Examination (MMSE) score between 21 and 27.
• Patients will be assessed by the treating neurologist as mentally capable of understanding the implications of study participation.
• Each patient is familiar with the procedures of the study, and agrees to participate in the study program by giving oral and written informed consent. ;Part B: patients with Alzheimer's disease
• The clinical diagnosis AD will be established according to the revised NINCDS-ADRDA criteria for diagnosing probable AD.
• Age 55-75.;Part C: patients with frontotemporal lobe dementia
• The clinical diagnosis possible FTLD will be established according the revised International Consensus Criteria for frontotemporal lobar degeneration, and supported by neuropsychological deficits and frontal and/or temporal atrophy (MRI) or hypoperfusion (ASL, SPECT). All patients will undergo extensive history taking and neurological examination in order to exclude other causes of frontal dysfunction.
• Age 50-70.;Part D: patients with dementia with Lewy bodies
• The diagnosis DLB will be made according to clinical criteria for probable DLB.
• Age 55-75.

Exclusion Criteria

• Contra-indication to MRI scanning (pacemaker and defibrillator, intraorbital or intraocular metallic fragments, cochlear implants, one or more metal eartubes, intracranial clips, a non-removable insulin pump, a non-removable neurostimulator, a mechanical cardiac valve, an hydrocephalus pump, ferromagnetic implants, intra-uterine device, permanent make-up, tattoos above the shoulders, pregnancy, operation in 6 weeks preceding the MRI, claustrophobia, inability to lie still for a period of 20 minutes in the MRI scanner, Fear or problems during the RS-FMRI scan).
• Clinically relevant abnormal history of physical and mental health as determined by medical history taking and physical examinations obtained during the screening visit (as judged by the investigator).
• Other causes that can explain cognitive symptoms.
• Clinically relevant abnormal laboratory results, ECG and vital signs, or physical findings at screening (as judged by the investigator).
• Positive test for hepatitis B, C or HIV.
• Subjects using, on average, more than 4 units of alcohol per day, and unable to refrain from alcohol use during the study days.
• Subjects smoking, on average, more than 5 cigarettes per day, and unable to refrain from smoking during the study days.
• Subject is a habitual and heavy consumer of caffeinated beverages (more than 6 cups of coffee or equivalent/day) at the time of the study and/or is not able to refrain from use of (methyl) xanthines (e.g. coffee, tea, cola, chocolate) during study days.
• Positive drug or alcohol test at screening and/or study days.
• History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism or excretion of the study drug.
• Participation in an investigational drug trial in the 3 months prior to administration of the initial dose of study drug or more than 4 times per year.
• Donation or loss of blood (> 500 mL) within 3 months prior to screening.
• Inadequate venous accessibility as judged by the physician or nurse.
• Use of benzodiazepine within 48 hours before a study day.
• Use of monoamine oxidase inhibitors (MAOIs) from 14 days prior to the first study day until 7 days after the last study day (incl. linezolid).
• Severe asthma or obstructive pulmonary disease or active pulmonary infections (e.g. pneumonia).
• Pregnancy or breast feeding.
• Any other condition that in the opinion of the investigator would complicate or compromise the study, or the well being of the subject.
• Use of medication in the 2 weeks prior to the first study day that is, in the opinion of the investigator, interfering with the study or the study medication.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Resting state network activity as measured with RS-FMRI.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>1) Cognitive functioning as measured with different subtests of the Neurocart<br /><br>(a validated multimodal CNS-test battery):<br /><br>• Visual Analogue Scale (VAS) Bond & Lader (mood, alertness and calmness)<br /><br>• VAS for nausea<br /><br>• Adaptive tracking<br /><br>• Simple reaction time<br /><br>• Visual N-back test<br /><br>• Stroop test<br /><br>• Symbol-digit substitution test<br /><br>• Visual Verbal Learning Test (VVLT; 15 words)<br /><br><br /><br>2) Pharmacokinetics of galantamine and citalopram:<br /><br>• The time-course of the serum levels of galantamine and citalopram </p><br>