Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL) Study

Unraveling the Early Phases of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL)

This is an observational study to better understand the risk factors and progression of CADASIL, a leading cause of vascular cognitive impairment and dementia (VCID). 575 participants will be enrolled and can expect to be on study for up to 5 years.

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is the most common monogenic vascular dementia. Individuals with CADASIL are destined to develop vascular cognitive impairment and dementia (VCID), which can be studied in pre-symptomatic and prodromal disease stages to detect the earliest changes in biological fluids, neuroimaging, and the emerging phenotype of symptomatic VCID.

The objective of the proposed research is to exploit an autosomal dominant vascular dementia as a model to investigate specific features of VCID and to examine interactions with risk factors impacting the aging life course.

The study will enroll a total of 575 participants with a CADASIL family history who have had a genetic test for a NOTCH3 variant. Participants will complete: a clinical interview, a neurological exam, neurocognitive and behavior assessments, MRI, and a blood draw at each study visit. Participants will complete 3 in-person visits in total as part of this study: baseline, visit 2 (18 months after baseline), visit 3 (36 months after baseline). Additional contact will occur by phone, mail, email or the internet as needed and will be referred to as "remote visits".

Inclusion Criteria for CADASIL Participants:

1. Must be at least 18 years old

2. Positive NOTCH3 genetic testing; OR a positive skin biopsy; OR a willingness to have a NOTCH3 genetic test completed prior to enrolling AND are at-risk for, or diagnosed clinically with, CADASIL

3. Willing to commit to three in-person visits (a baseline visit, an 18-month follow-up, and a 36-month follow-up) and to remote visits as needed by phone, email, mail or internet

4. Willing to provide documentation of all current medications to study team

   a. All medications will be allowed throughout the course of study. Documentation of medications will be used for analyses to assess potential impact of medications on study outcomes.

5. Willing and able to undergo an MRI scan and blood draw at each in-person visit

6. Must have a designated "study companion"

   a. A "study companion" is someone who knows the participant well (has greater than or equal to 3 hours/month of contact with the CADASIL participant) and can provide additional information to the study team (either remotely or in-person).

7. A functional capacity less than 4 on the Modified Rankin Scale

Inclusion Criteria for Healthy Controls (HC):

1. Must meet same criteria as CADASIL participants, EXCEPT have negative NOTCH3 genetic testing

Exclusion Criteria:

1. History of severe learning disability, intellectual disability, or other neurological disease or event not attributable to CADASIL
2. History of serious alcohol or drug abuse within the past year
3. Unwilling to undergo NOTCH3 genetic testing if there is no test on file