1. Research Purpose and Background
To evaluate efficacy and safety of acupuncture treatment on mild cognitive impairment, investigating whether 24 sessions of acupuncture treatment for 12 weeks in patients with mild cognitive impairment improves cognitive function compared to sham acupucnture control.
The neuroimaging method will be used to evaluate the differences of brain activities and brain structural and functional changes related to working memory and to figure out the mechanisms of central nervous system through analysis of the correlation between neuroimaging and clinical efficacy.

2. Subject / Intervention / Outcome measurements
1) Subjects: Mild cognitive impairment

2) Intervention
- Treatment group: Acupuncture treatment (GV20, EX-HN1, LI04, ST36)
- Control group: using streitberger device, non-penetrating on the same acupoints.

3) Outcome measurments
i) Primary outcome
- Digit span test (week 12)

ii) Secondary outcome
- Digit span test (week 4, week 8)
- Digit symbol substitution test (week 4, week 8, week 12)
- MoCA-K (Korean version of Montreal Cognitive Assessment) (week 12)
- SNSB (Seoul Neuropsychological Screening Battery-II ) (week 12)
- BDI-II (Beck Depression Inventory, Second Edition) (week 12)

- Task memory task performance score (week 12)
- Brain activity change by task memory task performance (week 12)
- Changes in brain activity due to emotional imaging stimuli (week 12)
- Evaluation of cerebral blood flow (week 12)
- Changes in functional and structural networks of the brain (week 12)

iii) safety assessment outcome
- Adverse events (every visit)

3. Research hypothesis
We hypothesized that when acupuncture was given, it would induce changes in brain structural and functional network and cerebral blood flow.
To prove this hypothesis, we will evaluate the activity of the related brain area using the working memory task which evaluates the memory and the space-time constructing ability, and the brain structural and functional networks which performs the central executive control. We will also evaluate the difference in cerebral blood flow changes using magnetic resonance imaging (MRI). We will figure out the neurological mechanism of improvement of cognitive function in acupuncture treatment by correlation analysis between therapeutic effect of acupucnture and changes of central nervous system detected by MRI.

Treatment

Subjects are randomly assigned to either acupuncture group or sham acupuncture group. In the acupuncture group, acupuncture penetrates the skin, whereas in the sham acupuncture group, the acupuncture does not penetrate the skin. Both groups receive acupuncture or sham acupuncture treatment on nine acupoints(GV20, EX-HN1, LI4, ST36) twice a week for twelve weeks (total 24 sessions). During the clinical trials, both groups restricted all treatments for improvement of cognitive functions.

Arm Label

Target Number of Participant

Arm Type

Arm Description

STRICTA Checklist item
1) Acupuncture rationale
1a) Style of acupuncture (e.g. Traditional Chinese Medicine, Japanese, Korean, Western medical, Five Element, ear acupuncture, etc) : Korean body acupuncure
1b) Reasoning for treatment provided, based on historical context, literature sources, and/or consensus methods, with references where appropriate : We selected the optimal treatment regimen based on university textbooks on meridian and acupuncture, and literature review of clinical trials investigating acupuncture therapy on mild cognitive impairment and dementia.
1c) Extent to which treatment was varied : None

2) Details of needling
2a) Number of needle insertions per subject per session (mean and range where relevant) : 9
2b) Names (or location if no standard name) of points used (uni/bilateral) : GV20, EX-HN1, LI4(bilateral), ST36(bilateral)
2c) Depth of insertion, based on a specified unit of measurement, or on a particular tissue level : 5 - 30 mm
2d) Response sought (e.g. de qi or muscle twitch response) : None
2e) Needle stimulation (e.g. manual, electrical) : manual
2f) Needle retention time : 15 minutes
2g) Needle type (diameter, length, and manufacturer or material). : 0.30 * 30mm, sterilized stainless steel needle(Asia-med GmbH & Co. KG, Kirchplatz 1,Germany)

3) Treatment regimen
3a) Number of treatment sessions : acupunture group - 24 sessions, sham acupuncture group - 24 sessions
3b) Frequency and duration of treatment sessions. : twice per week for 12 weeks (total 24 sessions)

4) Other components of treatment
4a)  Details of other interventions administered to the acupuncture group (e.g. moxibustion,  cupping, herbs, exercises, lifestyle advice) : None
4b)  Setting and context of treatment, including instructions to practitioners, and information and explanations to patients. : Hospital outpatient department

5)  Practitioner background : Specialist in oriental neuropsychiatry or more than one-year career resident under the guidance of a oriental psychiatric specialist

Arm Label

Target Number of Participant

Arm Type

Arm Description

6) Control or comparator interventions
6a) Rationale for the control or comparator in the context of the research question, with sources that justify this choice : As placebo control, non-penetrating sham acupuncture will be used.
6b) Precise description of the control or comparator. If sham acupuncture or any other type of acupuncture-like control is used, provide details as for Items 1 to 3 above. : Non-penetrating acupuncture treatment on the same acupoints using Streitberger device.

Gender

Age

Description

1) Patients who meet the criteria for mild cognitive impairment (MCI)
2) Men and women aged 50 to 70
3) Suffering memory loss of more than 3 months
4) Education level of more than 6 years
5) a Korean-type Montreal Cognitive Assessment (MoCA-K) score < 23
6) a CDR (Clinical Dementia Rating) score of 0.5 and GDS (Global Deterioration Scale) grade 2-3
7) a Modified Hachinski Ischemic Score (HIS) score of 4 or less
8) Voluntarily signed the informed consent form

1) Patients who meet the criteria for dementia of DSM-5 (Diagnostic and Statistical Manual of Mental Disorder)
2) Presenting cerbral lesions or brain damage
3) History of cerebral hemorrhage or cerebral infarction
4) Neurological disorderssuch as Parkinson's disease, epilepsy, brain tumor, and etc.
5) Mental disorder such as major depressive disorder, schizophrenia, bipolar disorder, and etc.
6) Participations in other clinical trials within the last 4 weeks
7) Receiving acupuncture treatments within the last 4 weeks due to cognitive impairment
8) Taking medications related to dementia
9) Pregnant or lactating women
10) Obstructive phobia or metal implantation
11) Patient who have experienced hypersensitivity reactions after acupuncture treatment, or who are difficult to cooperate with acupuncture treatment
12) Others judged inappropriate as subjects by researchers

Digit span test

week 12

Digit span test

week 4, week 8

Digit Symbol Substitution Test (DSST)

week 4, week 8, week 12

Korean Version of Montreal Cognitive Assessment (MoCA-K)

12 weeks

Seoul Neuropsychological Screening Battery-II (SNSB-II)

week 12

Korean Beck Depression Inventory-II (BDI-II)

week 12

State-Trait Anxiety Inventory (STAI)

week 12

working memory task performance score

week 12

Brain activity change by working memory task performance

week 12

Brain activity change by emotional image stimulation

week 12

Changes of cerebral blood flow

week 12

Changes in functional and structural networks of the brain

week 12

Adverse events

every visit