Vascular dementia and heart failure represent major health burden to morbidity, mortality and quality of life. Comorbidities (hypertension, aging, diabetes, etc.) affect all organs, but the brain and heart are especially sensitive to these chronic stresses resulting in cognitive impairment (a mental disorder) and heart failure (a non-mental disorder). These comorbidities also induce a reduction in microvascular density, called microvascular rarefaction. We have build a consortium, CRUCIAL, which will develop a coordinated program to investigate the role of microvascular rarefaction in cognitive impairment and heart failure. Diagnosis of microvascular rarefaction is limited by the inability to assess microvascular density. We will develop advanced imaging tools taking advantage of the newest MRI technology including non-contrast and artificial intelligence methods to assess brain and heart microvascular rarefaction. We will also develop other non-invasive measures that will be cheaper and easier to widely disseminate in clinical practice (sublingual and retinal microvascular imaging, and blood microvesicle analysis). We will then apply these techniques to prospective and retrospective patient cohorts with cognitive impairment and heart failure to demonstrate that rarefaction can be used as a biomarker to diagnose and stratify patients. Microvascular regression is now recognised as an active process. We will therefore investigate, through animal models, the molecular mechanism of vessel rarefaction in the presence of comorbidities that could be targeted therapeutically. Therapeutic options for cognitive impairment or heart failure are currently limited to treating co-morbidities. The aim of CRUCUAL is to deliver diagnostic tools to clinician and therapeutic pathways to pharma that target microvascular health in order to prevent cognitive and cardiac disease progression, reduce morbidity and ultimately improve quality of life for patients.