Study on the Key Technology of Acupoint Modulation-based Brain Electric Field Therapy for the Treatment of Post-stroke Cognitive Impairment
Phase: NA
Conditions: Post-Stroke Cognitive Impairment (PSCI)
Sponsor: Ruijie Ma

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Cover  
 
 
Research on key technologies of brain electric field therapy based on 
acupoint regulation for the treatment of post-stroke cognitive impairment 
 
Study type: Clinical study 
Research Center: The Third Affiliated Hospital of Zhejiang Chinese 
Medical University (Team leader unit) 
The Second Affiliated Hospital of Zhejiang University School of 
Medicine 
Hangzhou Hospital of Traditional Chinese Medicine 
Zhejiang Provincial Hospital of Traditional Chinese Medicine 
Zhejiang Provincial People's Hospital 
Department of this hospital: Acupuncture Department 
Signature of the person in charge of the hospital: 
 
Date: May 2025 
The study will be conducted in accordance with this clinical study protocol and GCP 
 
 
 
 
 
 
 
 
 
 
 
 

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Contents 
I. RESEARCH BACKGROUND ........................................................................................ 3 
Ii. Main research content, objectives, program and progress, and key problems to be solved:
 ................................................................................................................................................ 4 
1. Research content................................................................................................................. 4 
2. Objectives of the study ....................................................................................................... 4 
3. Study protocol .................................................................................................................... 5 
3.1 Study protocol .................................................................................................................. 5 
3.2 Treatment Options ............................................................................................................ 9 
3.3 Emergency management ................................................................................................ 14 
3.4 Technical route ............................................................................................................... 15 
Iii. Adverse Events (described according to the subject) ..................................................... 16 
1. Definitions of adverse events and serious adverse events ................................................ 16 
2 Obtain information on adverse events ............................................................................... 16 
3. Observation and recording of adverse events................................................................... 16 
4. Management of adverse events and serious adverse events ............................................. 16 
4. Ethics and quality ............................................................................................................. 17 
5. Data management ............................................................................................................. 17 
6. Statistical analysis ............................................................................................................ 18 
1. Statistical software ........................................................................................................... 18 
2. Data Description ............................................................................................................... 18 
3. Statistics............................................................................................................................ 18 
4. Statistical Analysis Plan ................................................................................................... 18 
Vii. Final report and publication .......................................................................................... 18 
Viii. Quality control ............................................................................................................. 18 
Ix. References ....................................................................................................................... 19 
 
 
 
 
 
 
 
 
 
 

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Study protocol 
I. Research background 
Stroke is a global public health problem, which has become the leading cause of death and 
disability in China. With the rapid aging of the Chinese population, its incidence continues to 
rise[1-3]. According to the "Report on the prevention and Treatment of Stroke in China (2023)", 
on average, one person in China will have a first or recurrent stroke every 10 seconds, and one 
person will die from stroke every 28 seconds. At present, there are 4 million new stroke cases 
in China every year, and there are 12.42 million stroke cases in people aged 40 years and above, 
and the incidence population is getting younger. Among the survivors, about 75% are left with 
disability and 40% are severely disabled, which will lead to huge economic losses and physical 
and mental pain for the patients' families. 
Cognitive Impairment after Stroke (Post - Stroke Cognitive Impairment, PSCI) is a 
common complication of Stroke patients in 6 months after the Stroke event Cognitive 
Impairment to Cognitive Impairment diagnosis standard. PSCI is defined as a secondary to 
incident stroke and cognitive decline as the core characteristics of clinical phenomenon, these 
obstacles include cognitie impairment caused by a variety of types of stroke, is after stroke 
survivors functions rely on one[4,5] of the main determinants. The prevalence of PSCI is about 
30%-50% within 6 months, of which 10% will progress to dementia. In addition, patients with 
PSCI face a risk[6-8] of death of up to 61% within 5 years. Around the world have launched 
specific guidelines, calls for strengthening the focus of the major complications and input, 
however the PSCI treatment still limited to stroke secondary prevention measures and treatment 
of alzheimer's disease drugs, are lack of high-level clinical evidence, therefore needs to be 
effective treatments to improve the prognosis[9, 10] of patients. 
PSCI is a dynamic development process, and its occurrence time, influence factors, 
clinical manifestation and prognosis of recovery of individual differences, unique diagnostic 
system of traditional Chinese medicine can help to analyze the condition of PSCI evolution, 
law research may help to explain the evolution of syndrome and to provide reference for 
treatment. There is no special effects for the treatment of PSCI drugs, and drug treatment were 
lack of high-level evidence to prove that, in recent years with the development of imaging, 
artificial intelligence and electromagnetic physics non-drug therapy has gradually become 
one[11] of research hotspots in the field of PSCI in recent years. It is worth noting that 
represented by transcranial electrical stimulation of non-invasive brain stimulation is a direct 
role in the therapy of PSCI brain lesions, is often used to combine the curative [12, 13]effect of 
acupoint stimulation in order to achieve better. At the same time, the acupuncture therapy in 
the prevention and control of PSCI reflects a good efficacy [14]and safety. Many clinical studies 
suggest that cupping therapy can improve the PSCI cognitive impairment of patients, improve 

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their quality of life, and cupping therapy can also be treated by syndrome differentiation and 
treatment for patients to provide targeted, to compensate for the limitations of western medicine 
drugs. 
This study intends to study the evolution law of post-stroke cognitive impairment, and to 
carry out 
a 
multi-center, large-sample randomized controlled clinical trial of 
electroacupuncture intervention for PSCI through the standardization of multi-dimensional and 
multi-modality data of PSCI patients, so as to establish the characteristic technology of TCM 
diagnosis and treatment for post-stroke cognitive impairment suitable for promotion. To 
establish the clinical diagnosis and treatment pathways and standards for the dominant diseases 
of traditional Chinese medicine. So as to establish the efficacy evaluation system of PSCI based 
on TCM syndrome diagnosis and evolution law, realize the precise diagnosis and treatment 
mode of PSCI with traditional Chinese and Western medicine, and improve the overall efficacy 
and quality of life of patients. 
 
Second, the main research content, goal, plan and schedule, and to solve the key problem: 
1. The research content 
Of this study was to explore to establish based on the four diagnostic information, 
subjective scores to the modal data more objective efficacy evaluation system, build 
multimodal and multidimensional cognitive impairment after stroke of Chinese and western 
medicine clinical database, application of multivariable space-time map neural network 
(MTGNN) and the Transformer, Build collections of TCM syndrome identification and 
treatment decisions and curative effect of prediction function for the integration of cognitive 
impairment after stroke model, through the study of automatic syndromes, inspection index, 
depend on biological signal between time and space, to adapt to the reality the complex 
characteristics of medical data, implement effective quantitative predictions to effect change, 
To provide a scientific evaluation tool for the recovery of cognitive impairment after stroke 
treated with traditional Chinese medicine. 
Based on multi-center and large-sample clinical randomized controlled trials, an 
individualized and precise treatment plan will be established, the TCM efficacy evaluation 
system of post-stroke cognitive impairment will be innovated, the clinical prevention and 
treatment standards will be formulated, the stimulation parameters of acupoint regulation will 
be clarified, and the precise diagnosis and treatment standards of TCM for post-stroke cognitive 
impairment will be explored. 
 
2. Research objectives 
(1) To observe the improvement of cognition after brain electroacupuncture intervention 

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for cognitive impairment after stroke. 
(2) Based on the task-related information analysis and analysis methods in the multi-mode 
data of TCM syndrome data, clinical assessment, biochemical indicators, brain magnetic 
resonance imaging, electroencephalogram and so on, the systematic syndrome diagnosis and 
clinical evaluation criteria were established, the evolution rule of TCM syndrome of stroke was 
systematically clarified, and the individualized and precise treatment plan was established. 
Based on multi-center and large-sample clinical randomized controlled trials, the establishment 
of precise diagnosis and treatment standards of traditional Chinese medicine for post-stroke 
cognitive impairment was explored. 
(3) To construct an artificial intelligence big data model of TCM syndrome evolution of 
post-stroke cognitive impairment based on multimodal data, and to explore the establishment 
of an objective efficacy evaluation system based on four diagnosis information, subjective 
scoring and multimodal data. 
 
3. The research plan 
Before starting the study, the investigator clearly and orally explained the study and its 
potential risks and benefits to the patient or her licensor. After obtaining consent from the 
patient or her licensor, the patient or her licensor and the investigator signed and dated the 
informed consent form. Patients or their designees could be screened and subsequently enrolled 
in the study only after they had signed the informed consent form. 
Patients who provide written informed consent are then assessed for study eligibility: 
(1) Patients' demographic data and medical history; 
(2) vital signs; 
3.1 Study protocol 
This project intends to collect a total of 68 patients with PSCI in five centers (a total of 
340 persons), including 34 persons in the general acupuncture group and 34 persons in the 
electroacupuncture group. The characteristics of PSCI in each group are studied to 
systematically clarify the evolution rule of TCM syndromes of stroke, establish individualized 
and precise treatment plan, and based on multi-center randomized controlled trial. To explore 
the establishment of precise diagnosis and treatment standards of traditional Chinese medicine 
(TCM) for post-stroke cognitive impairment. 
This study was an experimental study. Patients were screened strictly according to the 
diagnostic criteria, inclusion criteria and exclusion criteria. After confirmation of enrollment, 
they were randomly divided into groups according to the random number table until the total 
number of observed cases was completed. The main research object for the third hospital 
affiliated to zhejiang university of Chinese medicine, acupuncture, the second hospital 

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affiliated to zhejiang university school of medicine, acupuncture, traditional Chinese 
acupuncture, Chinese medicine hospital in zhejiang province and zhejiang province people's 
hospital of hangzhou clinical diagnosis of PSCI patients. 
 
3.1.1 sample size calculations 
The mean change was 0.837 in the experimental group and 0.531 in the control group, and 
the between-group difference was 0.249 and 0.307, respectively. The within-group standard 
deviation was 0.3, α=0.025 (one-sided), Power 1-β was 0.8, and the dropout rate was 15%. 
According to the data to get a total sample size of 340 people, that is, each branch (a total of 
five center) are needed in patients with 68 people (normal acupuncture group including 34 
people, 34). 
 
3.1.2 Randomized controlled trial design and implementation 
(1) Randomization 
The study used the Central Randomization System, and the random order was drawn from 
the randomization system of the Third Affiliated Hospital of Zhejiang Chinese Medical 
University. Applicants by contacting the third hospital affiliated to zhejiang university of 
traditional Chinese medicine two random member, told the participants information, random 
search random result, group information and will inform the applicant. The randomized 
participants did not participate in the intervention, data collection or statistical analysis of the 
study. This study of random solutions by random personnel is responsible for the warehousing, 
the staff is not involved in this study. 
 
(2) blinded design and implementation 
Because the double-blind operation of acupuncture and conventional drug treatment could 
not be well carried out in this study, this study adopted a single-blind (blinded to the patients) 
design. In the whole process of the study, the principle of three separation was implemented: 
the operators, the efficacy evaluation personnel and the statistical analysis personnel were 
separated, and the three personnel could not communicate with each other in the whole process 
of the study. That is, third-party professional statisticians who did not know the grouping 
information performed the efficacy evaluation and statistical analysis of the results, in order to 
avoid the bias of the data results caused by single blindness. 
 
3.1.3 Diagnostic criteria 
3.1.3.1 western medicine diagnostic criteria 
In this study, stroke included cerebral infarction and cerebral hemorrhage. The diagnostic 

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criteria of western medicine was based on the "Diagnostic Points of Major Cerebrovascular 
Diseases in China 2019" formulated by the Chinese Society of Neurology. 
(1) Diagnostic criteria for cerebral infarction 
① Acute onset of focal or global neurological deficits;  
(2) cerebral infarction confirmed by imaging, or symptoms and signs lasting more than 24 
hours, or leading to death within 24 hours; 
③  Non-ischemic causes were excluded. 
(2) Diagnostic criteria for cerebral hemorrhage 
① Sudden focal neurological deficit or headache, vomiting, varying degrees of 
disturbance of consciousness;  
 
②  Cranial imaging showed intracerebral hemorrhage; 
③  excluding other causes of cerebral hemorrhage. 
(3) PSCI diagnostic criteria: Western medicine diagnostic criteria for vascular cognitive 
impairment in the Chinese Guidelines for the Diagnosis and Treatment of Vascular Cognitive 
Impairment (2024 edition) formulated by the Vascular Cognitive Impairment Branch of the 
Chinese Stroke Association: ① There are cognition-related complaints and one or more 
cognitive domains are impaired by neuropsychological tests; ② Evidence of vascular brain 
injury: including vascular risk factors, stroke history, neurological syndromes of 
cerebrovascular injury, and imaging evidence of cerebrovascular injury, but not necessarily all 
of the above at the same time; (3) vascular brain injury dominated in cognitive impairment: 
especially in merger dementia symptoms, should clearly define the role of vascular brain 
damage in cognitive impairment and clinical features need to conform to one of the following 
situations: 1) The onset of cognitive impairment is sudden, and the occurrence of cognitive 
impairment is related to one or more stroke events in time, showing a stepwise or fluctuating 
progression, and the cognitive impairment is within 6 months after the stroke event. 
 
3.1.3.2 TCM diagnostic criteria 
According to the Criteria for Diagnosis and Efficacy Evaluation of Stroke issued by the 
State Administration of Traditional Chinese Medicine: 
Main symptoms: unconscious consciousness, hemiplegia, language Jian astringent or no 
language, partial body sensory abnormalities, tongue deviation. 
Secondary symptoms: vertigo, headache, choking on drinking, dysphagia, non-blink eyes, 
ataxia. 
According to the diagnostic criteria, patients with more than two main symptoms, or one 
main symptom with two secondary symptoms, can be diagnosed as stroke. On the basis of 

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meeting the diagnosis of stroke, patients with clinical symptoms of cognitive impairment in 
accordance with the Guidelines for the Diagnosis and Treatment of Vascular mild cognitive 
Impairment in Traditional Chinese Medicine 2024 Edition were included in the study 
diagnostic criteria. 
 
3.1.4 Inclusion criteria 
(1) Meet the western medical diagnostic criteria of vascular cognitive impairment 
according to the western medical diagnostic criteria of vascular cognitive impairment in the 
Guidelines for Diagnosis and Treatment of Vascular cognitive Impairment in China (2024 
edition) formulated by the Vascular Cognitive Impairment Branch of the Chinese Stroke 
Association. 1) patients with cognitive-related complaints and impairment of one or more 
cognitive domains in neuropsychological tests; 2) presence of evidence of vascular brain injury, 
including vascular risk factors, stroke history, neurological syndromes of cerebrovascular 
injury, and imaging evidence of cerebrovascular injury, but not necessarily all of the above; 3) 
The dominant role of vascular brain injury in cognitive impairment: especially when combined 
with the pathological manifestations of dementia, the dominant role of vascular brain injury in 
cognitive impairment should be clarified, and the clinical features should meet the following 
conditions: The onset of cognitive impairment was sudden, and the occurrence of cognitive 
impairment was related to one or more stroke events in time, showing a stepwise or fluctuating 
progression, and the cognitive impairment appeared within 6 months after the stroke event. 
(2) meet the TCM diagnostic criteria of vascular cognitive impairment in the Guidelines 
for the Diagnosis and Treatment of Vascular Mild cognitive Impairment (2024); 
(3) simple Mental State scale (Mini - getting the State Examination, MMSE) score in 12 
to 24 points, Montreal Cognitive Assessment scale (Montreal Cognitive Assessment, MoCA) 
score in the < 24 points; Patients with cognitive impairment but without severe dementia; The 
national institutes of health Stroke Scale (NIH Stroke Scale, NIHSS) scoring eight points or 
less; Ascertain Dementia 8 (AD-8) score < 2; 
(4) aged between 35-80 years old;  
(5) have basic communication skills, mainly Mandarin (communication language is 
sufficient), and have at least one stable caregiver; 
(6) Informed consent was obtained.  
 
3.1.5 Exclusion criteria 
（1）Merger zang-fu organs such as heart, liver, kidney and severe primary chronic 
diseases such as endocrine system and hematopoietic system, serious heart cerebrovascular 
disease; 

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（2）Patients who are prone to skin diseases such as herpes, ulceration or scar 
constitution on the body surface, and are not suitable for acupuncture treatment; 
（3）Not suitable for repeated MRI examination, such as claustrophobia, aneurysm 
embolization, etc. 
（4）Before the onset of existing cognitive impairment or other serious neurological and 
psychiatric disorders, control unstable patients; 
（5）Other patients deemed by the clinical experimentalists to be unfit for the study; 
（6）Participated in clinical research of related diseases in the past 3 months; 
 
3.1.6 Exclusion and drop-out criteria 
Exclusion criteria (those who have been enrolled but meet one of the following criteria 
should be excluded) : (1) Those who do not meet the inclusion and exclusion criteria are found 
in the trial; (2) obvious adverse reactions occurred during the treatment; (3) The subjects were 
not treated according to the treatment plan after enrollment. 
Drop-out criteria (patients who had been enrolled but had not completed the clinical 
protocol were considered drop-out in the following circumstances) : (1) patients withdrew or 
lost follow-up; (2) serious adverse reactions or adverse events occurred during the treatment. 
 
3.1.7 Discontinuation criteria 
(1) Specialists will be responsible for the evaluation of severe adverse reactions during the 
study to determine whether to continue or terminate the study; 
(2) if the subjects developed serious complications or other serious diseases during the 
study period and needed to take emergency measures; 
(3) the subjects could not continue the study for other reasons. 
 
3.1.8 Adverse events 
The number and reasons of adverse events and dropout from the trial were recorded in 
detail. 
 
3.2 Treatment Regimens 
In this study, a randomized controlled trial of acupuncture and moxibustion for post-stroke 
cognitive impairment was conducted, which systematically clarified the evolution law of TCM 
syndromes of stroke, established an individualized and precise treatment plan, and explored the 
establishment of precise diagnosis and treatment standards of TCM for post-stroke cognitive 
impairment based on the randomized controlled trial. The proposed study period: January 1, 

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2025 (after obtaining ethical approval) to December 31, 2026. Treatment methods are described 
as follows. 
 
3.2.1 Sham EA group: 
Conventional medicine, rehabilitation treatment and ordinary acupuncture treatment: 
① Conventional drug therapy (basic principles of conventional treatment) : according to 
the patient's condition, the basic treatment such as anti-platelet aggregation, lipid-regulating, 
stable plaque, blood pressure and blood glucose control was given, and the specific treatment 
referred to the "Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 
2023". 
(2) rehabilitation treatment, rehabilitation of patients before rehabilitation evaluation, 
rehabilitation goals determine patients, to formulate individualized rehabilitation plan. The 
therapist covered the name of the picture with his hand, and asked the patient to read the content 
of the card and say its purpose. 10 cards/time, 1 time/day; The complete pony puzzle was given 
to the patient, and the patient was asked to take the picture off, and then the patient was asked 
to put it back together, 2 times/time, 1 time/day; Executive function training and problem-
solving skills training: rehabilitation therapists should observe and evaluate the training from 
simple to complex; Time and place orientation training; Activities of daily living training; 
Psychological support therapy. The therapy was given 5 times a week for 30 minutes each time 
for 3 months. 
③ Sham electroacupuncture treatment: 
1) Acupoint selection: main acupoint selection: bilateral para-frontal line (MS2), Tianzhu 
(BL10), Fengchi (GB20), Fuxue (Blood vessels), parietal midline line (MS5) and para-parietal 
line (MS8). The corresponding acupoints: kidney deficiency and blood stasis syndrome plus 
Geshu (BL17) and Shenshu (BL23); Zusanli (ST36) and Sanyinjiao (SP6) were added for qi 
deficiency and blood stasis syndrome. For internal obstruction of phlegm and heat, Yinlingquan 
(SP9) and Fenglong (ST40) were added. Sanyinjiao (SP6) and Taixi (KI3) were added for Yin 
deficiency and fire exuberant syndrome. Pishu (BL20) and Shenshu (BL23) were added to 
spleen-kidney deficiency syndrome. (Refer to "Guidelines for the Diagnosis and Treatment of 
Vascular Mild cognitive Impairment of Traditional Chinese Medicine (2024)" for the syndrome 
type and acupoint selection). 
2) Positioning: Referring to the national standard of the People's Republic of China 
(GB/T 12346-2021) "Name and Location of meridians and acupoints", and referring to the 
national standard of the People's Republic of China (GB/T 21709.2-2021) "Technical 
Specifications for Acupuncture and Moxibustion Part 2: "Scalp Acupuncture" and China 
Medical Science and Technology Press in 2024, "Sixteen meridians of high-dimension bin 

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electroacupuncture". 
3) Operation: in a sitting position, the skin at the acupuncture site was routinely disinfected, 
and the local acupoints were selected with 0.25×40mm filiform needles to smooth reinforcing 
and reducing. At the remote acupoints, 0.25×40mm filiform needle was used for straight 
needling, and the reinforcing method was applied for lifting and thrusting Deqi. The wires of 
electroacupuncture apparatus were connected on the ipsilateral para-frontal line (MS2) and 
Tianzhu (BL10), and sham electroacupuncture was performed with an electroacupuncture 
apparatus that could not output current. 
4) Treatment: once a day, 5 times a week, a total of 8 weeks, a total of 40 times. 
5) Needles and fixtures: The needles and fixtures are disposable Huatuo brand acupuncture 
and moxibustion needles produced by Suzhou Medical Supplies Factory Co., LTD. The 
manufacturer's license is Jiangsu Drug Supervision and Equipment Production License No. 
20010020, and the registration certificate No. 220162200970. The specification is 
φ0.25×40mm (1.5 inch). The electroacupuncture instrument is SDZ-IIB model, produced by 
Suzhou Medical Supplies Factory Co., LTD., but the wire has been cut before the factory, and 
the current cannot be generated. 
 
3.2.2 Electroacupuncture group: 
On the basis of conventional medicine and rehabilitation treatment (ordinary acupuncture 
group), acupuncture electric field therapy was performed: 
① Acupoint selection: the main acupoints and the matching acupoints were selected as 
the sham EA group. 
② Positioning: referring to the Name and Location of meridian points of the national 
standard of the People's Republic of China (GB/T 12346-2021), and referring to the Technical 
operation specification of Acupuncture and Moxibustion of the People's Republic of China 
(GB/T 21709.2-2021) Part 2: Head needle and Chinese medicine science and technology press, 
2024 "including higher dimensional marina 16 unique". 
③ Operation: in a sitting position, the skin of the acupuncture site was routinely 
disinfected, and the local acupoints were selected with 0.25×40mm filiform needle for flat 
reinforcement and flat reduction. At the remote acupoints, 0.25×40mm filiform needle was 
used for straight needling, and the reinforcing method was applied for lifting and thrusting Deqi. 
The electroacupuncture instrument wires were connected at MS2 and BL10 on the ipsilateral 
side, and EA was applied to the head in one pair on each side. 
④ Electroacupuncture parameters: dense wave, frequency 100Hz, current size according 
to the patient's tolerance, treatment time 30 minutes. 
⑤ Treatment course: once a day, 5 times a week, a total of 8 weeks, a total of 40 times. 

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6. Needle and electric acupuncture apparatus: needle with suzhou medical supplies factory 
co., LTD. Hua tuo brand disposable acupuncture needle, production enterprise licence: Sue 
drug safety machinery production license no. 20010020, registration number: Sue machinery 
note no. 220162200970. The specification is φ0.25×40mm (1.5 inch). The electroacupuncture 
instrument is SDZ-IIB model, produced by Suzhou Medical Supplies Factory Co., LTD. 
 
Observation period and time point: 
There were 24 weeks in total, including 1 week in screening period (week 0), 1 week in 
baseline period (week 0), 8 weeks in treatment period (weeks 1-8 after enrollment), and 16 
weeks in follow-up period (weeks 9-24 after enrollment). If the patient's diagnosis was 
confirmed, the screening period and the baseline period could be combined for 1 week. 
Baseline period (week 0) : The main indicators were completed: ①MMSE scale; ②
MoCA scale; ③CDR scale; ④NTB scale; Secondary outcome measures ① Functional near-
infrared spectroscopy (fNIRS) ② electroencephalogram (EEG) ③MRI +DWI perfusion 
imaging ④ Modified RANKIN Scale ⑤ Quality of Life scale (SS-QOL) and Barthel index 
⑥ Pittsburgh sleep quality Index (PSQI) ⑦ Hamilton Depression Scale (HAMD) 
Follow-up period (week 12) : the main indicators were ①MMSE scale ②MoCA scale 
③CDR scale ④NTB scale, and the secondary indicators were ① modified RANKIN scale 
② SS-QOL and Barthel index ③ PSQI scale ④ HAMD. 
Follow-up period (24th week) : the main indicators were completed: ①MMSE scale; ②
MoCA scale; ③CDR scale; ④NTB scale; 
 
3.2.3 Efficacy index and evaluation 
(1) Primary outcome measures 
1) MMSE scale: It is simple and easy to perform, widely used at home and abroad, and 
is the first choice for dementia screening. The scale includes the following 7 domains: time 
orientation, place orientation, immediate memory, attention and calculation, delayed memory, 
language and visuospatial ability. A total of 30 items were included in the scale. Each item was 
scored 1 point for correct answers and 0 point for incorrect or uncertain answers. The test scores 
were closely related to the educational level. The normal cut-off points were: illiterates > 17 
points, primary school > 20 points, junior high school and above > 24 points. The patients were 
evaluated before treatment, 12 weeks and 24 weeks after treatment. 
2) MoCA, which included 11 items in 8 cognitive domains including attention and 
concentration, executive function, memory, language, visual structure skills, abstract thinking, 
calculation and orientation. The total score is 30 points, and ≥26 points are normal. Assessments 

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were performed before treatment and 12 and 24 weeks after the end of treatment. 
3) Neuropsychological test battery (NTB) : Is composed of nine cognitive tests, 
including visual matching memory, wechsler memory scale (WMS) WMS word matching, 
Rey auditory memory vocabulary learning test, WMS test of digit span, language fluency, 
and category fluency test, can be more comprehensive assessment of the cognitive function 
and its damage degree. All patients were assessed at baseline, 12 weeks and 24 weeks after 
the treatment. 
(2) Secondary efficacy indicators 
1) functional near infrared imaging: technical parameters: use between 700-900 - nm 
wavelength near infrared spectrum instrument and record the change of the blood oxygen level 
and cerebral blood flow. The changes of blood oxygen level and cerebral blood flow were 
recorded at 0 week before treatment and 8 weeks after treatment. 
2) Electroencephalogram (EEG) : EEG was recorded. The EEG was performed at 0 week 
before treatment and 8 weeks after treatment. 
2) magnetic resonance imaging (MRI) : has important value in diagnosis and evaluation 
of stroke, the comprehensive assessment of electric effects on brain structure and function. In 
week 0 before and after treatment respectively for 8 weeks. 
3) nerve functional assessment: Modified RANKIN Scale (Modified RANKIN Scale, 
mRS), respectively 0 weeks before and after treatment to evaluate 12 weeks and 24 weeks 
after treatment. 
4) the quality of life: the modified Barthel index rating scale (modified Barthel index, 
MBI) in 0 weeks before and after treatment to evaluate 12 weeks and 24 weeks after 
treatment. 
5) Sleep quality assessment: Pittsburgh sleep quality index (PSQI) was used to evaluate 
sleep quality. PSQI was composed of seven dimensions: subjective sleep quality, sleep onset 
time, sleep duration, sleep interference, use of hypnotics, daytime dysfunction and sleep 
efficiency. The total score of the seven dimensions was the total score of PSQI. In this study, 
sleep quality was divided into "very good" (0-5 points), "good" (6-10 points), "fair" (11-15 
points) and "poor" (16-21 points). In week 0 before treatment and after treatment to evaluate 
12 weeks and 24 weeks after treatment. 
6) The Hamilton Depression Scale (HAMD) was used to evaluate the improvement of 
depression: <7 points indicated no, 7-17 points indicated possible, 17-24 points indicated 
definite, and >24 points indicated severe depression. The patients were evaluated at 0 week 
before treatment, 12 weeks after treatment, and 24 weeks after treatment. 
7) in evaluation of syndromes: refer to the Chinese administration of traditional Chinese 
medicine department of the mild cognitive impairment of vascular origin of traditional Chinese 

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medicine diagnosis and treatment guidelines (2024), 2 by the attending physician or above title 
of doctor of traditional Chinese medicine according to the stroke onset symptoms and signs of 
TCM four diagnostic data acquisition, the advice which assist, doctor evaluation by the 
supervisor. The patients' syndromes were diagnosed dialectically. The patients were evaluated 
at 0 week before treatment, 12 weeks after treatment, and 24 weeks after treatment. 
8) health measuring 12 profiles: use the SF - 12 scale assessment, the scale covers eight 
aspects: function, physical character, body pain, general health, mental health, social function, 
mental health, emotional role. The overall score range of 0-100, said the higher the score, the 
better health. In each dimension of health, standardized scores of 50, said compared with the 
general population, individual health level in the dimension. Outcomes were assessed at the 
end of treatment (week 8). 
 
3.3 Emergency response 
During the trial, acupuncture should be performed under the guidance of a specialist or by 
a senior doctor. If the patient's disease worsens or cannot be relieved by the existing treatment 
during the treatment, which seriously affects daily work and life, emergency adjustment of 
treatment plans and emergency measures can be adopted after the evaluation and diagnosis of 
a specialist, and the specialist can evaluate whether to stop the study. The use of all kinds of 
emergency drugs or other treatment measures the date and time and dose must record in a timely 
manner. 
 

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3.4 Technical route 
 
 
 
 

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Iii. Adverse Events (described according to the subject) 
1. Definitions of adverse events and serious adverse events 
(1) adverse events: currently, the cognitive impairment after stroke in acupuncture 
treatment and no significant adverse events, but there are some unforeseeable factors, such as 
demographic characteristics, age, female and low education level; Stroke-related factors 
included history of stroke or recurrent stroke, hemorrhagic stroke, multiple lesions, large 
volume lesions, dominant hemisphere lesions, etc. After acupuncture, some patients may 
experience fatigue, head and neck discomfort, etc. 
(2) Serious adverse events were defined as adverse events occurring during the study 
period that met one or more of the following criteria: death; Life-threatening; Requiring or 
prolonged hospitalization; Permanently or severely disabled; Causing congenital malformation 
defects. 
Medical events that do not result in death, life threatening, or hospitalization are considered 
serious adverse events when they are judged by appropriate medical judgment to be likely to 
cause harm to the subject or to require medical or surgical treatment to avoid the occurrence of 
the above conditions.  
 
2. Obtain information about adverse events  
All adverse events that were either directly observed by the physician or spontaneously 
reported by the participant were reported by the study physician in concise medical terms. In 
addition, subjects were asked about adverse events each time they were asked after the start of 
treatment to collect trial data. The question could be, "Have you had any health problems since 
you started taking tongue measurements?" "Or" Have you had any unwell health problems 
since you started receiving XX?" "Etc. 
 
3. Observation and recording of adverse events  
Any symptoms, signs, and laboratory abnormalities that occurred from the time of signing 
the informed consent to the end of the last visit were included. The occurrence of adverse events, 
including the time of occurrence, severity, duration, measures taken, and outcomes were 
described. Adverse events were recorded in the designated pathology Report Form Adverse 
Events Table.  
 
4. Management of adverse events and serious adverse events  
(1) Severity: Physicians can use the following definitions to judge the severity of all 
adverse events and serious adverse events as the end point/data cutoff point of the study. 
Mild adverse events were transient and easily tolerated by patients. 

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Moderate adverse events made the subject uncomfortable and prevented the normal 
activities of the subject.  
Severe adverse events affected subjects' activities of daily living to a considerable extent 
and may have resulted in loss of function or be life-threatening. 
(2) Management of adverse events: During the study period, if a patient has adverse 
reactions such as fatigue and weakness, local skin allergy, please tell your study physician 
immediately, and he/she will suspend the study and observe and deal with your discomfort. The 
tongue image information method of this study has a high safety. If you have any injury in the 
process of this study that has been confirmed by relevant institutions and related to this study, 
the researchers will compensate and compensate you in accordance with the relevant national 
laws and regulations. 
For the adverse events that occurred during the trial, the type, degree, occurrence time, 
duration, treatment measures, and treatment process should be recorded in the medical record 
and pathological report form, and whether they were related to the trial should be 
comprehensively analyzed. After the occurrence of adverse events, the investigator can decide 
whether the subject should discontinue the trial according to the patient's condition. Patients 
who discontinued the trial because of serious adverse events should be followed and their 
outcomes recorded. 
(3) Recording and reporting of serious adverse events: if a serious adverse event occurred 
during the trial, regardless of whether it was related to the trial, emergency measures should be 
taken immediately, and the principal investigator and the ethics committee should be notified 
by telephone within 24 hours. A serious adverse event report form was then completed and 
promptly reported to the above departments. 
 
Iv. Ethics and Quality  
Prior ethics committee approval will be obtained before the start of this study. 
It is important to obtain authorized consent for the use and/or disclosure of personal and/or 
health data before enrolling patients. To protect patient privacy, the patient's initials will be 
recorded on the CRF. 
Case report form data collected from the study centers will be checked for consistency, 
and a data query form will be issued for inconsistent data, requiring clarification by the 
physician. 
 
5. Data management 
The investigators will fill in the case report form and collect or record the collected data 
in Excel according to the requirements of the study protocol. Chen Bowen and Fu Luyao are 

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responsible for data management to ensure the authenticity, completeness and accuracy of the 
clinical trial data. At the end of the study, investigators will submit completed and signed case 
report forms for all enrolled patients to the data management center. Case-report form data 
collected from the sites will be checked for consistency, and a question form will be issued in 
response to inconsistent data, requiring clarification by the investigator. 
 
6. Statistical Analysis 
1. Statistical software 
The data were analyzed by a third party statistician who was not involved in the 
preliminary study. Statistical software SPSS 26.0 and GraphPad Prism 8.0 were used for 
statistical analysis. 
2. Data Description 
Measurement data were described by mean ± standard deviation (), median, maximum, 
minimum and quartile, and enumeration data were described by percentage (%).
s
x  
3. Statistics 
SPSS 26.0 and GraphPad Prism 8.0 software were used for data analysis. Quantitative 
variables (normal distribution) were described by mean and standard deviation (X±s) and 
compared by Analysis of Variance (ANOVA). The non-normal distribution data were 
described by median and quartile [M(QL-QU)], and the rank sum test was used for comparison. 
Categorical variables were described by frequency and percentage, and compared by chi-square 
test and Fisher's exact test. Univariate and multivariate Logistic regression models were used 
to explore the relationship between different exposure factors and cognitive function of patients. 
Mixed linear models were used to capture individual differences and to analyze the differences 
in multimodal brain function data between groups. All tests were two-sided, and P<0.05 was 
considered statistically significant. 
4. Statistical Analysis Plan 
Done by professional statisticians. After all data entry and review, the statistician should 
complete the statistical analysis work in time and issue a written statistical analysis report. 
 
Vii. Final report and publication 
After the study is completed, the study report will include a description of the study's 
objectives, the methods used in the study, and the results and conclusions.  
 
Viii. Quality control 
(1) The test SOP should be formulated by the research group. 
(2) A special training meeting was held one month before the official start of the clinical 

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trial, and unified training was conducted for all investigators. The training mainly focused on 
the project implementation plan and various standard operating procedures (Sops), so that each 
clinical researcher could be familiar with the research process and specific implementation 
rules, and ensure the reliability of the clinical research conclusions. 
(3) All observations in clinical research should be verified and repeatedly confirmed to 
ensure the reliability and originality of the data, and to ensure that the results and conclusions 
in clinical research are derived from the original data. 
(4) To control the bias of the trial, special personnel should be employed to collect and 
count the trial data. A professional data management company was commissioned for clinical 
data management. 
(5) The quality inspection of clinical research should be strictly carried out once a month. 
 
Ix. References 
[1]  
MA Q, LI R, WANG L, et al. Temporal trend and attributable risk factors of stroke 
burden in China, 1990-2019: an analysis for the Global Burden of Disease Study 2019 [J]. The 
Lancet Public health, 2021, 6(12): e897-e906. 
[2]  
TU W J, ZHAO Z, YIN P, et al. Estimated Burden of Stroke in China in 2020 [J]. 
JAMA network open, 2023, 6(3): e231455. 
[3]  
XIA X, YUE W, CHAO B, et al. Prevalence and risk factors of stroke in the 
elderly in Northern China: data from the National Stroke Screening Survey [J]. Journal of 
neurology, 2019, 266(6): 1449-58. 
[4]  
HUANG Y Y, CHEN S D, LENG X Y, et al. Post-Stroke Cognitive Impairment: 
Epidemiology, Risk Factors, and Management [J]. Journal of Alzheimer's disease : JAD, 2022, 
86(3): 983-99. 
[5]  
JOKINEN H, MELKAS S, YLIKOSKI R, et al. Post-stroke cognitive impairment 
is common even after successful clinical recovery [J]. European journal of neurology, 2015, 
22(9): 1288-94. 
[6]  
LO J W, CRAWFORD J D, DESMOND D W, et al. Profile of and risk factors for 
poststroke cognitive impairment in diverse ethnoregional groups [J]. Neurology, 2019, 93(24): 
e2257-e71. 
[7]  
LEYS D, HeNON H, MACKOWIAK CORDOLIANI MA, et al. Poststroke 
dementia [J]. The Lancet Neurology, 2005, 4(11): 752-9. 
[8]  
QUINN T J, RICHARD E, TEUSCHL Y, et al. European Stroke Organisation and 
European Academy of Neurology joint guidelines on post-stroke cognitive impairment [J]. 
European stroke journal, 2021, 6(3): I-xxxviii. 
[9]  
SUN J H, TAN L, YU J T. Post-stroke cognitive impairment: epidemiology, 
mechanisms and management [J]. Annals of translational medicine, 2014, 2(8): 80. 
[10]YU K H, CHO S J, OH M S, et al. Cognitive impairment evaluated with Vascular 
Cognitive  
Impairment Harmonization Standards in a multicenter prospective stroke cohort in Korea 
[J]. Stroke, 2013, 44(3): 786-8. 
[11] Chen L. Research progress of non-pharmacological therapy for post-stroke cognitive 
impairment [J]. Chin & Foreign Med Research, 2024, 22(07): 181-4. (in Chinese) 
[12] Jiang Xin-lin, Zhu Ming-Yue, Fan Lei et al. [12] JIANG X L, ZHU M Y, FAN L, et 
al. Research progress of non-invasive brain stimulation technology in the treatment of post-
stroke cognitive impairment [J]. Chinese Journal of Practical Clinical Medicine, 2024, 28(13): 
144-8. 
[13] Guo Tingting, Ji Bo, Liu Yitian et al. [13] GUO T T, Ji B, LIU Y T, et al. Research 

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on the application rules of stimulation parameters of electroacupuncture and transcranial 
electrical stimulation in the treatment of dementia based on data mining [J]. Shanghai Journal 
of Traditional Chinese Medicine. 2023, 57(04): 65-71. 
[14]LI Y, CUI R, LIU S, et al. The efficacy and safety of post-stroke cognitive impairment 
therapies: an umbrella review [J]. Frontiers in pharmacology, 2023, 14: 1207075.