Etiology and Pathogenesis of Alzheimer’s Disease Based on the Theory of Traditional Chinese Medicine

Alzheimer’s Disease (AD) is increasingly threatening people in almost every country physically and economically. The treatment methods for delaying cognitive decline in Chinese Medicine are comprehensive and diverse. This paper is intended to illustrate the etiology and pathogenesis of AD from the perspective of Traditional Chinese Medicine (TCM) and categorizes treatments available for AD in Chinese medicine. It is aimed at clarifying the treatment ideas and methods for AD and providing new references for clinical treatment.

September 21, 2022 marked the 29th World Alzheimer’s Day. According to WHO, the number of people with dementia worldwide is increasing in epidemic proportions, with the projected numbers being 78 million in 2030 and 139 million in 2050. AD accounts for 60-70% of the total cases. Meanwhile, direct medical costs and social care costs for dementia are enormous, and they are estimated to surpass US$2.8 trillion by 2030 [1], not to mention the emotional cost of the family members which cannot be measured. TCM has been widely used in maintaining health and treating diseases for thousands of years in China. In the course of its development, TCM has gradually created an independent theory system for cognitive disorders.

AD is a progressive neurodegenerative disease with clinical manifestation of gradual Cognitive Impairment (CI) due to the degeneration and death of brain cells [2]. Although there was no discussion on the name of AD or dementia in ancient Chinese medical books, some documented diseases in the name of ‘dai symptom’ or ‘chi’ or ‘jian wang (being forgetful). The term “chi dai” (dementia) was firstly put forward in the medical book “Secret Prescriptions of a Divine Doctor --- Huo Tuo” compiled by Sun Simiao, King of medicine in Tang dynasty [3] (Hua Tuo was a divine doctor living in about A.D. 145-208). CI belongs to the category of “chi dai” in TCM and shows symptoms like “language errors”, “amnesia”, “idiocy”, and “retard thinking” [4]. Therefore, strictly speaking, dementia is Zheng (TCM syndrome) according to the theory of TCM, not a disease and its etiology and pathogenesis are complicated and can be classified as follows.

Genetic factors or fetal problems

According to Huangdi Neijing, the earliest medical classic in China, known as ‘the ancestor of medical books’, the health condition of an individual is determined by that of his parents as the life of the fetus is derived from the sperm of the father and the blood of the mother. It takes something like a wall as an example, and says the mother is like the part beneath the ground and lays the foundation for an individual’s life while the father is like the structure above the ground and shields the individual from exogenous pathogenic factors [5]. Wan Quan, a Ming dynasty pediatrician, claimed that if there was something wrong with the mother, abortion might happen; if there was something wrong with the fetus, disharmony among its internal organs would develop, thus blindness, deafness, dullness, dementia and epilepsy were all associated with birth defects [5]. Therefore, it can be concluded that some AD cases are associated with congenital factors.

Deficiencies in kidney essence, blood and Qi

A great number of medical experts throughout Chinese history elaborated on the relationship between the brain and the kidney. The brain sits in the skull and is comprised of marrow. Huangdi Neijing-Suwen says all that in the skull belongs to the brain and all nutrition needed for the brain comes from the kidney essence. The kidney stores essence and holds qi --- believed to flow through meridians in your body. When there is abundant kidney essence and qi, the brain gets enough nutrition, then the hearing is sensitive, and the individual is full of energy and quick in responses. Otherwise, the brain will suffer from malnutrition problems, which results in loss of memory, problems of thinking, slow reaction, motor difficulties, and mental dullness [6].

Danxi Z [7] the well-known medical expert of the Yuan dynasty, enjoyed the reputation of having cured many patients who did not have to take a second visit after taking his medicine. He maintained that overthinking induces damage to the spleen, which results in deficiencies of body qi and blood, which causes a lack of nourishment in the brain, and eventually results in cognitive problems.

What’s more, as the aging process goes on, one’s kidney essence and qi get deficient naturally, which is thought to be a critical factor in cognitive decline. Sujing H, et al. [8] concluded after the study that deficiency in kidney essence is the most significant cause of dementia. They explained that deficiency in brain essence resulted in brain impairment, and then symptoms like hypomnesis, slow response, motor difficulties, and mental dullness developed. Another research was carried out by Xin T and his team members. Their findings showed that AD is mainly caused by deficiencies of blood and Qi. Thus they claimed that though the location of the disease is in the brain, yet its onset was particularly closely related to the spleen, kidney, liver, and heart. Similarly, a deficiency of qi affects the generation of blood. Deficiency of blood in turn affects the generation of qi. Prolonged deficiency of qi brings about the insufficiency of yang. Meanwhile, prolonged deficiency of blood induces an insufficiency of yin. Subsequently, the persistent depletion of yin endangers yang and leads to the progression of the disease. This will also cause the brain to lose nourishment which causes cerebral atrophy [4]. Mianmian L, et al. [9] elaborated in their article by quoting from Huangdi Neijing: Suwen a similar viewpoint that the location of the disease seemed to be in the brain, but the root of the disease lay in Five Zang (heart, lung, spleen, kidney and liver) because the normal thinking of the brain depends on the balance of qi, blood, yin and yang in the Five Zang. The Five Zang exist side by side and play apart together. If the Five Zang is dysfunctional, that will affect the mental activity of the brain and cause major cognitive dysfunction.

Phlegm stasis and blood stasis

Phlegm stasis is one pathological factor for AD. Shiduo C, et al. [10] the author of Dialectics in the Qing dynasty, believed that the weakness of the spleen and stomach resulted in poor digestion, which consequently led to the accumulation of phlegm in the chest. The phlegm stasis would block the circulation of qi, the result of which was that the upper qi was insufficient while the lower qi is surplus. As time went on, one’s, marrow deficiency develops and brain functions would be progressively damaged and cognitive impairment developed eventually for a lack of nutrition. And the situation would get even worse because of the qi being surplus in the lower part of the body at the same time. Therefore, he insisted that "there is no magic way to cure dementia, and to prevent phlegm from accumulating is to cure dementia". That is to say, the way to cure dementia depends mainly on eliminating phlegm by improving the functions of the spleen and stomach.

Blood stasis is believed to be another main factor leading to dementia. Zhang Zhongjing, a world-famous physician in the Eastern Han Dynasty, firstly proposed the view in the book Shang Han Za Bing Lun that prolonged blood stasis leads to forgetfulness [11]. Medical experts Zhang Jingyue in the Ming dynasty and Tang Rongchuan in the Qing dynasty followed that view and further developed it stressing that congestion and accumulation of blood vessels in the heart might lead to stagnation of qi and blood stasis and poor blood circulation. When the qi and blood supplies were normal, the brain received sufficient nutrition and works well. Otherwise, when the supplies were disturbed, there would be a loss of qi and blood, which leads to cerebral atrophy eventually [12].

TCM theory has been saying that ‘old people have more blood stasis’, ‘chronic disease causes blood stasis’, and ‘prolonged deficiencies result in blood stasis’. Another well-known medical expert in the Qing dynasty, Qingren W [13] again wrote in his book Corrections on the Errors of Medical Works that people with blood stasis were forgetful. Furthermore, the function decline of Five Zang with increasing age is closely associated with blood stasis as well. The pathological changes of blood stasis in the cerebral collaterals, either inside or outside the collaterals, can lead to the decline of brain function, even the occurrence of stroke or dementia [14].

Emotional factors

Medical expert Zhang Jingyue mentioned above had an immense influence on the development of Chinese medicine. The book Jingyue Quanshu, summed up not only his lifelong therapeutic concepts and formulations in treating diseases and his academic achievements in TCM but his predecessors’ as well. In that book, there exist systematic illustrations of the relationship between emotions and certain diseases like paranoid and dementia. In his opinion, emotions like resentment, frustration, irritability, or shame, rage, or excessive anxiety affect the flow of qi and blood. Long-term negative emotions will lead to qi stagnation and blood deficiency, which results in amnesia and delayed reaction and the like. Therefore, the treatment of AD mainly depends on regulating qi and tranquilizing the mind [12]. Another famous doctor of the Qing Dynasty, Yu Genchu, listed, in his book ‘Revised Popular Treatise on Cold Pathogenic Diseases’, the symptoms of dementia such as stiff look, slow responses, dull eyes, and lack of communication, etc. He further diagnosed it as a mental disorder caused by depression [5].

Exogenous pathogenic factors and problems with eating

TCM emphasizes the integrity of the human body and the close relationship between humans and their natural environment. TCM terms all exogenous pathogenic factors as Xie qi. In Huangdi Neijing: Suwen, it is stressed that once the body’s natural rhythm is disrupted, Xie qi will have an opportunity to attack. The imbalance of rhythm can lead to the disorder of cold and heat in the human body, thus affecting the qi of Five Zang and causing forgetfulness [15]. On the other hand, many years of clinical evidence provided by TCM doctors have proved that improper diet also contributes to CI because overconsumption of unhealthy food, cigarette smoking and the use of alcohol are all believed to be other causative factor of spleen and stomach damage, which, as stated above, eventually leads to CI [4].

Zheng (syndrome) is the basic unit and key term in TCM theory. The conclusion of Zheng is based on analyzing all symptoms and signs. TCM emphasizes ‘dui zheng xia yao’. That is to say, all treatment methods come from the differentiation of syndrome [16], which means unique treatment for unique situations. For example, for cases caused by blood stasis, the treatment method is to activate blood to remove blood stasis, open orifices and unblock collaterals by using Tongqiao Huoxue Decoction. For those with a deficiency of spleen and kidney yang, use the modified amount of Jinkui Shenqi Pill to invigorate qi and spleen, and nourish kidney essence [17]. If acupuncture therapy is employed, different sets of nerve points will be selected for different syndromes [18].

TCM encompasses a wide range of herbal medicines and non-pharmacological practices, such as acupuncture and moxibustion. Therefore, treatments available in CM are diverse and can be generally categorized by forms as follows.

Traditional Chinese Herbs (TCH)

Dialectical treatment is the unique characteristic of traditional Chinese medicine, and also the basic principle to be followed in treating diseases. TCH enjoys many advantages in the treatment of cognitive dysfunction, and their efficacy has been confirmed in a number of studies [19,20]. However, the problem is that the functioning of Chinese herbs is complicated and the effectiveness and safety of TCH cannot be clearly defined. Therefore, TCH has been widely known for its effectiveness and low cost by Chinese people, yet, it is not globally accepted. Fortunately, with the development of technology, modern extraction techniques can be employed to investigate the chemical and active components of TCH and their metabolic mechanisms in vivo, which is of great importance for the world’s understanding of TCM [21,22]. Encouragingly, a range of studies, published in China, India, Singapore and other countries have proved some herbs to be effective in improving cognitive function [4].

Traditional Chinese formula

Many classical prescriptions documented in ancient medical books have been tested effective and passed down. In addition, some contemporary well-known medical experts have developed some well-proven clinical recipes. For example, Junxia M, et al. [23] have tested the efficacy of Congnao decoction in treating patients with mild and moderate cognitive impairment. Jinjin L, et al. [24] used clinically modified Kidney-nourishing Decoction to treat AD and has proved that its curative effect rate can reach 90.00%.

Chinese patent medicine

Some Chinese patent medicine, also called ready-made medicine, have been verified effective by many investigators for improving cognitive function, including Liuwei Dihuang Bolus, Qinggong Shoutao Bolus, Buyang Huanwu Tang, etc. [4,25].

Chen L, et al. [26] observed the clinical effects of Compound polygonum multiflorum extraction in treating AD. Their findings indicated that it could obviously correct the memory and cognitive impairment of patients with dementia, help to reduce the degree of dementia and improve the ability to daily life and social activities of patients. Zhang Qinyuan’s clinical research demonstrated that Shenghuang Yizhi Granule has a satisfactory effect on the improvement of patients' living ability and memory and its effect was superior to that of Piracetam [27]. What’s more, many active compounds have been isolated from traditional Chinese herbs, many of which have been proven effective and have fewer side effects for alleviating dementia and neurodegenerative syndrome. And those active compounds could be promising ingredients for later paten medicine [28].

Non-pharmacological treatments

Acupuncture and moxibustion have been attracting increasing attention due to their effectiveness and few side effects [4,25].

Acupuncture is a technique for balancing the flow of qi and has been one of the most representative non-pharmaceutical treatments in TCM. According to the study carried out by Yu J, et al. [29], acupuncture can ameliorate some symptoms commonly associated with vascular dementia. Recently, Jia Y, et al. [30] carried out a 28-week controlled study and their findings indicated that acupuncture could improve cognition and global clinical status in patients with mild-to-moderate AD.

Moxibustion is also commonly accepted in East Asia as a treatment for cognitive impairment [31]. Unlike acupuncture, it is a technique for facilitating the flow of qi. Sungmin Aum and his team members have conducted a study aiming at identifying the underlying Mechanism of moxibustion in treating AD patients.

Moreover, warming needle moxibustion, which combines both Acupuncture and moxibustion has been demonstrated significantly effective as well in achieving overall improvement for AD patients improving cognitive function and daily living ability, reducing the symptoms of AD, and increasing the total effective rate [32].

To sum up, AD belongs to the category of "dementia" in TCM, and its Etiology and Pathogenesis are complicated and usually involve multiple internal organs, inborn factors, or congenital factors. Therefore, TCM studies the body condition holistically and the treatment of AD relies on dialectically regulating qi, blood, yin and yang, deficiency or surplus, etc.. Besides, ever since ancient times, TCM has been laying its emphasis not on the cure of diseases, but on the prevention of diseases, which is the essence of TCM theory.

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