Taiwan Associated Genetic and Nongenetic Small Vessel Disease

Study Overview
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Brief Summary
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The TAG-SVD enrolled patients with clinical and neuroimaging features of cerebral small vessel disease (CSVD). All enrolled patients will receive next-generation sequence (NGS) with probes designed to target five candidate CSVD genes, and patients will be divided into genetic or non-genetic groups accordingly. Their clinical features and outcome will be followed for at least 2 years.

Official Title
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Deciphering, Construction and Validation of Magnetic Resonance Imaging Maps, Clinical Features and Outcomes in Genetic and Nongenetic Cerebral Small Vessel Diseases

Conditions
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Cerebral Small Vessel Diseases, Cadasil, HTRA1-Related Autosomal Dominant Cerebral Angiopathy, COL4A1-Related Brain Small Vessel Disease With Haemorrhage, Fabry Disease, Magnetic Resonance Imaging, Next-generation Sequencing, Stroke

Intervention / Treatment
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* Diagnostic Test: MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have at least one of the following symptoms/signs or history stroke (especially small vessel occlusion type of ischaemic stroke, spontaneous ICH or young stroke) cognitive impairment or dementia gait disturbance parkinsonism (especially vascular parkinsonism features) headache (especially migraine) positive family history of hereditary CSVD MRI evidence of CSVD (MRI may be done for other reasons), including mild to moderate white matter hyper intensity, any lacune, or any cerebral microbleed Exclusion Criteria: MRI evidence of CSVD due to other inflammatory, malignancy, or structural lesions patients or family members not willing to sign informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Genetic group<br>Patients who have positive DNA results by NGS screening of the following 5 genes: NOTCH3 (19q13.12), HTRA1 (10q26.13), GLA (Xq22.1), TREX1 (3p1.31) and COL4A1 (13q34). | Diagnostic Test: MRI<br>* Patients will repeat study-protocol MRI at baseline (enrollment) and at least once in 1 year or 2 years follow-up (depends on availability).<br>|
| Nongenetic group<br>Patients who have negative DNA results by NGS screening . | Diagnostic Test: MRI<br>* Patients will repeat study-protocol MRI at baseline (enrollment) and at least once in 1 year or 2 years follow-up (depends on availability).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with incident stroke | Clinical stroke, including transient ischemic attack, ischemic stroke, or intracerebral hemorrhage. The stroke is defined by a focal neurological deficits lasting more than 24 hours, with accompanied neuroimaging evidence of infarct or hemorrhage in corresponding brain area. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with incident dementia | Vascular cognitive impairment (VCI), vascular dementia (VaD), or Alzheimer's dementia or Vascular dementia according to latest diagnostic criteria. Alzheimer's disease diagnostic criteria: National Institute of Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease (PMID: 21514247) Vascular dementia diagnostic criteria: Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition | 2 years |