Table 2.

Inclusion and exclusion criteria for patients with sporadic SVDs, CADASIL and healthy controls.

General selection criteria for all groups
Inclusion criteria	Exclusion criteria
–Age 18 years or older –Capacity to give written informed consent –Independent in activities of daily living (Modified Rankin score ≤ 3)	–Pregnant or breastfeeding women and women of childbearing age not taking contraception –Contraindication to MRI or unable to undergo MRI protocol due to physical condition –Other major neurological or psychiatric conditions affecting the brain and interfering with the study design (e.g. multiple sclerosis, Parkinson's disease) –Life expectancy <2 years
Additional selection criteria specific to patients with sporadic SVDs
Inclusion criteria	Exclusion criteria
History of a clinical lacunar stroke in the last 5 years with a corresponding small subcortical infarct visible on MRI or CT, compatible with the clinical syndrome OR Cognitive impairment defined as visiting a memory clinic with cognitive complaints and objective cognitive impairment (based on a validated cognitive measurement tool such as, but not limited to, CAMCOG) with confluent white matter hyperintensities on MRI (defined as Fazekas ≥ 2)	- Evidence for a monogenic form of SVDs - In case of inclusion for clinical lacunar stroke: ≥50% luminal stenosis in large arteries supplying the infarct area Major-risk for cardioembolic source of embolism (defined as permanent or paroxysmal atrial fibrillation, sustained atrial flutter, intracardiac thrombus, prosthetic cardiac valve, atrial myxoma or other cardiac tumors, mitral stenosis, myocardial infarction in the last 4 weeks, left ventricular ejection fraction < 30%, valvular vegetations, or infective endocarditis) Other specific causes of stroke (e.g. arteritis, dissection, vasospasm, drug misuse)
Additional selection criteria specific to patients with CADASIL
Inclusion criteria	Exclusion criteria
A diagnosis of CADASIL established by molecular genetic testing of the NOTCH3 gene (presence of an archetypical, cysteine-affecting mutation) or the presence of granular osmiophilic material in ultrastructural, electron microscopy analysis of skin biopsy. NB: thus both symptomatic and asymptomatic patients are included.	Not applicable
Additional selection criteria specific to controls
Inclusion criteria	Exclusion criteria
No additional inclusion criteria applicable	- A history of stroke or of cognitive complaints for which the person has previously sought medical advice - So-called “silent” SVDs defined as confluent white matter hyperintensities (Fazekas ≥ 2) or lacunes on the 3T brain MRI scan on baseline visit 1