Effect of acupuncture on brain regions modulation of mild cognitive impairment: A meta-analysis of functional magnetic resonance imaging studies

Acupuncture has attracted growing interest as an alternative treatment for several neurological conditions, especially mild cognitive impairment (MCI). This condition, considered an intermediate stage between normal aging and dementia, affects approximately 15.5% of Chinese adults over 60 years of age and represents a major public-health problem. Patients with MCI exhibit subtle cognitive decline, primarily memory-related, without significantly impairing their daily activities, but with a ten-fold higher risk of developing dementia. Currently, no medications are specifically approved to treat MCI, making the search for effective non-pharmacological interventions essential.

Recent advances in neuroimaging, particularly functional magnetic resonance imaging, have provided new perspectives for understanding the central mechanisms through which acupuncture may benefit patients with MCI. Previous studies have demonstrated that acupuncture can improve cognitive and memory function, possibly through mechanisms such as reduction of toxic protein accumulation in the brain, decreased neuronal inflammation, and improved connectivity among neurons. However, individual studies have limitations due to small sample sizes, resulting in inconsistent findings about which brain regions are effectively modulated by acupuncture.

This study used a rigorous methodological approach known as coordinate-based meta-analysis, specifically the SDM-PSI method (Seed-based d Mapping with Permutation of Subject Images). The researchers conducted a systematic search across multiple databases, including PubMed, EMBASE, Web of Science, and Chinese databases such as CNKI, looking for studies that used functional MRI to evaluate the effects of acupuncture on MCI. Only studies that provided precise brain coordinates and used the regional homogeneity (ReHo) method for image analysis were included. This method measures the synchronization of brain activity in specific regions, serving as a marker of local brain function.

Seven studies met the inclusion criteria, totaling 94 patients in the treatment group and 112 in the control group.

The results revealed that acupuncture produced significant increases in brain activity in six specific regions after treatment. The most relevant areas included the right insula and the left anterior cingulate gyrus, regions fundamental for emotional processing, attention, and decision-making. The right thalamus, known as a brain information relay center, also showed greater activity, as did the right middle frontal gyrus, related to working memory and executive functions. Additionally, the right median cingulate and middle temporal gyri showed hyperactivation after acupuncture.

When the researchers separately analyzed the more rigorous studies (randomized clinical trials and longitudinal studies), they confirmed that the right insula and left anterior cingulate gyrus remained the principal regions modulated by treatment. When comparing patients with MCI and healthy individuals after acupuncture, differential activity was observed in the right supramarginal gyrus in patients.

The clinical implications of these findings are promising for patients and health care professionals. The insula is associated with sensory, motor, visual, memory, and executive function processing, while the anterior cingulate gyrus plays a crucial role in cognitive attention and affective motivation. Hyperactivation of these regions suggests that acupuncture can effectively modulate brain circuits compromised in MCI. The thalamus, as a diverse hub involved in alertness regulation, attentional selection, and working memory, represents another important therapeutic target.

For practitioners, these results provide a solid scientific basis for the use of acupuncture as a complementary intervention in MCI, especially given the absence of specifically approved pharmacological treatments. The most commonly used acupuncture points in the included studies were Taichong (LR-3) and Taixi (KI-3), located on the feet, suggesting protocols that can be standardized for clinical practice.

However, the study has important limitations that should be considered. First, all included studies were conducted in China, limiting the applicability of the results to other populations. The small sample size of individual studies (22-64 participants per study) may have contributed to heterogeneity across results. Methodological issues were also identified: only one study adequately reported the method of randomization, none mentioned allocation concealment or blinding, and most used healthy individuals as controls rather than sham acupuncture.

Diversity in acupuncture protocols, including different points, treatment durations, and techniques used, may also have influenced the findings. Furthermore, no adverse events were reported during treatments.

In conclusion, this meta-analysis provides robust scientific evidence that acupuncture has specific modulatory effects on brain regions in patients with mild cognitive impairment. The main affected areas — right insula, left anterior cingulate gyrus, right thalamus, and frontal and temporal gyri — are closely related to cognitive, emotional, and decision-making functions that are frequently compromised in MCI. These findings offer a neurobiological foundation for understanding how acupuncture may benefit patients with early cognitive decline. Going forward, the researchers recommend multicenter studies with larger samples, standardized protocols, and adequate controls using sham acupuncture.

The development of machine-learning predictive models to assess individual response to acupuncture also represents a promising direction, potentially allowing personalized treatment and reducing medical costs for patients who are unlikely to respond.