Evaluation of [18F]MC225 to measure P-glycoprotein function in neurodegenerative disease

Other illness

• 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 (< 45 ml/min) - Allergy to MR contrast or dye - Tattoo (>20cm)

• Alzheimer’s disease patients: Patients who meet the criteria for Alzheimer’s disease and are mentally competent to give informed consent: 1. Documented cognitive decline 2. Progressive course of cognitive decline 3. Complaints in at least one of the following areas:  a. Memory  b. Language  c. Visuospatial functions  d. Executive functions 4. Absence of cerebrovascular disease or signs of other neurodegenerative disease except for Alzheimer’s disease In addition, patients must show biomarkers positive for AD: • Amyloid deposition in the brain demonstrated by:   • Low Aβ42 in CSF and/or • Positive amyloid imaging on PIB-PET • Evidence of neuronal damage shown by one or more of the following:   • Increased tau or phosphorylated tau in CSF • Decreased FDG uptake in the parietotemporal lobe • Disproportionate atrophy of the medial, basal, and lateral temporal lobes, generalized atrophy and/or biparietal atrophy The diagnosis of Alzheimer’s disease must be confirmed by a multidisciplinary team including neurologists, psychologists, and internists. sCAA patients: Patients must meet the criteria for probable CAA as defined by the Boston Criteria 2.0, and must be mentally competent to provide informed consent and have had no symptomatic brain hemorrhage in the past 90 days. Inclusion criteria: 1. Pathological confirmation not required 2. Age ≥50 years 3. Clinical presentation with at least one of the following:   • Spontaneous intracerebral hemorrhage   • Transient focal neurological episodes   • Cognitive impairment or dementia MRI criteria Must demonstrate either: • Option A: At least two strictly lobar hemorrhagic lesions on T2*-weighted MRI in any combination:  • Intracerebral hemorrhage  • Cerebral microbleeds  • Cortical superficial siderosis (multiple distinct foci)  • Convexity subarachnoid hemorrhage (multiple distinct foci)  OR • Option B: One lobar hemorrhagic lesion plus one white matter feature:  • Severe perivascular spaces in the centrum semiovale (>20 visible in one hemisphere)  • Multispot pattern of white matter hyperintensities (>10 subcortical FLAIR dots bilaterally) In the absence of: • Deep hemorrhagic lesions on T2*-weighted MRI • Any other cause of hemorrhagic lesions • Cerebellar hemorrhages (not counted as lobar or deep) Parkinson’s disease patients: Patients must be diagnosed with PD by a neurologist and meet the following criteria: • Presence of bradykinesia and at least one of the following:  • Rigidity  • Rest tremor  • Postural instability (not related to visual, cerebellar, or proprioceptive causes) • No other explanation for the symptoms on MRI • Absence of cerebrovascular disease or signs of other neurodegenerative diseases except for Parkinson’s disease