Memory, Ageing, and the Cholinergic System a combined fMRI and PET study

Recruitment & Eligibility

Status: Complete

Sex: All

Target Recruitment: 42

Inclusion Criteria

group 1:
•healthy older subjects (age 50-80 years)

group 2:
•patients with mild cognitive impairment (< 2 SD in Verbal learning and memory test, 50-80 years)

both groups:
•informed consent
•normal neurological examination
•normal physical examination of the body including auscultation of the lungs and heart as well as abdominal palpation
•normal ECG
•Systolic blood pressure 100-160 mmHg
•Diastolic blood pressure 50-100 mmHg
•heart frequency 50-100

Exclusion Criteria

instable cardiovascular diseases, neurologic or psychiatric diseases (except for mild cognitive impairment in the MCI group), insable diseases of the lungs, instable gastrointestinal diseases, instable diseases of the kidneys and the urinary tract, thyreotoxicosis, cancer, pregnancy, breast feeding, persons standing in dependency on the sponsor or investigator, placement into an institution due to governmental or judicial order, participation in other interventional studies potentially interfering with the currrent study, existing therapy with acetylcholinesterase inhibitors, missing secure measure to prevent pregnancy

additionally for experiments with Rivastigmin:
–hypersensitivity to rivastigmin or other carbamate derivetives
–Asthma bronchiale
–liver insufficiency
–renal insufficiency
–gangrene
–coronary heart disease
–cardiac rhythm disturbances like bradycardia, tachycardia, Sick Sinus Syndrome
–gastric or duodenal ulces
–mechanic constipation or mechanic urinary retention
–intestinal obstruction
–concomitant application of cholinesterase inhibitor
–application of anticholinergic agents
–Hypotension

for the fMRI experiments
–pacemaker or other implanted stimulation devices
–Infusion device / medication pump
–metal parts in or at the body
– tattoos
–claustrophobia
–grinding of metallic objects up to 1 week before fMRI measures

healthy subjects:
–prior application of radioactive substances or ionising radiation during nuclear medicine investigations, hypersensitivity to MP4A.

Patients with mild cognitive impairment:
–participation in other nuclear medicine investigations if exceeding limits named in § 88 Abs. 2 Strahlenschutzverordnung
–prior application of radioactive substances or ionising radiation during nuclear medicine investigations in a radiation therapy
–hypersensitivity to MP4A.

Study & Design

Study Type: interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Experiment 1:<br>- group difference in the effect of AChE-activity on brain activity underlying episodic memory and attention<br>= Interaction effect of group on regional correlation of the equilibrium constant k3, measured using positron emission tomography (PET) with the blood oxygen level dependent (BOLD) signal, measured using functional magnetic resonance imaging (fMRI)<br><br><br><br>Experiment 2: <br>- group difference in the effect of cholinergic stimulation on brain activity (BOLD signal) underlying episodic memory and attention<br><br>- dependence of the effect of cholinergic stimulation on regional AChE-activity<br><br>= correlation of the difference Verum-Placebo in the BOLD-signal (fMRI) with k3 (PET)

Secondary Outcome Measures

Name	Time	Method
Experiment 1:<br>– group difference in acetylcholine esterase (AChE)-activity (k3, see above)<br>– group difference in brain activity (BOLD signal) underlying episodic memory and attention<br>– group difference in the effect of regional AChE-activity on behavioural memory and attention measures = interaction effect of group on correlation between k3 and behavioural test measures in memory and attention tests<br>– adverse events (AEs) and group differences in AEs<br><br>Experiment 2: <br>–group difference in the effect of cholinergic stimulation on behavioural memory and attention measures = group difference in the difference between VErum and Placebo in behavioural test measures in memory and attention tests<br>– adverse events (AEs) and group differences in AEs

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