**3. Traditional Chinese medicine for behavioral and psychological symptoms of dementia (BPSD)**

Behavioral and psychological symptoms of dementia (BPSD) is the serious clinical problem of dementia. Usually major tranquilizers are used, but they

**91**

**Figure 2.**

*the treatment period.*

because of deterioration of BPSD.

*Traditional Chinese Medicine in Geriatrics, Evidences, and the Guideline*

cause extrapyramidal side effects. We reported that Yigan San (抑肝散) could improve BPSD without extrapyramidal side effects [3]. Mild-to-severe demented patients who had BPSD (18 men and 34 women; age 80.3 ± 9.0 [mean ± SD] years) were investigated. Participants were randomly assigned to the YGS group (n = 27) or control (drug-free) group (n = 25) and treated for 4 weeks. The Neuropsychiatric Inventory (NPI) test for the assessment of BPSD. Meanwhile, cognitive function was estimated by the Mini-Mental State Examination (MMSE), and ADL by the Barthel Index were tested at baseline and the end of the treatment. The frequency of extrapyramidal symptoms (EPS) and other adverse events were recorded. All participants in both groups completed the trial. In the control group, 11 patients required treatment with tiapride hydrochloride

*Changes of MMSE of BDW and placebo groups. BDW improves mini mental score examination about 2.5 in* 

Significant improvements BPSD (from 37.9 ± 16.1 to 19.5 ± 15.6, mean ± SD) (**Figure 3**) and Barthel index (from 56.4 ± 34.2 to 62.9 ± 35.2) were observed in the YGS group, but not in the control group. MMSE was not changed in both groups. EPS were not observed in either group, but dizziness and impaired postural sway were observed in 6 patients treated in control group, may be caused by tiapride hydrochloride. At the same time, we also found that Yigan San could improve typical hallucination in Dementia with Lewy Bodies (DLB), as shown in **Figure 4** [4]. Yigan San was developed by Xue Ji (薛己) in 16th century. He devised this recipe for emotional liability of children. But this recipe was not widely spread in China, and Japanese doctors in Edo era applied it to adults. They found that it is effective for persons who are easy to anger. I applied it to some demented patients who easily anger. Therefore, I carried out Randomized Control Trial (RCT) described above. Now then, we found 219 papers with key word "yokukansan (Japanese

*DOI: http://dx.doi.org/10.5772/intechopen.94277*

*Traditional Chinese Medicine in Geriatrics, Evidences, and the Guideline DOI: http://dx.doi.org/10.5772/intechopen.94277*

### **Figure 2.**

*An Overview and Management of Multiple Chronic Conditions*

considered that chidai was caused by brain atrophy. Wang Qing Ren is the first man

*Change of MMSE(lt) and ADAScog of 2 groups, donepezil plus KUT combination (*○*) vs. donepezil only (*△*). Combination group showed significant improvement to single donepezil group. Colored areas in the brain* 

We demonstrated that a combinatorial use of donepezil plus Jia wei weng dan tang (加味温胆湯), was more beneficial than donepezil alone in both cognition and brain perfusion (**Figure 1**) in demented people. Although cholinergic-related adverse effects might be expected, such events did not occur in the combination group. Therefore, despite a small sample size and a short observation period study, donepezil and Jia wei weng dan tang may work synergistically in a safe fashion to

Same time, we showed that bawei dihuan wang (八味地黄丸、BDW) could improve the cognitive function of Alzheimer disease patient. **Figure 2** shows that BDW improves Mini Mental Score Examination about 2.5 in the treatment period [2]. BDW was described in the ancient text book Jin kui Yao lue (金匱要略) written by Zhan Zhong jing (張仲景) in 2nd century. He wrote that this recipe delayed aging, i.e., effective for Qi (気) deficiency in Kidney organ (shen xu, 腎虚). Therefore, it is used for geriatric syndrome and frailty of aged people. It contains Rehmaniae Radix, Corni Fructus, Dioscoreae Rhizoma, Alismatis Rhizoma, Hoelen, Moutan Cortes,

**3. Traditional Chinese medicine for behavioral and psychological** 

Behavioral and psychological symptoms of dementia (BPSD) is the serious clinical problem of dementia. Usually major tranquilizers are used, but they

who described dementia in a scientific manner.

*reveal areas in which significant blood flow increases in the combination group.*

enhance an availability of acetylcholine [1].

Cinnamomi Cortes and Aconi tuber.

**symptoms of dementia (BPSD)**

**90**

**Figure 1.**

*Changes of MMSE of BDW and placebo groups. BDW improves mini mental score examination about 2.5 in the treatment period.*

cause extrapyramidal side effects. We reported that Yigan San (抑肝散) could improve BPSD without extrapyramidal side effects [3]. Mild-to-severe demented patients who had BPSD (18 men and 34 women; age 80.3 ± 9.0 [mean ± SD] years) were investigated. Participants were randomly assigned to the YGS group (n = 27) or control (drug-free) group (n = 25) and treated for 4 weeks. The Neuropsychiatric Inventory (NPI) test for the assessment of BPSD. Meanwhile, cognitive function was estimated by the Mini-Mental State Examination (MMSE), and ADL by the Barthel Index were tested at baseline and the end of the treatment. The frequency of extrapyramidal symptoms (EPS) and other adverse events were recorded. All participants in both groups completed the trial. In the control group, 11 patients required treatment with tiapride hydrochloride because of deterioration of BPSD.

Significant improvements BPSD (from 37.9 ± 16.1 to 19.5 ± 15.6, mean ± SD) (**Figure 3**) and Barthel index (from 56.4 ± 34.2 to 62.9 ± 35.2) were observed in the YGS group, but not in the control group. MMSE was not changed in both groups. EPS were not observed in either group, but dizziness and impaired postural sway were observed in 6 patients treated in control group, may be caused by tiapride hydrochloride. At the same time, we also found that Yigan San could improve typical hallucination in Dementia with Lewy Bodies (DLB), as shown in **Figure 4** [4].

Yigan San was developed by Xue Ji (薛己) in 16th century. He devised this recipe for emotional liability of children. But this recipe was not widely spread in China, and Japanese doctors in Edo era applied it to adults. They found that it is effective for persons who are easy to anger. I applied it to some demented patients who easily anger. Therefore, I carried out Randomized Control Trial (RCT) described above. Now then, we found 219 papers with key word "yokukansan (Japanese

### **Figure 3.**

*Changes of NPI in the YGS group and control. NPI significantly improved from baseline to endpoint only in the YGS group.*

**Figure 4.** *Change of hallucination sub score of NPI in DLB patients. Hallucination improved by YGS treatment.*

name of Yigan San)." Nakatani Y et al. reported that Yigan San has a neuroprotective effect [5]. Yigan San contains Atractylodis Lanceae Rhizama, Hoelen, Cnidii Rhizoma, Angelicae Radix, Bupleuri Radix, Glycyrrhizae Radix, and Uncariae Ramulus et Uncus. Active ingredients are not sure but Ikarashi Y et al. reported that Geissoschizine methyl ether (GM) in Uncaria hook and 18β-glycyrrhetinic acid (GA) in Glycyrrhiza may concern to several pharmacological actions of YiGan San [6].

## **4. Aspiration pneumonia**

Pneumonia is now the 4th reason of death of Japanese, and most of them are aspiration pneumonia in the elderly. Absence or attenuation of the cough [7] and swallowing [8] reflex in elderly patients causes micro aspiration. We investigated the effects of Banxia Houpu Tang (半夏厚朴湯、BHT), on the swallowing [9] (**Figure 5**) and cough [10] (**Figure 6**) reflexes in elderly stroke patients. Finally, we found that BHT reduced pneumonia risk in the elderly [11]. Elderly participants

**93**

**Figure 5.**

**Figure 6.**

*(shortened) only in the BHT group.*

by double blind RCT [12].

*shortened (improved) in the BHT group.*

*Traditional Chinese Medicine in Geriatrics, Evidences, and the Guideline*

who had history of aspiration pneumonia (mean age 84.0, M:F = 28:67) were randomly assigned to the BHT treatment group (n = 47) or the control group (n = 48) and took BHT or placebo for 12 months. The occurrence of pneumonia, mortality due to pneumonia, and the daily amount of self-feeding were measured. As a result, four participants in the BHT group developed pneumonia, and one of them died as a result, while 14 participants in the control group developed pneumonia, and 6 of them died. There was a significant difference between the two groups in pneumonia onset ((**Figure 7**, *P* = .008), and a tendency toward significance in pneumonia-related mortality (*P* = .05). The relative risk of pneumonia in the BHT group compared with the control group was 0.51 (95% confidence interval (CI 0.27–0.84, *P* = .008) and that of death from pneumonia was 0.41 (95% CI = 0.10– 1.03, *P* = .06). No adverse events were observed from treatment with BHT. The BHT group was able to maintain self-feeding better than the control group (*P* = .006). Very recently, the suppressing effect of BHT for aspiration pneumonia was confirmed

*Change of the cough reflex in BHT treated and the control groups. The threshold of the reflex significantly* 

*Changes of the swallowing reflex in BHT and the control groups. The reflex significantly improved the time* 

*DOI: http://dx.doi.org/10.5772/intechopen.94277*

*Traditional Chinese Medicine in Geriatrics, Evidences, and the Guideline DOI: http://dx.doi.org/10.5772/intechopen.94277*

### **Figure 5.**

*An Overview and Management of Multiple Chronic Conditions*

name of Yigan San)." Nakatani Y et al. reported that Yigan San has a neuroprotective effect [5]. Yigan San contains Atractylodis Lanceae Rhizama, Hoelen, Cnidii Rhizoma, Angelicae Radix, Bupleuri Radix, Glycyrrhizae Radix, and Uncariae Ramulus et Uncus. Active ingredients are not sure but Ikarashi Y et al. reported that Geissoschizine methyl ether (GM) in Uncaria hook and 18β-glycyrrhetinic acid (GA) in Glycyrrhiza may concern to several pharmacological actions of YiGan

*Change of hallucination sub score of NPI in DLB patients. Hallucination improved by YGS treatment.*

*Changes of NPI in the YGS group and control. NPI significantly improved from baseline to endpoint only in the* 

Pneumonia is now the 4th reason of death of Japanese, and most of them are aspiration pneumonia in the elderly. Absence or attenuation of the cough [7] and swallowing [8] reflex in elderly patients causes micro aspiration. We investigated the effects of Banxia Houpu Tang (半夏厚朴湯、BHT), on the swallowing [9] (**Figure 5**) and cough [10] (**Figure 6**) reflexes in elderly stroke patients. Finally, we found that BHT reduced pneumonia risk in the elderly [11]. Elderly participants

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San [6].

**Figure 4.**

**Figure 3.**

*YGS group.*

**4. Aspiration pneumonia**

*Changes of the swallowing reflex in BHT and the control groups. The reflex significantly improved the time (shortened) only in the BHT group.*

### **Figure 6.**

*Change of the cough reflex in BHT treated and the control groups. The threshold of the reflex significantly shortened (improved) in the BHT group.*

who had history of aspiration pneumonia (mean age 84.0, M:F = 28:67) were randomly assigned to the BHT treatment group (n = 47) or the control group (n = 48) and took BHT or placebo for 12 months. The occurrence of pneumonia, mortality due to pneumonia, and the daily amount of self-feeding were measured. As a result, four participants in the BHT group developed pneumonia, and one of them died as a result, while 14 participants in the control group developed pneumonia, and 6 of them died. There was a significant difference between the two groups in pneumonia onset ((**Figure 7**, *P* = .008), and a tendency toward significance in pneumonia-related mortality (*P* = .05). The relative risk of pneumonia in the BHT group compared with the control group was 0.51 (95% confidence interval (CI 0.27–0.84, *P* = .008) and that of death from pneumonia was 0.41 (95% CI = 0.10– 1.03, *P* = .06). No adverse events were observed from treatment with BHT. The BHT group was able to maintain self-feeding better than the control group (*P* = .006). Very recently, the suppressing effect of BHT for aspiration pneumonia was confirmed by double blind RCT [12].

### **Figure 7.**

*Cumulative rate of pneumonia in BHT treatment group and the control group. There is a significant difference in pneumonia occurrence rate between the groups.*

BHT was described in Jin kui Yao lue (金匱要略) by Zhan Zhong jing (張仲景) in 2nd century. It contains Pinelliae Tuber, Hoelen, Magnoliae Cortex, Perillae Herba, and Zingiberis Rhizoma. It is written that when women feel something block her throat, try this recipe. Now it is considered as throat dysesthesia, and BHT is widely applied to neurosis, depression, and psychophysiological disorder.

### **5. Chronic constipation**

There were over 1.34 million patients suffering from cerebrovascular diseases in 2008 reported by Ministry of Health, Labour and Welfare in Japan. Poststroke patients often cause constipation. Stratified by stroke severity on the National Institutes of Health Stroke Scale, the incidence of constipation in poststroke patients were reported from 38.9% to 88.2% [13]. Poststroke patients with functional constipation, assessed by the Rome III criteria were recruited in a study on the effects of the traditional Chinese medicine Da Jian Zhong Tang (大建中湯) on constipation. Thirty-four patients (17 men and 17 women; mean age: 78.1 ± 11.6 years) were randomly assigned to 2 groups; all patients received conventional therapy for constipation, and patients in the Da Jian Zhong Tang group received 15 g/day of Da Jian Zhong Tang for 4 weeks. We recorded Constipation Scoring System (CSS) points and the Gas Volume Score (GVS) (the measure of the intestinal gas volume calculated from plain abdominal radiographs) before and after a 4-week observation period. The total score on the CSS improved significantly in the Da Jian Zhong Tang group compared to the control (*p* < 0.01) (**Figure 8**). In addition, some CSS subcategories (defecation frequency, feeling of incomplete evacuation, and need for enema/disimpaction) significantly improved in the Da Jian Zhong Tang group (*p* < 0.01, *p* = 0.049, and *p* = 0.03, respectively). The GVS was also significantly reduced in the Da Jian Zhong Tang group (**Figure 9**, *p* = 0.03) [14]. Da Jian Zhong Tang was also described in Jin kui Yao lue (金匱要略) by Zhan Zhong jing (張仲景) in 2nd century. Zhan Zhong jing wrote that this recipe was effective for patients who felt severe abdominal pain, abdominal coldness and gut sharply moved. It is very

**95**

**6. Guideline**

**Figure 9.**

**Figure 8.**

*(improved) in Da Jian Zhong tang group.*

Zingiberis Siccatum Rhizoma.

*Traditional Chinese Medicine in Geriatrics, Evidences, and the Guideline*

alike to ileus, and this recipe had been used for ileus prevention after abdominal surgery. Da Jian Zhong Tang contains Ginseng Radix, Zanthoxyli Fructus, and

*Bowel gas volume at baseline and the endpoint of Da Jian Zhong tang treatment (a case).*

*Change of CCS points in the Da Jian Zhong tang treated group and the control. CSS significantly reduced* 

as the independent chapter in their guideline 2015 [15]. As a result, Yigan San,

Concerning these evidences, Japan Geriatric Society treated traditional medicine

*DOI: http://dx.doi.org/10.5772/intechopen.94277*

*Traditional Chinese Medicine in Geriatrics, Evidences, and the Guideline DOI: http://dx.doi.org/10.5772/intechopen.94277*

### **Figure 8.**

*An Overview and Management of Multiple Chronic Conditions*

BHT was described in Jin kui Yao lue (金匱要略) by Zhan Zhong jing (張仲景) in 2nd century. It contains Pinelliae Tuber, Hoelen, Magnoliae Cortex,

*Cumulative rate of pneumonia in BHT treatment group and the control group. There is a significant difference* 

There were over 1.34 million patients suffering from cerebrovascular diseases in 2008 reported by Ministry of Health, Labour and Welfare in Japan. Poststroke patients often cause constipation. Stratified by stroke severity on the National Institutes of Health Stroke Scale, the incidence of constipation in poststroke patients were reported from 38.9% to 88.2% [13]. Poststroke patients with functional constipation, assessed by the Rome III criteria were recruited in a study on the effects of the traditional Chinese medicine Da Jian Zhong Tang (大建中湯) on constipation. Thirty-four patients (17 men and 17 women; mean age: 78.1 ± 11.6 years) were randomly assigned to 2 groups; all patients received conventional therapy for constipation, and patients in the Da Jian Zhong Tang group received 15 g/day of Da Jian Zhong Tang for 4 weeks. We recorded Constipation Scoring System (CSS) points and the Gas Volume Score (GVS) (the measure of the intestinal gas volume calculated from plain abdominal radiographs) before and after a 4-week observation period. The total score on the CSS improved significantly in the Da Jian Zhong Tang group compared to the control (*p* < 0.01) (**Figure 8**). In addition, some CSS subcategories (defecation frequency, feeling of incomplete evacuation, and need for enema/disimpaction) significantly improved in the Da Jian Zhong Tang group (*p* < 0.01, *p* = 0.049, and *p* = 0.03, respectively). The GVS was also significantly reduced in the Da Jian Zhong Tang group (**Figure 9**, *p* = 0.03) [14]. Da Jian Zhong Tang was also described in Jin kui Yao lue (金匱要略) by Zhan Zhong jing (張仲景) in 2nd century. Zhan Zhong jing wrote that this recipe was effective for patients who felt severe abdominal pain, abdominal coldness and gut sharply moved. It is very

Perillae Herba, and Zingiberis Rhizoma. It is written that when women feel something block her throat, try this recipe. Now it is considered as throat dysesthesia, and BHT is widely applied to neurosis, depression, and

psychophysiological disorder.

*in pneumonia occurrence rate between the groups.*

**5. Chronic constipation**

**Figure 7.**

**94**

*Change of CCS points in the Da Jian Zhong tang treated group and the control. CSS significantly reduced (improved) in Da Jian Zhong tang group.*

### **Figure 9.**

*Bowel gas volume at baseline and the endpoint of Da Jian Zhong tang treatment (a case).*

alike to ileus, and this recipe had been used for ileus prevention after abdominal surgery. Da Jian Zhong Tang contains Ginseng Radix, Zanthoxyli Fructus, and Zingiberis Siccatum Rhizoma.
