Evidence‑Based Management of CADASIL

Blood‑Pressure Management

Initiate antihypertensive therapy and titrate doses to achieve a target systolic blood pressure < 140 mm Hg in all CADASIL patients, recognizing that the optimal CADASIL‑specific target has not been defined. [1][2]

Prescribe aspirin 75–325 mg daily for CADASIL patients who have experienced an ischemic stroke or transient ischemic attack (TIA). [3][2]
For stroke/TIA patients, a single antiplatelet alternative may be clopidogrel 75 mg daily or aspirin + extended‑release dipyridamole (25/200 mg twice daily). [3][4]
Antiplatelet agents are preferred over oral anticoagulants unless a separate indication (e.g., atrial fibrillation) exists. [3][2]
Dual antiplatelet therapy with aspirin + clopidogrel should not be continued beyond three months after a stroke or TIA because it raises bleeding risk without demonstrated benefit. [5][2]

Initiate high‑dose statin therapy in CADASIL patients to lower low‑density lipoprotein (LDL) cholesterol below 100 mg/dL; consider a target LDL < 70 mg/dL in those with a prior ischemic stroke. [2][4]
Statins should be prescribed irrespective of baseline cholesterol levels because of their pleiotropic vascular‑protective effects. 2

Advise all CADASIL patients who smoke to quit and provide smoking‑cessation interventions, as smoking accelerates atherosclerosis and vascular disease progression. 2

Recommend standard glucose‑control measures (diet, exercise, glucose‑lowering agents) but note that intensive lowering to HbA1c < 7 % has not been shown to prevent stroke in CADASIL. [5][2]

Encourage regular moderate‑intensity physical activity as part of comprehensive vascular‑risk reduction. 4

Full‑intensity anticoagulation with unfractionated heparin or low‑molecular‑weight heparin is not recommended for acute ischemic stroke or TIA in CADASIL unless a compelling separate indication exists. [5][2]

Carotid endarterectomy and carotid stenting are not indicated for CADASIL because the pathology involves small vessels rather than large‑vessel atherosclerotic stenosis. [1][6]

Perform an annual evaluation of cardiovascular risk factors and assess adherence to prescribed therapies. 6
Monitor blood pressure at every clinical encounter to ensure targets are maintained. 6

CADASIL was the first monogenic cerebral small‑vessel disease identified, with the pathogenic NOTCH3 mutation first described in 1996【7】.

Unlike other monogenic cerebral small‑vessel diseases (e.g., ADA2, COL4A1, TREX1), NOTCH3/CADASIL produces minimal symptomatic extracerebral disease; however, asymptomatic skin involvement (granular osmiophilic material in dermal arteries) is frequently observed【8】.

Hypertension control is the only intervention that has been shown to lower the risk of cerebral small‑vessel disease progression in CADASIL patients【7】.
No disease‑modifying therapies are currently available for CADASIL, in contrast to other hereditary small‑vessel disorders such as ADA2, COL4A1, and TREX1【7】.