Issue:
119
Page: 28-29
Clinical Efficacy of a Chinese Herbal Combination for Mild Cognitive Impairment
by Heather S. Oliff, PhD
HerbalGram.
2018; American Botanical Council
Reviewed: Tian J, Shi J, Li T, et al. Efficacy and
safety of an herbal therapy in patients with amnestic mild cognitive
impairment: A 24-week randomized phase III trial. Evid
Based Complement Alternat Med. 2017;2017:4251747. doi:
10.1155/2017/4251747.
Mild cognitive
impairment (MCI) refers to a stage of cognitive impairment between what is
expected with normal aging and the onset of Alzheimer’s disease (AD). Amnestic
MCI (aMCI) is the most common subtype of MCI and is characterized by impairment
of episodic memory without impairment of activities of daily living (ADL).
Treating aMCI may prevent or delay the onset of AD. The purpose of
this multicenter, randomized, double-blind, double-placebo,
parallel-controlled, phase III study was to evaluate the efficacy and
safety of a Chinese herbal formulation to improve cognition and memory in
patients with aMCI.
Chinese-speaking
adults (N = 324; 55-80 years of age) with MCI who were living in the community
(as opposed to senior care facilities) were recruited from nine memory clinics
in China from September 2008 to May 2010.
Included patients
had memory complaints that were corroborated by an informant; abnormal memory
function according to the Chinese version of the Adult Memory and Information
Processing Battery (AMIPB) Logical Memory Delayed Story Recall (DSR) subtest;
normal general cognition based on the Mini-Mental State Examination (MMSE); no
or minimal impairments in ADL; scores of 12 or less on the Hamilton Depression
Rating Scale (HAM-D) and 4 or less on the Hachinski Ischemic Score (HIS) scale;
adequate vision and hearing; and no or mild medial temporal atrophy or
hippocampal volume atrophy on a magnetic resonance imaging (MRI) scan. In
addition, included patients were not significantly impaired cognitively or
functionally according to the National Institute of Neurological Disorders and
Stroke and Alzheimer’s Disease and Related Disorders Association criteria for
AD and met the criteria for stage 2-3 on the Global Deterioration Scale (GDS).
Patients were
excluded if they had evidence of a focal brain lesion; a previous head injury
with loss of consciousness or immediate confusion after the injury; a
neurologic disease that might affect cognition; uncontrolled hypertension or
diabetes mellitus; a history of significant cerebrovascular disease, a central
nervous system infarct or infection, a major psychiatric disorder, or alcohol
or substance abuse. Patients also were excluded if they had documented evidence
of an active gastric or duodenal ulcer within the previous three months; active
malignancy or prostate cancer within the preceding 24 months; or chronic or
acute renal, hepatic, or metabolic disorder; among other criteria.
Following a two-week placebo run-in phase, patients had an MRI scan and
then were randomly assigned to receive for 24 weeks either an herbal capsule
(five capsules three times per day) and a placebo that was identical to
donepezil tablets (Aricept; Eisai Inc.; Tokyo, Japan) (n = 216), or 5 mg per
day donepezil and a placebo that was identical to the herbal capsules (n =
108).
The herbal capsule (shenwu capsule; North China Pharmaceutical Group
Corporation; Hebei Province, China) contained 4.24% Asian ginseng (Panax ginseng, Araliaceae)
root, 21.28% he shou wu (Polygonum multiflorum, Polygonaceae)
tuber, 14.89% epimedium (Epimedium brevicornum, Berberidaceae) leaf,
14.89% Acorus tatarinowii (Acoraceae) rhizome, 14.90% Sichuan
lovage
(Ligusticum sinense, Apiaceae) rhizome, and 29.80% lobed kudzu vine
(Pueraria spp., Fabaceae) root extracts.
Cognition was the primary outcome assessed using the Alzheimer’s
Disease Assessment Scale-cognitive subscale (ADAS-cog). The secondary outcomes
measured memory with the DSR logical memory subtest. Assessments were made at
screening and weeks 12 and 24. An additional evaluation was carried out at week 48, although
with a limited number of participants (n = 23). The safety assessment included
examinations of general physical vital signs (e.g., breathing, heart rate, and
blood pressure), electrocardiography (ECG), laboratory testing, and
documentation of adverse events (AEs).
A total of 44 patients discontinued treatment, with two patients in the
herbal therapy group discontinuing due to AEs. Baseline demographics and
characteristics (including MMSE, GDS, and HAM-D scores) were not significantly
different between groups. Both groups had excellent compliance (herbal therapy:
92.6% and donepezil: 95.3%). ADAS-cog and DSR scores were significantly
improved from baseline to week 24 in both treatment groups (P <
.001), and there were no significant between-group differences in these scores
at 24 weeks. The inferiority analysis showed that the herbal treatment was not
inferior to donepezil. The herbal therapy produced an average 4.19-point
improvement in ADAS-cog scores from baseline to week 24 (an improvement of at
least 3.3 points is considered clinically significant). At week 48 (24 weeks
after the treatment period ended), scores for both groups trended toward
original baseline values. The rate of conversion from MCI to AD in 23 subjects
(11 patients from the herbal therapy group and 12 patients from the donepezil
group) was assessed at one site. At week 24, none of the patients converted to
AD in either group.
AEs were reported by 18.1% of the herbal therapy group and 57.4% of the
donepezil group. The most frequent AEs assessed as probably related to the
herbal therapy were thirst (6.5%) and sore throat (4.2%). The herbal therapy group
compared to the donepezil group had significantly lower rates of diarrhea (0%
vs. 12.5%, respectively), nausea (2.1% vs. 16.7%), and insomnia or abnormal
dreams (2.3% vs. 16.7%) (P < .05 for all). There were no significant
changes in vital signs, physical examination findings, ECG status, or
laboratory values.
The authors
concluded that the herbal therapy was safe and has similar clinical
benefits to donepezil with fewer AEs in patients with confirmed MCI. A
limitation of the study is that there was no true placebo group. Although there
was a positive control (donepezil), all patients knew that they were being
treated with one of two active preparations, so a placebo response cannot be
ruled out. Another limitation is that 24 weeks may not be long enough to see a
long-term response in patients with MCI. Additional research is needed to
identify the key bioactive constituents of these plants that may be responsible
for the observed effects and confirm whether the herbal therapy delays the
progression from MCI to dementia.
—Heather
S. Oliff, PhD
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