In this trial, patients who agreed to random assignment were allocated to a randomized acupuncture group (R-acupuncture group) or control group. Those who declined randomization were assigned to a nonrandomized acupuncture group (NR-acupuncture group). Patients in the R-acupuncture group and NR-acupuncture group received up to 21 acupuncture sessions during a period of 6 weeks plus routine care, while the control group received routine care alone. Cognitive function, activities of daily living, and quality of life were assessed by mini-mental state examination (MMSE), Activities of Daily Living Scale (ADL), and dementia quality of life questionnaire (DEMQOL), respectively. All the data were collected at baseline, after 6-week treatment, and after 4-week follow-up. No significant differences of MMSE scores were observed among the three groups but pooled-acupuncture group had significant higher score than control group. Compared to control group, ADL score significantly decreased in NR-acupuncture group and pooled-acupuncture group. For DEMQOL scores, no significant differences were observed among the three groups, as well as between pooled-acupuncture group and control group. Additional acupuncture to routine care may have beneficial effects on the improvements of cognitive status and activities of daily living but have limited efficacy on health-related quality of life in VaD patients.
Vascular dementia (VaD) is thought to be resulted from various types of ischemic and hemorrhagic brain lesions which lead to intellectual and physical disability [
Maintaining or improving quality of life in people with VaD is currently a key outcome of health services and the increasing number of psychosocial interventions targeting this population [
Acupuncture is a core component in traditional Chinese medicine (TCM) and can be traced back more than 3000 years in China. It is often used as a treatment for dementia [
Based on our previous study [
Patients were eligible for this trial only after they had met rigorous criteria for probable VaD as defined by the National Institute of Neurological Disorders and Stroke-AIREN criteria (NINDS-AIREN). Inclusion criteria also included a score of 0 to 23 on the mini-mental state examination (MMSE), disease duration of more than 2 months, onset of the disease at age less than 80 years, and the availability of a reliable caregiver. All subjects included in the trial were evaluated with the Hachinski Ischemic Score (HIS). A HIS of
We performed the study according to common guidelines for clinical trials (Declaration of Helsinki, International Conference on Harmonisation (ICH)/WHO Good Clinical Practice standards (GCP) including certification by an external audit). The trial protocol has been approved by the Research Ethical Committee of The First Hospital affiliated to Tianjin College of Traditional Chinese Medicine (20073055). All study participants provided written, informed consent.
Patients who agreed to be randomly assigned were allocated to a randomized acupuncture group (R-acupuncture group) or control group. Block randomization with a block size of 4 was by sequential, sealed, opaque envelopes. It occurred after the acupuncturist’s evaluation (concealed allocation) using a computer-generated, random-allocation sequence (random list generated with SAS 8.2). Furthermore, participants who did not consent to randomization were assigned to a nonrandomized acupuncture group (NR-acupuncture group). We ensured that the patients, data collection staff, and data analysts were blinded during the study period; they were all unaware of the randomization. The acupuncturists were not blinded to the treatments they delivered because acupuncture manipulation made this impossible. During the intervention, acupuncturist and the personnel who collected data were segregated by an opaque screen immediately after the treatment started and were instructed not to exchange information with each other.
Patients in the R-acupuncture group and NR-acupuncture group received acupuncture treatment plus routine care, while those in the control group received routine care alone. Routine care here refers to the use of certain medications. These medicines include antiplatelet agents (aspirin or ticlopidine), antihypertensive, diuretics, and nimodipine and should be taken following the advice of physician. In addition, they received a weekly phone call to inquire of their health status to provide individual attention. Acupuncture was administrated by 5 therapists with more than 6 years of experience and a Chinese medicine practitioner license from the Ministry of Health of the People’s Republic of China. Based on the TCM theory, the main acupoints we selected were as follows: GV20 (baihui), EX-HN1 (sishencong), GV24 (shenting), CV17 (tanzhong), PC6 (neiguan), CV12 (zhongwan), CV6 (qihai), SP10 (xuehai), and ST36 (zusanli). Moreover, the following acupoints could be added as auxiliary acupoints: GB 20 (fengchi), ST40 (fenglong), LR3 (taichong), SP6 (sanyinjiao), and ST25 (tianshu). The acupuncture point prescriptions used were individualized to each patient and were at the discretion of the acupuncturist. Acupuncture was performed by means of standard stainless-steel needles (0.25 Φ × 25 mm and 0.25 Φ × 40 mm, Beijing Hanyi Medical Instrument Center) and manually stimulated to elicit needle sensation (de qi). The treatment consisted of 21 sessions of 30 minutes’ duration, and each was administered once every other day over a period of 6 weeks.
Demographic measures collected at the baseline evaluation included age, gender, common complications of VaD, HIS, and outcome variables.
Cognitive status, including orientation, memory, calculation, language, and constructional apraxia, of the VaD patients was assessed using the MMSE. Total scores for this measure range from 0 to 30, with lower scores indicating lower cognitive functioning.
Activities of daily living were determined by Activity of Daily Living Scales (ADL). It has been developed specifically for use with VaD, consisting of 20 daily-living abilities, where higher scores indicate lower levels of activities of daily living (scores range from 0 to 60).
Health-related quality of life is measured by dementia quality of life questionnaire (DEMQOL). It is a tool with which to evaluate whether the interventions and services achieve this. It covers five domains of quality of life and uses both self-reporting and rating by family guardian or staff member as proxy. Higher scores indicate better quality of life and vice versa. It has good internal consistency, interior reliability, and concurrent validity and can generate a measure of utility.
All the outcomes were assessed at baseline, after 6-week treatment and after 4-week follow-up.
According to previous study, there was a significant difference between the pre- and post-treatment for the treatment group than that for the control group with an increase of 4.27 ± 2.05. We calculated the number of sample size, using the following formula:
A per protocol analysis was done based on patients with no major protocol violations by the end of 4-week follow-up after randomization. Data are expressed as mean ± standard deviation (SD), or frequencies and percentages, according to the type of variable. For the between-group comparisons at baseline, either the Chi-Square test or one-way ANOVA was used. An analysis of covariance with additional covariate of age was performed to account for potential baseline differences. Repeated-measures analysis of variance was used to determine whether significant differences exist across time. Furthermore, results were evaluated by pooling all patients who received acupuncture treatment into one group. Pooled-acupuncture group which actually contained patients in R-acupuncture group and NR-acupuncture group were compared with the control group.
In the present population-based study, patients managed in the community as well as those managed in hospital (Tianjin, china) were recruited from June 2007 to February 2010. Figure
Trial flow chart.
The demographic and clinical features at baseline are shown in Table
Subjects’ baseline characteristics.
R-acupuncture ( |
NR-acupuncture ( |
Control ( |
|
---|---|---|---|
Gender |
|||
Men |
12 (54.55) | 6 (31.58) | 11 (50.00) |
Women |
10 (45.45) | 13 (68.42) | 11 (50.00) |
Age (M ± SD, y) | 67.24 ± 9.33 |
57.21 ± 10.80 |
67.45 ± 10.14 |
Hypertension, |
17 (77.27) | 17 (89.47) | 15 (68.18) |
Diabetes mellitus, |
2 (9.10) | 4 (21.05) | 4 (18.18) |
Coronary heart disease, |
9 (40.91) | 7 (36.84) | 8 (36.37) |
HIS (M ± SD) | 9.55 ± 2.37 | 11.32 ± 2.16 | 11.00 ± 2.14 |
MMSE (M ± SD) | 18.27 ± 4.08 | 17.74 ± 3.33 | 17.77 ± 3.99 |
ADL (M ± SD) | 42.91 ± 13.97 | 43.84 ± 11.42 | 49.86 ± 14.97 |
DEMQOL (M ± SD) | 72.41 ± 7.02 | 64.68 ± 6.68 | 72.27 ± 9.23 |
Repeated-measures analysis of variance on MMSE scores revealed a time effect (
The changes of score in MMSE across time. Comparison among R-acupuncture group, NR-acupuncture group, and control group (a) and between pooled-acupuncture group and the control group (b). R-acupuncture = randomized acupuncture group, Control = control group, NR-acupuncture = nonrandomized acupuncture group, and P-acupuncture = pooled-acupuncture group. T1 = at baseline, T2 = after 6-week treatment, and T3 = after 4-week follow-up.
Figure
The changes of score in ADL across time. Comparison among R-acupuncture group, NR-acupuncture group, and control group (a) and between pooled-acupuncture group and the control group (b). R-acupuncture = randomized acupuncture group, Control = control group, NR-acupuncture = nonrandomized acupuncture group, P-acupuncture = pooled-acupuncture group. T1 = at baseline, T2 = after 6-week treatment, and T3 = after 4-week follow-up.
Figure
The changes of score in DEMQOL across time. Comparison among R-acupuncture group, NR-acupuncture group, and control group (a) and between pooled-acupuncture group and the control group (b). R-acupuncture = randomized acupuncture group, Control = control group, NR-acupuncture = nonrandomized acupuncture group, and P-acupuncture = pooled-acupuncture group. T1 = at baseline, T2 = after 6-week treatment, and T3 = after 4-week follow-up.
During the acupuncture treatment, 25% experienced discomfort at the sites of needle insertion or simulated needle insertion, and 20% had bruising. No serious adverse events were documented.
The aim of our study was to examine whether acupuncture has additional value in patients with VaD compared to treatment with routine care alone. Results indicate that, compared to patients in control group, those in pooled-acupuncture group showed significant improvements in cognitive status and activities of daily living. Moreover, patients who declined randomization and therapeutic outcomes after acupuncture were better than those who consented to. Additional acupuncture to routine care is of limited efficacy in VaD patients whose health-related quality of life has already deteriorated.
Recent international policy guidelines aim to promote independence in dementia and show a rising interest in how nonpharmacological interventions could help maintain everyday functional independence as long as possible [
There is growing evidence implicating dementia is a risk factor for stroke and stroke is associated with an increased risk of subsequent dementia [
We took a pragmatic approach, aiming to evaluate acupuncture in a manner that would reflect as closely as possible the conditions of daily medical practice. The additional inclusion of patients who declined randomization allowed us to investigate any potential selection effects. One explanation for the significant improvements in NR-acupuncture group may attribute to potent placebo effects. Previous studies have shown that expectancy, a crucial component of placebo, plays an important role in acupuncture treatment efficacy [
Treatment of VaD also includes prevention and attenuation of potential risk factors [
In a pragmatic trial, it is not usually appropriate to use a placebo control and blinding, as these are likely to have a detrimental effect on the trial’s ecological validity [
Our study shows that additional acupuncture to routine care may have beneficial effects on the improvements of cognitive status and activities of daily living but have limited efficacy on health-related quality of life in VaD patients.
Vascular dementia
Randomized acupuncture group
Nonrandomized acupuncture group
Mini mental state examination
Ability of daily life scale
Dementia quality of life questionnaire
Traditional Chinese medicine
Hachinski Ischemic Score
Alzheimer’s disease
Standard deviation.
The authors declare that there is no conflict of interests regarding the publication of this paper.
The authors thank the research staff at The First Hospital affiliated to Tianjin College of Traditional Chinese Medicine (Wei Guan and Chuan Xiao), The Second Hospital affiliated to Tianjin College of Traditional Chinese Medicine (Zhan-kui Wang and Hui Shi), Tianjin Hospital of Traditional Chinese Medicine (Lei Wang), and Tiantuo community Hospital (Hong Zhu). The study was supported by Program for New Century Excellent Talents in University (NCET-09-0007), Technology New Star Program of Beijing (2009B46), and the Bureau of Public Health of Tianjin (07059).