Blood-brain Barrier Permeability in Alzheimer's Disease

Study Overview
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Brief Summary
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The main aim of the present study is to improve our understanding of the role of blood-brain barrier function in dementia of the Alzheimer's type. The investigators hypothesize that microvascular dysfunction - more specifically cerebral perfusion and blood-brain barrier leakage - is a determinant of cognitive decline and cortical atrophy in Alzheimer's disease.

Conditions
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Alzheimer's Disease

Participation Criteria
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Eligibility Criteria
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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) 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)
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 7 patients diagnosed with dementia of the Alzheimer's type<br> | |
| 13 patients with mild cognitive impairment<br> | |
| 19 healthy controls<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The main study measures are blood brain barrier permeability as measured by T1-weighted dynamic contrast MRI |  | 22 months |