Scoping Review of Prospective Clinical Studies, Projects, and Clinical Study Protocol for Korean Medicine Treatment on Dementia

Je-Beom Kim; Dong-Yoon Lee; Da-Jung Ha; Chan-Young Kwon; Kim, Je-Beom; Lee, Dong-Yoon; Ha, Da-Jung; Kwon, Chan-Young

doi:10.13048/jkm.21028

JKM > Volume 42(3); 2021 > Article

Kim, Lee, Ha, and Kwon: Scoping Review of Prospective Clinical Studies, Projects, and Clinical Study Protocol for Korean Medicine Treatment on Dementia

Original Article

The Journal of Korean Medicine 2021; 42(3): 99-118.

Published online: September 01, 2021

DOI: https://doi.org/10.13048/jkm.21028

Scoping Review of Prospective Clinical Studies, Projects, and Clinical Study Protocol for Korean Medicine Treatment on Dementia

Je-Beom Kim¹^{, ¶}

, Dong-Yoon Lee¹^{, ¶}

, Da-Jung Ha²

, Chan-Young Kwon³^{, *}

¹Dong-eui University College of Korean Medicine

²Department of Internal Medicine, Dong-eui University College of Korean Medicine

³Department of Oriental Neuropsychiatry, Dong-eui University College of Korean Medicine

Correspondence to: Chan-Young Kwon, Department of Oriental Neuropsychiatry, Dong-eui University College of Korean Medicine 52–57, Yangjeong-ro, Busanjin-gu, Busan, Republic of Korea, Tel: +82-51-850-8808, Fax: +82-51-867-5162, E-mail: beanalogue@deu.ac.kr

¶ These authors contributed equally to this work

Received March 6, 2021 Revised July 9, 2021 Accepted July 28, 2021

Abstract

Objectives

The aim of this study is to review and analyze the trends in prospective clinical research (PCR), project, clinical study protocol of Korean medicine (KM) for dementia.

Methods

We searched PCRs of KM on dementia in six electronical databases, up to January 28, 2021. Moreover, the clinical research protocol and projects of KM for dementia were searched.

Results

Total eight PCRs, nine projects, and three clinical study protocols were included. In the PCRs, there were one randomized controlled trial, five before and after study, and two comparative group before-after studies. Four of them used herbal medicine, two used acupuncture, one study used both herbal medicine and acupuncture, and the other one used moxibustion. Jowiseungchung-tang was the most frequently used herbal medicine. BL62, KI6 were used in electro-acupuncture, auricular-Shenmen in auricular acupuncture, and GV20 in moxibustion. The most frequent outcome was Korean-Dementia Rating Scale (K-DRS). One reported significant increase in K-DRS score, one reported 60% improvement, and the other studies mostly reported no significant difference. In the projects including 20 clinical studies of dementia, herbal medicine, integrative medicine and acupuncture were mainly used. In the protocols, herbal medicine, complex KM intervention, and integrative medicine were used.

Conclusions

Currently, the number of PCRs of KM for dementia is very scarce. Therefore, the researcher’s interest in this field and national research support should be made more, and the quality of clinical research in the future can be further improved by supplementing the limitations of previously published clinical research.

Keywords: Dementia, Korean medicine, Acupuncture, Herbal medicine, Review

Fig. 1

PRISMA Flow chart of literature selection process

Fig. 2

Risk of bias summary of included RCT

Fig. 3

Risk of bias summary of included non-RCTs

Table 1

Characteristics of included studies

First Author (Year)	Number of subjects	Mean age (mean ± SD)	Gender ratio (m:w)	Setting	Education years (mean ± SD)	Underlying disease	Type of dementia	Disease duration	Disease severity	Diagnosis	Intervention	Treatment period	Treatment Frequency
Kim (1998)⁹⁾	45	NR	14:31	H	NR	NR	AD	NR	Mild: 9 Moderate: 14 Severe: 22	DSM-IV	HM according to Sasang constitution, acupuncture (Taegeuk acupuncture)	65–330 d (mean 145 d)	NR
Park (2001)¹⁴⁾	6	83.8 ± 7.2	NR	H	NR	NR	VD	NR	NR	NINCDS-A DRDA	EA (BL62, KI6)	1 session (15 min)	1 session
Cho (2003)¹⁵⁾	31	71.4 ± 6.6	8:23	H	6.1 ± 4.9	NR	Early AD	NR	NR	Diagnosis from clinical psychologist and oriental neuropsychia trist	HM (Jowiseungchungtang)	6 mon	4 sessions/day
Kim (2003)¹⁶⁾	(A): 15 (B): 10	(A): 70.86 ± 6.54 (B): 69.66 ± 3.78	(A): 5:10 (B): 2:8	H	NR	NR	(A): Early AD (B): Normal	NR	NR	Diagnosis from clinical psychologist and oriental neuropsychia trist	(A): HM (Jowiseu ngchungt ang) (B): no treatment	9 mon	4 sessions/day
Jung (2004)¹⁷⁾	33	70.3 ± 4.1	14:19	H	5.5 ± 5.3	NR	Early AD	NR	NR	Diagnosis from oriental neuropsychia trist	HM (Gongjin-dan)	100 d	Everyday
Eom (2005)¹⁸⁾	22→16	69.88 ± 5.58	6:10	H	8.00 ± 5.59	NR	Early AD	NR	NR	DSM-IV NINCDS-A DRDA	HM (Kunneotang)	12 mon	NR
Kim (2010)¹⁹⁾	(A): 31 (B): 7	75.9	(A): 7:24 (B): 4:3	CH	NR	NR	(A): 5 VD, 26 AD (B): Normal	NR	NR	NR	AA (auricular-Shenmen)	1 session (15 min)	1 session
Shine (2011)²⁰⁾	(A): 10 (B): 10	(A): 80.3 (B): 77.9	All females	CH	(A): 3.8 (B): 4.1	NR	(A): 9 SD, 1 AD (B): 7 SD, 2 AD, 1 VD	NR	K-MMSE under 20 GDS under 4 Under Moderate	Diagnosis from neurologist or neuropsychia trist	(A): moxibust ion (GV20) (B): no treatment	2 wk	1 session/day 5 day/week

Abbreviations. (A), group A; (B), group B; AA, auricular acupuncture; AD, Alzheimer’s disease; CH, convalescent hospital; DSM, the Diagnostic and Statistical Manual of Mental Disorders EA, electro-acupuncture; GDS, Global Deterioration Scale; H, hospital; HM, herbal medicine; K-DRS, Korean-Dementia Rating Scale; K-MMSE, Korean Mini-Mental State Examination; NINCDS-ADRDA, the National of Neurological Communicative Disease and Stroke & the Alzheimer’s Disease and Related Disorders; NR, not reported; VD, vascular dementia.

Table 2

Composition of herbal medicine

First Author (Year)	Composition of Herb Medicine
Jung (2004)¹⁷⁾	Gongjin-dan: Moschus(麝香) 10g, Corunus Cervi Parvum(鹿茸) 75g, Angelicae Gigantis Radix(當歸) 75g, Fructus Corni(山茱萸) 75g, Honey(蜂蜜) 235g Devide to 100 pieces and take 1 piece per one time
Cho (2003)¹⁵⁾ Kim (2003)¹⁶⁾	Jowiseungchungtang: Coicis Semen(薏苡仁) 8g, Castanae Fructus(乾栗) 8g, Raphani Semen(蘿葍子) 6g, Longanae Arillus(龍眼肉) 6g, Playticodi Radix(桔梗) 4g, Liriopis Tuper(麥門冬) 4g, Acori Rhizoma(石菖蒲) 4g, Biotae Semen(柏子仁) 4g, Ziziphuy Semen(山棗仁炒) 4g, Massa medicate Fermentata(神麯炒) 4g, Ephedrae Herba(麻黃) 3g, Polygalae Radix(遠志) 3g, Maximowioziae Fructus(五味子) 3g, Amomi Semen(貢砂仁) 3g
Eom (2005)¹⁸⁾	Kunneotang: Acori graminei Rhizoma(石菖蒲) 2g, Polygalae Radix(遠志) 2g, Massa medicate Fermentata(神麯) 2g

Table 3

Outcomes and results of included studies

First Author (Year)	Main Outcomes	Results
Kim (1998)⁹⁾	1. Clinical improvement	1. Improved to almost normal state (n = 14), some improvement (n = 13), no change (n = 16), became worse (n = 2)
Park (2001)¹⁴⁾	1. EEG 1) Before treatment vs during treatment 2) Before treatment vs after treatment	1-1) Before > during the treatment in F4, F8 position (p < 0.05) 1-2) No significant difference (p > 0.05)
Cho (2003)¹⁵⁾	1. K-DRS	1. No significant difference (t = 0.791, r = 0.435)
Kim (2003)¹⁶⁾	1. K-DRS 2. ERP 1) P300 component amplitude 2) p300 component latency	1. No significant difference (p < 0.171) 2-1) No significant difference 2-2) In (A), the latency didn’t have significant difference, whereas (B) significantly increased (p < 0.001)
Jung (2004)¹⁷⁾	K-DRS	Pre < post (t = 9.907, r = 0.573)
Eom (2005)¹⁸⁾	1. MMSE-K 2. K-DRS 3. ERP	1. Pre < post (p = 0.122) 2. Pre > post (p = 0.681) 3. P300 amplitude was significantly decreased (p < 0.05). P300 latency didn’t have significant difference
Kim (2010)¹⁹⁾	1. EEG 1) Comparison before vs after 15min in (A), (B) 1-1) change of α wave 1-2) change of β wave 1-3) change of δ wave 1-4) change of θ wave 2) Comparison change of before and after 15 min in (A) and (B)	1-1) No significant difference in (B) but F4, FP2, FCZ, F8, FC4 were significantly increased in (A) (p < 0.05) 1-2) No significant difference in (B) but T8 was significantly increased in (A) (p < 0.05) 1-3) No significant difference in (B) but F7, FP1, FZ, FP2, FCZ, C4, FC4, CP4, T8, P7, P3, O1, OZ, O2, P4, P8 were significantly increased in (A) (p < 0.05) 1-4) No significant difference in (B) but O1, OZ, O2 were significantly increased in (A) (p < 0.05) 2) No significant difference between (A) and (B)
Shine (2011)²⁰⁾	Correct answer measurement of K-BNT (measured 4 times)	1. Correct answer was significantly increased in (A) between 1st and 2nd time (p < 0.05) 2. Decreased in 3rd and 4th times

Abbreviations. EEG, electroencephalogram; ERP, event-related potential; K-BNT, Korean version-Boston Naming Test; K-DRS, Korean-Dementia Rating Scale.

Appendices

Appendix 1.

Search strategy in each database (search date: 2021.1.28.)

Database	Search terms
MEDLINE	(Dementia[MH] OR dement[TIAB] OR Alzheimer[TIAB] OR “Lewy body”[TIAB] OR Huntington[TIAB] OR Parkinson[TIAB] OR “Pick disease”[TIAB] OR “cognitive impairment”[TIAB]) AND (“Medicine, Korean Traditional”[MH] OR Acupuncture[MH] OR “Acupuncture Therapy”[MH] OR “Acupuncture Points”[MH] OR Electroacupuncture[MH] OR Auriculotherapy[MH] OR Drugs, Chinese Herbal[MH] OR Meditation[MH] OR Mindfulness[MH] OR “Relaxation Therapy”[MH] OR Qigong[MH] OR “Tai ji”[MH] OR “Korean medicine”[TIAB] OR acupunct[TIAB] OR electroacupunct[TIAB] OR electro-acupunct[TIAB] OR acupoint[TIAB] OR “herbal medicine”[TIAB] OR decoction[TIAB] OR meditation[TIAB] OR mindful[TIAB] OR relaxation[TIAB] OR qigong[TIAB] OR “Ch’i Kung”[TIAB] OR “Qi Gong”[TIAB] OR Taichi[TIAB] OR “Tai Chi”[TIAB] OR “Tai Ji”[TIAB]) AND (Korea[MH] OR Korea*[TIAB])
OASIS	치매 OR 알츠하이머
KISS	치매 AND (한약 OR 침) OR 알츠하이머 AND (한약 OR 침)
RISS	치매 AND (한약 OR 침) OR 알츠하이머 AND (한약 OR 침)
EMBASE	(‘dementia’/exp OR dement:ab,ti OR Alzheimer:ab,ti OR ‘Lewy body’:ab,ti OR Huntington:ab,ti OR Parkinson:ab,ti OR ‘Pick disease’:ab,ti OR ‘cognitive impairment’:ab,ti) AND (‘Korean medicine’/exp OR ‘acupuncture’/exp OR ‘acupuncture point’/exp OR ‘electroacupuncture’/exp OR ‘herbal medicine’/exp OR ‘meditation’/exp OR ‘mindfulness’/exp OR ‘relaxation training’/exp OR ‘qigong’/exp OR ‘Tai Chi’/exp OR ‘Korean medicine’:ab,ti OR acupunct:ab,ti OR electroacupunct:ab,ti OR electro-acupunct:ab,ti OR acupoint:ab,ti OR ‘herbal medicine’:ab,ti OR decoction:ab,ti OR meditation:ab,ti OR mindful:ab,ti OR relaxation:ab,ti OR qigong:ab,ti OR ‘Chi Kung’:ab,ti OR ‘Qi Gong’:ab,ti OR Taichi:ab,ti OR ‘Tai Chi’:ab,ti OR ‘Tai Ji’:ab,ti) AND ‘South Korea’/exp OR Korea*:ab,ti
CENTRAL	(MeSH descriptor: [Dementia] explode all trees OR (dement* OR Alzheimer* OR “Lewy body” OR Huntington* OR Parkinson* OR “Pick disease” OR “cognitive impairment”):ti,ab) AND (MeSH descriptor: [Medicine, Korean Traditional] explode all trees OR MeSH descriptor: [Acupuncture] explode all trees OR MeSH descriptor: [Acupuncture Therapy] explode all trees OR MeSH descriptor: [Acupuncture Points] explode all trees OR MeSH descriptor: [Electroacupuncture] explode all trees OR MeSH descriptor: [Auriculotherapy] explode all trees OR MeSH descriptor: [Drugs, Chinese Herbal] explode all trees OR MeSH descriptor: [Meditation] explode all trees OR # MeSH descriptor: [Mindfulness] explode all trees OR MeSH descriptor: [Relaxation Therapy] explode all trees OR MeSH descriptor: [Qigong] explode all trees OR MeSH descriptor: [Tai ji] explode all trees OR (“Korean medicine” OR acupunct* OR electroacupunct* OR electro-acupunct* OR acupoint* OR “herbal medicine” OR decoction* OR meditation OR mindful* OR relaxation OR qigong OR “Ch’i Kung” OR “Qi Gong” OR Taichi OR “Tai Chi” OR “Tai Ji”):ti,ab) AND (MeSH descriptor: [Korea] explode all trees OR Korea*:ti,ab) In Trials

Appendix 2.

Projects of Korean medicine for dementia (search date: 2021.2.26.)

Appendix 3.

Clinical study protocol of Korean medicine for dementia (search date: 2021.2.26.)

참고문헌

1. Cheng A, Leung Y, Brodaty H. 2021; A systematic review of the associations, mediators and moderators of life satisfaction, positive affect and happiness in near-centenarians and centenarians. Aging & Mental Health. 1–17. https://doi.org/10.1080/13607863.2021.1891197

2. Kim KW, Kim HN, Ahn HY, Kim YJ, Hwang JE, Kim BN, et al. 2016. Korean dementia observatory 2016. Gyeonggi: National Institute of Dementia;Available from: URL: http://gysilver.or.kr/?page_id=4422&wr_id=330

3. Melis RJF, Haaksma ML, Muniz-Terrera G. 2019; Understanding and predicting the longitudinal course of dementia. Current Opinion in Psychiatry. 32:2. 123–129. https://doi.org/10.1097/YCO.0000000000000482

4. Shaji KS, Sivakumar PT, Rao GP, Paul N. 2018; Clinical Practice Guidelines for Management of Dementia. Indian Journal of Psychiatry. 60:Suppl 3. S312–S328. https://doi.org/10.4103/0019-5545.224472

5. Cummings JL, Morstorf T, Zhong K. 2014; Alzheimer’s disease drug-development pipeline: few candidates, frequent failures. Alzheimer’s Research & Therapy. 6:4. 37 https://doi.org/10.1186/alzrt269

6. Lee DW, Shin GJ, Lee WC. 1995; A Comparative Consideration of Treatment on Dementia in Oriental and Occidental Medicine. The Journal of Dong Guk Oriental Medicine. 4:67–80.

7. Xu QQ, Shan CS, Wang Y, Shi YH, Zhang QH, Zheng GQ. 2018; Chinese Herbal Medicine for Vascular Dementia: A Systematic Review and Meta-Analysis of High-Quality Randomized Controlled Trials. Journal of Alzheimer’s disease: JAD. 62:1. 429–456. https://doi.org/10.3233/JAD-170856

8. Huang Q, Luo D, Chen L, Liang FX, Chen R. 2019; Effectiveness of Acupuncture for Alzheimer’s Disease: An Updated Systematic Review and Meta-analysis. Current Medical Science. 39:3. 500–511. https://doi.org/10.1007/s11596-019-2065-8

9. Kim BG, Hyun KC, Kim JW, Whang WW. 1998; A clinical study on the effects of oriental medical treatment on Dementia of Alzheimer type. J of Oriental Neuropsychiatry. 9:1. 25–43.

10. Bae DB, Park J, Lyu Y, Lee G, Jung H, Kang H, et al. 2012; The Case Report of 3 Dementia Patients Treated by Needle-Embedding Therapy. J of Oriental Neuropsychiatry. 23:3. 99–116. http://dx.doi.org/10.7231/JON.2012.23.3.099

11. Ahn HI, Hyun MK. 2019; Effectiveness of integrative medicine program for dementia prevention on cognitive function and depression of elderly in a public health center. Integrative Medicine Research. 8:2. 133–137. https://doi.org/10.1016/j.imr.2019.04.008

12. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. 2019. Cochrane Handbook for Systematic Reviews of Interventions. John Wiley & Sons;Available from: URL: https://handbook-5-1.cochrane.org/

13. Kim SY, Park JE, Lee YJ, Seo HJ, Sheen SS, Hahn S, et al. 2013; Testing a tool for assessing the risk of bias for nonrandomized studies showed moderate reliability and promising validity. Journal of Clinical Epidemiology. 66:4. 408–414. https://doi.org/10.1016/j.jclinepi.2012.09.016

14. Park WS, Lee TY, Kim SY, Leem GG, Yuk SW, Lee CH, et al. 2001; The Immediate Effect of Electroacupuncture at the B62(Shinmaek) K6(Chohae) on the EEG of Vascular Dementia. The Journal of Korean Acupuncture & Mxibustion Society. 18:2. 67–78.

15. Cho S, Kim J, Kim H, Chung K, Whang W. 2003; A Study of Jowiseungchungtang in patients with mild Dementia of Alzheimer type. J of Oriental Neuropsychiatry. 14:1. 17–26.

16. Kim B, Kim J, Kim H, Chung K, Whang W. 2003; The effects on Jowiseungchungtang of patients with early DAT using auditory ERP and K-DRS. J of Oriental Neuropsychiatry. 14:2. 1–17.

17. Jung H, Jang H, Sung W, Lee S, Son J, Han S. 2004; A study of Gongjin-dan in patients with mild Dementia of Alzheimer type. J of Oriental Neuropsychiatry. 15:2. 141–148.

18. Eom HJ, Kim JW, Park E, Kim H, Whang WW. 2005; The Effects on Kunneotang of Patients with Early Dementia of Alzheimer Type -12 Months Clinical Study-. J of Oriental Neuropsychiatry. 16:1. 43–66.

19. Kim MR, Lee GE, Lee SE, Park IS, Park JH, No DJ, et al. 2010; The Effect of Auricular Acupuncture at the Shinmun on the Electroencephalogram(EEG) in patients with dementia. J of Oriental Neuropsychiatry. 21:3. 45–64.

20. Shine YJ, Choi YG, Jang WS. 2011; The Effect of Moxibustion Therapy on Dementia Patients ; Evaluated by K-BNT. The Journal of East-West Medicine. 36:2. 51–61.

21. Lee D. 2020; Analysis of Clinical Korean Medicine Studies on Dementia : Focused on Korean Literatures for 10 Years. Journal of Society of Preventive Korean Medicine. 24:1. 37–48. https://doi.org/10.25153/spkom.2020.24.1.004

22. Takayama S, Tomita N, Arita R, Ono R, Kikuchi A, Ishii T. 2020; Kampo Medicine for Various Aging-Related Symptoms: A Review of Geriatric Syndrome. Frontiers in nutrition. 7:86–86. https://doi.org/10.3389/fnut.2020.00086

23. Ren ST, Wang L, Wu YR, Liu WW, Liu XJ, Wang YX, et al. 2018; Research Progress on Effective Ingredients of Traditional Chinese Medicine for Alzheimer’s Disease. Journal of Huaihai Institute of Technology, 27(3). 27–33. https://doi.org/10.3969/j.issn.1672-6685.2018.03.007