The Missing Link in the Pathophysiology of Vascular Cognitive Impairment
Design of the Heart-Brain Study
Astrid M. Hooghiemstra (Amsterdam UMC)
Anne Suzanne Bertens (Leiden University Medical Center)
Anna E. Leeuwis (Amsterdam UMC)
Esther E. Bron (Erasmus MC)
Michiel L. Bots ( University Medical Centre Utrecht)
Hans Peter Brunner-La Rocca (Maastricht University)
Anton J M De Craen (Leiden University Medical Center)
Rob J. van der Geest (Leiden University Medical Center)
Jacoba P. Greving ( University Medical Centre Utrecht)
L. Jaap Kappelle ( University Medical Centre Utrecht)
Wiro J. Niessen (Erasmus MC, TU Delft - ImPhys/Quantitative Imaging)
Robert J. van Oostenbrugge (Maastricht University)
Matthias J P van Osch (Leiden University Medical Center)
Albert de Roos (Leiden University Medical Center)
Albert C. van Rossum (Amsterdam UMC)
Geert Jan Biessels ( University Medical Centre Utrecht)
Mark A. van Buchem (Leiden University Medical Center)
Mat J A P Daemen (Universiteit van Amsterdam)
Wiesje M. van der Flier (Amsterdam UMC)
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Abstract
Background: Hemodynamic balance in the heart-brain axis is increasingly recognized as a crucial factor in maintaining functional and structural integrity of the brain and thereby cognitive functioning. Patients with heart failure (HF), carotid occlusive disease (COD), and vascular cognitive impairment (VCI) present themselves with complaints attributed to specific parts of the heart-brain axis, but hemodynamic changes often go beyond the part of the axis for which they primarily seek medical advice. The Heart-Brain Study hypothesizes that the hemodynamic status of the heart and the brain is an important but underestimated cause of VCI. We investigate this by studying to what extent hemodynamic changes contribute to VCI and what the mechanisms involved are. Here, we provide an overview of the design and protocol. Methods: The Heart-Brain Study is a multicenter cohort study with a follow-up measurement after 2 years among 645 participants (175 VCI, 175 COD, 175 HF, and 120 controls). Enrollment criteria are the following: 1 of the 3 diseases diagnosed according to current guidelines, age ≥50 years, no magnetic resonance contraindications, ability to undergo cognitive testing, and independence in daily life. A core clinical dataset is collected including sociodemographic factors, cardiovascular risk factors, detailed neurologic, cardiac, and medical history, medication, and a physical examination. In addition, we perform standardized neuropsychological testing, cardiac, vascular and brain MRI, and blood sampling. In subsets of participants we assess Alzheimer biomarkers in cerebrospinal fluid, and assess echocardiography and 24-hour blood pressure monitoring. Follow-up measurements after 2 years include neuropsychological testing, brain MRI, and blood samples for all participants. We use centralized state-of-the-art storage platforms for clinical and imaging data. Imaging data are processed centrally with automated standardized pipelines. Results and Conclusions: The Heart-Brain Study investigates relationships between (cardio-)vascular factors, the hemodynamic status of the heart and the brain, and cognitive impairment. By studying the complete heart-brain axis in patient groups that represent components of this axis, we have the opportunity to assess a combination of clinical and subclinical manifestations of disorders of the heart, vascular system and brain, with hemodynamic status as a possible binding factor.
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