The Relevance of the Blood-brain Barrier to Cognitive Dysfunction and Alzheimer's Disease

Study Overview
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Brief Summary
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This study attempts to replicate the findings published in Nature Medicine by Nation and colleagues (2019). By using a large observational cohort (DZNE - Longitudinal Cognitive Impairment and Dementia Study; DELCODE) consisting of cognitively healthy individuals, individuals with subjective cognitive decline, mild cognitive impairment, and dementia due to Alzheimer's disease, an association between the blood-brain barrier and cognitive dysfunction is investigated. The integrity of the blood-brain barrier is investigated by using a novel MRI protocol as well as a novel biomarker in the cerebrospinal fluid.

Official Title
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The Relevance of the Blood-brain Barrier to Cognitive Dysfunction and Alzheimer's Disease

Conditions
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Blood Brain Barrier, Alzheimer Disease, Cognitive Dysfunction, Dementia

Intervention / Treatment
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* Diagnostic Test: Contrast agent enhanced MRI using Gadovist


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: - ≥ 50 years with neuropsychologically confirmed no cognitive dysfunction, mild cognitive impairment or mild dementia Exclusion cirteria: no current or prior history of any neurological or psychiatric condition, which might affect cognitive function no neurodegenerative disease other than AD specifically no extensive vascular white matter dementia or vascular dementia

Ages Eligible for Study
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Minimum Age: 50 Years

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 |
| --- | --- |
| Cognitive normal<br>Individuals who do not show clinical or neuropsychological deficits. | Diagnostic Test: Contrast agent enhanced MRI using Gadovist<br>* By using the contrast agent Gadovist we aim to visualize the blood-brain barrier. Furthermore, we aim to measure a newly developed biomarker of the blood-brain barrier in the cerebro-spinal fluid.<br>|
| Mild cognitive impairment<br>Individuals who show deficits in neuropsychological test procedures but who do not exhibit substantial problems in daily life. Those individuals are part of the DELCODE cohort and were initially recruited in a memory clinic. | Diagnostic Test: Contrast agent enhanced MRI using Gadovist<br>* By using the contrast agent Gadovist we aim to visualize the blood-brain barrier. Furthermore, we aim to measure a newly developed biomarker of the blood-brain barrier in the cerebro-spinal fluid.<br>|
| Dementia due to Alzheimer's disease<br>Individuals diagnosed with dementia due to Alzheimer's disease by relying on anamnesis, neuropsychological test results, results of MRI and biomarkers found in the cerebrospinal fluid. Those individuals are part of the DELCODE cohort and were initially recruited in a memory clinic. | Diagnostic Test: Contrast agent enhanced MRI using Gadovist<br>* By using the contrast agent Gadovist we aim to visualize the blood-brain barrier. Furthermore, we aim to measure a newly developed biomarker of the blood-brain barrier in the cerebro-spinal fluid.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Marker of blood-brain dysfunction using MRI | Dynamic T1 contrast enhanced sequence using Gadovist | 1 day | 
| Markers of blood-brain dysfunction using CSF | Platelet-derived growth factor receptor-β in CSF | 1 day |