Table 1.
The characteristic of RCTs included.
| References | Sample size | Diagnosis criteria | AD categories | Age, Mean ± SD/Range | Intervention regimen and methods | Outcomes | |||
|---|---|---|---|---|---|---|---|---|---|
| Experimental group | Control group | Experimental group | Control group | Effectiveness | Safety | ||||
| Feng et al. (2019) | 20/20 | OCDAD, NIA-AA | – | 68 ± 9 | 69 ± 7 | • Eletroacupuncture: 40 mm needle, dense-sparse wave, (10 Hz/50 Hz, 0.5~5.0 mA); acupoints: Fengfu—(15 mm into the skin, don't retain), Baihui—(15 mm into the skin, retained for 30 min), Shenting—(15 mm into the skin, retained for 30 min), Shangyintang—(15 mm into the skin, retained for 30 min), Temple—(25 mm into the skin, retained for 30 min), Dazhong—(25 mm into the skin, retained for 30 min); one time every 2 days, 3 days every week, last for 12 weeks |
• Donepezil hydrochloride 5 mg/tablet, 5 mg/d, taken before bed, last for 12 weeks |
MMSE | Incidence of adverse events (e.g., dizziness, headache, palpitation) |
| Jiang et al. (2018) | 20/20/20/20 | Guidelines for the diagnosis and treatment of dementia and cognitive impairment in China | Mild to moderate | 60~80 | 60~80 | • Jinsanzhen acupuncture combined with Jiannaosan Acupuncture: 25 mm needle; acupoints: Jinsanzhen acupuncture points: Naosanzhen (Naohu and Naokong), Zhisanzhen (Shenting and Benshen), Niesanzhen (two inches above the tip of the ear and one inch behind the ear, one inch before the ear)—(1–1.2 inch flat stab down into the skin, retained for 30 min); once a day, continuously treated for 7 days, rested for 2 days, and then started next round, last for 12 weeks. Jiannaosan: 5 g every time, 2 times/d, last for 12 weeks Jinsanzhen acupuncture Acupoints: same with the former group |
• Jiannaosan 5 mg every time, 2 times/d, last for 12 weeks • Donepezil hydrochloride Taken at bed time, 5 mg/d for the first 4 weeks, 10 mg/d for the remaining 8 weeks, last for 12 weeks |
MMSE, ADL | – |
| Chen et al. (2018) | 48/48 | NIA-AA | – | 65~84 | 67~85 | • Acupuncture Acupoints: baihui, renzhong, neiguan, sanyinjiao, xuanzhong, fenglong, taixi; twice a day. The course of treatment was 3 months in both groups • Donepezil hydrochloride 5 mg/time, 1 time/d |
• Donepezil hydrochloride The methods of drug treatment was same with experimental group | MMSE, ADL | – |
| Jia et al. (2017) | 35/36 | ADRDA, DSM-IV-R | Mild to moderate | 75.11 ± 6.53 | 74.50 ± 6.83 | • Acupuncture Acupoints: 1.5 inch needle; acupuntpoints: Danzhong (15 mm into skin), Zhongwan, Waiguan, Zusanli, Qihai (15~25 mm perpendiculary into skin, rotated at small-amplitude and high-frequency with reinforcing method for 30 s), Xuehai (15~25 mm into skin low-frequency reducing method for 30 s), three times/w, last for 12 weeks • Simulant donepezil hydrochloride 5 mg/d, last for 12 weeks |
• Donepezil hydrochloride 5 mg/tablet, 5 mg/d for the first 4 weeks, 10 mg/d for the remaining 8 weeks, last for 12 weeks • Sham- acupuncture Acupuncture points: 2 cm away from the acupoint, 0.2 inches into superficial tissue; three times/w, last for 12 weeks |
MMSE, ADAS-cog, ADL | Incidence of adverse events (e.g., abnormal blood, urine, stool routine examination, liver and kidney function) |
| Peng et al. (2017) | 25/25 | DSM-IV-R, NINDS-AIREN | – | 69.4 ± 5.4 | 69.5 ± 5.3 | • Eletroacupuncture A continuous wave, 50 Hz, 2–4 v; acupoints: Shenting, Baihui, Dazhui, Fengfu, Mingmen and Yongquan (0.5~0.8 inch into skin, retained for 25 min), once a day, 10 days a courses, for 3 courses, last for 4 weeks • Huperzine 0.2 mg each dose, 1 dose a day, last for 4 weeks |
• Huperzine 0.2 mg each dose, 1 dose a day, last for 4 weeks | MMSE, HDS-R | – |
| Lou et al. (2017) | 60/60 | NIA-AA | Mild to moderate | 60.56 ± 2.97 | 61.26 ± 2.83 | • Acupuncture Acupoints: Baihui, Sishencong, Fengfu, Yongquan, Taixi, Shenyu, Sanyinjiao, Zusanli, Fenglong; retained for 30 min frequency of treatment: once a day at first, adjusted of syndrome differentiation as treatment time went, last for 24 weeks. • Conventional therapy Donepezil Hydrochloride: 5 mg/tablet, 5 mg/d, for 24 weeks. Acupoint application: heart, kidney, forehead, subcortex, shenmen, Jiaogan; 6 h/d, once a day for 24 weeks |
• Conventional therapy The methods of drug treatment was same with experimental group | MoCA, ADL | – |
| Guan (2017) | 30/30 | DSM-IV, DSDEE-SD | – | 70.5 ± 9.3 | 69.3 ± 10.2 | • Acupuncture Acupoints: frontal midline, parietal midline, temporal front line, temporal posterior line, shenyu, xuanzhong, taixi, zusanli, shuigou, et al.; once a day, 6 times as a course of treatment, a day of rest after one course of treatment; last for 8 weeks • Donepezil, Dirongcuzhi granule Donepezil: take 5 mg before going to bed every day; last for 8 weeks Dirongcuzhi granule: take one dose twice a day; last for 8 weeks |
• Donepezil, Dirongcuzhi The methods of drug treatment was same with experimental group | MMSE, ADAS-cog, ADL | – |
| Wei et al. (2016) | 33/33 | NINDS-SIANR | – | 61~76 | 60~77 | • Acupuncture: acupoints: Baihui, Yongquan, 1–1.5 inches penitrationpenitration into the skin retained for 30 min, once a day, last for 12 weeks • Huperzine 0.2 mg/time, once a day, last for 12 weeks |
• Huperzine The methods of drug treatments was similar to the experimental group | MMSE, HDS-R, ADL | Incidence of adverse events (e.g., abdominal distension and abnormal blood routine) |
| Lin (2016) | 30/30/30 | DSM-IV, DSDEE-SD | Mild to moderate | 50~80 | 50~80 | • Acupuncture Four Shen Needles (about 1.5 inches before and after Baihui), three Brain Needles (ventricle, bilateral brain space), three Zhi Needles (Shenting, bilateral Benshen), and three Temporal Needles (ear tip straight up 2 inches, front and back 1 inch, respectively), Taixi, Taichong, Zusanli, Sanyinjiao, Fenglong, Qihai, and Xuehai; continuous needling for 5 days, rest for 2 days, 4 weeks for 1 course of treatment, continuous observation of three courses of treatment • Acupuncture, Donepezil The methods of acupuncture was the same as mentioned above. Donepezil: 5 mg each time, once a day, 4 weeks as a course of treatment, continuous observation of three courses |
• Donepezil The methods of drug treatments was similar to the experimental group | MMSE, ADAS-cog, ADL | – |
| Wang et al. (2015) | 36/36 | NINCDS-ADR-DA, DSDEE-SD | Mild to moderate | 72.05 ± 3.70 | 70.31 ± 3.79 | • Eletroacupuncture: acupoints: Baihui—(0.8–1.0 inch diagonal stab upward into the skin, retained for 30 min), Dazhui—(0.5–1.0 inch diagonal stab downward into the skin, retained for 30 min), once a day, 6 day every week, last for 12 week | • Donepezil hydrochloride Taken at bed time, 10 mg/tablet, 5 mg/d for the first 4 weeks, 10 mg/d for the remaining 8 weeks, last for 12 weeks |
MMSE | – |
| Gu et al. (2014) | 72/69 | DSM-IV-R, NINCDS-ADRDA | Mild to moderate | 75 ± 7 | 72 ± 7 | • Acupuncture: 40, 50 mm needle; acupoints: Shenting—(13–21 mm plaque into the skin, retained for 30 min), Baihui—(8–13 mm plaque into the skin, retained for 30 min), Fengchi—(26–34 mm plaque into the skin, retained for 30 min), Wangu—(16–32 mm plaque into the skin, retained for 30 min), Danzhong—(5–13 mm plaque into the skin, retained for 30 min), Qihai, Zhongwan—(40 mm straight into the skin, retained for 30 min), Xuehai, Zusanli—(13–26 mm straight into the skin, retained for 30 min) combined with (Tongli, Sanyinjiao, Taixi, Yinlingquan, Tianshu, Fenglong, Taichong), once a day, 6 days every week, 4 weeks for a course, for 4 courses, last for 16 weeks | • Donepezil hydrochloride Taken at bed time, 5.0 mg/tablet, 5 mg/d for the first 4 weeks, 10 mg/d for the remaining 12 weeks. 16 weeks in all |
MMSE, ADAS-cog, ADL | Incidence of adverse events (e.g., fainting during acupuncture, sticking needle) |
| Yan et al. (2014) | 20/20 | ICD-10 | Mild to severe | 60~78 | 60~80 | • Acupuncture: 0.5–1.0 inch needle; acupoints: Shenting, Benshen, Sishencong, Shenmen and Taixi matched with Neiguan, Yintang, Taichong, Jianshi, Danzhong, Lianquan, Zhaohai, Zusanli, Yanglingquan, Qihai, Guanyuan, Yinlingquan, Yifeng, Tinggong, Fengchi, Tianzhu, Shuaigu, Tianshu, Hegu, straight stab into the skin, retained for 20 min, once a day, 5 days every week, 4 weeks a course, last for 3 courses, last for 12 weeks |
• Donepezil hydrochloride Taken at bed time, 5.0 mg/tablet, 5 mg /d, last for 12 weeks | MMSE | – |
| Wang et al. (2014) | 27/28 | DSM-IV | Mild to moderate | 70.3 ± 8.0 | 70.7 ± 9.1 | • Acupuncture Acupoints: coronal suture, sagittal suture, lambdoidal suture, frontotemporal sutures—(25–35 mm into the skin at an 15° angle, twirling 200 rpm/min for 1–2 min at the interval of 15 min, retained for 30 min). once a day, 10 days as a course, last for 20 days • Donepezil hydrochloride 5~10 mg/tablets, once a day, 10 days as a course, last for 20 days |
• Donepezil hydrochloride Same with experimental group |
MMSE, ADAS-cog | – |
| Zhu (2014) | 40/40 | CDR, DSDEE-SD | – | 71 ± 2 | 66 ± 2 | • Acupuncture Acupoints: Baihui, Sishencong, Zusanli, Taixi, Dazhong, Xuanzhong, Ganyu, Sanyinjiao, Qihai, Geyu. Zusanli, Taixi, Dazhong and Xuanzhong were treated with warm needle moxibustion for 2 strong points, respectively, and were replaced after the needle cooled gradually; once a day, 10 days as a course of treatment, last for 3 months of treatment |
• Piracetam 1.4 g each time, 3 times a day, 10 days for 1 a course of treatment, last for 3 months |
CDR | – |
| Lin et al. (2014) | 18/18 | DSM-IV, NINCDS-ADR-DA | Mild | 73.44 ± 3.37 | 74.21 ± 2.68 | • Elecrtoacupuncture: a continuous wave, 80–100 times/min; acupoints: Baihui, Sishencong, Neiguan, Sanyinjiao, 15 mm penetration into the skin, retained for 30 min, once a day, last for 12 weeks |
• Donepezil hydrochloride: taken every night before bed, 5 mg/one tablet, 5 mg/every time, last for 12 weeks | MMSE, ADAS-cog, ADL | – |
| Li T. et al. (2014) | 40/40 | NINCDS-ADR-DA | Mild to moderate | 68.43 ± 7.56 | 67.32 ± 6.35 | • Acupuncture Acupoints: Shenyu, Gaunyuan, Yongquan, Zusanli, Sanyinjiao, Shenmen, Fengchi. 0.3 × 30 mm needle for scalp acupuncture and 0.3 × 40 mm needle for body acupuncture, last for 12 weeks • Rehabilitation training A series of professional training related to skills improvement of life, such as memory, logical thinking, space, and time, live skills, last for 12 weeks |
• Rehabilitation training The methods of rehabilitation training was similar to experimental group | MMSE, ADL | – |
| Yin et al. (2013) | 30/30 | NINCDS-ADR-DA, DSM-IV-R | – | 60~85 | 60~85 | • Acupuncture 1.5 inch needle; acupoints: Qianding to Xuanli, Baihui to Qubin—(30–45 mm into the skin at the interval of 15°, twirling 200 rpm for 1 min, retained for 45 min), once a day, last for 12 weeks • Donepezil hydrochloride 5 mg/d, once a day, last for 12 weeks |
• Donepezil hydrochloride The methods of drug treatment was same with the experimental group | MMSE, CDR, ADL | Incidence of adverse events (e.g., abnormal blood, urine, stool routine examination, liver, and kidney function) |
| Sun (2013) | 35/35 | DSDEE-SD | – | 64.71 ± 9.10 | 64.4 ± 9.12 | • Acupuncture Acupoints: Sishencong, retained for 30 min, last for 4 weeks • Donepezil hydrochloride 5 mg/time, 1 time/d, last for 4 weeks |
• Donepezil hydrochloride The methods of drug treatments was similar to experimental group | MMSE, ADL | – |
| Hu et al. (2010) | 40/40 | NINCDS-ADR-DA, DSM-IV | – | 69.38 ± 6.54 | 68.08 ± 6.90 | • Acupuncture: 1.5 inch needle, acupoints: Danzhong—(0.2–0.5 inch diagonal stab upward into the skin, twirling at high frequency for 30 s), Zhongwan—(1.5 inch straight stab into the skin, twirling at high frequency for 30 s), Qihai—(0.8–1.0 inch straight stab into the skin, twirling at high frequency for 30 s), Xuehai—(1.0–1.5 inch straight stab into the skin, twirling at low frequency sharply for 30 s), Zusanli—(0.5–1.0 inch straight stab into the skin, twirling at high frequency for 30 s), Waiguan—(0.5–1.0 inch straight stab into the skin, twirling at high frequency for 30 s); last for 12 weeks |
• No treatment | MMSE, ADL | – |
| Jia et al. (2010) | 25/26 | NINCDS-ADR-DA, DSM-IV-R | – | 50~90 | 50~90 | Acupuncture: 1.5 inch needle, acupoints: Danzhong—(0.2–0.5 inch diagonal stab upward into the skin, twirling at high frequency for 30 s), Zhongwan—(1.5 inch straight stab into the skin, twirling at high frequency for 30 s), Qihai—(0.8–1.0 inch straight stab into the skin, twirling at high frequency for 30 s), Xuehai—(1.0–1.5 inch straight stab into the skin, twirling at low frequency sharply for 30 s), Zusanli—(0.5–1.0 inch straight stab into the skin, twirling at high frequency for 30 s), Waiguan—(0.5–1.0 inch straight stab into the skin, twirling at high frequency for 30 s); last for 12 weeks |
Piracetam: 1.2 g every time, three times/d, last for 12 weeks | MMSE, ADL | – |
| Zhu et al. (2010) | 20/20/20/20 | DSM-IV-R | Mild to moderate | 60~80 | 60~80 | • Acupuncture 10–75 mm needle, acupoints: Baihui—(0.5–0.8 inch flat stab into the skin, twirling 120 rpm for 1 min, retained for 30 min), Shenyu—(0.5–1.0 inch straight stab into the skin, twirling 120 rpm for 1 min, retained for 30 min), Xuehai—(1–1.5 inch straight into the skin, retained for 30 min), Geyu—(0.5–0.8 inch diagonally stab into the skin, retained for 30 min), once a day, 7 days for a course, last for 8 weeks • Acupuncture combined with Yizhijiannao Yizhijiannao tablets, 5.5 g a time, three times/d, last for 8 weeks |
• Yizhijiannao Yizhijiannao tablets, 5.5 g a time, three times/d, last for 8 weeks • Donepezil hydrochloride Taken in the morning, 5 mg/d, last for 8 weeks |
MMSE | – |
| Li et al. (2009) | 20/20/20 | DSM-IV-R, NINCDS-ADR-DA | Mild to moderate | 55~80 | 55~80 | • Acupuncture Acupoints: Shenyu—(1.0 inch straight stab into the skin, retained for 30 min), Geyu—(0.5 inch diagonally stab into the skin, retained for 30 min), Shenmen—(0.5 inch stab into the skin, retained for 30 min), Baihui—(1.0 inch flat stab into the skin); last for 12 weeks • Acupuncture combined with Yizhijiannao The methods of acupuncture was same with acupuncture group. Yizhijiannao tablets: 5.0 g every time, three times/d, last for 12 weeks |
• Yizhijiannao The methods of Yizhijiannao was same with experimental group | MMSE, ADAS-cog | – |
| Liu et al. (2008) | 40/40 | NINCDS-ADR-DA | Mild to severe | 69.16 ± 2.12 | 68.09 ± 6.24 | Acupuncture: 1.5 inch needle, Acupoints: Yingxiang—(one inch above the seal—HT 32, retained for 1 h, manipulate the needle every 10 min), once a day, 5 consecutive days every week, last for 10 weeks |
Duxil: 40 mg/tablet, one tablet every time, two times/a day, 5 consecutive days a week, last for 10 weeks | MMSE, HDS-R | – |
| Zhao et al. (2007) | 16/16 | DSM-IV-R, DSDEE-SD | – | 62~81 | 62~81 | Acupuncture: 40 mm needle, acupoints: Baihui and Dazhui—(0.5 inch stab into the skin, twirling for 5 min, retained for 40 min), last for 8 weeks | Nimodipine: 20 mg every time, three times/d, last for 8 weeks | MMSE, HDS-R, ADL |
– |
| Luo et al. (2006) | 48/48 | DSM-III, ICD-10 | – | 50~80 | 50~80 | Elecrtoacupuncture: acupoints: a continuous wave, 2~4 times per second, acupoints: Dazhui, Shenyu, Taixi (bilateral), Zusanli (bilateral), retained for 25 min, 25 days as a course, 3–5 day break between course, last for 75 days |
Hydergine: 50 mg/time, three time/d, last for 90 days | MMSE | – |
| Jiang et al. (2004) | 24/20 | NINCDS-ADR-DA, DSM-IV-R, DSDEE-SD | – | 65.1 ± 6.4 | 64.3 ± 5.2 | Acupuncture: 40 mm needle, acupoints: Baihui, Sishencong, Shenyu, Sanyinjiao, Taixi, Zusanli, and Fenglong—(stab into the skin and twirl, retained for 30 min), Fengchi, Shenmen, Neiguan, Taichong, Geyu, Xuehai—(stab into the skin and twirl); once a day, five times a week, 4 weeks as a course, last for 8 weeks | Huperzine: 50 μg/tablet, 100 μg a time, two times/d, 1 month a course, last for 8 weeks | MMSE, CDR, ADL | – |
| Dong et al. (2002) | 11/10 | DSM-III-R | – | 46~80 | 46~80 | • Electroacupuncture A continuous wave at first, pulse frequency: 180 times per minute, dense-sparse wave after 15 min; acupoints: Baihui and Dazhui—(Electroacupuncture 180 rpm), Shenyu, Shenmen, Neiguan, Sanyinjiao—(stab and twirl, retained for 40 min), Sishencong and Fengchi—(Electroacupuncture 180 rpm), Taixi, Zusanli, Fenglong, Taichong—(stab and twirl, retained for 40 min), Neiguan, Jianshi, Danzhong, Lianquan, Yanglingquan, Yinlingquan, Yifeng, Tinggong, Yintang, Tianshu, Hegu; once a day, 5 days a week, 4 weeks a course, last for 12 weeks |
• Huperzine A Tablets: 100 μg a time, two times a day, 1 month a course, last for 12 weeks | MMSE, ADL | Severity of adverse events (e.g., headache, dizziness, palpitation) |
| Li et al. (2002) | 37/35/18/14 | DSM-IV-R | Mild to severe | 65 ± 6/67 ± 4 | 66 ± 4/65 ± 7 | • Electroacupuncture A continuous wave, 2–4 Hz, 40 mm needle, acupoints: Baihui, Sishencong, Fengchi, Shenyu—(stab into the skin in the way of Nianzhuanbu), combined with Taichong, Sanyinjiao, Neiguan, Fenglong, Geyu and Xuehai. Once a day, 6 days every week, last for 8 weeks • Electroacupuncture combine with Dangguishaoyaosan The methods of electroacupuncture was same with electroacupuncture group Dangguishaoyaosan: Angelica and Ligusticum chuanxiong (6 g), Paeoniflorin, Poria Cocos, and Rhizoma Atractylodis Macrocephalae (9 g), Alisma orientalis (10 g), decocted in water, one dose/d, for 8 weeks |
• Dangguishaoyao san The methods of Dangguishaoyaosan was same as ectroacupuncture combine with Dangguishaoyaosan group • Nimodipine 20–40 mg a time, three times/d, last for 8 weeks |
MMSE, HDS, ADL | – |
| Hou et al. (2000) | 30/30 | DSDEE-SD | Mild to severe | 60~78 | 61~78 | Acupuncture: acupuntpoints: Fengchi, Baihui, Sishencong, Shenmen, Zusanli, Neiguan combined with Taichong, Taixi, Sanyinjiao and Fenglong (retained for 30 min). Once a day, 30 days for a course, last for 2 courses, last for 60 days |
250 ml normal saline, Nicholin 0.75 g, intravenous drip, once a day, last for 60 days | HDS-R | – |
| Ou et al. (1999) | 16/14 | DSM-IV; ICD-10 | Mild to severe | 65.53 ± 6.8 | 64.72 ± 7.6 | Electroacupuncture: a continuous wave, 2–4 Hz,1.5 inch needle; acupoints: Baihui, Sishencong and Shenyu (main points), combine with Taichong, Guanyuan, Sanyinjiao and Zusanli—(stab into the skin in the way of twirling for 15 min, retained for 30 min), once a day, 6 days a week, last for 8 weeks | Nimodipine: 20–40 mg a time, 3 times/d, last for 8 weeks | HDS | – |
OCDAD, Operational criteria for the diagnosis of Alzheimer's disease; NIA-AA, National Institute of Aging -Alzheimer's Association; MMSE, Mini-Mental State Examination; ADL, activity of daily living; NINCDS-ADR-DA, The National Institute of Neurological and the Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association; DSM-IV-R, Diagnostic and Statistical Manual of Mental Disorders, fourth edition-revised; ADAS-cog, Alzheimer's disease assessment scale; NINDS-AIREN, National Institute of Neurological Disorders and Stroke-association/Internationale pour la Recherche et l'Enseignement en Neurosciences; HDS-R, Revised Hasegawa Dementia Scale; MoCA, Montreal Cognitive Assessment; DSDEE-SD, Diagnosis, Syndrome Differentiation and Efficacy Evaluation Criteria of Senile Dementia; NINDS-SIANR, The National Institute of Neurological Diseases and Stroke and the Swiss International Association for Neuroscience Research; ICD-10, The International Classification of Diseases; CDR, Clinical Dementia Rating; DSM-III-R, Diagnostic and Statistical Manual of Mental Disorders, third edition-revised.