This study aims to evaluate whether digital cognitive training and/or intensive lipid-lowering therapy with a PCSK9 inhibitor can improve cognitive function in patients with intracranial atherosclerosis (ICAS).
ICAS is a common cause of stroke and is also linked to thinking and memory problems. The study will enroll 420 adults aged 55-80 years who have 50-99% narrowing of an intracranial artery, subjective memory complaints, and LDL cholesterol ≥1.8 mmol/L, but who are not demented.
Participants will be randomly assigned to one of four groups in a 2×2 factorial design:
1. No cognitive training + standard statin therapy 2. Cognitive training + standard statin therapy 3. No cognitive training + intensive statin plus PCSK9 inhibitor 4. Cognitive training + intensive statin plus PCSK9 inhibitor
Cognitive training consists of 30 minutes of tablet-based exercises, 5 days per week for 12 weeks. The intensive lipid-lowering group receives a PCSK9 inhibitor (Recaticimab) injection at weeks 0, 4, and 12, on top of maximally tolerated statin.
The main outcome is change in a composite cognitive score from baseline to 24 weeks. Secondary outcomes include changes in specific cognitive domains, MRI markers of brain structure and function, and safety measures.
The study is multicenter, open-label with blinded outcome assessment, and is conducted under the approval of the ethics committee of Peking Union Medical College Hospital.
Age 55-80 years old
The number of years of education is greater than or equal to 6 years
50%-99% stenosis of the intracranial artery confirmed by MRA, CTA or DSA
Head CT or MRI confirmed that there were no infarct lesions/softening foci larger than 3 cm in the brain
Extracranial vascular stenosis ≥ 50%
Acute cerebrovascular events within 90 days
Contraindications to MRI (metal implants in the body, claustrophobia, etc.)
Visual and auditory impairments, as well as communication difficulties, that affect cognitive training