neurodegenerative disease
Conditions
Interventions
None listed
Sponsors
Universitair Medisch Centrum Groningen
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Alzheimer's disease (n=10) Patients who meet the criteria for Alzheimer*s disease and are mentally competent to give informed consent: I. Documented cognitive decline II. Progressive course of cognitive decline III.Complaints in the following areas a. memory b. language c. visuospatial functions d. executive functions IV. Absence of cerebrovascular disease or signs of other neurodegenerative disease except for Alzheimer*s disease. and show biomarkers positive for AD: I. amyloid-depositions in the brain showed by low Aβ42 in CSF and/or positive amyloid imaging at a PIB-PET II. Neuronal damages showed by increased tau/ptau in CSF or; decreased FDG uptake at the parietotemporal lobe or; disproportional atrophy of the medial, basal and lateral temporallobes, generalised atrophy and/or biparietal atrophy. 2. Mild Cognitive Impairment (n=10) Patient is not meeting the criteria for Alzheimers disease, but shows: - Decline in one or more cognitive domains (showed by a neuropsychological examination) - No interference of symptoms with daily life The diagnosis Alzheimer*s disease is made by a multidisciplinary team consisting of psychiatrists, neurologists, psychologists and internists. - Absence of cerebrovascular disease or signs of other neurodegenerative disease except for MCI The diagnosis MCI is made by a multidisciplinary team consisting of neurologists, psychologists and internists 3. Parkinson's disease Symptoms of bradykinesia and one of the following symptoms (25): - rigidity - rest tremor - instability (not related to visual, cerebellar or proprioceptive disorders) - no other explanation for abovementioned symptoms at MRI - The diagnosis Parkinson*s disease is made by a neurologist - Absence of cerebrovascular disease or signs of other neurodegenerative disease except for Parkinson*s disease The diagnosis Parkinson*s disease is made by a neurologist.
Exclusion criteria
Exclusion criteria: A potential subject who meets any of the following criteria will be excluded from participation in this study: - History of neuropsychiatric disorders such as epilepsy, major depression, or schizophrenia - Claustrophobia Use of medication with known P-gp influence, according to the Farmacotherapeutisch Kompas: - Digoxine - Dabigatran - Everolimus - Verapamil - Tacrolimus - Rosuvastatin - Lercanidipin - Repaglinide - Aliskiren - Aminoglycosides - Vancomycine - NSAIDs - Acyclovir - Trimethoprim - Amfotericine B - Ciprofloxacine - H2 receptor antagonists - Methotrexate - St. John*s Wort - Loperamide - Rifampicine - Carbamazepine - Fenobarbital - Fenytoine - Hypericum - Primidon The list contains pharmaceuticals with P-gp influence mentioned in the FK, for other pharmaceuticals, the influence on P-gp will be checked using kennisbank KNMP or Pubmed) Exclusion Criteria contrast-enhanced MRI: - Metallic objects or fragments placed in the body - Artificial metal joints or implants - Pacemaker - Clips/Stents in blood vessel - Claustrophobia - a history of mastocytosis - Pregnancy or breastfeeding - Kidney failure (20cm)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Tracer kinetics of [18F]MC225 reflect the BBB P-gp function and will be assessed as outcome measure for P-gp efflux function in different brain regions of interest (ROIs). Those will be compared in between groups of Alzheimer, Parkinson, MCI and healthy volunteers | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. [15O]H2O-PET influx curves will be added as variable in the kinetic analysis using PMOD, to assess possible influence of cerebral blood flow. The CBF measures obtained with [15O]H2O-PET will be compared with VT measures of the [18F]MC225 PET scan to see if uptake of [18F]MC225 is influenced by cerebral perfusion rate. 2. Since [15O]H2O-PET is the gold standard for quantitative imaging of cerebral perfusion, the results of [15O]H2O-PET will also be compared with the perfusion part of the MRI VAI sequence. In this way the perfusion MRI can be validated as less invasive method to measure cerebral perfusion and be used in future projects. 3. To compare venous blood samples with arterial bloodsamples, and to validate wheter pharmokinetic modeling with arterial samples could be replaced with less invasive venous samples. | — |
Countries
Netherlands
Outcome results
None listed