Neural Mechanism of Cognitive Reserve in Acupuncture Stimulation: Protocol for a Randomized, Placebo-Controlled Functional Near-Infrared Spectroscopy Trial
Authors: Shin Hyeonsang , Seong Woohyun , Woo Yeonju , Kim Joo-Hee , Park Kwang-Rak , Lee Dong Hyuk 
Published: January 2025

Background
Dementia is a clinical syndrome characterized by a progressive decline in various cognitive domains. Since there is still no treatment for dementia, early diagnosis and prevention are the best approaches. In this context, the cognitive reserve (CR) concept has received considerable attention in dementia research with regard to prognosis. It originates from discrepancies between the degree of brain pathology and clinical manifestations. Acupuncture, as a complementary intervention, has long been widely applied in neurological diseases in East Asia. At the macroscale level, how acupuncture stimulation affects neural activity concerning CR in normal aging and dementia is largely unknown.

Objective
The aim of this study is to investigate the acute neural mechanisms of acupuncture stimulation concerning CR in the normal aging group and the group with cognitive impairment using neuroimaging methods.

Methods
This study is a randomized, placebo-controlled trial. Participants without (n=30) and with cognitive impairment (n=30) will be randomly assigned to the verum or sham acupuncture groups. The verum acupuncture group will receive acupuncture stimulation at acupoints related to cognitive function and gain deqi sensation. The sham acupuncture group will receive superficial needling at nonacupoints not related to cognitive function. Each group will undergo cognitive function tests, functional near-infrared spectroscopy imaging before and after acupuncture stimulation, and an assessment of CR. The primary outcomes will be differences in resting brain activities according to disease status, differences in resting brain connectivity before and after acupuncture stimulation between the 2 groups, and changes in brain activity in relation to the CR index. The secondary outcomes will be brain connectivity or network metrics associated with CR and differences in neural activity between the cognitive task and resting states.

Results
The recruitment began in August 2023; to date, there have been 50 participants, divided into 20 in the group with cognitive impairment and 30 in the unimpaired group. The recruitment process will continue until February 2025.

Conclusions
CR refers to the individual susceptibility to age-related brain changes and pathologies in cognitive impairment, and it is a factor affecting the trajectories of the disease. Although acupuncture is a widely used intervention for various neurological diseases, including dementia, its mechanism associated with CR at the macroscale has not been clearly identified. This study could contribute to identifying the neural mechanisms of acupuncture stimulation associated with CR using neuroimaging methods and provide a basis for future longitudinal research.

Trial Registration
Clinical Research Information Service of the Republic of Korea KCT0008719; https://tinyurl.com/ydv5537n

International Registered Report Identifier (IRRID)
DERR1-10.2196/66838