NEW DIAGNOSTIC AND THERAPEUTIC STRATEGIES FOR VASCULAR COGNITIVE IMPAIRMENT (VCI): LEARNING FROM BIOMARKERS AND MULTI-PART APPROACHES IN STROKE

Abstract

The term vascular cognitive impairment (VCI) is used to describe individuals with significant cognitive impairments produced by cerebrovascular disease (CVD). Risk factors for VCI are the same as traditional risk factors for CVD. Early identification of subjects at higher risk of VCI is important for the development of effective preventive strategies. Circulating biomarkers have emerged as potential tools for early diagnosis, as they could provide in vivo measures of the underlying pathophysiology. New interventions should be tested in large multicenter pre-clinical and clinical trials to speed-up the translation process. The Barcelona-AsIA (Asymptomatic Intracranial Atherosclerosis) study and ISSYS (Investigating Silent Strokes in hYpertensives) study are two excellent examples of large cohorts to explore biological predictors of VCI. Hypertension, intracranial atherosclerosis, and silent cerebrovascular lesions (SCL) detected by brain magnetic resonance imaging (MRI) are associated with an increased risk of cognitive decline. In that prospective observational study in 1000 hypertensive patients, aged 50-70 years, with no prior history of stroke or dementia, we studied the presence of mild cognitive impairment (MCI) and the relationship between SCL, an array of blood biomarkers, and cognition. MULTI-PART (Multicentre Preclinical Animal Research Team) is an international collaborative approach to overcoming the translational roadblock in neuroprotection and neuroregeneration research with the key objective to establish and implement a platform for international multicenter preclinical stroke trials using the repertoire of randomized clinical trial design and the complexities of a multicenter, multimodel paradigm. We will show examples of blood biomarkers that add predictive value to clinical and radiological models to anticipate the appearance of VCI. We are developing and implementing international, multicenter ‘phase III’-type preclinical trials of promising, novel ischemic stroke therapies to inform the possible transition from animal modeling to clinical trial. In addition, demonstrating neuroprotection and/or neurorepair in this prototypical acute CNS disorder would have vast implications for the development of treatments in many other chronic neurological and neuropsychiatric diseases such as VCI. Combining prediction of VCI through novel biomarkers and a new trial paradigm (MULTI-PART) could serve as a novel strategy to push translation of cellular/molecular mechanistic VCI studies.