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

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.

Study Overview

• Status: Completed
• Conditions: Cognitive Dysfunction; Dementia; Alzheimer Disease; Blood Brain Barrier
• Intervention / Treatment: Diagnostic test: Contrast agent enhanced MRI using Gadovist

• Study Type: Observational
• Enrollment (Actual): 101

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Charite Universitatsmedizin Berlin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

A description of the study population is provided by DZNE - Longitudinal Cognitive Impairment and Dementia Study (DELCODE).

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cognitive normal; Individuals who do not show clinical or neuropsychological deficits.	Diagnostic test: Contrast agent enhanced MRI using Gadovist; 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.
Mild cognitive impairment; 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; 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.
Dementia due to Alzheimer's disease; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: Prof. Dr. med. Jochen Fiebach (Senior Physician)

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2019
• Primary Completion (Actual): September 30, 2021
• Study Completion (Actual): September 30, 2021

Study Registration Dates

• First Submitted: September 13, 2019
• First Submitted That Met QC Criteria: September 17, 2019
• First Posted (Actual): September 18, 2019

Study Record Updates

• Last Update Posted (Actual): November 11, 2021
• Last Update Submitted That Met QC Criteria: November 5, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction
• Other Study ID Numbers: BHSkog

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No