Acupuncture benefits memory, learning, and the brain in an Alzheimer’s disease study. In a controlled experiment, researchers discovered two important clinical benefits provided by stimulation of scalp acupuncture points; acupuncture improves spatial learning and memory. Additionally, the researchers discovered that acupuncture improves brain glucose metabolism. Let’s take a look at the results.

Researchers at the Beijing University of Chinese Medicine demonstrate that electroacupuncture improves spatial memory and learning in mice with Alzheimer’s disease (AD). To test electroacupuncture’s effectiveness for the treatment of Alzheimer’s disease and its related upregulation of glucose metabolism in the hippocampus, the researchers chose three scalp acupuncture points. All three acupoints affect the Governing Vessel (Du Mai), an acupuncture channel traditionally used to nourish the spine and brain in Traditional Chinese Medicine (TCM). The findings were published by Cao et al. in the Frontiers in Aging Neuroscience journal.

The researchers first applied electroacupuncture (EA) for 20 minutes to DU20 (Baihui) and the extra point Yintang. Next, they inserted DU26 (Shuigou). This protocol was repeated once per day for five consecutive days. The Beijing University of Chinese Medicine researchers conclude that their findings demonstrate that this protocol not only improves spatial memory and learning in mice, but also enhances glucose metabolism in the hippocampus. This provides new insights for the development of effective clinical protocols for Alzheimer’s disease patients. The findings indicate that an integrative medicine approach to patient care (acupuncture plus usual care) is optimal.

Alzheimer’s disease is a neurodegenerative disorder that causes progressive memory loss, confusion, and dementia. Statistically, Alzheimer’s disease is a leading cause of dementia and the third leading cause of death [5] among elderly people. It is estimated that over 5 million USA residents are living with Alzheimer’s disease, a devastating clinical disorder for patients and families alike.

The hippocampus is an area of the brain that is important for the encoding and retrieval of memories. As a result, researchers studying Alzheimer’s disease often focus on the importance of the hippocampus in the pathogenesis of the disease. For example, researchers at the Salk Institute for Biological Studies have found that during the early stages of Alzheimer’s disease, the hippocampus is especially vulnerable to damage. "Neurofunctional imaging studies with an image reslicing technique provided by using software suggest that dysfunction of the amygdalohippocampal system causes memory impairment…. In patients with Alzheimer’s disease, marked hypometabolism was found extending to the amygdala, the hippocampal head, and the parietotemporal cortex, along with amygdalohippocampal atrophy."

Hypometabolism of glucose in the brain is correlated with dementia. Energy metabolism in the brain, regulated by the insulin cascade, is important to a variety of processes including learning, memory, and cognitive ability. This is why the Beijing University of Chinese Medicine research finding acupuncture effective for the enhancement of brain glucose metabolism is so important. Let’s take a closer look at how the brain’s cells function in this process.

Insulin helps to ferry glucose into cells, allowing for the production of ATP (adenosine triphosphate) by mitochondria. ATP produces energy necessary for physiological processes, including cellular activity. As ATP production declines, cells are starved for energy and cellular functions diminish. Hoyer found that "early and severe abnormalities were found in the cerebral glucose metabolism, which worsened in parallel with dementia symptoms. As a consequence, the synthesis of acetylcholine in the presynaptic neuron is markedly diminished, and a fall of ATP production from glucose by around 50% in the beginning of sporadic Alzheimer’s disease occurs, declining thereafter throughout the course of the disease." These findings indicate that acupuncture’s ability to enhance brain glucose metabolism has significant implications for Alzheimer’s disease patients.

A decrease in hippocampal volume is a direct indication of Alzheimer’s disease pathology. Research indicates that volume loss is correlated with diminished glucose metabolism. In fact, "hippocampal glucose metabolism reductions are found in both mild cognitive impairment and Alzheimer disease and contribute to their diagnostic classification." While aging alone seems to have a negative effect on brain glucose uptake, the "neurodegenerative processes in Alzheimer’s disease further decrease brain glucose metabolism because of reduced synaptic functionality and, hence, reduced energy needs, thereby completing a vicious cycle."  In addition, Cunnane et al. indicate that improving insulin sensitivity and glucose metabolism may have a positive effect on patients with Alzheimer’s disease. Here, we find that the Beijing University of Chinese Medicine research finding acupuncture effective for the enhancement of brain glucose metabolism is highly relevant to protection of hippocampal volume and therefore prevention of neurodegenerative processes, especially for Alzheimer’s disease patients.

In addition to the effect of glucose hypometabolism on the progression of Alzheimer’s disease, Hoyer states that there is clear evidence that memory is dependent on the functioning of the cholinergic system, and "there is increasing evidence that neuronal glucose metabolism is antagonistically controlled by insulin and cortisol."  Hoyer notes that insulin in the brain is derived from pancreatic β-cells, but it is also formed, in part, in pyramidal neurons, such as those in the hippocampus.  He found that insulin receptor function is stimulated by insulin while glucocorticoids and catecholamines cause receptor desensitization.

A number of other studies have also been conducted to investigate the connections between glucose metabolism and the cholinergic system in the hippocampus. These studies corroborate the aforementioned findings. For example, Umegaki et al. find that "degeneration of the hippocampal cholinergic system is one of the most robust pathological features" of Alzheimer’s disease.  Leon et al. offer the interpretation that "glucocorticoid-mediated regulation of glucose transport is altered in Alzheimer’s disease, and this may underlie both the hippocampal insensitivity to cortisol and the failure in these patients to mount a peripheral glucose response."

With this understanding of glucose hypometabolism in the pathology of Alzheimer’s disease, Cao et al. investigated the potential for acupuncture to upregulate glucose metabolism in APP/PS1 type mice. The researchers used four groups (normal control, Alzheimer’s disease control, Alzheimer’s disease receiving electroacupuncture, and Alzheimer’s disease receiving the drug donepezil) in order to compare the efficacy of the treatment modalities. Administration of donepezil, an acetylcholinesterase inhibitor, is an FDA (US Food and Drug Administration) approved drug therapy for Alzheimer’s disease.

Cao et al. administered the Morris Water Maze test to laboratory mice to examine differential effects on spatial learning and memory. In addition, micro-PET imaging was used to test the rate of glucose metabolism in the brain. The use of micro-PET over standard PET (positron emission tomography) overcomes resolution limitations and is therefore appropriate for use when examining laboratory mice. Cao et al. found that both electroacupuncture and donepezil were effective for improving memory and glucose metabolism; however, electroacupuncture was found more effective for improving memory and glucose metabolism than donepezil.

The impact of these findings is substantial. They demonstrate that electroacupuncture may be beneficial to Alzheimer’s disease patients by both improving spatial learning and memory and by improving glucose metabolism in the hippocampus. This study, in conjunction with others, indicates that DU20 (Baihui) exerts a neuroprotective effect. Perhaps one of the most important findings is that acupuncture reduces brain β-amyloid plaque overexpression in Alzheimer’s disease type mice. Further, the research by Cao et al. demonstrates that acupoints along the Du Mai channel - especially DU20 (Baihui) - are indicated for the treatment of Alzheimer’s disease. This is consistent with Traditional Chinese Medicine principles regarding the use of Governing Vessel acupoints.

Additional research is necessary to explore how these effects translate into clinical improvements for human patients. A large sample size study using a multi-center investigation model will help to quantify specific benefits to patients, including prevention of brain damage, memory loss, and generalized dementia. Specifically, examination of acupuncture protocols to protect hippocampal volume are of primary importance. Requirements for further investigations are substantial because controlled investigations will need to sort the specific benefits derived from acupuncture treatments from benefits derived from usual care.

Given the devastating and widespread nature of Alzheimer’s disease, it is reasonable to fund extensive clinical and laboratory trials in an effort to combat this illness. Another possibility for the enhancement of patient outcomes may be to quantify benefits provided by acupuncture, examine the specific pathways activated that provide the effective mechanisms of therapeutic action, and to provide or develop medications that activate identical pathways in an effort to identify effective medicines for Alzheimer’s disease patients. A combined effort, both clinically and in the development of new medicines, is a reasonable approach, given the urgency of treatment needs for patients.

Access to care presents additional challenges. Many Alzheimer’s disease patients are not fully ambulant, lack health insurance provisions for acupuncture therapy, or are in nursing facilities with limited access to licensed acupuncturists. As a result, the challenge is twofold. Researchers must quantify specific treatment protocols and access to care must be administrated based on the evidence. The process of treatment protocol implementation will be facilitated by evidence based research and evidence based credentialing of licensed acupuncturists, as with the NCCAOM (National Certification Commission For Acupuncture and Oriental Medicine).

References
1.  Jin Cao et al., "Behavioral Changes and Hippocampus Glucose Metabolism in APP/PS1 Transgenic Mice via Electro-Acupuncture at Governor Vessel Acupoints," Frontiers in Aging Neuroscience 09 (January 24, 2017), doi:10.3389/fnagi.2017.00005. Pg 1

2.  Maciocia, Giovanni. The Foundations of Chinese Medicine: A Comprehensive Text for Acupuncturists and Herbalists. 2nd ed. Edinburgh: Elsevier Churchill Livingstone, 2013. pg 840
3.  Cao et al., "Behavioral Changes and Hippocampus Glucose Metabolism"
4.  nia.nih.gov/alzheimers/publication/alzheimers-disease-fact-sheet pg 1
5.  nia.nih.gov/alzheimers/publication/alzheimers-disease-fact-sheet pg 1
6.  nia.nih.gov/alzheimers/publication/alzheimers-disease-fact-sheet pg 1

7.  Kumaran, Dharshan. "Short-Term Memory and the Human Hippocampus." Journal of Neuroscience 28, no. 15 (April 9, 2008), doi:10.1523/jneurosci.0046-08.2008. pg 3838?
ncbi.nlm.nih.gov/pubmed/18400882

8.  Yangling Mu and Fred H Gage, "Adult Hippocampal Neurogenesis and Its Role in Alzheimer’s Disease," Molecular Neurodegeneration 6, no. 1 (2011), doi:10.1186/1750-1326-6-85. Pg 1
ncbi.nlm.nih.gov/pmc/articles/PMC3261815/