research article shen-zhi-ling oral liquid improves...

Research ArticleShen-Zhi-Ling Oral Liquid Improves Behavioral andPsychological Symptoms of Dementia in Alzheimerrsquos Disease

Weidong Pan1 Qiudong Wang2 Shin Kwak3 Yu Song1 Baofeng Qin1

Mingzhe Wang1 and Yoshiharu Yamamoto4

1 Department of Neurology Shuguang Hospital Affiliated to Shanghai University of TCM 528 Zhang-Heng RoadPu-Dong New Area Shanghai 201203 China

2Department of Neurology Pudong New Area Hospital of Traditional Chinese Medicine 460 Xiuchuan RoadPu-Dong New Area Shanghai 201200 China

3 Center for Disease Biology and Integrative Medicine Graduate School of Medicine The University of Tokyo 7-3-1 HongoBunkyo-ku Tokyo 113-8655 Japan

4 Educational Physiology Laboratory Graduate School of Education The University of Tokyo 7-3-1 Hongo Bunkyo-kuTokyo 113-0033 Japan

Correspondence should be addressed to Weidong Pan panwdmedmailcomcn

Received 12 December 2013 Revised 26 February 2014 Accepted 13 March 2014 Published 18 May 2014

Academic Editor Wenxia Zhou

Copyright copy 2014 Weidong Pan et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

We evaluated the effects of the traditional Chinese medicine (TCM) Shen-Zhi-Ling oral liquid (SZL) on the behavioral andpsychological symptoms of dementia (BPSD) in patients with Alzheimerrsquos disease (AD) Among 98 patients with AD and BPSDenrolled (mean age 572plusmn 89 years old) 91 (M = 55 F = 36 mean age 572plusmn 97 years old) completed the study Patients took eitherSZL (119899 = 45) or placebo granules (119899 = 46) in a double-blindmanner for 20weekswhilemaintaining other anticognitivemedicationsunchanged Changes in BPSD between week 0 week 10 week 20 and week 25 were assessed using the behavioral pathology inAlzheimerrsquos disease (BEHAVE-AD) rating scale and the neuropsychiatric inventory (NPI) detrended fluctuation analysis (DFA)represented by diurnal activity (DA) evening activity (EA) and nocturnal activity (NA) according to actigraphic recordings SZLbut not placebo oral liquid delayed the development of BPSD significantly according to the changes in some of the clinical scoresand the EA and NA parameters of DFA at week 20 compared with week 0 No side effects were observed in laboratory tests Theresults indicate that SZL might delay the development of BPSD in AD patients and thus is a potentially suitable drug for long-termuse

1 Introduction

Cognitive deficits and behavioral and psychological symp-toms of dementia (BPSD) are typical features of patientswith dementia such as Alzheimerrsquos disease (AD) vasculardementia (VD) and other forms of senile dementia [1]The symptoms include agitation aberrant motor behavioranxiety elation irritability depression apathy disinhibitiondelusions hallucinations and sleep or appetite changesBPSD constitute a major component of the dementia syn-drome irrespective of its subtype The current limits of theeffectiveness of pharmacotherapies highlight the value in

delaying the progression of the disease and the functionaldecline [2]

Herbal remedies have a long history of use (particularlyin East Asian countries) for alleviating various symptoms andhave been increasingly used as alternative medicines world-wide including the United States [3] Traditional Chinesemedicines (TCM) ameliorate various symptoms particularlyageing-related symptoms [4 5] and hence are likely to bebeneficial for neurodegeneration diseases such as Parkinsonrsquosdisease and motor neuron disease [6ndash8] Good compliancefor long-term use with few side effects may be another meritof TCM suitable for AD patients

Hindawi Publishing CorporationEvidence-Based Complementary and Alternative MedicineVolume 2014 Article ID 913687 6 pageshttpdxdoiorg1011552014913687

2 Evidence-Based Complementary and Alternative Medicine

Table 1 Characteristics of the patients with Alzheimerrsquos disease before and after additional treatment

Characteristic Shen-Zhi-Ling group1st week (119899) 10th week (119899) 20th week (119899) 25th week (119899)

Age (years) 572 plusmn 97

Sex (MF) 2817Duration of VD (years) 57 plusmn 49

MMSE 134 plusmn 18 129 plusmn 31 120 plusmn 23 118 plusmn 16

Huperzine A (120583gd) 32330 plusmn 1739 (32) 33441 plusmn 1693 (32) 31929 plusmn 1686 (31) 34932 plusmn 1884 (31)Aniracetam (mgd) 4896 plusmn 1793 (28) 4917 plusmn 1668 (28) 4905 plusmn 1834 (29) 4976 plusmn 1123 (29)Memantine hydrochloride (mgd) 667 plusmn 528 (28) 681 plusmn 447 (30) 683 plusmn 496 (29) 692 plusmn 567 (30)Donepezil hydrochloride (mgd) 821 plusmn 376 (16) 849 plusmn 402 (15) 873 plusmn 269 (15) 933 plusmn 694 (15)Rivastigmine (mgd) 338 plusmn 126 (23) 347 plusmn 172 (14) 355 plusmn 209 (13) 375 plusmn 166 (14)Galantamine reminyl (mgd) 2589 plusmn 2263 (26) 2531 plusmn 2361 (25) 2587 plusmn 2139 (26) 2682 plusmn 2291 (26)

Characteristic Placebo group1st week (119899) 10th week (119899) 20th week (119899) 25th week (119899)




Huperzine A (120583gd) 35830 plusmn 1914 (34) 33441 plusmn 1693 (34) 32703 plusmn 1798 (33) 35830 plusmn 1914 (32)Aniracetam (mgd) 5066 plusmn 1087 (26) 4988 plusmn 1712 (25) 5055 plusmn 1923 (27) 5172 plusmn 1193 (27)Memantine hydrochloride (mgd) 671 plusmn 447 (29) 667 plusmn 509 (30) 659 plusmn 509 (29) 698 plusmn 447 (30)Donepezil hydrochloride (mgd) 823 plusmn 674 (14) 837 plusmn 533 (15) 866 plusmn 271 (16) 892 plusmn 758 (15)Rivastigmine (mgd) 345 plusmn 165 (25) 351 plusmn 108 (24) 361 plusmn 187 (25) 367 plusmn 172 (25)Galantamine reminyl (mgd) 2612 plusmn 2284 (29) 2608 plusmn 2165 (29) 2559 plusmn 2041 (29) 2751 plusmn 1966 (29)AD Alzheimerrsquos disease MMSE Mini-Mental State Examination

In this study we evaluated the effects of the TCM Shen-Zhi-Ling oral liquid (SZL) on the symptoms of BPSD in ADpatients Pan et al adopted a recently developed methodanalyzing scores of wrist activity measured with a motionlogger [9] and showed that analysis of diurnal activity (DA)nocturnal activity (NA) and evening activity (EA)may reflectthe fluctuational degrees of BPSD and can provide a usefulassessment of BPSD accompanied by clinical scores for ADThe aim of the present study was to evaluate the amelioratingeffects of SZL on impaired BPSD of AD patients using thequantitative and objective parameters recorded by a Micro-Mini-Motionlogger (Ambulatory Monitoring Inc)

2 Methods

21 Subjects Subjects with Mini-Mental State Examination(MMSE) scores between 10 and 24 and satisfying the fourthedition of the Diagnostic and Statistical Manual of Men-tal Disorders DSM-IV-TR Fourth Edition (DSM-IV) fordementia from January 2010 to October 2013 at the Depart-ment of Neurology of Shuguang Hospital Affiliated to theShanghai University of TCM were recruited into the studyWe examined 198 patients who had been diagnosed withcognitive disorders however only 98 patients who sufferedfromAD (mean age plusmn SD 572plusmn89 years old mean durationof illness 59 plusmn 51 years) were found to be suitable forthis research Current diagnostic options in living patientsinclude a combination of clinical history the exclusion of

other causes of cognitive impairment and cognitive andmental state examination [10] Structural imaging techniqueswith computed tomography (CT) magnetic resonance imag-ing (MRI) single-photon emission computed tomography(SPECT) positron emission tomography (PET) andor withclinical signs and symptoms were used as an aid to diagnosisand to help differentiate AD from other types of dementiasuch as vascular dementia frontal temporal dementia andParkinsonrsquos disease with dementia The patients were ran-domly assigned to the SZL (119899 = 49 6427 plusmn 118) or placebogroup (119899 = 49 6391 plusmn 139) (Table 1) and given randomnumbers by a study coordinator who also encoded the drugswithmatching randomnumbers Neither the patients nor theresearchers monitoring the outcome knew which patient wasreceiving which treatment until the study was over and therandom code was broken Antidementia drug administrationwas not changed throughout the experiment The study wasapproved by The Ethics Committee of Shuguang HospitalAffiliated to Shanghai University of TCM and performedunder the principles outlined in the Declaration of HelsinkiAll subjects provided informed consent in accordance withinstitutional requirements prior to participation in the study

22 Additional Treatment Sheng-Zhi-Ling oral liquid (SZL)the TCM used in this study is an oral liquid consisting of 10kinds of traditional Chinese medicine Codonopsis pilosulaCassia Twig Paeonia lactiflora honey-fried Licorice rootPoria Cocos Rhizoma Zingiberis Radix Polygalae Acorus

Evidence-Based Complementary and Alternative Medicine 3

tatarinowii Ossa Draconis and Concha Ostreae SZL iscommonly used in treating for ldquoinsufficiency of vitality (Qi)and innutrition of the mind (heart)rdquo in China Placebo oralliquid consisted of one-tenth of the volume of SZL togetherwith an added bitterant and it hadno TCM activity Patientswere instructed to take one bottle (10 cc including 500mgcrude drug) of SZL or placebo soluble liquid (10 cc including50mg crude drug) three times a day at least 30min before orafter the ingestion of other drugs for 20 consecutive weeksThe shape and color of SZL and the placebo oral liquid werevery similar and could not be distinguished from one anotherby appearance or aqueous solution taste SZL and the placebooral liquids were made by ShandongWohua PharmaceuticalsCo Ltd The trial was carried out as a randomized double-blind parallel group study

23 Assessments Behavioral pathology in Alzheimerrsquos dis-ease (BEHAVE-AD) [11] BEHAVE-AD addresses delusionshallucinations activity disturbances aggressiveness diurnalrhythm disturbances affective disturbances and anxietiesand phobias The BEHAVE-AD scores of all patients wereevaluated 4 times on the day before the actigraph recordingsin the series time windows during the 25 weeks of follow-up by the same neurologists such as before taking additionalTCMmedicine and inweek 10 week 20 andweek 25 (5weeksafter stopping the additional treatment)

Neuropsychiatric inventory (NPI) [12] NPI was usedto assess 10 behavioral disturbances occurring in patientsdelusions hallucinations dysphoria anxiety agitationaggre-ssion euphoria disinhibition irritabilityability apathy andaberrant motor activity The NPI scores were assessed basedon information from the patients or caregivers using the sametime windows as when evaluating BEHAVE-AD

Analysis of actigraphy all patients wore a small watch-type activitymonitor equippedwith a computer (Micro-Mini-Motionlogger Ambulatory Monitoring Inc Ardsley NewYork) on the wrist of their nondominant hand for 7 consecu-tive days in the series time windows (10 weeks each and then5 weeks) during the 25-week follow-up Data acquired duringthe diurnal activity (DA between 6 am and 6 pm) eveningactivity (EA between 6 pm and 9 pm) and nocturnalactivity (NA between 9 am and 6 am) periods were usedin the analyses [9] Discontinuous data were combinedusing an integrative method and then analyzed by detrendedfluctuation analysis (DFA) which evaluates the correlationsbetween time scales and magnitudes of fluctuation (standarddeviations) within each time scale [13 14] We compared thefluctuation of these parameters in the series time windowsduring the 25 weeks of follow-up

For the safety assessments each patient underwent aphysical examination by a physician and laboratory tests forblood counts and biochemistry and urinalysis at each visit

24 Statistical Analysis Repeated-measure ANOVA wasconducted to test the differences among week 0 week 10week 20 and week 25 for the scores of BEHAVE-ADNPI and the actigraph parameters in the SZL and placebogroups When a significant difference was detected a post

hoc test (Bonferroni test) was conducted between the SZLand placebo groups A significant difference was defined as119875 lt 005 SPSS windows version 170 was used for statisticalanalyses All data are expressed as the mean plusmn standarddeviation

3 Results

Seven patients dropped out of the study two patients in theSZL group were unable to tolerate the bitter taste of SZLwhile two in the SZL group and three in the placebo groupdropped out due to a conflict with other TCM prescribedfor concomitant diseases Neither physical examination norlaboratory tests revealed any adverse changes after additionaltreatment in either group at the end of the study

The post hoc test revealed no significant differencesat baseline (week 0) and other each time point (week 10week 20 and week 25) in age duration of AD MMSEBEHAVE-AD NPI scores actigraph parameters or in thedosages of huperzine A aniracetam memantine hydrochlo-ride donepezil hydrochloride rivastigmine and galantaminereminyl between the SZL and placebo groups (Tables 1 and2)

No significant changes were observed at week 10 bychecking the clinical scores and DFA parameters for the twogroups When the effects of SZL at week 20 were evaluatedby BEHAVE-AD scores significant and persistent improve-ments were found in hallucinations activity disturbancesaggressiveness and anxieties and phobias compared with theplacebo group Except for paranoid and delusion ideation allBEHAVE-AD scores at week 20 had improved in the placebogroup compared with week 0 while there was little change inthe SZL group At week 20 half of the NPI mean scores suchas for delusions hallucinations agitation aberrant motorbehavior and sleep disturbances in the SZL group weremuchlower (less improvement) compared with the placebo groupwhile these scores in the placebo group were significantlyhigher at week 20 compared with those in the patients atweek 0 Interestingly the EA and NA scores for the DFAactigraph recordings showed significantly lower values forthe SZL group compared with the placebo group at week 20while these patients in the placebo group had significantlyimproved values compared with the DFA values at week 0and the effects in the SZL group were maintained for 5 weeksat the endpoint of the research (Table 2) The appetites ofpatients in both the SZL and placebo groups at week 20 andweek 25 showed almost no changes compared with week 0

4 Discussion

We previously demonstrated that the changes of EA and NAin the DFA which is in accordance with the improvementof the BEHAVE-AD and NPI scores might be quantitativepredictors for evaluating the severity of BPSD in dementia[9] In this study we demonstrate that SZL a TCM ame-liorated the disability associated with BPSD in AD patientsusing the analysis of DFA of the actigraph records togetherwith the more conventional BEHAVE-AD and NPI scores


Table 2 Results of clinical evaluation between before and after the additional treatment of Sheng-Zhi-Ling Oral liquid (SZL) and placebo

Parameter Week 0 Week 10 Week 20 Week 25SZL Placebo SZL Placebo SZL Placebo SZL Placebo

BEHAVE-ADParanoid and delusionideation 311 plusmn 038 306 plusmn 036 312 plusmn 029 326 plusmn 066 315 plusmn 071 331 plusmn 106 321 plusmn 104 349 plusmn 123

Hallucinations 372 plusmn 059 379 plusmn 061 375 plusmn 148 395 plusmn 061 382 plusmn 091lowast

423 plusmn 138391 plusmn 091

448 plusmn 151998771

Activity disturbances 651 plusmn 028 648 plusmn 071 653 plusmn 041 674 plusmn 085 661 plusmn 137lowast


776 plusmn 178998771

Aggressiveness 506 plusmn 030 502 plusmn 039 513 plusmn 102 541 plusmn 099 536 plusmn 132lowast


648 plusmn 191998771

Diurnal rhythmdisturbances 261 plusmn 033 259 plusmn 047 276 plusmn 083 315 plusmn 042 311 plusmn 076 355 plusmn 092

324 plusmn 089 384 plusmn 078

998771

Affective disturbances 315 plusmn 023 318 plusmn 035 323 plusmn 059 331 plusmn 035 334 plusmn 064 388 plusmn 072 341 plusmn 058 417 plusmn 086998771

Anxieties and phobias 222 plusmn 033 219 plusmn 052 238 plusmn 041 269 plusmn 058 257 plusmn 057lowast 302 plusmn 038 271 plusmn 046 336 plusmn 047998771

NPI mean scoreDelusions 154 plusmn 059 153 plusmn 054 158 plusmn 061 182 plusmn 057 175 plusmn 089

lowast


241 plusmn 162998771



459 plusmn 161998771

Agitation 532 plusmn 091 541 plusmn 046 545 plusmn 096 648 plusmn 088 628 plusmn 109lowast


797 plusmn 153998771

Depression 421 plusmn 081 423 plusmn 016 426 plusmn 101 419 plusmn 072 419 plusmn 142 429 plusmn 038 437 plusmn 132 446 plusmn 081

Anxiety 234 plusmn 069 233 plusmn 041 238 plusmn 097 242 plusmn 086 243 plusmn 113 246 plusmn 104 239 plusmn 165 251 plusmn 142

Euphoria 363 plusmn 062 362 plusmn 068 373 plusmn 089 372 plusmn 056 375 plusmn 061 380 plusmn 069 381 plusmn 035 383 plusmn 092

Apathy 331 plusmn 072 329 plusmn 048 329 plusmn 084 333 plusmn 083 339 plusmn 097 327 plusmn 066 343 plusmn 077 339 plusmn 069

Disinhibition 274 plusmn 057 279 plusmn 049 276 plusmn 036 291 plusmn 055 273 plusmn 069 289 plusmn 058 281 plusmn 037 285 plusmn 084

Ignitability 326 plusmn 075 327 plusmn 077 329 plusmn 082 417 plusmn 052 385 plusmn 076 408 plusmn 083 372 plusmn 053 398 plusmn 056

Aberrant motorbehavior 428 plusmn 069 425 plusmn 087 427 plusmn 074 463 plusmn 073 426 plusmn 109

lowast


533 plusmn 109998771

Sleep disturbance 532 plusmn 083 525 plusmn 068 538 plusmn 123 607 plusmn 079 587 plusmn 173lowast


706 plusmn 137998771

Appetite 408 plusmn 057 411 plusmn 036 412 plusmn 087 428 plusmn 031 418 plusmn 039 417 plusmn 061 424 plusmn 057 403 plusmn 055

DFA of actigraph activityDiurnal activity 084 plusmn 011 083 plusmn 024 083 plusmn 019 084 plusmn 017 085 plusmn 015 088 plusmn 013 084 plusmn 019 089 plusmn 021

Evening activity 085 plusmn 012 086 plusmn 009 086 plusmn 013 091 plusmn 014 086 plusmn 035lowast


098 plusmn 023998771

Nocturnal activity 092 plusmn 013 091 plusmn 014 094 plusmn 015 099 plusmn 016 095 plusmn 016lowast


128 plusmn 017998771

lowast

119875 lt 005 compared with week 20 of placebo group 119875 lt 005 compared with week 0 of placebo group 119875 lt 005 compared with week 30 of placebo group998771

119875 lt 005 compared with week 0 of placebo group

SZL induced no significant adverse effects and was tolerableby more than 92 of the participants

The treatment of BPSD is as important as the treatment ofcore symptoms such as memory disturbance and disorienta-tion Acetylcholinesterase (AChE) inhibitors and N-methyl-d-aspartate (NMDA) receptor noncompetitive antagonistsare commonly used for the treatment of AD They areeffective at treating core symptoms and in BPSD treatment[15ndash17] however the effects are not completely satisfactoryThey can cause adverse effects such as nausea extrapyra-midal symptoms drowsiness and other symptoms [18]Many researchers have attempted to identify more effectivemedicines from traditional therapy or translational therapyfor serious neurodegeneration disease [19ndash21] The presentpreliminary data have replicated the previous finding thatSZL could protect neurons by reducing the expression of APPmRNA in cerebral cortex and hippocampus and decreasingthe expression of caspase-3 to reduce the apoptosis of neurons[22] In TCM theory insufficiency of body vitality (Qi) might

cause abnormal body physical activity and a loss of the abilityto control body movements Innutrition of the mind (heart)may cause affective disorders andpoor cognitive function andresult in fatigue of the mind These patients will present withhallucinations activity disturbances aggressiveness diurnalrhythm disturbances anxieties and phobias agitation aber-rant motor behavior depression and even sleep disturbance[23] Among the 10 components of SZL Codonopsis pilosulaand Cassia Twig might increase the vitality of the body andwarm the body thus providing more energy to control ldquoQirdquoproperly [24 25] Radix Polygalaeand Acorus tatarinowii areboth sedatives and heart invigorating and can also modifycognitive function [26 27] Ossa Draconis and ConchaOstreae are well-known sedatives and researchers in manycountries have demonstrated that they have a sleep-inducingfunction for treating sleep disorders [28] The remainingherbs in the SZL concoction can increase blood circulationin the brain (Paeonia lactiflora honey-fried Licorice rootand Poria Cocos) [29 30] Whether the components of SZL


contain inhibitory effects on fibril formation has not beendemonstrated Although the groups consisted of only smallnumbers of patients that resulted in differences at baselinedespite randomization it was unlikely that this altered theoutcome given the magnitude of change from baseline withSZL treatment SZL is tolerable for long-term administrationand hence is likely a suitable choice as an additional drug forlong-term control of the symptoms of BPSD for AD DFAwhich determines the deviations in 3 parameters (DA EAand NA) obtained by actigraph recordings can be quanti-tatively used for assessing the severity of BPSD in patientssuffering from AD The small sample size is a limitation ofour pilot study In addition normative data for both healthyelderly and BPSD patients need to be established Actigraphymay be feasible and useful when predicting a prognosis ormaking therapeutic decisions related to patients with AD-BPSD

Disclosure

Full financial disclosures (for the past year (end of paper)) allauthors have no stock ownership in medically related fieldsno consultancies no advisory boards no partnerships nogrants no intellectual property rights no expert testimonyno employment and no contracts as well as no royalties toreport

Conflict of Interests

All authors have no conflict of interests and declare they haveno further financial disclosures to make

Authorsrsquo Contribution

Weidong Pan participated in the entire study formulated thestudy concept and design provided statistical expertise andassisted with drafting of the paper Shin Kwak participatedin the entire study and assisted with concept and designand drafting of the paper Qiudong Wang participated insome of the study and data compilation Yu Song participatedin some of the study and data compilation Baofeng Qinparticipated in some of the study and data compilationMingzhe Wang participated in some of the study and datacompilation Yoshiharu Yamamoto participated in some ofthe study and critical revision of the paper for importantintellectual content

Acknowledgments

The authors wish to express their appreciation for thepatience and dedication of the clinical research and hospitalstaff involved in this clinical study and to the subjectsand their families This study was sponsored and sup-ported by the National Natural Science Foundation of China(81373619) and the Shanghai Pujiang Programme of the Sci-ence and Technology Commission of Shanghai Municipality(09PJ1409300)

References

[1] J Cerejeira L Lagarto and E B Mukaetova-Ladinska ldquoBehav-ioral and psychological symptoms of dementiardquo Frontiers inNeurology vol 3 article 73 2012

[2] D Mapelli E Di Rosa R Nocita and D Sava ldquoCognitivestimulation in patients with dementia randomized controlledtrialrdquo Dementia and Geriatric Cognitive Disorders Extra vol 3no 1 pp 263ndash271 2013

[3] P A G M De Smet ldquoHerbal remediesrdquo The New EnglandJournal of Medicine vol 347 no 25 pp 2046ndash2056 2002

[4] W Pan X Chen J Bao Y Bai et al ldquoThe use of integrativetherapies in patients with amyotrophic lateral sclerosis inShanghai Chinardquo Evidence-Based Complementary and Alterna-tive Medicine vol 2013 Article ID 613596 6 pages 2013

[5] W Pan S Kwak G Li Y Chen and D Cai ldquoTherapeuticeffect of Yang-Xue-Qing-Nao granules on sleep dysfunction inParkinsonrsquos diseaserdquo Chinese Medicine vol 8 article 14 2013

[6] W Pan Y Liu Z Fang et al ldquoA compound belonging totraditional Chinese medicine improves nocturnal activity inParkinsonrsquos diseaserdquo Sleep Medicine vol 12 no 3 pp 307ndash3082011

[7] W Pan S Kwak Y Liu et al ldquoTraditional chinese medicineimproves activities of daily living in parkinsonrsquos diseaserdquoParkin-sonrsquos Disease vol 2011 Article ID 789506 7 pages 2011

[8] W Pan X Su J Bao J Wang et al ldquoOpen randomized clinicaltrial on JWSJZ decoction for the treatment of ALS patientsrdquoEvidence-Based Complementary and Alternative Medicine vol2013 Article ID 347525 5 pages 2013

[9] W Pan S Yoshida Q Liu et al ldquoQuantitative evaluation ofseverity of behavioral and psychological symptoms of dementiain patients with vascular dementiardquo Translational Neurodegen-eration vol 2 article 9 2013

[10] O L Lopez E McDade M Riverol and J T Becker ldquoEvolutionof the diagnostic criteria for degenerative and cognitive disor-dersrdquo Current Opinion in Neurology vol 24 no 6 pp 532ndash5412011

[11] B Reisberg ldquoBehavioral intervention approaches to the treat-ment and management of Alzheimerrsquos disease a researchagendardquo International Psychogeriatrics vol 8 supplement 1 pp39ndash44 1996

[12] J L Cummings MMega K Gray S Rosenberg-Thompson DA Carusi and J Gornbein ldquoThe neuropsychiatric inventorycomprehensive assessment of psychopathology in dementiardquoNeurology vol 44 no 12 pp 2308ndash2314 1994

[13] W Pan K Ohashi Y Yamamoto and S Kwak ldquoPower-law temporal autocorrelation of activity reflects severity ofparkinsonismrdquo Movement Disorders vol 22 no 9 pp 1308ndash1313 2007

[14] K Ohashi L A N Amaral B H Natelson and Y YamamotoldquoAsymmetrical singularities in real-world signalsrdquo PhysicalReviewEmdashStatistical Nonlinear and SoftMatter Physics vol 68no 6 Article ID 065204 2003

[15] I D Maidment C G Fox M Boustani J Rodriguez R CBrown and C L Katona ldquoEfficacy of memantine on behavioraland psychological symptoms related to dementia a systematicmeta-analysisrdquo Annals of Pharmacotherapy vol 42 no 1 pp32ndash38 2008

[16] D Paleacu D Mazeh I Mirecki M Even and Y BarakldquoDonepezil for the treatment of behavioral symptoms inpatients with Alzheimerrsquos diseaserdquoClinical Neuropharmacologyvol 25 no 6 pp 313ndash317 2002


[17] S Gauthier H Feldman J Hecker et al ldquoEfficacy of donepezilon behavioral symptoms in patients with moderate to severeAlzheimerrsquos diseaserdquo International Psychogeriatrics vol 14 no4 pp 389ndash404 2002

[18] K R Obermann J C Morris and C M Roe ldquoExploration of100 commonly used drugs and supplements on cognition inolder adultsrdquoAlzheimerrsquos amp Dementia vol 9 no 6 pp 724ndash7322013

[19] H Lu W Pan J Wang et al ldquoThe current status of integrativetherapies in treating Parkinsonrsquos disease in Six General Hospi-tals in Shanghairdquo International Journal of Integrative Medicinevol 1 p 17 2013

[20] C F Evans H Davtyan I Petrushina et al ldquoEpitope-basedDNA vaccine for Alzheimerrsquos disease translational study inmacaquesrdquo Alzheimerrsquos amp Dementia 2013

[21] M Maiwulanjiang K Y Zhu J Chen et al ldquoSong bu lidecoction a traditional uyghur medicine protects cell deathby regulation of oxidative stress and differentiation in culturedPC12 cellsrdquo Evidence-Based Complementary and AlternativeMedicine vol 2013 Article ID 687958 11 pages 2013

[22] D-J Wang S-M Lin and Z-H Yu ldquoEffects of TX0201 fromheart-Regulating Formula on expressions of APP mRNA andCaspase-3 in brain of rats of Alzheimerrsquos diseaserdquo Shang HaiZhong Yi Yao Da Xue Xue Bao vol 24 no 4 pp 51ndash54 2010

[23] M Porkert The Theoretical Foundations of Chinese MedicineSystems of Correspondence MIT Press Cambridge UK 1973

[24] J Y He S Zhu Y Goda et al ldquoQuality evaluation ofmedicinally-used Codonopsis species and Codonopsis Radixbased on the contents of pyrrolidine alkaloids phenylpropanoidand polyacetylenesrdquo Journal of Natural Medicines vol 68 no 2pp 326ndash339 2013

[25] J Y He S Zhu K Komatsu et al ldquoGenetic polymorphism ofmedicinally-usedCodonopsis species in an internal transcribedspacer sequence of nuclear ribosomal DNA and its applica-tion to authenticate Codonopsis Radixrdquo Journal of NaturalMedicines vol 68 no 1 pp 112ndash124 2014

[26] A G Wu V K Wong S W Xu et al ldquoOnjisaponin B derivedfrom Radix Polygalae enhances autophagy and accelerates thedegradation of mutant 120572-synuclein and huntingtin in PC-12cellsrdquo International Journal of Molecular Sciences vol 14 no 11pp 22618ndash22641 2013

[27] P Han T Han W Peng and X R Wang ldquoAntidepressant-likeeffects of essential oil and asarone a major essential oil compo-nent from the rhizome of Acorus tatarinowiirdquo PharmaceuticalBiology no 5 pp 51589ndash51594 2013

[28] H Zhang L Zhang and Y Liu ldquoStudies on chemical compo-nents and pharmacological activities of os draconis (longgu)and osteae conchardquo Zhongguo Zhong Yi Yao Za Zhi vol 36 no13 pp 1839ndash1840 2011

[29] J J Wu W Y Sun S S Hu et al ldquoA standardized extract fromPaeonia lactiflora and Astragalus membranaceus induces apop-tosis and inhibits the proliferation migration and invasion ofhuman hepatoma cell linesrdquo International Journal of Oncologyvol 43 no 5 pp 1643ndash1651 2013

[30] Y Y Zhao H T Li Y L Feng et al ldquoUrinary metabonomicstudy of the surface layer of Poria cocos as an effective treatmentfor chronic renal injury in ratsrdquo Journal of Ethnopharmacologyvol 148 no 2 pp 403ndash410 2013

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Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


Table 1 Characteristics of the patients with Alzheimerrsquos disease before and after additional treatment

Characteristic Shen-Zhi-Ling group1st week (119899) 10th week (119899) 20th week (119899) 25th week (119899)




Huperzine A (120583gd) 32330 plusmn 1739 (32) 33441 plusmn 1693 (32) 31929 plusmn 1686 (31) 34932 plusmn 1884 (31)Aniracetam (mgd) 4896 plusmn 1793 (28) 4917 plusmn 1668 (28) 4905 plusmn 1834 (29) 4976 plusmn 1123 (29)Memantine hydrochloride (mgd) 667 plusmn 528 (28) 681 plusmn 447 (30) 683 plusmn 496 (29) 692 plusmn 567 (30)Donepezil hydrochloride (mgd) 821 plusmn 376 (16) 849 plusmn 402 (15) 873 plusmn 269 (15) 933 plusmn 694 (15)Rivastigmine (mgd) 338 plusmn 126 (23) 347 plusmn 172 (14) 355 plusmn 209 (13) 375 plusmn 166 (14)Galantamine reminyl (mgd) 2589 plusmn 2263 (26) 2531 plusmn 2361 (25) 2587 plusmn 2139 (26) 2682 plusmn 2291 (26)

Characteristic Placebo group1st week (119899) 10th week (119899) 20th week (119899) 25th week (119899)




Huperzine A (120583gd) 35830 plusmn 1914 (34) 33441 plusmn 1693 (34) 32703 plusmn 1798 (33) 35830 plusmn 1914 (32)Aniracetam (mgd) 5066 plusmn 1087 (26) 4988 plusmn 1712 (25) 5055 plusmn 1923 (27) 5172 plusmn 1193 (27)Memantine hydrochloride (mgd) 671 plusmn 447 (29) 667 plusmn 509 (30) 659 plusmn 509 (29) 698 plusmn 447 (30)Donepezil hydrochloride (mgd) 823 plusmn 674 (14) 837 plusmn 533 (15) 866 plusmn 271 (16) 892 plusmn 758 (15)Rivastigmine (mgd) 345 plusmn 165 (25) 351 plusmn 108 (24) 361 plusmn 187 (25) 367 plusmn 172 (25)Galantamine reminyl (mgd) 2612 plusmn 2284 (29) 2608 plusmn 2165 (29) 2559 plusmn 2041 (29) 2751 plusmn 1966 (29)AD Alzheimerrsquos disease MMSE Mini-Mental State Examination

In this study we evaluated the effects of the TCM Shen-Zhi-Ling oral liquid (SZL) on the symptoms of BPSD in ADpatients Pan et al adopted a recently developed methodanalyzing scores of wrist activity measured with a motionlogger [9] and showed that analysis of diurnal activity (DA)nocturnal activity (NA) and evening activity (EA)may reflectthe fluctuational degrees of BPSD and can provide a usefulassessment of BPSD accompanied by clinical scores for ADThe aim of the present study was to evaluate the amelioratingeffects of SZL on impaired BPSD of AD patients using thequantitative and objective parameters recorded by a Micro-Mini-Motionlogger (Ambulatory Monitoring Inc)

2 Methods

21 Subjects Subjects with Mini-Mental State Examination(MMSE) scores between 10 and 24 and satisfying the fourthedition of the Diagnostic and Statistical Manual of Men-tal Disorders DSM-IV-TR Fourth Edition (DSM-IV) fordementia from January 2010 to October 2013 at the Depart-ment of Neurology of Shuguang Hospital Affiliated to theShanghai University of TCM were recruited into the studyWe examined 198 patients who had been diagnosed withcognitive disorders however only 98 patients who sufferedfromAD (mean age plusmn SD 572plusmn89 years old mean durationof illness 59 plusmn 51 years) were found to be suitable forthis research Current diagnostic options in living patientsinclude a combination of clinical history the exclusion of

other causes of cognitive impairment and cognitive andmental state examination [10] Structural imaging techniqueswith computed tomography (CT) magnetic resonance imag-ing (MRI) single-photon emission computed tomography(SPECT) positron emission tomography (PET) andor withclinical signs and symptoms were used as an aid to diagnosisand to help differentiate AD from other types of dementiasuch as vascular dementia frontal temporal dementia andParkinsonrsquos disease with dementia The patients were ran-domly assigned to the SZL (119899 = 49 6427 plusmn 118) or placebogroup (119899 = 49 6391 plusmn 139) (Table 1) and given randomnumbers by a study coordinator who also encoded the drugswithmatching randomnumbers Neither the patients nor theresearchers monitoring the outcome knew which patient wasreceiving which treatment until the study was over and therandom code was broken Antidementia drug administrationwas not changed throughout the experiment The study wasapproved by The Ethics Committee of Shuguang HospitalAffiliated to Shanghai University of TCM and performedunder the principles outlined in the Declaration of HelsinkiAll subjects provided informed consent in accordance withinstitutional requirements prior to participation in the study

22 Additional Treatment Sheng-Zhi-Ling oral liquid (SZL)the TCM used in this study is an oral liquid consisting of 10kinds of traditional Chinese medicine Codonopsis pilosulaCassia Twig Paeonia lactiflora honey-fried Licorice rootPoria Cocos Rhizoma Zingiberis Radix Polygalae Acorus









3 Results




4 Discussion








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648 plusmn 191998771



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241 plusmn 162998771



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lowast


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Disclosure






Acknowledgments


References





































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
























3 Results




4 Discussion








448 plusmn 151998771



776 plusmn 178998771



648 plusmn 191998771



998771




lowast


241 plusmn 162998771



459 plusmn 161998771



797 plusmn 153998771








lowast


533 plusmn 109998771



706 plusmn 137998771





098 plusmn 023998771



128 plusmn 017998771

lowast








Disclosure






Acknowledgments


References





































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of






















448 plusmn 151998771



776 plusmn 178998771



648 plusmn 191998771



998771




lowast


241 plusmn 162998771



459 plusmn 161998771



797 plusmn 153998771








lowast


533 plusmn 109998771



706 plusmn 137998771





098 plusmn 023998771



128 plusmn 017998771

lowast








Disclosure






Acknowledgments


References





































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


















Disclosure






Acknowledgments


References





































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of




































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















research article shen-zhi-ling oral liquid improves...

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