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Journal of Chinese Integrative Medicine ›› 2012, Vol. 10 ›› Issue (7): 766-776.doi: 10.3736/jcim20120707

• Original Clinical Research • Previous Articles     Next Articles

Chinese herbal medicine for patients with mild to moderate Alzheimer disease based on syndrome differentiation: A randomized controlled trial

Lu Yu1, Shui-miao Lin1(), Ru-qian Zhou1, Wei-jun Tang2, Pin-xian Huang3, Ying Dong3, Jian Wang1, Zhi-hua Yu1, Jiu-lin Chen1, LiWei4, San-li Xing1, Hui-juan Cao5, Hong-bin Zhao1   

  1. 1. Shanghai Geriatric Institute of Chinese Medicine, Shanghai 200031, China
    2. Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200040, China
    3. Department of Preventive Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
    4. College of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
    5. Center for Traditional Chinese Medicine and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
  • Received:2012-03-27 Accepted:2012-04-17 Online:2012-07-20 Published:2018-07-15
  • Contact: Lin Shui-miao E-mail:trastayl@hotmail.com

Background: Alzheimer disease (AD) is a chronic neurodegenerative disease that is characterized by its gradual progression. At present, the cause and mechanism of AD are yet unclear, and there is no effective therapy for treating it. With development of global aging, the prevalence rate of AD is increasing. The life quality of elderly people is affected severely by AD that is ultimately life-threatening. Recently, study on treating AD with traditional Chinese medicine (TCM) has deepened.
Objective: To explore the therapeutic effects of a syndrome differentiation-based TCM regime in treating patients with mild to moderate AD for improving cognition, and to evaluate the changes in brain function of AD patients observed by resting-state functional magnetic resonance imaging (fMRI) technique.DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Adopting the internationally recognized criteria developed by National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer’s Disease and Related Disorders Association, the clinical trial was conducted on 131 patients with mild to moderate AD from 5 communities and 7 social welfare institutions. Participants were accepted after informed consent was received, and laboratory tests and a head imaging study were conducted. The patients were randomly divided into Chinese medicine group (CMG) (66 cases) or Western medicine group (WMG) (65 cases). Patients in the CMG were treated monthly with Chinese medicine according to syndrome differentiation. Patients in the WMG were treated with donepezil at a dose of 5 mg once daily. The therapeutic course lasted 48 weeks.MAIN OUTCOME MEASURES: The scores of Mini-Mental State Examination (MMSE), Fuld Object-Memory Evaluation (FOM), Block Design (BD) and Digit Span (DS) were used to evaluate the cognitive function; resting-state fMRI was used for observing brain function. The questionnaires and fMRI were performed before and after treatments.
Results: The cognitive functions of the patients in the CMG and WMG were improved after treatment. MMSE score was improved significantly in both groups (P<0.05 or P<0.001). After 48 weeks of treatment, 70.91% patients in the CMG had an improved MMSE score and 20% got worse, however, 55.77% patients in the WMG were improved in MMSE score and 34.62% got worse. Scores of FOM denominator and BD increased significantly in both groups; scores of FOM numerator and DS were also increased in the CMG (P<0.05 or P<0.01). The results of fMRI suggested that both Chinese medicine and donepezil treatment improved the connectivity between posterior cingulated gyrus and specific areas in the brain. The influence range of Chinese medicine primarily impacted on the left parietal lobe, being less than the influence range of donepezil, which primarily affected both sides of frontal lobes.
Conclusion: TCM treatment based on syndrome differentiation is effective in improving cognitive function of patients with mild to moderate AD and increasing the brain function by increasing connectivity between posterior cingulated gyrus and specific areas in the brain.

Key words: drugs, Chinese herbal, Alzheimer disease, cognition disorders, resting-state functional magnetic resonance imaging, randomized controlled trial

Figure 1

Flow diagram of this randomized trial"

Table 1

MMSE scores of Chinese medicine group and donepezil group at different time points (x±s)"

Group Time point n MMSE score
Chinese medicine Before treatment 64 18.34±4.07
After 24-week treatment 56 20.57±5.67**
After 48-week treatment 55 20.71±5.70**
Donepezil Before treatment 62 17.48±4.50
After 24-week treatment 51 18.67±6.17*
After 48-week treatment 52 18.62±6.55*

Table 2

Scores of FOM, BD and DS of Chinese medicine group and donepezil group at different time points (x±s, scores)"

Group Time point n FOM numerator FOM denominator BD DS
Chinese medicine Before treatment 64 13.09±4.15 5.970±2.20 16.13±11.22 8.03±2.04
After 24-week treatment 56 14.16±4.24** 6.48±2.66* 16.66±11.18 8.43±2.05
After 48-week treatment 55 14.18±4.87** 6.58±2.51** 20.80±12.61** 8.71±2.27*
Donepezil Before treatment 62 13.11±3.84 5.50±2.10 14.44±10.87 8.37±2.42
After 24-week treatment 51 13.59±4.50 6.30±2.18** 15.33±11.99 8.41±2.84
After 48-week treatment 52 13.69±5.21 6.10±2.60* 16.94±13.96* 8.39±2.72

Table 3

Localization of the main cerebral regions with significant difference (P<0.01) in comparison of before and after treatment in Chinese medicine group"

Coordinate Cerebral region t value Number of voxels
X Y Z
–42 –60 –34 Left posterior cerbellar lobe 3.91 20
–6 –16 –10 Brain stem 3.66 115
–10 –48 66 Left parietal lobe 3.29 72
–34 –8 –34 Left hook back –3.08 15
38 –36 –34 Right anterior lobe of cerebellum –4.54 27
–18 –16 –34 Cerebellum –4.28 140
46 20 –34 Right temporal lobe –5.05 117
–26 44 –18 Left superior frontal gyrus –3.32 27
26 –80 –14 Right lateral occipital margin back –4.17 70
50 –32 30 Right inferior parietal lobule –4.13 651
46 –80 30 Right temporal lobe angular gyrus –3.16 17

Figure 2

Distribution of cerebral regions connected with posterior cingulated gyrus in Chinese medicine group The regions whose connectivity is improved after treatment are marked by red; the regions whose connectivity is declined after treatment are marked by blue. The images were the results tested by resting-state functional magnetic resonance imaging."

Table 4

Localization of the main cerebral regions with significant difference (P<0.01) in comparison of before and after treatment in donepezil group"

Coordinate Cerebral region t value Number of voxels
X Y Z
–42 –60 –6 Left temporal lobe 4.04 55
–2 –16 –6 Left brain stem 3.74 51
–26 –4 –6 Left lenticular nucleus 3.47 85
–14 –84 22 Left occipital lobe wedge back 3.01 44
10 –68 26 Right occipital lobe wedge back 3.23 19
–10 –28 70 Left frontal lobe 4.39 334
–6 28 18 Left anterior cingulated gyrus –3.63 45

Figure 3

Distribution of cerebral regions connected with posterior cingulated gyrus in donepezil group The regions whose connectivity is improved after treatment are marked by red; the regions whose connectivity is declined after treatment are marked by blue. The images were the results tested by resting-state functional magenetic resonance imaging."

Table 5

Localization of the main cerebral regions with significant difference (P<0.01) in comparison of the differences of before treatment and after treatment between two groups"

Coordinate Cerebral region t value Number of voxels
X Y Z
2 20 26 Anterior cingulated gyrus 3.42 18
–46 –48 –46 Left posterior lobe of cerebellum –3.74 44
34 12 –42 Right temporal lobe –3.60 55
–26 32 –22 Left inferior frontal gyrus –3.12 24
–10 –72 –6 Left occipital margin back –3.57 142
–54 4 2 Left superior temporal gyrus –3.74 27
46 –32 26 Right inferior parietal lobule –3.25 17
–14 52 26 Left superior frontal gyrus –3.02 44
–42 –80 34 Left parietal lobe wedge back –4.54 134
–2 –40 22 Left posterior cingulated gyrus –3.33 23
2 52 42 Right frontal gyrus –3.43 16

Figure 4

Distribution of cerebral regions connected with posterior cingulated gyrus The regions whose connectivity is improved after treatment evaluated by the difference between D-values of Chinese medicine group and donepezil group are marked by red; the regions whose connectivity is declined after treatment evaluated by the difference between D-values of Chinese medicine group and donepezil group are marked by blue. The images were the results tested by resting-state functional magenetic resonance imaging."

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