STUDY PROTOCOL article

Front. Neurol.

Sec. Dementia and Neurodegenerative Diseases

Volume 16 - 2025 | doi: 10.3389/fneur.2025.1592829

This article is part of the Research TopicNeuroinflammation, Neurodegeneration, and Auditory-Vestibular DisordersView all 11 articles

Evaluating the Safety and Feasibility of Remote Ischemic Conditioning (RIC) for Slowing Cognitive Decline in Mild Alzheimer's Dementia

Provisionally accepted
  • 1Department of Neurology, Beijing Luhe Hospital, Capital Medical University, Beijing, China
  • 2Division of Critical Care Medicine, Mayo Clinic, Rochester, MN, USA, Rochester, United States
  • 3Department of Neurology, School of Medicine, Wayne State University, Detroit, Michigan, United States

The final, formatted version of the article will be published soon.

Objective. Alzheimer's disease (AD) is characterized by complex pathological mechanisms involving neuroinflammation, oxidative stress, and vascular dysfunction.Remote Ischemic Conditioning (RIC) has shown potential in addressing these pathways by improving cerebral blood flow, reducing oxidative stress, and modulating inflammatory responses. This protocol focuses on evaluating the safety, feasibility, and preliminary efficacy of RIC as a multi-target intervention for delaying cognitive decline in patients with mild Alzheimer's dementia, aiming to improve cognitive outcomes and overall quality of life.Results. This study is a randomized, controlled, single-center, prospective clinical trial designed to evaluate the safety, feasibility, and preliminary efficacy of RIC in patients with mild Alzheimer's dementia. Eligible participants will be recruited and randomly assigned to either the RIC group or a control group receiving sham RIC, with 20 patients in each group. Participants will receive either RIC or sham RIC once daily over a 3month period. Outcome measures will assess cognitive function, psychological well-being, and inflammatory and neurodegenerative biomarkers. Psychiatric adverse events will be monitored throughout the treatment using the Hamilton Anxiety Rating Scale (HAMA) and the Hamilton Depression Rating Scale (HAMD-17). Cognitive function and daily living abilities will be evaluated at baseline, 3 months, 6 months, and 12 months post-treatment using the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating (CDR), and the Activities of Daily Living (ADL) scales. In addition, blood samples will be collected at each time point to measure plasma biomarkers of β -amyloid species and serum inflammatory cytokines to assess potential changes in cognitive decline, disease progression, and inflammation. The primary endpoint is safety, with the expectation that RIC will not increase psychiatric adverse events as reflected in HAMA and HAMD-17 scores. Primary efficacy endpoints include improvements in MMSE, MoCA, CDR, and ADL scores, indicating potential cognitive benefits and enhanced daily functioning. Secondary endpoints will analyze biomarkers to evaluate disease progression and inflammation levels before and after treatment.This trial aims to determine the safety, feasibility, and potential effectiveness of RIC as a multi-target intervention for mild Alzheimer's dementia by integrating cognitive and neuropsychological assessments with biological markers, providing a foundation for future studies.

Keywords: Alzheimer Disease, non-pharmacological intervention, Cognition Disorders, neurodegenerative biomarkers, Multi-target Intervention

Received: 13 Mar 2025; Accepted: 03 Jun 2025.

Copyright: © 2025 Huang, Ji, Tong, Cai, Elmadhoun, Zeng, Geng and Ding. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Yanfang Zeng, Department of Neurology, Beijing Luhe Hospital, Capital Medical University, Beijing, China
Yuchuan Ding, Department of Neurology, School of Medicine, Wayne State University, Detroit, MI 48201, Michigan, United States

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