cSVD is by far the most prevalent vascular contributor to cognitive impairment in the population. However, accurate quantitative estimates of the predictive ability of cSVD for dementia risk are lacking. Moreover, stratification of cognitive decline and dementia risk in cSVD patients according to imaging characteristics as well as evidence of coexisting neurodegenerative disease and vascular comorbidity are lacking. Hypertension is the strongest known risk factor for cSVD but there are currently no guidelines for the management of cSVD (or emerging guidelines based on weak evidence, and no specific mechanism-based treatments, leading to empirical and heterogeneous clinical practice, which in most instances consists of ignoring these lesions. This clinical blind spot represents a major missed opportunity for the prevention of cognitive decline and dementia.~This study aims to explore the relation of brain and retinal microvasculature image characteristics (imaging biomarkers), as well as molecular biomarkers derived from blood, with presence or absence of extensive cSVD and with cognitive and other clinical characteristics in two groups of 200 patients 60+ years of age. The first group will consist of patients with little or no white matter hyperintensities on brain MRI (no or minor MRI features of cSVD); while the second will include patients with moderate to severe white matter hyperintensities (MRI features of extensive cSVD).~This will create a unique deeply characterized resource for epidemiological and mechanistic investigations of cSVD, which can also serve as a pilot setting to test the trajectories and requirements for individualized patient care of cSVD patients.~The combination of retinal microvascular measurements using innovative multimodal imaging is entirely novel to our knowledge. In the context of the RHU SHIVA program, the same retained imaging protocol will be implemented for 400 young adults, which will provide insight into trajectories of these retinal biomarkers across the adult lifespan).~For the molecular biomarkers allow the validation of genomic, epigenomic, transcriptomic, proteomic, and metabolomic biomarkers for cSVD identified through secondary use of large existing cohort studies in the general population (3C, i-Share cohorts), in persons with memory complaints (MEMENTO cohort), and in collaboration with other cohorts with the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, also as part of the RHU SHIVA program.
Cerebral small Vessel Disease (cSVD), characterized by an alteration of the structure and function of small penetrating brain arteries, is highly prevalent in older persons from the general population and represents a leading cause of stroke and a major contributor to cognitive decline and dementia risk. In France >4 million persons aged 60+ are estimated to have moderate to extensive covert cSVD (ccSVD), i.e. features of SVD on brain imaging without a history of clinical stroke. Better detection and management of covert cSVD would have a major impact on preventing disability and costs related to stroke, cognitive impairment and dementia. However, there are no specific mechanistic treatments for cSVD and hardly any recommendations worldwide on how to prevent and treat cSVD and related cognitive impairment. The aim of the present study, through the identification of novel cutting-edge multimodal biomarkers, is to develop innovative diagnostic and risk prediction tools for cSVD and its complications and to contribute to accelerating the discovery of novel drug targets and therapeutics strategies for cSVD.