Blood-brain Barrier Permeability in Alzheimer's Disease

Three groups of participants will be included: 20 patients diagnosed with dementia of the Alzheimer's type; 20 patients with prodromal Alzheimer's disease, which represents a preclinical stage of AD in which patients already have memory impairment and at least one AD biomarker (i.e. hippocampal atrophy or abnormal amyloid and tau protein content in the cerebrospinal fluid); and 20 healthy controls. Patients will be recruited from the memory clinics of the Maastricht University Medical Center and the Leiden University Medical Center.

Inclusion Criteria:

Patients with AD:

• Informed consent before participation in the study
• Received standard diagnostic procedure according to the Parelsnoer Initiative procedure
• Diagnosed with dementia of the Alzheimer's type
• Clinical dementia rating (CDR) of 1, which means a mild to moderate stage of dementia
• MMSE ≥ 20 and patients are mentally competent (in general, individuals with an MMSE ≥ 18 are considered mentally competent)

Patients with prodromal AD:

• Informed consent before participation in the study
• Received standard diagnostic procedure according to the Parelsnoer Initiative procedure
• Diagnosis of prodromal dementia according to the Dubois criteria (16)
• CDR of 0.5, which suggests a very mild stage of dementia
• Memory impairment defined as Delayed Recall on Verbal Learning Test (15 WLT) < 1.5 SD
• MMSE ≥ 20 and patients are mentally competent.
• Medial temporal lobe atrophy scale MTA ≥ 1 (17) OR abnormal levels of Aß42, t-tau or p-tau

Healthy participants:

• Informed consent before participation in the study
• No Diagnosis of dementia, prodromal dementia, or mild cognitive impairment.
• MMSE ≥ 26
• No substantial memory complaints (according to participant ánd partner/relative)
• Age, gender and education is matched to the patient groups.

Exclusion Criteria:

• Contraindications for scanning (e.g. brain surgery, cardiac pacemaker, metal implants, claustrophobia, large body tattoos)
• Contraindications for contrast agent Gadovist (renal failure) as determined by the estimated Glomular Filtration Rate eGFR < 30 mL/min.
• Major vascular disorders (e.g. stroke, heart disease)
• Psychiatric or neurological disorders: Major depression (< 12 months); history of schizophrenia; bipolar disorder; psychotic disorder NOS or treatment for a psychotic disorder (< 12 mnd); cognitive impairment due to alcohol abuse; epilepsy; Parkinson's disease; MS; brain surgery; brain trauma; electroshock therapy; kidney dialysis; Meniere's disease; and brain infections.
• Structural abnormalities of the brain
• Cognitive impairment due to alcohol/drug abuse
• Absence of reliable informant (for patient groups)