Heart-Brain Connection crossroads (HBCx)

The Heart-Brain Connection crossroads consortium aims to investigate hemodynamic changes as a potentially reversible cause of vascular cognitive impairment, taking a multidimensional (i.e. crossroads) approach. The consortium is led by prof. dr. Mat Daemen and prof. dr. Geert Jan Biessels.

Cardiovascular disease and dementia are closely related. Cognitive impairment is common among people with cardiovascular or cerebrovascular disease. One in three dementia cases is attributable to vascular injury. This potentially preventable vascular burden in cognitive impairment is referred to as Vascular Cognitive Impairment (VCI).

Central hypothesis of the Heart-Brain Connection programme: hemodynamic changes are an important and potentially reversible cause of vascular cognitive impairment.


In the first Heart-Brain Connection (HBC1; CVON 2012-06) programme we have established a national interdisciplinary collaborative network to study, diagnose and treat VCI. Through clinical studies in patients with exemplar hemodynamic phenotypes, i.e. patients with chronic heart failure (HF), carotid occlusive disease (COD), and memory clinic patients with clinically manifest VCI, we established the role of hemodynamics in VCI, in particular flow, along the heart brain axis. Furthermore, we established a comprehensive diagnostic heart-brain axis protocol for hospital- and population-based studies as well as animal studies, addressing the role of hemodynamics in VCI.

In HBC1 we indeed showed the importance of the heart brain connection in VCI, COD and CHF patients as 18-35% of CHF and COD patients have minor to major VCI and 9-15% of COD and VCI patients have signs of chronic heart failure. Moreover, the Rotterdam study shows that myocardial infarction, atrial fibrillation (AF) and subclinical markers of cardiac dysfunction predispose to cerebral damage and dementia.

Our findings in HBC1 clearly confirmed the importance of the heart-brain axis in VCI. HBC1 explored the etiological role of hemodynamic factors in VCI, particularly addressing flow (i.e. cardiac output, large artery flow, cerebral perfusion). One important lesson that we learned from the results of HBC1 is that cerebral perfusion measured as a static parameter does not explain in full the relation between the heart and the brain in VCI. In HBCx we therefore added two new dimensions to the hemodynamic concept of HBC1 to further build on our central hypothesis that hemodynamic changes are an important and potentially reversible cause of VCI. While in HBC1 we primarily focused on the role of hypoperfusion, we now address variability and regulation of cerebral perfusion as well as factors that modulate the impact of hemodynamics on the brain.


The HBC-crossroads (HBCx) programme that started in 2019 further builds on the central hypothesis that hemodynamic changes are an important and potentially reversible cause of VCI, now taking a more multidimensional (i.e. crossroads) approach to hemodynamics, also addressing flow regulation and variability and factors that modulate the impact of hemodynamic disturbances in VCI.

We evaluate the role of hemodynamics in VCI in

  • Key cardiac conditions (atrial fibrillation, valvular disease, heart failure/venous congestion)
  • Vascular factors (blood pressure variability, vascular reactivity, endothelial (dys)function)
  • The primary cerebral co-morbidity of VCI, amyloid pathology (i.e. assess interplay hemodynamics and amyloid)

We will also address age, sex, and environment as modulating factors.

Our overarching objectives are to:

  • Further establish the role of hemodynamics, also beyond hypoperfusion, in VCI
  • Earlier detect the patient at risk for developing VCI by improved diagnostic tools and analyses and
  • implementation of the HBC approach in routine patient care
  • Identify treatable targets

Our short-term ambitions (5 years) for this theme are:

  • To identify those hemodynamic factors that play a key role in VCI and can be targets for intervention.
  • To understand the contribution of factors that modulate the impact of HD on cognition, such as age, sex and the environment to refine the integrated care in the heart-brain clinics (early recognition), and to precise the targets for intervention
  • To deliver novel markers of treatable targets (e.g. amyloid and novel markers in plasma, MRI
  • signatures of early cardiovascular disease, but also cognitive screening in cardiac population)
  • To improve patient care by implementing the HBC approach/concept in routine patient care offering integrated care in heart-brain clinics
  • To spread the importance of the HBC concept in the (inter)national patient, clinical and research field and include patients and private partners herein.

Our long-term ambition (2030-2035) are:

  • Improved understanding of the contribution of HD in the pathophysiology of VCI
  • Early detection of the chronic CVD patient at risk of VCI
  • Novel treatment strategies for CI in the CVD patient targeting HD factors
  • Changing clinical diagnostic and therapeutic guidelines for the chronic CVD patient at risk for VCI
  • 25% reduction of VCI in CVD patients

The framework of HBCx includes mechanistic studies, proof of concept treatment studies targeting hemodynamics, and the implementation of the HBC concept in heart-brain clinics in daily care. We build on the rich HBC1 dataset, refine the analyses and will also establish new cohorts and link up with other existing cohort studies such as RACE-V.

HBCx is funded by the Dutch Heart Foundation under grant agreement 2018-28.

Collaborators / partners