Efficacy and Safety Study of Digital Cognitive Training and PCSK9 Inhibitor-Enhanced Lipid-lowering Strategy in Patients With Intracranial Atherosclerotic Stenosis: A 2×2 Randomized Controlled Trial

Inclusion Criteria

Inclusion Criteria: 1. Age 55-80 years old 2. The number of years of education is greater than or equal to 6 years 3. 50%-99% stenosis of the intracranial artery confirmed by MRA, CTA or DSA 4. Head CT or MRI confirmed that there were no infarct lesions/softening foci larger than 3 cm in the brain 5. LDL-C ≥ 1.8mmol/L at baseline 6. Decline in cognitive function of the complainant 7. MMSE ≥ 24 points; no severe impairment of daily living and social functioning, and the daily living ability scale (ADL, 14-item BADL and IADL combined version, total score range of 14-56 points) \<=18; and the investigator's clinical assessment does not meet the diagnosis of dementia (DSM-V or NIA-AA diagnostic criteria) 8. Proficient in operating electronic products such as mobile phones and tablets 9. Complete the operation evaluation through the introduction period (see the definition of the introduction period) 10. Agree to receive maximally tolerated statin and PCSK9 inhibitor therapy during the study period 11. Able to cooperate with neuropsychological and multimodal magnetic resonance examinations Exclusion Criteria: 1. Extracranial vascular stenosis ≥ 50% 2. Acute cerebrovascular events within 90 days 3. Contraindications to MRI (metal implants in the body, claustrophobia, etc.) 4. Visual and auditory impairments, as well as communication difficulties, that affect cognitive training 5. Clinically diagnosed vascular dementia 6. Neuroimaging showing significant white matter lesions (Fazekas grade 3) or multiple microbleeds 7. Non-atherosclerotic intracranial artery stenosis (such as vasculitis, moyamoya disease, dissection, etc.) 8. Neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, etc.) 9. Severe comorbidities (tumors, multiple sclerosis, severe cardiopulmonary and renal diseases, intracranial aneurysms) 10. Other diseases that may affect cognition have been ruled out; severe anxiety, depression, or schizophrenia; a new stroke occurring within the 3 months prior to baseline; hereditary or inflammatory small vessel diseases; presence of any of the following clear sources of cardioembolic events: mitral stenosis, mechanical heart valves, endocarditis, intracardiac clots or vegetations, dilated cardiomyopathy, chronic or paroxysmal atrial fibrillation, ejection fraction less than 30% 11. Planning to use medications that may affect cognitive function within the past 3 months or in the following 24 weeks, including large amounts of sedatives, anti-anxiety drugs, cognitive enhancers, and cholinergic agents.(12) Previously treated with a PCSK9 inhibitor 12. Having a clear contraindication or severe intolerance to PCSK9 inhibitors or statins (such as a history of severe allergic reactions) 13. Presence of significant liver or muscle safety abnormalities at baseline, or the investigator deems the patient unsuitable for intensive lipid-lowering therapy (for example, significantly elevated ALT or AST, significantly elevated CK, etc.; the thresholds can be based on the reference ranges of each center's laboratory and specified in the protocol in advance) 14. Other circumstances deemed inappropriate for enrollment by the investigator