THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE

Volume 22, Number 9, 2016, pp. 695705

Mary Ann Liebert, Inc.
DOI: 10.1089/acm.2016.0070

Original Articles

Memory Impairment, Dementia, and Alzheimers

Disease in Classical and Contemporary Traditional
Chinese Medicine
Brian H. May, PhD,1 Mei Feng, BMed,2 Iris W. Zhou, PhD,1 Su-yueh Chang, BFor,1
Shao-chen Lu, MAppSci,1 Anthony L. Zhang, PhD,1 Xin-feng Guo, PhD,2
Chuan-jian Lu, PhD,2 and Charlie C.L. Xue, PhD1,2

Abstract

Objectives: To identify and analyze records of the treatment of dementia and memory disorders in the classical
Chinese medical literature that were consistent with the signs and symptoms of Alzheimers disease (AD), with
the aim of determining which traditional medicines have histories of use for these disorders.
Methods: Encyclopedia of Traditional Chinese Medicine (Zhong Hua Yi Dian), a database of more than 1000
classical and premodern Chinese medical books, was systematically searched. Search terms were identified
from dictionaries, medical nomenclatures, guidelines, and specialist clinical manuals on aging, neurology, or
brain disorders. Inclusion and exclusion criteria were used to identify citations of conditions whose signs and
symptoms were consistent with the clinical features of AD. Passages of text identified by these terms were
copied to Microsoft Excel spreadsheets, together with the identity of the source book and all relevant information on the disorder and the intervention. Each distinct passage of text was considered a citation. The
frequencies of the traditional formulas used as interventions and their constituent ingredients were calculated.
Results: The selection criteria identified 1498 citations of dementia and memory impairments derived from 277
different books written from circa 363 to 1945 AD. In 91 of these citations, memory impairment was associated
with aging and was broadly consistent with the clinical features of AD. Although the interventions varied in
name, Poria cocos, Polygala tenuifolia, Rehmannia glutinosa, Panax ginseng, and Acorus species consistently
appeared as ingredients in multiple formulas for memory impairment in the context of aging.
Conclusions: Memory impairment in older age was a recognized condition in the classical literature. Many of
the traditional medicines frequently used as ingredients in classical formulas for memory impairment consistent
with clinical features of AD remain in contemporary use, and experimental studies suggest biological activities
relevant to AD.
Notes on Terminology

For Chinese terms, the Pin Yin system of transliteration is

used. Chinese book names are translated into English, but
formula names can be untranslatable so these are given in
Pin Yin only. For names of traditional medicines in the text,
the full Latin binomial and the Chinese name in Pin Yin are
given in the first instance. In the text, Chinese disease or
symptom names are in lower case italic (e.g., chi dai), herb
names are given in lower case (e.g., yuan zhi), formula
names have the first letter capitalized (e.g., Gui pi tang), and
book names have each letter capitalized and appear in italics

(e.g., Zhong Hua Yi Dian). A full glossary of the Chinese

terms and names in Pin Yin used in the text appears in the
supplementary material (Supplementary Table S1; Supplementary materials are available online at www.liebertpub.com/
acm). This includes a complete listing of the scientific names
of TMs, Chinese characters, and parts used.
Introduction

eclines in memory and cognitive function associated

with aging are clinical features of Alzheimers disease
(AD), vascular dementia (VaD), and other neurocognitive

1
China-Australia International Research Centre for Chinese Medicine, School of Health and Biomedical Sciences, RMIT University,
Bundoora, Victoria, Australia.
2
Guangdong Provincial Academy of Chinese Medical Sciences and Guangdong Provincial Hospital of Chinese Medicine, Guangzhou,
China.

695

696

disorders.1 In the United States, AD is the most common type

of dementia, followed by VaD.2 AD is named after Alois
Alzheimer, who identified neuritic plaques and neurofibrillary tangles in the brain of a woman who had died with
dementia in 1906.3 Clinical features of AD include progressive impairments in memory, learning, social cognition, and
language.1 AD pathology involves neuronal death and brain
atrophy, which are typically associated with deposition of the
protein b-amyloid to form insoluble plaques and accumulation of an abnormal form of the protein tau inside neurons
to form neurofibrillary tangles.1,4,5 In VaD, cognitive impairments are typically associated with a history of cerebral infarctions and hypertension.1,6 AD and VaD can be
accompanied by behavioral and psychological symptoms of
dementia, including agitation and depression.7
AD is a significant and increasing health issue in contemporary China and other Asian countries.8,9 Traditional medicines (TMs) are commonly used in China for prevention and/or
treatment of dementia, and research into TMs for dementia is a
growing field.10 Some conventional drugs used for AD have
plant origins, including the acetylcholinesterase inhibitors
galantamine, which is found in Galanthus, Lycoris, Narcissus,
and Leucojum species,11 and rivastigmine, which is a semisynthetic derivative of physostigmine from Physostigma venenosum Balf.12 Therapies of Asian botanical origin for which
there is evidence of efficacy include huperzine A, derived from
Huperzia serrata (Thunb. ex Murray) Trevis.13,14 and EGb761,
which is a standardized extract of Gingko biloba L. leaves.15,16
Other plants used in traditional medicines show promise based
on animal and human studies.1723
While evaluation of plants and plant-derived compounds
using experimental methods remains the mainstay of drug
discovery from natural products, traditional use has been
proposed as a valid source of evidence,24 and text mining of
the literature on traditional medicine has been used to research disease names25 and identify plants and compounds
for further study.2631
In a previous study of Chinese TMs for dementia, Great
Compendium of Chinese Medical Formulae (Zhong Yi Fang
Ji Da Ci Dian [ZYFJDCD]), the largest printed book on
Chinese formulas was searched; this includes 96,592 individual formula entries extracted from more than 685
books.32 In recent times, voluminous collections of traditional Chinese medical literature have become available as
digitized versions.33 The current paper presents the results
of a systematic analysis of Encyclopaedia of Traditional
Chinese Medicine (Zhong Hua Yi Dian [ZHYD]), which is a
database of more than 1000 classical and premodern medical books written or published before 1950.33,34 About half
(55.2%) of the books in ZYFJDCD also appear in ZHYD,35
but these two sources differ in other important ways.
ZYFJDCD is a curated book that does not include unnamed
formulas; each named formula is listed once, except when
the ingredients are substantially different; clinical applications tend to reflect the oldest citation, although there are
some later additions; and the index is used to find formulas
for a disease.32 In contrast, ZHYD contains the full text of
each book.34 As a result, an electronic search can identify all
citations of all formulas used as treatments for a particular
disease or symptom in all the included books. Therefore, the
appearance of a formula in multiple different books provides
proxy measures of how many authors considered that for-

MAY ET AL.

mula worthy of inclusion and which formulas were more or

less popular as interventions for the disease. Such an approach was not feasible with use of ZYFJDCD.
An earlier study by the current authors investigated individual TMs for dementia based on searches of materia
medica (ben cao) entries in ZHYD36 and compared the results to the comprehensive contemporary book Great Compendium of Chinese Medicines (ZYDCD).37 In the present
study, the data derive from the formula and clinical literature and do not overlap with the earlier study.
In contemporary Chinese medicine, dementia may be described by using modern terms, including senile dementia
(lao nian xing chi dai), Alzheimers disease (a er ci hai mo ji
bing), and vascular dementia (xue guan xing chi dai) or the
traditional terms chi dai (dementia, mental feebleness),
jian wang (memory impairment, forgetfulness), and related
terms.3840 These traditional terms were based on clinical
presentation and had broader scopes of meaning than modern
terms, so it cannot be assumed that a disorder described by
using these traditional terms would have resulted from AD
pathology and would now be diagnosed as AD. However, descriptions of disorders in traditional books can be identified
whose signs and symptoms were consistent with the clinical
features of AD or other disorders. This enables comparisons
between the historical and contemporary literatures.
The present study identified and analyzed records in
ZHYD of the treatment of dementia and memory disorders to
determine the following: (1) whether the signs and symptoms in any of the records were consistent with AD; (2)
which formulas and formula ingredients were most frequently used for age-related memory disorders; (3) whether
the results were consistent with the studies of ZYFJDCD41
and ZHYD materia medica books;36 and (4) whether the
results were consistent with contemporary Chinese materia
medica books and guidelines.38
Materials and Methods

As the sample of classical literature, ZHYD was chosen because it is representative and largely inclusive of other large
collections of the classical and premodern Chinese medical
literature.33,35 The general approach to searching this database,
data extraction, and coding has been described elsewhere.42
Briefly, search terms were identified from dictionaries,
medical nomenclatures, and guidelines3840,4345 and traditional specialist clinical manuals on aging, neurology, or brain
disorders.4656 Trial searches were conducted by using each
term. Terms for which the scope of meaning was nonspecific
were excluded. The final search terms were grouped into jian
wang and synonyms, chi dai and synonyms, and other terms
relating to memory disorders (Supplement 1).
All passages of text identified by these terms were copied
to Microsoft Excel (Microsoft Corp., Redmond, WA) spreadsheets (by I.W.Z., S.L., S.C., B.H.M.), together with the
identity of the source book and all relevant information on the
disorder and intervention. Each distinct passage of text was
considered a single citation irrespective of how many times
the search term was mentioned. Duplications were identified
and removed. Inclusion and exclusion criteria were used to
identify conditions whose signs and symptoms were consistent with the features of AD. Each citation was read and
allocated codes (by S.C., I.W.Z.). Complex citations were

DEMENTIA AND ALZHEIMERS DISEASE IN CLASSICAL AND CONTEMPORARY CHINESE MEDICINE

read by two or more researchers (S.Z., B.H.M., I.W.Z.), and

additional input was sought to resolve difficult issues.
Exclusion criteria were as follows: (1) conditions with
sudden or recent onset (trauma, fever, epidemic, or seasonal
disorder); (2) disorders specific to children or young people,
or female obstetric disorders; (3) psychiatric disorders with
symptoms unlike those of AD (e.g., dian kuang, madness);
(4) conditions likely due to a cerebrovascular accident (e.g.,
zhong feng, hemiplegia, paralysis), Parkinsons disease (e.g.,
tremor), or epilepsy (e.g., seizures); (5) no TM intervention;
(6) materia medica entry listing clinical applications of a
single substance; and (7) book written after 1949. Citations
that mentioned symptoms consistent with behavioral and
psychological symptoms of dementia were not excluded.
Inclusion criteria were as follows: (1) specific TM intervention comprising one or more ingredients intended as a
treatment for one or more of the search terms; (2) mention
or description of memory impairment; and (3) mention of
older people, aging, or promotion of longevity.
Citations satisfying all the exclusion criteria plus the first
inclusion criterion were reported as level 1. Citations also
satisfying the second and third inclusion criteria were reported
as level 2. Level 1 is based on formulas for conditions that could
not be eliminated as possible instances of AD. Level 2 is a
subgroup in which memory impairment was a symptom and the
formula was associated with aging. Data were entered into
SPSS software (IBM, Armonk, NY) for analysis. Results were
cross-referenced to the total data sets of the previous analyses of
ZYFJCDC41 and the ZHYD materia medica entries.36
For the contemporary literature on materia medica, the
comprehensive ZYDCD was selected; this contains 5757 entries with clinical applications.36 For contemporary TM formulas, Chinese Guidelines for the Diagnosis and Treatment of
Alzheimers Disease and Other Dementias38 was used. These
two sources provided points of comparison between the classical and contemporary clinical applications of individual TMs
and formulas. Scientific names of TMs are from Pharmacopoeia of the Peoples Republic of China and ZYDCD.37,57
Results

After removal of duplicates, 1878 citations of TM interventions were analyzed. The most commonly used search

697

term was jian wang (1059 citations) followed xi wang (274

citations), both of which refer to memory impairments. The
chi dai group of terms were infrequent (63 citations).
For level 1, 1498 citations were identified (Supplementary
Table S2). These were derived from 277 different books
written from circa (c.) 363 AD to 1945. Most of the books
were written during the Ming (13691644) and Qing (1645
1911) dynasties (Table 1).Prescriptions for Universal Relief (Pu Ji Fang, c.1406), which is the largest book in ZHYD,
provided 171 citations. The next most productive book was
the Song dynasty encyclopedia Complete Record of Sacred
Benevolence (Sheng Ji Zong Lu, c.1117) with 56 citations.
The level 1 citations referred to 105 unnamed formulas
and 527 different formula names. Gui pi tang was the most
common formula name, followed by Tian wang bu xin dan,
Ding zhi wan (aka Ding zhi xiao wan), and Tao ren cheng qi
tang (Table 2). All formulas included 14,415 ingredients
(mean, 9.6 ingredients/formula) comprising 398 different
TMs. The most frequently used TMs were sclerotium of
Poria cocos (Schw.) Wolf (fu ling or fu shen, 1143), root of
Panax ginseng C.A. Mey. (ren shen, 867), root of Polygala
tenuifolia Willd. (yuan zhi, 761), root and rhizome of Glycyrrhiza species (gan cao, 670); root of Angelica sinensis
(Oliv.) Diels (dang gui, 522), and rhizome of Acorus species
(chang pu, shi chang pu, 417) (Table 3). Rehmannia glutinosa Libosch. (di huang) root was used 538 times, with the
steamed root (shu di, 261) being the most common form.
When the level 2 criteria were applied, the remaining 91
citations derived from 40 books (c.6521839) with the
most productive being Longevity and Life Preservation
(Shou shi bao yuan, c.1406). Two citations referred to
unnamed formulas, and the remainder cited 56 different
named formulas. Of these, Shou xing wan was the most
frequent (n = 12) followed by Xiao dan, modified Gu ben
wan, and Ju sheng wan (Table 4). Remaining on the list
were Gui pi tang (n = 2), Tian wang bu xin dan (n = 2), Er
dan wan (n = 1), and modified Ding zhi wan (n = 1). A total
of 970 ingredients representing 140 different TMs were
contained in the formulas. The most commonly used ingredients were P. cocos (fu ling, fu shen, 78), P. tenuifolia
(yuan zhi, 61), R. glutinosa (di huang, shu di, sheng di, 51),
P. ginseng (ren shen, 47), and Acorus species (chang pu,
shi chang pu, 34) (Table 5).

Table 1. Citations of Formula Interventions by Dynasty

All data
(after duplicate removal)
Historical period (dynasty)a
Before Tang Dynasty (617)
Tang and 5 Dynasties (618959)
Song Jin Dynasties (9601271)
Yuan Dynasty (12721368)
Ming Dynasty (13691644)
Qing Dynasty (16451911)
Minguo period (19121949)
Modern period (1950)
Total

Level 1
(after exclusions)

Frequency (n) Percentage Frequency (n) Percentage

10
91
175
129
804
639
23
7
1878

0.5
4.8
9.3
6.9
42.8
34.0
1.2
0.4
100.0

5
71
134
95
667
512
14
0
1498

0.3
4.7
8.9
6.3
44.5
34.2
0.9
0
100.0

Level 2
(memory impairment and aging)
Frequency (n)

Percentage

0
5
9
6
52
19
0
0
91

0
5.5
9.9
6.6
57.1
20.9
0
0
100

a
The dividing points between dynasties are open to interpretation, so the years have been adjusted to avoid overlap. When authors lived
across two dynasties, the dynasty usually cited for the book was adopted. See May et al.42 for how book years were determined.

698

MAY ET AL.

Table 2. Most Frequent Classical Formulas for Dementia

and Memory Impairment After Exclusion Criteria: Level 1
Formula name
Gui pi tang

Frequency (n)

Formula ingredients; first book in group (year)

118 (134)

Bai zhu, Fu shen, Huang qi, Long yan rou, Suan zao ren, Ren
shen, Mu xiang, Gan cao; Yan Shi Ji Sheng Fang (c.1253)
Shu gan di huang, Bai fu ling, Fu shen, Dang gui, Yuan zhi, Shi
chang pu, Hei shen, Ren shen, Mai men dong, Tian men dong,
Jie geng, Bai bu, Bai zi ren, Du zhong, Gan cao, Dan shen, Suan
zao ren, Wu wei zi; Yang Shi Jia Cang Fang (c.1108)
Ren shen, Fu ling, Chang pu, Yuan zhi; Bei Ji Qian Jin Yao Fang
(c.652)
Tao ren, Da huang, Mang xiao, Gan cao, Gui zhi; Lei Zheng Huo
Ren Shu (c. 1108)
Shui zhi, Meng chong, Da huang, Tao ren; Fu Ren Da Quan Liang
Fang (c.1237)
Shao yao, Sheng di huang, Mu dan pi, Xi jiao; Lei Zheng Huo Ren
Shu (c.1108)
Sang piao xiao, Fu shen, Yuan zhi, Chang pu, Ren shen, Dang gui,
Long gu, Gui jia; Zheng Lei Ben Cao (c.1082)
Fu shen, Chen xiang; Shi Yi De Xiao Fang (c.1345)
Dan shen, Dan sha, Yuan zhi, Fu shen, Ren shen, Chang pu, Shu di
huang, Tian men dong, Mai men dong, Gan cao; Su Wen Bing Ji
Qi Yi Bao Ming Ji (c.1186)
Ren shen, Huang qi, Chen pi, Bai shao yao, Dang gui, Gan cao,
Bai fu ling, Wu wei zi, Yuan zhi, Bai zhu, Gui xin, Shu di
huang; Yi Fang Kao (c.1584)
Huang qi, Fu ling, Fu shen, Ban xia qiu, Dang gui, Chuan xiong,
Yuan zhi, Rou gui, Suan zao ren, Bai zi ren, Wu wei zi, Ren
shen, Gan cao; Yi Fang Ji Yi (c.1554)
Bai shao yao, Mai men dong, Huang qin, Dang gui, Fang feng, Bai
zhu, Chai hu, Jie geng, Xiong qiong, Bai fu ling, Xing ren, Shen
qu, Pu huang, Ren shen, Ling yang jiao, She xiang, Long nao,
Rou gui, Da dou juan, E jiao, Bai lian, Gan jiang, Niu huang, Xi
jiao, Xiong huang, Gan shan yao, Gan cao, Jin bo, Da zao; Tai
Ping Hui Min He Ji Ju Fang (c.992)
Tian nan xing, Zhu sha, Hu po; Qi Xiao Liang Fang (c.1470)

Tian wang bu xin dan

65 (75)

Ding zhi (xiao) wan

38 (59)

Tao ren cheng qi tang

29 (30)

Di dang tang/wan

28

Xi jiao di huang tang

23

Sang piao xiao san

20

Zhu que wan

Er dan wan

20
17

Ren shen yang rong tang

14

Yang xin tang

13

Niu huang qing xin wan

12

Shou xing wan

12 (15)

First book in group: the oldest book within the group of included citations, not the first book that included the formula. Dates are
approximate. Formulas with the same name can vary in their ingredients, and the same combination of ingredients may have different
names. In these data, formulas with the same core ingredients and the same name are grouped together, while those with different main
ingredients are separated. Also, formulas with the same ingredients but different names have been grouped together. The frequency is for
the name in the left column, and the number in parentheses includes modified versions of the formula. For scientific names of ingredients
written in Pin Yin and Chinese characters for traditional medicines and book names, see list in Supplementary Table S1.
c, circa.

Discussion

Of the candidate search terms, the most productive were

those that contained the term wang which means forget.
The terms associated with chi dai identified considerably
fewer citations, and only one remained after the criteria for
aging were applied (Supplemental Table 1). Overall, references to old people were few in the literature, so most of the
associations with aging were for promoting longevity. One
of the earliest citations was in Essential Prescriptions Worth
a Thousand Gold for Emergencies (Bei Ji Qian Jin Yao
Fang, c.652), in which the formula Wu bu wan was used for
Kidney qi deficiency, frequent forgetting (xi wang), dissociation (huang hu), and a host of other symptoms, as
well as for promoting longevity and slowing aging. However, this formula did not gain popularity. The same book
listed Kai xin san, which included four of the most common
ingredients (chang pu, yuan zhi, ren shen, fu ling) and was
recommended for preventing memory loss in old age.

Descriptions of the nature of the memory loss tended to

be brief, but some citations provided details suggestive of
the profound memory deficits characteristic of AD. In Records of Pattern Discrimination (Bian Zheng Lu, c.1687),
the formula Shen jiao tang was for jian wang with the following characteristics: when the person talks to someone,
they soon forget what they said; when someone speaks to
the person, they cannot remember what they were told; it is
as if nothing had been said. However, it made no mention
of age.
There was a marked change in the list of frequent formulas when the criteria for aging were added (Tables 2 and
4). Although several high-frequency formulas, such as Gui
pi tang, were still included, it was at low frequencies. Instead, the most frequently cited formula was Shou xing wan,
which is named after a god of longevity called Shou xing.
This first appeared in the official formula manual of the
Song dynasty, Prescriptions from the Great Peace Imperial
Grace Pharmacy (Tai Ping Hui Min He Ji Ju Fang, c.1107)

DEMENTIA AND ALZHEIMERS DISEASE IN CLASSICAL AND CONTEMPORARY CHINESE MEDICINE

699

Table 3. Traditional Medicines Frequently Used in Formulas

for Memory Impairment After Exclusion Criteria: Level 1

Chinese name
c,d
Fu ling/shen
Ren shen/Hong shen
c,d
Yuan zhi

Gan cao

c,d

c,d

Di huang

c,d

Dang gui
Chang pu

c,d

Bai zhu
c

Poria cocos (Schw.) Wolf [sclerotium]

Panax ginseng C.A. Mey. [root]
Polygala tenuifolia Willd.; P. sibirica
L. [root]
Glycyrrhiza uralensis Fisch.; G. inflata
Bat. G. glabra L. [root and rhizome]
Rehmannia glutinosa Libosch. [root]

Yes
Yes
Yes

Angelica sinensis (Oliv.) Diels [root]

Acorus tatarinowii Schott; A.
gramineus Sol. Aiton [rhizome]
Ziziphus jujuba Mill. var. spinosa
(Bunge) Hu ex H. F. Chou [fruit]
Atractylodes macrocephala Koidz.
[rhizome]
Ophiopogon japonicus (L.f)
Ker-Gawl. [root]
Zingiber officinale (Willd.) Rosc.
[rhizome]
Cinnamomum cassia Presl [twig, bark]
Astragalus membranaceus (Fisch.)
Bge. var. mongholicus (Bge.) Hsiao;
A. membranaceus (Fisch.) Bge.
[root]
Cinnabar
Schisandra chinensis (Turcz.) Baill.
[fruit]
Paeonia lactiflora Pall. [root]
Platycladus orientalis (L.) Franco
[seed]
Aucklandia lappa Decne. [root]
Fossilized bones/teeth
Honey
Asparagus cochinchinensis (Lour.)
Merr. [root]
Dioscorea opposita Thunb. [rhizome]
Platycodon grandiflorus ( Jacq.) A.DC.
[root]
Dimocarpus longan Lour. [fruit]

No
Yes

342

Jiang
Gui c
Huang qi

296 (182 Sheng

jiang)
294 (244 Rou gui)
283

Zhu sha/Dan sha

Wu wei zi

c
c

271
236

189
184

Mu xiang
Long gu/chi
Feng mi
Tian men dong

Long yan rou

1143 (438 Fu shen)

867
781

350

Mai men dong

Shan yao
Jie geng

Scientific name [part]a

538 (261 Shu di,

222 Sheng di)
522
417 (168
Shi chang pu)
367

Suan zao ren

Bai shao
Bai zi ren

Frequency (n)

670

c,d

c,d

184
183 (125 Long gu)
182
172
142
148

c,d

For memory
impairment in
contemporary
materia medicab

136

Yes
No

Yes
No
No
No
No
No

Yes
No
No
Yes
No
Yes
No
No
Yes
No
Yes

Scientific names based on Pharmacopoeia of the Peoples Republic of China 2010 and/or Great Compendium of Chinese Medicines.
Clinical applications based on Pharmacopoeia of the Peoples Republic of China.
Used in materia medica books in Encyclopedia of Traditional Chinese Medicine for memory impairment.
d
Used in materia medica books in Encyclopedia of Traditional Chinese Medicine for memory impairment and aging.
b
c

for jian wang and many symptoms atypical of dementia, so

this citation was excluded. In later books, however, the
applications of Shou xing wan were expanded. In Compendium of Materia Medica (Ben Cao Gang Mu, c.1578), it
was used for phlegm clouding the orifices (which means
that the persons consciousness is dull or obscured), dissociation, and jian wang plus disordered speech, which are
all symptoms consistent with AD. In Wondrous Lantern for
Peering into the Origin and Development of Miscellaneous
Diseases (Za Bing Yuan Liu Xi Zhu, c.1773), Shou xing
wan was combined with the formula Dao tan tang to treat
phlegm clouding the orifices, speaks as if demented, and
memory loss.

Although the lists of frequent formulas were different at

level 1 and level 2, the individual ingredients of the formulas showed no marked differences (Tables 3 and 5). This
indicates that while the formula names varied considerably,
formulas for memory impairment tended to include similar
core ingredients.
Comparison with previous studies

The previous ZYFJDCD study used the index terms jian

wang and chi dai for searching. These identified 127 formula citations for memory impairment and 19 formulas for
memory impairment plus aging,41 which are considerably

700

MAY ET AL.

Table 4. Most Frequent Classical Formulas for Memory Impairment Plus Aging: Level 2
Formula name
b

Shou xing wan

Xiao dan

Ju sheng wan

Frequency (n)

Formula ingredientsa; first book in group (year)

12 (15)
4

See Table 2
Shu di huang, Rou cong rong, Wu wei zi, Tu si zi, Bai zi ren, Tian men
dong, She chuang zi, Fu pen zi, Ba ji, Shi hu, Xu duan, Ze xie, Ren
shen, Shan yao, Yuan zhi, Shan zhu yu, Chang pu, Gui xin, Bai fu
ling, Du zhong, Tian xiong, Zhong ru fen; use double amounts of
Yuan zhi and Fu ling for duo wang; San Yin Ji Yi Bing Zheng Fang
Lun (c.1174)
Ju sheng zi, Gan ju hua, Xuan fu hua, Wu bai zhi, Bai fu ling, Rou gui,
Bi cheng qie, Niu xi, Fu pen zi, Shu gan di huang, Yuan zhi, Han
lian zi; Yu Yao Yuan Fang (c.1267)
Dan shen, Tian men dong, Shu di, Ren shen, Yuan zhi, Zhu sha, Shi
chang pu, Mai men dong, Bai fu ling; Ji Yang Gang Mu (c.1626)
Shu yu, Cong rong, Niu xi, Tu si zi, Du zhong, Ze xie, Ba ji tian, Shan
zhu yu, Chi shi zhi, Wu wei zi, Gan di huang, Fu shen, Yuan zhi;
Pu Ji Fang (c.1406)
Dang gui, Chuan xiong, Bai shao, Sheng di huang, Bai zhu, Yuan zhi,
Bai fu shen, Suan zao ren, Mai men dong, Huang lian, Yuan shen,
Gan cao; Shou Shi Bao Yuan (c.1615)
Bai fu ling, Gui shen, Yuan zhi, Huang bai, Zhi mu, Sheng di huang,
Chen pi, Suan zao ren, Mai men dong, Ren shen, Shi chang pu, Bai
zhu, Gan cao, Bai shao yao; Fu Shou Jing Fang (c.1534)
Dao tan tang: Ban xia, Tian nan xing, Zhi shi, Chi fu ling, Ju hong, Gan
cao, Jiang. Plus Shou xing wan: Nan xing, Zhu sha, Hu po, Zhu xin
xue, Sheng jiang ye; Zheng Zhi Zhun Sheng- Za Bing (c.1602)
Ren shen, Bai zhu, Fu shen, Huang qi, Dang gui, Xuan shen, Chang pu,
Bai zi ren, Mai men dong, Shu di huang, Shan zhu yu, Sheng zao
ren, Long chi, Bai jie zi, Dan sha; Bian Zheng Lu (c.1687)
Fu ling, Ren shen, Gan cao, Niu ru, Bai sha mi; Wai Tai Mi Yao (c.752)
Ren shen, Huang qi, Bai zhu, Bai fu ling, Dang gui, Yuan zhi, Long
yan rou, Suan zao ren, Mu xiang, Gan cao, Bai zi ren, Jiang, Zao; use
double amount of Suan zao ren, Fu shen, Dang gui for jian wang;
Shou Shi Bao Yuan (c.1615)
Bai fu ling, Ren shen, Yuan zhi, Chang pu, Huang lian, Suan zao ren,
Bai zi ren, Dang gui, Sheng di huang, Mu xiang, Zhu sha; Fu Shou
Jing Fang (c.1534)
Du zhong, Ba ji, Ren shen, Wu jia pi, Wu wei zi, Tian xiong, Niu xi,
Fang feng, Yuan zhi, Shi hu, Shan yao, Gou ji, Di huang, Rou cong
rong, Lu rong, Tu si zi, Fu ling, Fu pen zi, Shi long rui, Bei xie, She
chuang zi, Shi nan, Bai zhu, Tian men dong; Bei Ji Qian Jin Yao
Fang (c.652)
Fu shen, Yi zhi ren, Fang feng, Ren shen, Sang ji sheng, Huo xiang ye,
Gan cao, Chen xiang, Shu gan di huang; Sheng Ji Zong Lu (c.1117)
Dang gui, Wu wei zi, Mai men dong, Tian men dong, Bai zi ren, Suan
zao ren, Ren shen, Bai fu ling, Xuan shen, Dan shen, Jie geng, Yuan
zhi, Huang lian, Sheng di huang; Ji Yang Gang Mu (c.1626)

3
b

Gu ben wan, modified

Wu bi shan yao wan

(aka Shan yu wan)

Bu xin tang

2
b

Dao tan tang plus shou xing wan

b
plus

Bu xin tang jia jian

Fu lao wan

Fu ling ren shen san

Gui pi tang jia wei

2
2

Ning zhi wan jia wei

Wu bu wan

Yan ling zhu san

Tian wang bu xin dan

2
b

Formulas with the same name can vary in their ingredients, and the same combination of ingredients may have different names. In these
data, formulas with the same core ingredients and the same name are grouped together, while those with different main ingredients are
separated. Also, formulas with the same ingredients but different names have been grouped together. The frequency is for the name in the
left column, and the number in parentheses includes modified versions of the formula. For scientific names of ingredients written in Pin Yin
and Chinese characters for TMs and book names, see list in Supplementary Table S1.
a
First book in group refers to the oldest book within the group of included citations, not the first book that included the formula. Dates
are approximate.
b
In Great Compendium of Chinese Medical Formulae search for memory impairment and aging.

fewer than in the present study. Of the 127 formulas for

memory impairment, 98 (77%) were also found in the ZHYD
search, including the most frequent formulas: Gui pi tang,
Tian wang bu xin dan, and Ding zhi wan. For memory
impairment plus aging, 14 (74%) of the formulas in the
ZYFJDCD search were also on the ZHYD list, including
Shou xing wan and modified Gu ben wan, but not Xiao dan
or Ju sheng wan. The present study also found that Shou
xing wan had the most impact among these formulas be-

cause it appeared in 12 books for memory impairment and

aging whereas some other formulas, such as Qiang ji tang,
appeared once and were not cited by later authors.
The ingredient frequency list at level 7 in May et al.
(2012)41 was similar to the level 2 list in Table 5. Although
ZYFJDCD included 176 TMs, compared with 970 TMs in
the present study, the lists are strikingly similar, with the
five most frequent TMs being the same on both lists. There
were many differences in the relative rankings of some

DEMENTIA AND ALZHEIMERS DISEASE IN CLASSICAL AND CONTEMPORARY CHINESE MEDICINE

701

Table 5. Traditional Medicines Frequently Used in Classical Formulas

for Memory Impairment Plus Aging: Level 2

Chinese name
c,d

Fu ling/shen
Yuan zhi

c,d
c

Di huang

c,d

Ren shen/Hong shen

c,d
Chang pu
c

Zhu sha/Dan sha

Suan zao ren

Dang gui
Wu wei zi

c,d

Gan cao

Shan zhu yu
Tian nan xing

Scientific name [part]a

78 (19 Fu shen)
61

Poria cocos (Schw.) Wolf [sclerotium]

Polygala tenuifolia Willd.; P. sibirica L.
[root]
Rehmannia glutinosa Libosch. [root]

Yes
Yes

Panax ginseng C.A. Mey. [root]

Acorus tatarinowii Schott; A. gramineus
Sol. Aiton [rhizome]
Cinnabar
Ziziphus jujuba Mill. var. spinosa (Bunge)
Hu ex H. F. Chou [fruit]
Angelica sinensis (Oliv.) Diels [root]
Schisandra chinensis (Turcz.) Baill.
[fruit]
Glycyrrhiza uralensis Fisch.; G. inflata
Bat. G. glabra L. [root and rhizome]
Ophiopogon japonicus (L.f) Ker-Gawl.
[root]
Dioscorea opposita Thunb. [rhizome]
Platycladus orientalis (L.) Franco [seed]
Cistanche deserticola Y. C. Ma; C.
tubulosa (Schrenk) Wight [aerial parts]
Cornus officinalis Sieb. & Zucc. [fruit]
Arisaema erubescens (Wall.) Schott; A.
heterophyllum Bl.; A. amurense
Maxim. [rhizome]
Eucommia ulmoides Oliv. [bark]
Zingiber officinale (Willd.) Rosc.
[rhizome]
Cinnamomum cassia Presl [bark]
Asparagus cochinchinensis (Lour.) Merr.
[root]
Amber
Atractylodes macrocephala Koidz.
[rhizome]
Morinda officinalis How [root]
Honey
Cuscuta chinensis Lam.; C. australis R.
Br. [seed]
Achyranthes bidentata Blume [root]

Yes
Yes

51 (28 Shu di, 14

Sheng di)
47
34 (17 Shi chang pu)
29
26

22
c

Mai men dong

c,d
Shan yao
Bai zi ren
Rou cong rong

Frequency

24
23

22
21
21
20

19
18 (1 Dan nan xing)

18
18 (14 Sheng jiang)

Du zhong
Jiang
c
Rou gui
Tian men dong

17
17

Hu po
Bai zhu

17
16

Ba ji tian
Feng mi
Tu si zi

15
15
14

Niu xi

For memory
impairment in
contemporary
materia medicab

14

No

Yes
Yes
No
No
Yes
No
Yes
Yes
No
No
No
No
No
No
No
Yes
No
No
No
No
no

Scientific names based on Pharmacopoeia of the Peoples Republic of China 2010 and/or Great Compendium of Chinese Medicines.
Clinical applications based on Pharmacopoeia of the Peoples Republic of China.
c
Used in materia medica books in Encyclopedia of Traditional Chinese Medicine for memory impairment.
d
Used in materia medica books in Encyclopedia of Traditional Chinese Medicine for memory impairment and aging.
b

TMs. For example, rhizome of Arisaema species (tian nan

xing) had a relatively higher frequency in the present
study, whereas rhizome of Atractylodes macrocephala
Koidz. (bai zhu) had a relatively lower frequency. These
differences were mainly due to the high frequencies of the
formulas Shou xing wan (which contains Arisaema species) and Gui pi tang (which contains Atractylodes) in the
ZHYD data.
In the study of ZHYD materia medica entries,36 the same
search terms were used. Four of the top five TMs in the
present study were cited for both memory impairment and
aging in the materia medica (Table 5). In general, the ingredients in the formulas for memory impairment and age

were also listed in the classical materia medica books as

used for memory impairment and disorders of aging, but not
all the TMs listed in these books for these two indications
appeared frequently in the formulas. For example, Dimocarpus longan (Lour.) Steud. fruit (long yan rou), and
Gentiana scabra Bge. root (long dan cao) were frequently
mentioned in the materia medica but were infrequent inclusions in the formulas. Conversely, some of the TMs that
were frequent inclusions in the formulas, such as Zingiber
officinale (Willd.) Rosc. rhizome (jiang), were not listed in
premodern materia medica books as useful for memory
disorders. This reflects a design feature of Chinese herbal
formulas in which certain ingredients target the principal

702

MAY ET AL.

Table 6. Formulas for Dementia in a Contemporary Guideline

and in the Encyclopedia of Traditional Chinese Medicine Search
Syndromes in guideline
Deficiency of sea of marrow
Spleen and kidney dual
deficiency
Deficiency of qi and blood
Turbid phlegm obstructing
the orifices
Blood stasis obstructing the
brain collaterals
Heart and liver fire

Endogenous toxins damaging

the brain collaterals

Formulas in guideline: ingredients

Qi fu yin
(modified): Ren shen, shu di, dang gui,
bai zhu, da zao, yuan zhi, plus lu jiao jiao, gui ban jiao,
e jiao, zhi gan cao.
Huan shao dan
(modified): Shu di, gou qi zi, rou
cong rong, ba ji tian, xiao hui xiang, niu xi, du zhong,
shan yu rou, fu ling, wu wei zi, shan yao, shi chang pu,
yuan zhi, chu shi.
Gui pi tang
(modified): Ren shen, huang qi, bai
zhu, dang gui, fu ling, long yan rou, yuan zhi, suan zao
ren, mu xiang, sheng jiang, da zao, zhi gan cao.
Xi xin tang
(modified): Ren shen, fu shen, ban
xia, chen pi, shen qu, fu zi, shi chang pu, hong zao, gan
cao.
Tong qiao huo xue tang
(modified): Chi
shao, chuan xiong, tao ren, hong hua, hong zao, lao
cong, sheng jiang, she xiang, huang jiu.
Tian ma gou teng yin
(modified): Tian ma,
gou teng, shi jue ming, zhi zi, huang qin, chuan niu xi,
du zhong, yi mu cao, sang ji sheng, ye jiao teng, fu
shen.
Huang lian jie du tang
(modified): Huang
lian, huang qin, huang bai, zhi zi, shui niu jiao fen,
quan xie, wu gong.

Formulas in ZHYD searcha

Qi fu yin (n = 2)
Huan shao dan (n = 1)

Gui pi tang (n = 118); see

Table 2
Xi xin tang (n = 1); Shou xing
(n = 12); see
wan
Table 2
Tao ren cheng qi tang
(n = 29); Di
(n = 21);
dang tang
see Table 2
Niu huang qing xin wan
(n = 12); see
Table 2
Huang lian e jiao tang
(n = 1)

Sea of marrow refers to the brain. Orifices refers to the sense organs of the head. The guideline is Tian (2012).38
a
Based on level 1.

disorder, while others aim at secondary symptoms or play

functional roles. Therefore, the presence of a TM on the
frequency lists in Tables 3 and 5 does not necessarily mean
it was intended for memory impairment.

the TMs. In general, TMs used historically for memory impairment associated with aging are still used in formulas for
senile dementia and AD.
Limitations of the study

Comparison with contemporary practice

In a recent clinical practice guideline for senile dementia, seven different formulas were suggested on the basis of
syndrome differentiation, as is typical of contemporary
Chinese medicine books38 (Table 6). This syndrome differentiation approach was not evident in the classical books,
which tended to provide a selection of formulas, each for
different combinations of symptoms. However, in some citations the syndrome could be inferred from the stated actions of the formula, the cause, or the symptoms and signs.
Of the seven formulas in the guideline, four were included in the ZHYD results: Gui pi tang, Qi fu yin, Huan
shao dan, and Xi xin tang (Table 6). The other three formulas specified in the guideline were not identified for
memory impairment in the ZHYD search results, but related
formulas were. For example, the blood stagnationremoving
formula Tong qiao huo xue tang was in the guideline,
whereas other formulas with similar actions, such as Tao ren
cheng qi tang and Di dang tang, were in ZHYD. In modern
books, Shou xing wan modified to include most of the highfrequency TMs and appears occasionally for memory impairment,58 but this formula was not mentioned in the
guidelines.38 When the TMs in Table 3 were compared with
ZYDCD, six of the top 10 were listed for memory in this
contemporary materia medica book. These two comparisons
suggest continuity in the use of some formulas and many of

The sample of Chinese literature used for this search was

large but not totally comprehensive; thus, it is possible that
addition of more premodern books could change the results.
However, on the basis of the comparison with ZYFJDCD,
the identity of the high-frequency TMs and formulas at level
1 are unlikely to be affected. Because chi dai and related
terms were relatively few, these results do not show how chi
dai was treated in the premodern period. However, the citations for chi dai seldom mentioned memory or aging, and
most were unlikely to have been AD.
The use of the criteria for aging made the results more
consistent with AD, but aging was infrequently mentioned
overall. As a result, this approach greatly limited the size of
the included data. Hence, it is debateable whether level 2
was more specific for AD than level 1. There is also the
question of whether the age-related memory impairments
cited in the historical literature were due to AD pathology.
Although citations that included references to cerebrovascular factors, tremor, and seizures were excluded, it remains
probable that such symptoms were present but unreported in
at least some of the included citations. In the absence of
autopsy evidence, whether AD was present is uncertain;
thus, it is possible that there was no AD in premodern China
and all citations referred to other abnormalities. What the
analyses did show was that the TMs used most frequently in
formulas for memory impairment were also used frequently

DEMENTIA AND ALZHEIMERS DISEASE IN CLASSICAL AND CONTEMPORARY CHINESE MEDICINE

for memory impairment in older people or with the aim of

slowing the effects of aging. In addition, these TMs remain
in use for AD and other dementias.
Another challenge in the interpretation of these data is
whether the TMs referred to in the premodern literature
were derived from the same species as considered official in
contemporary books. In the case of the TM chang pu, this
may be sourced from several Acorus species, and the source
species for other TMs have varied over time and according
to region. This issue needs to be considered when candidates
for clinical or experimental research are selected.36
Experimental studies on the five common TMs

Historical use alone does not provide evidence that any of

the TMs were effective for memory impairment or AD, but
experimental studies of the five most common TMs and/or
their constituents suggest benefits are plausible. P. ginseng
has improved cognitive outcomes in some clinical trials.59
In rats with experimentally induced memory impairment,
the ginsenosides Rg1 and Rg5 improved memory and task
performance60,61 and the ginsenosides Rg1, Rg3, and Rg5 have
all demonstrated downregulatory effects on b-amyloid.6062
The compound catalpol from R. glutinosa has shown neuroprotective effects in cells treated with b-amyloid,63,64 and
it may be able to increase the synthesis of neurotransmitter
acetylcholine.65
An extract of P. tenuifolia was reported to protect neurones
from damage by b-amyloid,66 and the compound tenuigenin
inhibited secretion of b-amyloid.67 In cognitively impaired
mice, a triterpenoid saponin from Polygala roots improved
learning and memory.68 A water extract of P. cocos was
reported to protect cells via suppression of oxidative stress
and apoptosis induced by b-amyloid.69 An extract of Acorus
tatarinowii protected cells from b-amyloidinduced neurotoxicity.70 In rats injected with b-amyloid, oral administration
of the compound b-asarone ameliorated b-amyloidinduced
cognitive impairment;71 in a mouse model, b-asarone decreased b-amyloid deposition and downregulated b-amyloid
levels in the cortex and hippocampus.72 The combination of
Polygala, Acorus, and Poria species showed antioxidant
functions and improved learning in memory-impaired mice.73
These and other TMs identified in these analyses may provide
fertile fields for research into interventions for the management of memory impairments and AD.
Conclusion

This study identified several citations in the classical literature that described conditions characterized by profound
memory impairment, but whether these were due to AD
pathology or other causes remains uncertain. What is evident is that memory impairment associated with aging was a
recognized condition. The formulas recommended for this
condition varied considerably in name, but certain ingredients, including P. cocos, P. tenuifolia, R. glutinosa, P. ginseng,
and Acorus species, appeared in multiple formulas and in
multiple books for memory impairment in the context of
aging. This same group of TMs also appeared in a systematic search of the largest printed compendium of Chinese
formulas.41 These five TMs remain in clinical use for
memory impairment,37,38 and experimental studies suggest
biological activities relevant to AD.59,6870,72,74

703

Acknowledgments

This project was funded by the China-Australia International Research Centre for Chinese Medicine and partially
supported by an International Research Grant from the
Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Province, China. The authors thank the
Preventive Health National Flagship Program, Commonwealth Scientific and Industrial Research Organization for
providing partial funding support in the early stages of this
project. They also thank Dr. Angela Yang, Dr. Claire Zhang,
Dr. Takako Tomoda, and Michael Owens for their help
during the project.
Author Disclosure Statement

No competing financial interests exist.

References

1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington,
VA: American Psychiatric Association, 2013.
2. Alzheimers Association. Alzheimers disease facts and
figures. Alzheim Dementia 2015;11:183.
3. Goedert M, Spillantini MG. A century of Alzheimers
disease. Science. 2006;314:777781.
4. Kumar A, Singh A, Ekavali. A review on Alzheimers
disease pathophysiology and its management: an update.
Pharmacol Rep 2015;67:195203.
5. Tenreiro S, Eckermann K, Outeiro TF. Protein phosphorylation in neurodegeneration: friend or foe? Frontier Molec
Neurosci 2014;7:42.
6. Wiesmann M, Kiliaan AJ, Claassen JA. Vascular aspects of
cognitive impairment and dementia. J Cereb Blood Flow
Metab 2013;33:16961706.
7. Cerejeira J, Lagarto L, Mukaetova-Ladinska EB. Behavioral
and psychological symptoms of dementia. Front Neurol 2012;
3:73.
8. Chan KY, Wang W, Wu JJ, et al. Epidemiology of Alzheimers disease and other forms of dementia in China, 1990
2010: a systematic review and analysis. Lancet 2013;381:
20162023.
9. Catindig JA, Venketasubramanian N, Ikram MK, Chen C.
Epidemiology of dementia in Asia: insights on prevalence,
trends and novel risk factors. J Neurol Sci 2012;321:1116.
10. Kim BY, Kang JS, Han JS, Jeon WK. Mapping the dementia research area at the micro-level using co-terms
analysis and positioning for traditional herbal medicine.
Chin J Integr Med. Sep 2014;20:706711.
11. Heinrich M, Lee Teoh H. Galanthamine from snowdrop the development of a modern drug against Alzheimers
disease from local Caucasian knowledge. J Ethnopharmacol
2004;92:147162.
12. Perry E. Commentary: Botanical potentials in Alzheimers
disease. J Altern Complement Med 2007;13:345346.
13. Ho YS, So KF, Chang RCC. Drug discovery from Chinese
medicine against neurodegeneration in Alzheimers and
vascular dementia. Chin Med-Uk. 2011;6.
14. Yang GY, Wang YY, Tian JZ, Liu JP. Huperzine A for
Alzheimers disease: a systematic review and meta-analysis
of randomized clinical trials. PloS One 2013;8.
15. Ihl R, Bachinskaya N, Korczyn AD, et al. Efficacy and
safety of a once-daily formulation of Ginkgo biloba extract
EGb 761 in dementia with neuropsychiatric features: a

704

16.
17.
18.
19.
20.

21.

22.

23.

24.
25.

26.
27.

28.
29.

30.

31.

MAY ET AL.

randomized controlled trial. Int J Geriatr Psych 2011;26:

11861194.
Amieva H, Meillon C, Helmer C, et al. Ginkgo biloba
extract and long-term cognitive decline: a 20-year followup population-based study. PloS One 2013;8.
May BH, Lit M, Xue CCL, et al. Herbal medicine for
dementia: a systematic review. Phytother Res 2009;23:
447459.
Fu LM, Li JT. A systematic review of single Chinese herbs
for Alzheimers disease treatment. Evid Based Complement Altern Med 2011:18.
Hugel HM, Jackson N, May BH, Xue CCL. Chinese
herbs for dementia diseases. Mini Rev Med Chem 2012;12:
371379.
Hugel HM, Jackson N. Herbs and dementia: a focus on
Chinese and other traditional herbs. In: Martin C, Preedy V,
eds. Diet and Nutrition in Dementia and Cognitive Decline.
Amsterdam: Elsevier; 2015: 795804.
May BH, Zhang AL, Robinson SR, Xue CCL. Chinese
herbs for cognitive decline: historical and contemporary
applications. In: Martin C, Preedy V, eds. Diet and Nutrition
in Dementia and Cognitive Decline. Vol 74. Amsterdam:
Elsevier, 2015:805818.
Apetz N, Munch G, Govindaraghavan S, Gyengesi E.
Natural compounds and plant extracts as therapeutics
against chronic inflammation in Alzheimers Disease - a
translational perspective. CNS Neurol Disord 2014;13:
11751191.
Su Y, Wang QH, Wang CF, et al. The treatment of Alzheimers disease using Chinese Medicinal Plants: from
disease models to potential clinical applications. J Ethnopharmacol 2014;152:403423.
Helmstadter A, Staiger C. Traditional use of medicinal
agents: a valid source of evidence. Drug Discov Today
2014;19:47.
Zhang CS, May B, Yan YH, et al. Terms referring to
psoriasis vulgaris in the classical Chinese medicine literature: a systematic analysis. Complement Ther Med 2016;
25:5560.
Buenz EJ, Bauer BA, Johnson HE, et al. Searching historical herbal texts for potential new drugs. BMJ 2006;333:
13141315.
Watkins F, Pendry B, Corcoran O, Sanchez-Medina A.
Anglo-Saxon pharmacopoeia revisited: a potential treasure in drug discovery. Drug Discov Today 2011;16:
10691075.
De Vos P. European materia medica in historical texts:
longevity of a tradition and implications for future use.
J Ethnopharmacol 2010;132:2847.
Shergis JL, Wu L, May BH, et al. Natural products for
chronic cough: text mining the East Asian historical literature for future therapeutics. Chron Respir Dis 2015;12:
204211.
Choi MJ, Choi BT, Shin HK, et al. Establishment of a
comprehensive list of candidate antiaging medicinal herb
used in Korean medicine by text mining of the classical
Korean medical literature, dongeuibogam, and preliminary evaluation of the antiaging effects of these herbs.
Evidence Based Complement Altern Med 2015;2015:
873185.
Pae SB, Yun BC, Han YK, et al. Cognitive-enhancing
herbal formulae in Korean medicine: identification of
candidates by text mining and literature review. J Altern
Complement Med 2016;22:413418.

32. Peng HR, ed. Zhong Yi Fang Ji Da Ci Dian (Great Compendium of Chinese Medical Formulae). Beijing: Peoples
Medical Publishing House, 1994.
33. May BH, Lu CJ, Xue CCL. Collections of Traditional
Chinese Medical literature as resources for systematic
searches. J Altern Complement Med 2012;18:11011107.
34. Hu R, ed. Zhong Hua Yi Dian (Encyclopaedia of Traditional Chinese Medicine). 4th ed. Changsha: Hunan Electronic and Audio-Visual Publishing House, 2000.
35. May BH, Lu YB, Lu CJ, et al. Systematic assessment of
the representativeness of published collections of the traditional literature on Chinese medicine. J Altern Complement Med 2013;19:403409.
36. May BH, Lu C, Lu Y, et al. Chinese herbs for memory
disorders: a review and systematic analysis of classical
herbal literature. J Acupunct Meridian Stud 2013;6:211.
37. Jiangsu New Medical Academy, ed. Zhong Yao Da Ci Dian
(Great Compendium of Chinese Medicines). Shanghai:
Shanghai Scientific and Technical Publishers, 1986.
38. Tian JZ, ed. Chinese Guidelines for the Diagnosis and
Treatment of Alzheimers Disease and Other Dementias.
Beijing: Peoples Health Publishing House, 2012.
39. Zhongjia Jizhu Jianduju, ed. Zhong Yi Bing Zheng Fen Lei
Yu Dai Ma (Standard Nomenclature for Disease Names and
Syndromes in Chinese Medicine). Beijing: Zhong Guo
Biao Zhun Chu Ban She, 1996.
40. Lin ZG, ed. Zhong Xi Yi Bing Ming Dui Zhao Da Ci Dian
(Great Dictionary of Comparisons between Chinese and
Western Medical Terms). Beijing: Ren Min Wei Sheng
Chu Ban Sha, 2002.
41. May BH, Lu CJ, Bennett L, et al. Evaluating the traditional
Chinese literature for herbal formulae and individual herbs
used for age-related dementia and memory impairment.
Biogerontology 2012;13:299312.
42. May BH, Zhang A, Lu YB, et al. The systematic assessment of traditional evidence from the premodern Chinese
medical literature: a text-mining approach. J Altern Complem Med 2014;20):937942.
43. World Health Organization. WHO international standard
terminologies on traditional medicine in the Western Pacific region. Manila: World Health Organisation Western
Pacific Region, 2007.
44. Wiseman N. English-Chinese Chinese-English Dictionary
of Chinese Medicine. Changsha: Hunan Science and Technology Press, 1996.
45. Li JW, Yu YA, Cai JF, et al, eds. Zhong Yi Da Ci Dian
(Great Dictionary of Chinese Medicine). 2nd ed. Beijing:
Peoples Medical Publishing House, 2005.
46. Zhang XY, ed. Zhong Yi Lao Nian Bing Xue (Manual of
Chinese Medicine Geriatrics). Shanghai: Shang Hai Ke
Xue Ji Shu Chu Ban She, 1992.
47. Chen H, ed. Shi Yong Zhong Yi Nao Bing Xue (Practical
Manual of Brain Disorders in Chinese Medicine). Beijing:
Xue Yuan Chu Ban She, 1993.
48. Gao FA, ed. Shi Yong Zhong Yi Lao Nian Nei Ke Bing
Xue (Practical Manual of Geriatric Disorders in Chinese
Medicine). Hefei: Anhui Ke Xue Ji Shu Chu Ban She,
1995.
49. Zhou WQ, Gao P, eds. Zhong Yi Lao Nian Bing Lin
Chuang Yan Jiu (Clinical Research in Chinese Medicine
Geriatrics). Beijing: Beijing Chu Ban She, 1995.
50. Xu PH, ed. Zhong Yi Nao Bing Xue (Manual of Brain
Disorders in Chinese Medicine). Beijing: Zhong Guo Yi
Yao Ke Ji Chu Ban She, 1998.

DEMENTIA AND ALZHEIMERS DISEASE IN CLASSICAL AND CONTEMPORARY CHINESE MEDICINE

51. Li QB, Mei R, eds. Lao Nian Chi Dai Zheng De Zhong Xi
Yi Zhen Duan Yu Zhi Liao (Diagnosis and Treatment of
Senile Dementia in Integrated Chinese-Western Medicine.
Beijing: Zhong Guo Yi Yao Ke Ji Chu Ban She, 1999.
52. Zhang M, ed. Shi Yong Zhong Yi Lao Nian Bing Xue
(Practical Manual of Chinese Medicine Geriatrics). Beijing:
Ren Min Jun Yi Chu Ban She, 2000.
53. Zhang DB, ed. Zhong Yi Shen Jing Jing Shen Bing Xue
(Manual of Neurological and Psychiatric Disorders in
Chinese Medicine). Beijing: Zhong Guo Yi Yao Ke Ji Chu
Ban She, 2000.
54. Li Y, Xie DM, eds. Gu Jin Zhong Yi Nao Bing Bian Zhi
Jing Yao (Essentials of the Treatment of Brain Disorders in
Ancient and Modern Chinese Medicine). Beijing: Ren Min
Jun Yi Chu Ban She, 2007.
55. Flaws B, Lake J. Chinese Medical Psychiatry: A Textbook
and Clinical Manual, 2nd ed. Boulder: Blue Poppy Press,
2003.
56. Shen SL, ed. Lao Nian Xing Chi Dai Ji Xiang Guan Ji Bing
(Senile Dementia and Related Diseases). Beijing: Ke Xue Ji
Shu Chu Ban She, 2006.
57. Chinese Pharmacopoeia Commission. Pharmacopoeia of
the Peoples Republic of China [Zhong Hua Ren Min Gong
He Guo Yao Dian]. Beijing: China Medical Science Press,
2010.
58. Maclean W, Lyttleton J. Clinical Handbook of Internal
Medicine: The Treatment of Disease with Traditional
Chinese Medicine. Vol 1. Sydney: University of Western
Sydney, 1998.
59. Wang Y, Yang G, Gong J, et al. Ginseng for Alzheimers
disease: a systematic review and meta-analysis of randomized controlled trials. Curr Topics Med Chem 2016;16:
529536.
60. Song XY, Hu JF, Chu SF, et al. Ginsenoside Rg1 attenuates
okadaic acid induced spatial memory impairment by the
GSK3beta/tau signaling pathway and the Abeta formation
prevention in rats. Eur J Pharmacol 2013;710:2938.
61. Chu S, Gu J, Feng L, et al. Ginsenoside Rg5 improves
cognitive dysfunction and beta-amyloid deposition in
STZ-induced memory impaired rats via attenuating neuroinflammatory responses. Int Immunopharmacol 2014;19:
317326.
62. Yang L, Hao J, Zhang J, et al. Ginsenoside Rg3 promotes
beta-amyloid peptide degradation by enhancing gene expression of neprilysin. J Pharm Pharmacol 2009;61:375
380.
63. Jiang B, Du J, Liu JH, et al. Catalpol attenuates the neurotoxicity induced by beta-amyloid( 142) in cortical
neuron-glia cultures. Brain Res 2008;1188:139147.

705

64. Liang JH, Du J, Xu LD, et al. Catalpol protects primary

cultured cortical neurons induced by Abeta( 142) through
a mitochondrial-dependent caspase pathway. Neurochemistry Int 2009;55:741746.
65. Wang JH, Xie H, Zhao TK, Kang B. Catalpol regulates
cholinergic nerve system function through effect on choline
acetyl-transferase not M receptor affinity. Biomed Pharmacother 2015;69: 291296.
66. Naito R, Tohda C. Characterization of anti-neurodegenerative
effects of Polygala tenuifolia in Abeta(2535)-treated cortical
neurons. Biol Pharmaceut Bull 2006;29:18921896.
67. Jia H, Jiang Y, Ruan Y, et al. Tenuigenin treatment decreases secretion of the Alzheimers disease amyloid betaprotein in cultured cells. Neurosci Lett 2004;367:123128.
68. Xue W, Hu JF, Yuan YH, et al. Polygalasaponin XXXII
from Polygala tenuifolia root improves hippocampaldependent learning and memory. Acta Pharmacolog Sinica
2009;30:12111219.
69. Park YH, Son IH, Kim B, et al. Poria cocos water extract
(PCW) protects PC12 neuronal cells from beta-amyloidinduced cell death through antioxidant and antiapoptotic
functions. Die Pharmazie 2009;64:760764.
70. An HM, Li GW, Lin C, et al. Acorus tatarinowii Schott
extract protects PC12 cells from amyloid-beta induced
neurotoxicity. Die Pharmazie 2014;69:391395.
71. Geng Y, Li C, Liu J, et al. Beta-asarone improves cognitive
function by suppressing neuronal apoptosis in the betaamyloid hippocampus injection rats. Biol Pharmaceut Bull
2010;33:836843.
72. Yang C, Li X, Mo Y, et al. Beta-asarone mitigates amyloidosis and downregulates RAGE in a transgenic mouse
model of Alzheimers disease. Cell Molec Biol 2016;36:
121130.
73. Lee MR, Yun BS, Park SY, et al. Anti-amnesic effect of
Chong-Myung-Tang on scopolamine-induced memory impairments in mice. J Ethnopharmacol 2010;132:7074.
74. Jiang B, Shen RF, Bi J, et al. Catalpol: a potential therapeutic for neurodegenerative diseases. Curr Med Chem
2015;22:12781291.

Address correspondence to:

Charlie C.L. Xue, PhD
School of Health and Biomedical Sciences
RMIT University
P.O. Box 71
Bundoora, Victoria 3083
Australia
E-mail: charlie.xue@rmit.edu.au