Intracranial atherosclerosis (ICAS) is one of the leading causes of ischemic stroke, accounting for 30–50% of ischemic stroke causes in Asian populations, much higher than the approximately 10% in Caucasians.1 In addition to triggering stroke and transient ischemic attack (TIA), chronic cerebral hypoperfusion due to ICAS can cause white matter damage and gradually lead to cognitive deterioration2.
Conditions
Interventions
Lipid-lowering intervention group:No digital cognitive training + maximum tolerance statin plus PCSK9 inhibitor
Control group:No digital cognitive training + maximum statin tolerance only
Combined intervention group:Digital cognitive training + maximum tolerance statin plus PCSK9 inhibitor
Training intervention group:Digital cognitive training + maximum statin tolerance only
Sponsors
Peking Union Medical College Hospital
Eligibility
Sex/Gender
All
Age
55 Years to 80 Years
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; 50%-99% stenosis of the intracranial artery confirmed by MRA, CTA or DSA; 3.Head CT or MRI confirmed that there were no infarct lesions/softening foci larger than 3 cm in the brain; 4.LDL-C >= 1.8mmol/L at baseline; 5.Decline in cognitive function of the complainant; 6.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); 7.Proficient in operating electronic products such as mobile phones and tablets; 8.Complete the operation evaluation through the introduction period (see the definition of the introduction period); 9.Agree to receive maximally tolerated statin and PCSK9 inhibitor therapy during the study period; 10.Able to cooperate with neuropsychological and multimodal magnetic resonance examinations;
Exclusion criteria
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; 13.Having a clear contraindication or severe intolerance to PCSK9 inhibitors or statins (such as a history of severe allergic reactions); 14.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); 15.Other circumstances deemed inappropriate for enrollment by the investigator;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The change of the subject's cognitive composite score at week 24 compared with the baseline period; | — |
Secondary
| Measure | Time frame |
|---|---|
| Change in the atherosclerotic burden of the whole brain at week 24 compared with the baseline period;Change of plaque load at the most stenosis of the subject at week 24 compared with the baseline period;The scores of the subjects' memory, executive, visuospatial, attention, and verbal cognitive domains changed from the baseline period at 12 and 24 weeks;Changes in the total MoCA score of the participants at weeks 12 and 24 compared to the baseline period; | — |
Countries
China
Contacts
Public ContactZijue Wang
Peking Union Medical College Hospital
Outcome results
None listed