China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI) to Prevent Cognitive Decline: Study Design and Progress

Background

Alzheimer’s disease (AD), the most common type of irreversible dementia, is predicted to affect 152 million people by 2050. Evidence from large-scale preventive randomized controlled trials (RCTs) on modifiable risk variables in Europe has shown that multi-domain lifestyle treatments for older persons at high risk of dementia may be practical and effective. Given the substantial differences between the Chinese and European populations in terms of demographics and living conditions, direct adoption of the European program in China remains unfeasible. Although a RCT has been conducted in China previously, its participants were mainly from rural areas in northern China and, thus, are not representative of the entire nation.There is an urgent need to establish cohorts that represent different economic, cultural, and geographical situations in order to explore implementation strategies and evaluate the effects of early multi-domain interventions more comprehensively and accurately.

Medtods

We developed an integrated intervention procedure implemented in urban neighborhood settings, namely China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI). CHINA-IN-MUDI is a 2-year multicenter open-label cluster-randomised controlled trial centered around a Chinese-style multi-domain intervention to prevent cognitive decline. Participants aged 60–80 years were recruited from a nationally representative study, i.e. China Healthy Aging and Dementia Study cohort. An external harmonization process was carried out to preserve the original FINGER design. Subsequently, we standardized a series of Chinese-style intervention programs to align with cultural and socioeconomic status. Additionally, we expanded the secondary outcome list to include genomic and proteomic analyses. To enhance adherence and facilitate implementation, we leveraged an e-health application.

Results

Screening commenced in July 2022. Currently, 1,965 participants have been randomized into lifestyle intervention (n = 772) and control groups (n = 1,193). Both the intervention and control groups exhibited similar baseline characteristics. Several lifestyle and vascular risk factors were present, indicating a potential window of opportunity for intervention. The intervention will be completed by 2025.

Conclusions

This project will contribute to the evaluation of the effectiveness and safety of intervention strategies in controlling AD risk and reducing clinical events, providing a basis for public health decision-making in China.

Availability of data and materials: The datasets during the current study are not publicly available due to privacy and ethical restrictions but are available from the corresponding author on reasonable request.

Aβ:

Amyloid β

AD:

Alzheimer’s disease

ADL:

ability of daily living

AI:

artificial intelligence

ApoE:

apolipoprotein E

BMI:

body mass index

CAIDE:

Cardiovascular risk factors for aging and dementia

CRF:

Case Report Form

CHINA-IN-MUDI:

China initiative for multi-domain intervention

DNA:

DeoxyriboNucleic Acid

EHR:

electronic health records

ERP:

event related potential

FINGER:

Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability

HEAD:

China HEalth Aging and Dementia Study

MCI:

mild cognitive impairment

MIND-China:

Multimodal INterventions to delay Dementia and disability in rural China

MMSE:

Mini-Mental State Examination

MRI:

magnetic resonance imaging

mITT:

modified intention-to-treat

NIA-AA:

National Institute on Aging-Alzheimer’s Association workgroup

NTB:

neuropsychological test battery

PD:

Parkinson disease

PET-CT:

Positron Emission Tomography-Computed Tomography

PSG:

polysomnography

QOL:

quality of life

RCTs:

randomized controlled trials

rsEEG:

resting-state electroencephalogram

SD:

standard deviation

SINGER:

the SINgapore GERiatric intervention study

sMRI:

structural Magnetic Resonance Imaging

We thank all participants for their willingness to participate in the study and the time they devoted to the study.

Funding: This study was supported by the Science and Technology Innovation 2030 Major Projects (2022ZD0211600) and the National Natural Science Foundation of China (82171491).

1. Joint first authors: Shi-Yue Li, Xin-Yan Xie, Dan Liu, Gui-Rong Cheng, Fei-Fei Hu, and De-Yang Zeng

Authors and Affiliations

1. Geriatric Hospital Affiliated to Wuhan University of Science and Technology, West Huangjiahu Road, Hongshan District, Wuhan, 430065, China

   S.-Y. Li, X.-Y. Xie, D. Liu, G.-R. Cheng, F.-F. Hu, D.-Y. Zeng, Y.-L. Zhou, H.-J. Chang, Y.-M. Ou, L. Xu, J.-J. Zhang, J.-Y. Wang, L.-Y. Huang, Y.-Y. Cui, J. Zhou, X.-C. Liu, J. Liu, Q.-Q. Nie, D. Song, C. Cai, G.-B. Han & Yan Zeng

2. Brain Science and Advanced Technology Institute, School of Medicine, Wuhan University of Science and Technology, West Huangjiahu Road, Hongshan District, Wuhan, 430065, China

   S.-Y. Li, X.-Y. Xie, D. Liu, G.-R. Cheng, F.-F. Hu, D.-Y. Zeng, J.-J. Zhang, J.-Y. Wang, L.-Y. Huang, Y.-Y. Cui, J. Zhou, X.-C. Liu, J. Liu, Q.-Q. Nie, D. Song, C. Cai, G.-B. Han, X. Yang, Wei Tan & Yan Zeng

3. School of Public Health, Wuhan University of Science and Technology, Wuhan, China

   S.-Y. Li, X.-Y. Xie, D. Liu, G.-R. Cheng, F.-F. Hu, D.-Y. Zeng, Y.-L. Zhou, H.-J. Chang, Y.-M. Ou, L. Xu, J.-J. Zhang, J.-Y. Wang, L.-Y. Huang, Y.-Y. Cui, J. Zhou, X.-C. Liu, J. Liu, Q.-Q. Nie, D. Song, C. Cai, G.-B. Han & Yan Zeng

4. Department of Neurology and National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Huashan Hospital, Shanghai Medical College, Fudan University, 12th Wulumuqi Zhong Road, Shanghai, 200040, China

   Jin-Tai Yu

5. Department of Neurology, Fujian Medical University Union Hospital, and Fujian Key Laboratory of Molecular Neurology, Institute of Neuroscience, Fujian Medical University, Fuzhou, China

   X.-C. Chen

6. Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China

   L.-F. Jia

7. Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing, China

   Y.-J. Wang & X.-L. Bu

8. Computer Science and Technology, Wuhan University of Science and Technology, Wuhan, China

   C. Qiu, F. Gao, J.-G. Gu & M.-F. Liu

9. Department of Laboratory Medicine, Hubei Provincial Hospital of Integrated Chinese & Western Medicine, Wuhan, China

   Y. Li

10. Wuchang Hospital affiliated to Wuhan University of Science and Technology, Wuhan, China

    Z.-X. Wu

Contributions

Author contribution: Clinical sites. 1. School of Medicine, Wuhan University of Science and Technology, PI: Yan Zeng (MD/PhD), and Geriatric Hospital Affiliated to Wuhan University of Science and Technology, Co-PI: Wei Tan (MD/PhD). 2. Huashan Hospital, Shanghai Medical College, Fudan University, PI: Jin-Tai Yu (MD/PhD). 3. Fujian Medical University Union Hospital, and Fujian Key Laboratory of Molecular Neurology, Institute of Neuroscience, Fujian Medical University, PI: Xiao-Chun Chen (MD/PhD). 4. Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, PI: Long-Fei Jia (MD/PhD). 5. Daping Hospital, Third Military Medical University, PI: Yan-Jiang Wang (MD/PhD). YZ, GC, DL, WT, JY, XC, LJ, YW conceptualized and designed the study; SL, XX, FH, DZ, XB, YL, YZ, HC, MO, LX, ZW, JZ, JW, LH, YC, JZ, CL, JL, QN, DS, CC, GH, and XX acquired, analysed, or interpreted of data; XX conducted statistical analysis; SL, XX, and YZ drafted and critically revised the manuscript; CQ, FG, JG, and LM carried out the development of app. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Wei Tan, Jin-Tai Yu or Yan Zeng.

Ethics approval and consent to participate: China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI) (ChiCTR, www.chictr.org.cn; Registration number: ChiCTR2300075181) was approved by the ethics committee of the Wuhan University of Science and Technology (protocol code: 2023035), Wuhan, China. This study has been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments. Written informed consents were obtained from all participants, or in the case of illiteracy and inability to write, from a proxy (usually a guardian or a family member), and were kept in the CHINA-IN-MUDI study administrative office.

Consent for publication: Not applicable.

Competing interests: The authors declare that they have no competing interests.

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