Efficacy and Safety Study of Digital Cognitive Training and PCSK9 Inhibitor-Enhanced Lipid-lowering Strategy in Patients With Intracranial Atherosclerotic Stenosis: A 2x2 Factorial, Randomized, Parallel-Group, Multicenter Trial

This study aims to evaluate whether digital cognitive training and/or PCSK9 inhibitor-enhanced lipid-lowering therapy on top of moderate-intensity statin 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 440 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, parallel-group design: No cognitive training + moderate-intensity statin therapy Cognitive training + moderate-intensity statin therapy No cognitive training + moderate-intensity statin plus PCSK9 inhibitor Cognitive training + moderate-intensity statin plus PCSK9 inhibitor Cognitive training consists of 30 minutes of tablet-based exercises, 5 days per week for 24 weeks (first 12 weeks as the intensive phase, followed by 12 weeks continuation phase). The PCSK9 inhibitor (Recaticimab) is administered subcutaneously according to the product label, on top of moderate-intensity statin. The main outcome is change in a composite cognitive score from baseline to 24 weeks. Secondary outcomes include changes in specific cognitive domains, serum LDL-C, 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.