Alzheimer’s disease is the most common form of dementia in the elderly people and is associated with progressive loss of memory and cognitive function. Because the cause of Alzheimer’s is unclear there is no cure for the condition.
Acupuncture has been used to improve memory and cognitive function in China for a long time and got increasingly attention around the world due to its well tolerance and minor side effect. However, the mechanism of acupuncture and its effectiveness on Alzheimer’s is not clear due to lack of scientific studies. Here some recent development of acupuncture from both preclinical research and clinical studies are summarized.
- Acupuncture promoted activity of hippocampal neural stem cells in Alzheimer’s model.
Acupuncture stimulation at specific acupoints improved cerebral microenvironment and promoted the proliferation and differentiation of transplanted hippocampal neural stem cells (NSCs) and improved cognitive function of Alzheimer’s model (Zhao et al., 2016). It has been reported in journal of Molecular Neurobiology.
NSCs, with the potential for neural regeneration, represent a promising clinical strategy for Alzheimer’s. However, under the influence of the host microenvironment, only few grafted NSCs survive, proliferate, and differentiate into functional neural cells, which eventually results in decreased anti-dementia efficacy. Recently, Dr. Lan Zhao and colleagues in China conducted a study to evaluate whether acupuncture will improve host microenvironment grated with NSCs in Alzheimer’s model. Acupuncture stimulation was applied, 24 hrs after hippocampal NSCs transplantation, at CV17, CV12, CV6, and bilateral ST36 acupoints for 30 s daily for 15 days. Five days after acupuncture, behavioural tests showed that acupuncture significantly improved cognitive functions compared with control group. Biochemical studies revealed that acupuncture markedly increased expression of neurotrophic factors, such as basic fibroblast growth factor, epidermal growth factor and brain derived neurotrophic factor in the hippocampal tissues compared with control group, indicating that acupuncture improved hippocampal microenvironment leading to better survival, proliferation and differentiation of hippocampal NSCs, resulting in improved cognitive function.
- Electroacupuncture suppressed neuronal apoptosis and improved cognitive impairment in the AD model
Many preclinical acupuncture studies reported encourage progress in understanding the mechanism underlying the effect of acupuncture. Guo et al., (2015) showed that acupuncture stimulation at DU20 and BL23 acupoints 30 min a day for 18 days with a rest every 7 days improved learning and memory function in Alzheimer’s model compared with control. Biochemical studies revealed that acupuncture stimulation suppressed the apoptosis, a cell death process in the hippocampus region, and a vulnerable brain area to Alzheimer’s. Acupuncture decreased apoptosis enhancing molecules and increased apoptosis resistant molecules in the Alzheimer’s model brain which was not seen in the control.
In another study (Lu et al., 2014), scientists looked the changes in neuronal activity of different brain regions using functional brain imaging technique – positron emission tomography (PET). They found that acupuncture stimulation at ST36 acupoint showed greater activity in the brain regions such as hippocampus, amygdalae and temporal lobe that are linked with memory and cognitive function. However stimulation at a sham acupoint showed increased activity in different brain areas.
- Clinical studies
2.1. Acupuncture may be more effective than drugs in treating Alzheimer’s disease
Acupuncture may be more effective than drugs in treating AD. Acupuncture improved effect of drugs for treating AD in terms of enhancing cognitive function. A systematic review study reported its data in the journal Medicine. Dr. Zhou (2015) and colleagues in China evaluated the effectiveness and safety of acupuncture in treating AD by systematic review and meta-analysis. Meta-analysis is a statistical technique used for contrasting and combining results from different studies in the hope of identifying patterns among studies. Ten randomized controlled studies with a total of 585 subjects were used in the study. They found that the combined results from 6 randomized controlled studies showed acupuncture is better than drug at improving scores on the Mini Mental State Examination (MMSE) scale, indicating the better enhancement in the cognitive function in acupuncture group compared with drug control. Evidence from pooled data of 3 trials revealed that acupuncture plus drug denepezil, an acetycholinesterase inhibitor, was more effective at improving MMSE scale than denepezil alone. In a broad review they found that only 2 out of 141 acupuncture clinical trials reported the incidence of acupuncture-related adverse effect. Only 7 of 3416 patients reported to have adverse reactions relevant to acupuncture.
Authors conclude that “Acupuncture may be more effective than drugs and may enhance the effect of drugs for treating AD in terms of improving cognitive function. Acupuncture may also be more effective than drugs at improving AD patients’ ability to carry out their daily lives.” However, more clinical studies with better protocol design and better standards are urgently needed to prove the effectiveness of acupuncture in treating AD in more countries.
Another clinical acupuncture study by Gu et al., (2014) showed that the patients with Alzheimer’s were given acupuncture at GV24, GV20, GB20, GB12, CV17, CV12, CV6, SP10 and ST36 and the other acupoints depending on the symptoms and physical signs, once a day, 6 days a week and 4 weeks as a session for total 4 sessions. In the control group, donepezil, was given for the same time period. The MMSE, the activity of daily living scale (ADL), Alzheimer’s disease assessment scale-cognition (ADAS-cog) and the digit span (DS) were monitored before treatment and assessed again after treatment. It was found that both acupuncture and drug treatment improved the MMSE, ADL and DS scores, decreased ADAS-cog scores compared with the scores recorded before treatment. The study showed that acupuncture treatment has at least the same effect as the drug treatment for patients with Alzheimer’s, without side-effects.
2.2. Acupuncture modulated functional connectivity of the hippocampus in Alzheimer’s disease
Memory loss is one of the early symptoms of AD, which is the most common form of dementia. The hippocampus is a major component of human brain and plays important roles in memory formation and spatial navigation. It is one of the first brain regions to develop neurodegeneration and suffer neuronal loss in Alzheimer’s. Short term memory loss and disorientation are among the early signs of Alzheimer’s. As the disease advances, symptoms include confusion, trouble with language and long term memory loss.
A recent study (Wang et al., 2014) using functional magnetic resonance imaging technique looked at the changes in functional connectivity between hippocampus and cerebral cortex in patients with Alzheimer’s disease. The study led by Dr. Zhiqun Wang showed that before acupuncture functional connectivity decreased in the hippocampus compared to healthy subjects. Following acupuncture stimulations at Hegu (LI4) and Taichong (L3) acupoints hippocampal functional connectivity increased compared to that of before acupuncture. This study showed that acupuncture stimulation at specific acupoints is able to modulate neuronal activities in the specific brain regions, indicating its specific therapeutic effects.
- Gu W et al., [Clinical observation of Alzheimer’s disease treated with acupuncture]. Zhongguo Zhen Jiu. 2014 Dec;34(12):1156-60. http://www.ncbi.nlm.nih.gov/pubmed/25876339
- Guo HD et al., Electroacupuncture Suppressed Neuronal Apoptosis and Improved Cognitive Impairment in the AD Model Rats Possibly via Downregulation of Notch Signaling Pathway. Evidence-Based Complementary and Alternative Medicine Volume 2015, Article ID 393569, 9 pages. http://www.hindawi.com/journals/ecam/2015/393569/
- Lu Y et al., Brain areas involved in the acupuncture treatment of AD model rats: a PET study. BMC Complementary and Alternative Medicine 2014, 14:178. http://www.biomedcentral.com/1472-6882/14/178
- Zhao L, et al., Acupuncture Improves Cerebral Microenvironment in Mice with Alzheimer’s Disease Treated with Hippocampal Neural Stem Cells. Mol Neurobiol. 2016 Aug 24. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/27558235
- Zhou J et al., The effectiveness and safety of acupuncture for patients with Alzheimer disease: a systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore). 2015 Jun; 94(22):e933. http://www.ncbi.nlm.nih.gov/pubmed/26039131
- Wang Z et al., Acupuncture modulates resting state hippocampal functional connectivity in Alzheimer disease. PLoS One. 2014 Mar 6;9(3):e91160. doi: 10.1371/journal.pone.0091160. http://www.ncbi.nlm.nih.gov/pubmed/24603951
Grateful acknowledgements are due to Drs Gu W, Guo HD, Lu Y, Zhao L, Zhou J and Wang Z and colleagues (This paper was based on their articles cited in above Reference section), as well as to Bai-Yun Zeng for his work in preparing this briefing paper.