Efficacy and Olfactory Network of Electro-acupuncture for Subjective Cognitive Decline: A Multicenter Randomized Controlled Trial and fMRI Study

Subjective cognitive decline (SCD) is the early diagnosis and treatment window period of Alzheimer's disease (AD), and the identification of SCD individuals who will progress to AD (pSCD) is a research hotspot. Based on olfactory fMRI,previous studies have found that SCD individuals showed damaged entorhinal neural circuits. After follow-up, the incidence of pSCD increased by three times. But,the spatiotemporal characteristics of the entorhinal neural circuits and whether it has the value of individualized prediction and intervention target need to be further studied. Thus, based on multi-center ambispective cohort study at home and abroad, we will (1) build a new paradigm of synchronous fMRI-EEG olfactory task state Oddball experiment, jointly representational similarity analysis, extract spatiotemporal characteristics of neural circuits damage, and discover and verify that the entorhinal neural circuits are vulnerable brain regions; (2) establish the middle fusion model of vulnerable brain region combined with the methods of olfactory task-fMRI activation image generation, functional connectome gradient,etc.; Then, establish late fusion multi-omics multi-task model combined with the new methods of molecularomics such as ultra-deep total proteomics and metabonomics proposed by the research group to accurately identify pSCD; (3) carry out the precise intervention of image-guided "olfactory three-needle" acupuncture with the entorhinal neural circuits as the target. Through clinical RCT research and mouse model, the remodeling mechanism of vulnerable brain regions will be clarified.This project will provide the basis for early diagnosis and treatment of the AD risk population.

Study Overview

• Status: Active, not recruiting
• Conditions: Subjective Cognitive Decline (SCD)
• Intervention / Treatment: Device: "TXJN" electro-acupuncture; Device: sham acupuncture

• Study Type: Interventional
• Enrollment (Estimated): 92
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Meet the diagnostic criteria for SCD diseases;
2. 55-79 years old;
3. ≥8 years of schooling;
4. Right-handed;
5. Sign the informed consent.

Exclusion Criteria:

1. Have received other antidepressant therapy or involved in other clinical trials in the previous 2weeks.
2. Infarct located in the left DLPFC.
3. Positive psychiatric history and major trauma exposure history, such as depression, epilepsy, etc., in the past.
4. Other serious concomitant diseases (aphasia, severe edema, venous thrombosis, arteriosclerosis occlusion, diabetic vascular disease, peripheral neuropathy, spinal lesions, brain trauma, intracranial infection, brain tumors, etc.) or secondary diseases (heart, liver, renal failure, etc.).
5. Infection around acupoints and/or intolerance to acupuncture manipulation.
6. MRI or rTMS contraindications (claustrophobia, metal implants, cochlear implants, impulsator, etc.).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group	Device: "TXJN" electro-acupuncture; Firstly, EA treatment will be administered at the Neiguan (PC6, bilateral), Shenting(GV23), Yingxiang(LI20, bilateral), Yintang(GV29) acupoints. Disposable stainless-steel needles (0.25 mm × 25 mm; Huatuo brand, Suzhou Medical Supplies Factory Co., LTD., Suzhou City, China) will be used. After skin disinfection, the acupuncturists will twist and thrust the needle handles to achieve the sensations of achiness, heaviness, and numbness (known as de qi) at all above-mentioned acupoints. Following needle manipulations, EA instruments (SDZ-V, Hwato brand, Suzhou Medical Supplies Factory Co., Ltd., Suzhou City, China) will be used to attach the needle handles at PC6, GV23, LI20, GV29, with a dilatational wave of 5 Hz and a current intensity of 2 ~ 4 mA depending on the patient's tolerance. The needles will be removed after 30 min. Participants will receive 24 sessions over 8 weeks at a frequency of 3 times per week.
Sham Comparator: Control group	Device: sham acupuncture; Firstly, EA treatment will be administered at the non-acupoints near above-mentioned real acupoints. Disposable stainless-steel needles (0.25 mm × 25 mm; Huatuo brand, Suzhou Medical Supplies Factory Co., LTD., Suzhou City, China) will be used. After skin disinfection, the acupuncturists will take the needle into the acupoints without the sensations of de qi. Following needle manipulations, EA instruments (SDZ-V, Hwato brand, Suzhou Medical Supplies Factory Co., Ltd., Suzhou City, China) will be used to attach the needle handles at non-acupoints without the current. The needles will be removed after 30 min. Participants will receive 24 sessions over 8 weeks at a frequency of 3 times per week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comprehensive Z score	The neuropsychological scale of 8 objective cognitive assessments used in the study (including AVLT (S and L), AFT, BNT, TMT (A and B), SCWT-C, DSST, DST, CDT) was converted into Z scores for description. Specific operations: Standardize the score of a single cognitive domain scale, create the corresponding Z-score data set, calculate the average value of each data in the group to generate a single Z-score, and sum the Z-score of each single cognitive domain to generate the overall Z-score. Patients were evaluated before treatment and 8 weeks later.	Before and 8 weeks after treatment
Multimodal magnetic resonance imaging of olfactory related neural circuits	Structural MRI(3DTIWI/3DT2WI/3Dflair), functional MRI(BOLD\NODDI\ASL\ QSM)	Before and 8 weeks after treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
mini-mental state examination, MMSE	Before and 8 weeks after treatment
Montreal Cognitive Assessment,MoCA	Before and 8 weeks after treatment
Subjective cognitive self-scoring	Before and 8 weeks after treatment
Hamilton Depression Scale，HAMD	Before and 8 weeks after treatment
the Geriatric Depression Scale,GDS	Before and 8 weeks after treatment
Hamilton Anxiety Scale,HAMA	Before and 8 weeks after treatment
auditory verbal learning test,AVLT	Before and 8 weeks after treatment
Rey complex figure test,CFT	Before and 8 weeks after treatment
Boston naming test,BNT	Before and 8 weeks after treatment
Animal fluency test,AFT	Before and 8 weeks after treatment
rail making test-A,TMT-A	Before and 8 weeks after treatment
rail making test-B,TMT-B	Before and 8 weeks after treatment
complex figure test, CFT	Before and 8 weeks after treatment
clock drawing test,CDT	Before and 8 weeks after treatment
Symbol Digit Modalities Test,SDMT	Before and 8 weeks after treatment
odor threshold test,OTT	Before and 8 weeks after treatment
The olfactory behavioral test	Before and 8 weeks after treatment
Spatial navigation behavior test	Before and 8 weeks after treatment
Pittsburgh sleep quality index,PSQI	Before and 8 weeks after treatment
TCM physique classification scale	Before and 8 weeks after treatment
TCM syndrome type scale of mild cognitive impairment	Before and 8 weeks after treatment

Other Outcome Measures

Outcome Measure	Time Frame
Acceptance survey	After 8 weeks of treatment
Adverse event	During treatment

Collaborators and Investigators

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2024
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: December 25, 2024
• First Submitted That Met QC Criteria: December 25, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: 2024-050-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No