CerebrAlcare Pills on CereBral Small VesseL DiseasE（CABLE）

Including systolic and diastolic blood pressure (mmHg).

The Rey Auditory Verbal Learning Test (RAVLT) provides a standardized procedure to evaluate a range of aspects of verbal learning and memory of supra-span lists of words. The test requires recalling as many words as possible in any order from a standard list of 15 unrelated words read out by the examiner. The total score ranges from 0-120, with a lower score indicating a worse outcome.

Generalized Anxiety disorder (GAD) is a widespread psychiatric syndrome involving significant consequences on people's health, with a total score of 21, where a higher score means a worse outcome. However, recent data show that this disorder has received little attention when compared to other anxiety disorders.

The Zung Self-Rating Depression Scale (SDS) consists of 20 items with a Likert type scale after each item. Each item is rated from 1 to 4, with scores ranging from 20 to 80, where higher scores mean worse results

The DHI has 25 items with 3 response levels, sub-grouped into three domains: functional, emotional, and physical. A shortened version, the Dizziness Handicap Inventory short form (DHIsf), reduced to 13 items with 2 response levels, has been shown to compare favourably to the original version. Scores range from 0-100, with higher scores indicating worse outcomes.

The HIT-6 consists of six items: pain, social functioning, role functioning, vitality, cognitive functioning, and psychological distress.Total HIT-6 score that ranges from 36 to 78, where a lower score indicates a greater impact of headache on the daily life of the respondent.

It includes a descriptive system(DS) and a visual analogue scale(VAS). Two indicators are index value(ranged 0-1) and visual score(ranged 0-100) with higher scores corresponding to better health status.

The Stroop Color and Word Test (SCWT) is a neuropsychological test extensively used to assess the ability to inhibit cognitive interference that occurs when the processing of a specific stimulus feature impedes the simultaneous processing of a second stimulus attribute, well-known as the Stroop Effect. Shorter the test time, the better the outcome.

Fazekas score is used to describe the different types of hyperintense signal abnormalities surrounding the ventricles and in the deep white matter. Periventricular hyperintensity (PVH) is graded as 0 = absence, 1 = "caps" or pencil-thin lining, 2 = smooth "halo", 3 = irregular PVH extending into the deep white matter. Separate deep white matter hyperintensity (DWMH) is rated as 0 = absence, 1 = punctate foci, 2 = beginning confluence of foci, 3 = large confluent areas. Higher scores indicats a worse outcome.

WMH volume is assessed on 3D fluid attenuated inversion recovery (FLAIR) sequence in mm3 or cm3. Larger volume indicates a worse outcome.

Lacunes were defined as rounded or ovoid lesions in the subcortical, basal ganglia, or brainstem, ranging from 3mm to 20mm in diameter, presenting with cerebral spinal fluid signal intensity on T2 and FLAIR, generally featuring a hyperintense rim on FLAIR and no increased signal on diffusion weighted imaging (DWI). Higher number of lacunae means a worse outcome.

Cerebral microbleeds are defined as rounded, hypodense foci within brain parenchyma on susceptibi lity weighted imaging (SWI) sequence, up to 10 mm in diameter, and were differentiated from microbleed mimics based on current guidelines. Higher number of cerebral microbleeds means a worse outcome.

Enlarged perivascular space was defined as small punctate or linear hyperintensities on T2 images in the basal ganglia or centrum semiovale. Higher number of enlarged perivascular spaces means a worse outcome.

Lower cerebrovascular reactivity (CVR), cerebral blood flow (CBF), and reduced radial peripapillary capillary network density, and parafoveal vessel densities of the superficial retinal capillary plexuses mean worse outcomes.

Chinese medical symptoms assessed by Blood Deficiency and Liver Hyperactivity Syndrome score. Scores range 0-21 and higher scores mean a worse outcome.

stroke included ischemic stroke, hemorrhagic stroke, TIA, et al.

BBB permeability is assessed by MRI and biomarker (including NSE, GFAP, S100β).

Blood was collected from the healthy (n=6), experimental (n=6) and placebo (n=6) groups at baseline, 3 months, and 12 months post-dosing. Alterations in protein profiles were detected by high performance liquid chromatography-mass spectrometry (HPLC-MS). GO classification and pathway enrichment were performed to analyse relevant protein changes. Serum metabolomics was determined using untargeted assays, and metabolite patterns in different groups were distinguished using orthogonal partial least squares analysis (OPLS-DA), compared with databases, and validated with the help of standards to finalise qualitative and quantitative analysis of metabolites and to identify differential metabolites. The Cell Counting Bead Analysis (CBA) Flex Set Flow Multifactor Assay Kit is used to detect serum levels of the inflammatory factors IL-1β, IL-6, IL-10, IL-12 and TNF-α. Western blot analysis is used to validate changes in the expression of 20 key proteins obtained from proteomic analysis.

Incidence of symptomatic stroke, myocardial infarction and vascular death.

Deaths from all causes to the research subjects

According to Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) criteria which classifies the severity of bleeding complications as follows: 1) severe or life-threatening bleeding-intracranial bleeding or bleeding that causes substantial hemodynamic compromise requiring treatment; 2) moderate bleeding-bleeding which needs blood transfusion; 3) minor bleeding-other bleeding, neither requiring transfusion nor causing hemodynamic compromise.

renal failure, hepatic failure, death.