Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is the most common form of hereditary vascular dementia. CADASIL is thought to be caused by mutations of the Notch3 gene on chromosome 19. The specific biological pathway for the disease course is not yet understood but great advances are being made by researchers around the world. CADASIL is characterized by migraine headaches, multiple small strokes, episodic sensory and visual problems, apathy, depression and progressive cognitive and functional decline, resulting in dementia. As a result of these impairments, individuals with CADASIL will experience significant changes in their quality of life over the disease course.

The purpose of the CADASIL Consortium is to develop a partnership among healthcare professionals, research scientists, friends and families to advance our knowledge to improve the care and treatment for persons impacted by CADASIL. Our research team aims to pave the way for new studies of and treatments for the disease course of vascular cognitive impairment and dementia (VCID) with the collection of critical data to describe CADASIL from its earliest stages before there are known biological impairments or clinical consequences. Because CADASIL is caused by a single gene, we are able to study it at an earlier time than other widespread, sporadic dementia syndromes.  As a consequence, the CADASIL Consortium can leverage data that are unknown for other more common forms of VCID. More specifically, we are investigating the clinical, brain imaging, blood biomarkers and genetic features of CADASIL so that we may better understand similar features in all types of vascular dementia. This study will also examine the impact that lifestyle and health factors have on the course and outcomes of vascular cognitive impairments across the aging life course. Information obtained will provide an unprecedented resource that can be shared for all scientists to expedite our understanding of, and treatments for, CADASIL and similar dementia syndromes.

Working directly with CADASIL families, we will characterize the initial presentation and course of clinical, neuroimaging, and blood markers. We will then compare these markers of disease with those from non-carrier family controls (NC). NC are persons from a CADASIL family who do not have the gene causing CADASIL. This approach will allow the team to identify at what point CADASIL individuals’ clinical, neuroimaging, and blood markers begin to differ from those of NC and which markers reliably indicate that an individual’s condition is worsening. In addition, the use of DNA analysis, medical history, and lifestyle questionnaires will enable the team to clarify genetic, health, and lifestyle factors which impact clinically meaningful conclusions in CADASIL.

Our study aims to enroll a total of 500 participants across North America. Eligible participants will have a genetic test for a NOTCH3 variant. As part of this study, participants will complete three in-person visits in total: 1.) the baseline visit; 2.) first follow-up visit (18 months after the baseline); 3.) second follow-up visit (36 months after baseline). Additional contact will occur by phone, mail, email, or via the Internet and is considered a “remote visit”.  Participants will complete the following at each study visit: a clinical interview, a neurological exam, neurocognitive and behavior assessments, a brain scan, and a blood draw.