Abstract
BACKGROUND: Acupuncture has been demonstrated to have a promising effect on Alzheimer's disease (AD), but the underlying neural mechanisms remain unclear. The retrosplenial cortex (RSC) is one of the earliest brain regions affected in AD, and changes in its functional connectivity (FC) are reported to underlie disease-associated memory impairment. The aim of this study was to examine the effect of acupuncture on FC with the RSC in patients with AD. METHODS: Demographic data, neuropsychological assessments, and resting-state functional magnetic resonance imaging (fMRI) data were collected from 14 AD patients and 14 normal controls (NCs) matched by age, sex, and educational level at baseline. After the baseline MRI scan, acupuncture stimulation on the Taichong (LIV3) and Hegu (LI4) points was performed for 3 min. Then, another 10 min of fMRI data were acquired after the needle was withdrawn. A dataset that included 100 healthy participants was also included to construct a reliable FC map of the RSC. Two sets of regions of interest (ROIs) in the RSC were selected to assess the sustained effect of acupuncture on FC with the RSC in AD patients and NCs. RESULTS: Two sets of RSC ROI-based analyses demonstrated robust positive connectivity with the hippocampus (HPC). Furthermore, multiple brain regions, including the bilateral thalamus, bilateral posterior cingulate cortex (PCC), bilateral subcallosal cingulate gyrus (SCG), bilateral orbitofrontal cortex (OFC), and right precuneus, showed decreased FC with the RSC in the AD group and increased FC with the RSC in the NC group after acupuncture compared to that at baseline. Acupuncture also specifically elicited increased FC between the RSC and the HPC as well as between the RSC and the parahippocampal gyrus in AD patients and decreased FC between the RSC and the visual cortices in NCs. Additionally, diminished FC with the RSC was correlated with neuropsychological scale scores in the AD group before acupuncture treatment. CONCLUSION: These findings confirm and extend previous studies suggesting that acupuncture at Taichong (LIV3) and Hegu (LI4) can exert bidirectional and benign regulatory effects on RSC connectivity in AD patients.