Acupuncture is significantly more effective than donepezil in improving cognitive function in patients with mild to moderate Alzheimer's disease

Acupuncture has shown the much better improvement in cognitive function than donepezil in patients with mild to moderate form of Alzheimer’s disease in a 24-week clinical trial. The study was published in the journal of BMC Complementary and Alternative Medicine.

Alzheimer’s disease (AD) is characterized by memory impairment and personality changes and is the most common type of dementia. The conditions lead to a loss of personal independence which has wide range of impact on the individual, families and societies; as it is predicted that the prevalence of AD will rise exponentially in elderly people from 1% at age of 65 to approximately 40-50% by the age of 95. So far the medications used to treat AD include cholinesterase-inhibitors such as donepezil which offers only modest symptomatic relief, but produced significantly higher rates of adverse effects and discontinuation of treatment. So, alternative treatment for the condition is urgently needed. Acupuncture has been used to alleviate some symptoms of AD in China for a long time.

Recently a randomized, drug-controlled, parallel group clinical study was conducted to determine the efficacy and safety of acupuncture compared with donepezil in patients with mild to moderate AD. Eighty seven patients qualified to the study were randomly allocated into two groups: acupuncture group (AG, n=43) and drug group (donepezil, DG, n=44).

The primary outcome measures included (1) Alzheimer's Disease Assessment Scale-Cog (ADAS-cog). (2) Clinician Interview-Based Impression of Change plus caregiver input (CIBIC-Plus). The second outcome measures were (1) Activities of Daily Living Inventory (ADAS-ADL23). (2) The Neuropsychiatric Inventory–Questionnaire (NPI). Those measures were performed at the baseline, 12-week treatment period, and 12-week follow-up period respectively.

Basic acupuncture acupoints included RN17 (danzhong), RN12 (zhongwan), RN6 (qihai), ST36 (zusanli), SJ5 (waiguan) and SP10 (xuehai). Complementary acupoints: LR3 (taichong), GB39 (xuanzhong), ST40 (fenglong), BL17 (geshu), ST44 (neiting), ST25 (tianshu) and RN4 (guan yuan), could be selected as auxiliary acupoints according to patient’s symptoms and tongue manifestation. The needles were retained in situ for 30 min each time. Acupuncture treatment was given three times weekly for 12 weeks. The patients in the DG group received 5 mg/day of donepezil hydrochloride for the first 4 weeks and then, 10 mg/day for 8 weeks.

The results shown that acupuncture treatment statistically significantly improved cognitive function, global clinical status compared with donepezil according to the scores of ADAS-cog, CIBIC-Plus both at the end of 12-week treatment and 12-week follow-up period. However, there was no significant difference in the activities of daily living and behavioral symptoms based on the scores of ADCSADL23 and NPI between AG and DG groups. Further, In the AG group, 5 cases of insomnia, 4 cases of constipation, 6 elderly male cases with benign prostate hyperplasia and 2 cases of knee arthritis reported that their symptoms were clearly improved. However, patients in the DG group did not show any equivalent improvements.

During the trial, 4 patients (9.3%) in AG experienced punctuate hemorrhage after the needles were taken out, and 1patient (2.3%) had bruising. No serious adverse effects were reported and no patients withdrew from the AG. Seven patients (15.9%) in DG reported some adverse effects, including dizziness, nausea, loss of appetite, diarrhea, constipation; fatigue and agitation. 4 of 7 cases (9.09%) withdrew from the trial.

The study showed that acupuncture treatment could significantly improve cognitive function, global clinical status in patients with mild to moderate AD, compared with donepezil, with less adverse effects.

Reference

Jia Y, Zhang X, Yu J, Han J, Yu T, Shi J, Zhao L, Nie K., Acupuncture for patients with mild to moderate Alzheimer's disease: a randomized controlled trial. BMC Complement Altern Med. 2017 Dec 29;17(1):556.     https://www.ncbi.nlm.nih.gov/pubmed/29284465

Acupuncture stimulation improved cognitive function in middle-aged people

Electro-acupuncture with low-frequency stimulation improved cognitive function in middle-aged women and men, reflected by the changes in P300 index. A report of pilot of randomized controlled clinical studies was published in journal of BMC Complementary and Alternative Medicine.

Aging is related to an increase in senile disorders such as Alzheimer’s disease. It has been recently reported that the number of patients with Alzheimer’s dementia is expected to reach 13.5 million by 2050 in the United States alone and will become a major problem worldwide over time. How to improve cognitive function is crucial to prevent senile-related conditions. The P300 is an important index that is used in clinical studies to evaluate reductions in memory and other cognitive functions and has been known to show decreased amplitude and delayed latency with aging. Acupuncture stimulation at some specific acupoints was reported to improve cognitive function and slow down the reduction of memory.

Recently Dr. KH Choi and colleagues conducted a pilot clinical study with randomised double-blinded controlled setting to evaluate the effect of low-frequency electro-acupuncture stimulation at BL62 and KI6 on cognitive function, using P300 index. Fifty-five healthy subjects in their 50s, including 26 males and 29 females were recruited and divided into real acupuncture (n=28) and sham acupuncture (n=27) groups. In real electro-acupuncture at an average of 24μA and 2 Hz stimulation at acupoints BL62 and KI6 lasted 30 mins each session, 12 sessions over one month. Brain activity of each subject was recorded by event related potentials (ERPs) of electroencephalogram before the first session and after the last session of acupuncture, then analysed using P300.

It was found that subjects in the real acupuncture group showed a tendency toward a decreasing P300 latency and increasing P300 amplitude after all 12 sessions of stimulation. In the women, the amplitude significantly increased at many perimeters, compared with sham group.

The authors suggested that the results of this study may serve as a foundation for the treatment of dementia and various brain disorders due to brain aging and impaired cognition. However, because the results of this study are limited to middle-aged women, further studies are necessary to determine the therapeutic effects in different age groups as well as in men and to discover the neurological mechanisms underlying the positive influence of low-frequency electrical stimulation on the brain.

Reference

KH Choi et al., Change in the P300 index–a pilot randomized controlled trial of low-frequency electrical stimulation of acupuncture points in middle-aged men and women. BMC Complementary and Alternative Medicine (2017) 17:246.    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415720/

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. 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.

Reference

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

Acupuncture may be more effective than drugs in treating Alzheimer’s disease

Acupuncture may be more effective than drugs in treating Alzheimer’s disease (AD). Acupuncture improves effect of drugs for treating AD in terms of enhancing cognitive function. A systematic review study reported its data in the journal Medicine.

There is increasing number of reports regarding clinical trials of acupuncture treatment for AD during past 10 years. Most of studies were performed in China and were published in Chinese. The effectiveness and safety of acupuncture on AD has not been systematic reviewed until recently.

Dr. Zhou 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 enhancement in the cognitive function. Evidence from pooled data of 3 trials revealed that acupuncture plus drug denepezil 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.

Reference:

J Zhou 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

Recent development in acupuncture for Alzheimer’s disease

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 basic research and clinical studies are summarized.

Recent search reports 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, 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, 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.

A clinical acupuncture study 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, a acetycholinesterase inhibitor, was given for the same time period. The minimum mental state examination (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 the same effect as the drug treatment for patients with Alzheimer’s, without side-effects.

References:

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

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

Acupuncture modulated functional connectivity of the hippocampus in Alzheimer’s disease

Memory loss is one of the early symptoms of Alzheimer’s disease, 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 disease. 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. There is currently no cure for Alzheimer’s disease.

Acupuncture has been used to improve memory and other cognitive functions in Alzheimer’s disease in China. However the underlying mechanisms of therapeutic effects of acupuncture treatment are unclear. A recent study 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.

Reference:

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

Acupuncture therapy for Alzheimer’s disease

Alzheimer’s disease (AD) is the most common form of dementia. It was first described by German neuropathologist and psychiatrist Alois Alzheimer in 1906 and was named after him. AD is a neurodegenerative disorder and is recognized to progress through three stages: preclinical, mild cognitive impairment and dementia. In preclinical stage, the biomarkers such as plasma amyloid beta measurement can be used as prognostic marker. A recent study identified a set of lipid metabolites in blood plasma that showed 90% accurate prediction of those who would go on to show cognitive impairment within 3 years. In mild cognitive impairment, patients have cognitive deficits, where the memory of recent facts and spatial orientation is affected but not functional impairment. In AD dementia, a decline in two or more cognitive domains have gradually progressed to the points that functioning at work or daily activities such as speech is impaired. Currently there is no cure for the disease. The medication is only symptomatic relief with adverse effects.

In China acupuncture is utilized to enhance memory and recently is used to treat Alzheimer’s. Clinical studies recruited 20 AD patients reported that acupuncture stimulation at the Baihui (GV 20), Shenshu (BL 23), Xuehai (SP 10) and Geshu (BL 17) acupoints for 12 weeks was very effective in improving AD symptoms judged by the scores of Alzheimer’s Disease Assessment Scale-Cognitive Section. The biochemical study showed that the concentration of isoprostane, a marker for peroxidation of fatty acid, was significantly decreased in cerebrospinal fluid, blood and urine of patients with AD after acupuncture treatments. Although this study had a small sample size it showed acupuncture is a promising alternative therapy for Alzheimer’s disease.

Reference:

H Zhu (2010) Zhongguo Zhen Jiu. 30(1):18-21.  http://www.ncbi.nlm.nih.gov/pubmed/20353108