A Study About the Impact of Intensive Instruction on the Use of Aricept and the Reasons for Discontinuation in Patients With Alzheimer's Disease
Phase: NA
Conditions: Alzheimer's Type Dementia
Sponsor: Mirai Iryo Research Center, Inc.

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A Study About the Impact of Intensive Instruction on the Use of 
Aricept and the Reasons for Discontinuation in Patients With 
Alzheimer's Disease 
  
Clinical study protocol  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
 
 
 
 
 
 
Protocol# ART-2013-01 
 (NCT01972204) 

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 List / abbreviations and definitions of abbreviations and terms  
 Acronym  
 Expression not to be omitted (definition)  
 AChE  
 Acetylcholine esterase : acetylcholinesterase  
 AD  
 Alzheimer's disease : Alzheimer's dementia  
 ADL  
 A ctivities of D aily L iving : daily living behavior  
 AE  
 Adverse event : adverse event  
 BPSD  
 Behavioral and Psychological Symptoms of Dementia : behavioral 
and psychological symptoms of dementia  
 CRC  
 C linical research coordinator: test coordinator over ter  
 DSM  
 Diagnostic and Statistical Manual of Mental Disorders : Diagnostic 
Statistics Manual of the American Psychiatric Association  
 FAST  
 Functional Assessment Staging : Dementia severity rating scale  
 MMSE - J  
 Mini-Mental State Examination - English : Mental State Short 
Time Test - Japan Version  
 NMDA  
 N-methyl-D-aspartate : N methyl D aspartic acid  
 SAE  
 Serious adverse event : serious adverse event  
  
 

Version_2013.Sept.5 
 
summary  
 item  
 Contents  
 Study name  
A Study About the Impact of Intensive Instruction on the Use of 
Aricept and the Reasons for Discontinuation in Patients With 
Alzheimer's Disease  
 The purpose  
The purpose of this study is to examine the influence of the 
instruction on the use of Aricept with educational brochure on the 
48-week medication persistence and to assess the reasons for 
discontinuation. 
 Examination 
design  
 Multicenter joint randomized parallel group comparison study 
comparative study  
 Target patient  
 Alzheimer type dementia patients  
  
 Selection criteria  
 1) Patients meeting DSM- IV diagnostic criteria for Alzheimer's 
dementia  
 2) Patients who agreed with this research ( consent from patients 
should be acquired as much as possible and consent from 
substitute is essential )  
 3) We agree to cooperate with this research, provide necessary 
patient information, patients with families or carers who can 
accompany at the regular visit date  
 4) Outpatient from home  
  
 Exclusion criteria  
 1) Patients receiving treatment for AChE inhibitors (donepezil, 
galantamine, rivastigmine) , and NMDA receptor antagonists 
(memantine) within 4 weeks before consent acquisition  
 2) Patients with dyspepsil hydrochloride preparations or 
hypersensitivity to piperidine derivatives  
 3) Patients are also other test drug which has received the 
administration of investigational drugs within 12 weeks before the 
start of administration of study drug  
 4) Other patients whose clinical research doctor deemed 
inappropriate as subjects  
 Target case 
number  
 150 cases  
 Drugs used  
 Aricept ® products (commercially available)  
 · Tablets 3 mg , tablets 5 mg , tablets 10 mg  
 Fine grain 0.5 %  
 · D tablets 3 mg , D tablets 5 mg , D tablets 10 mg  
 · Oral jelly 3 mg , Oral jelly 5 mg , Oral jelly 10 mg  
 · Dry syrup 1%  
 Normally, once 3 mg 1 day as donepezil hydrochloride in adults  
Starting from 1 to 2 weeks 5 mg  And orally administered.  For 
advanced Alzheimer's type dementia patients, 5 mg  In 4 weeks 

Version_2013.Sept.5 
 
or more, 10 mg  .  Further, it should be reduced according to 
symptoms.  
 Fine: Normal, for adults once a day 0.6 g  Starting from 1 to 2 
weeks 1.0 g  And orally administered.  For advanced Alzheimer 
type dementia patients, 1.0 g  In after more than 4 weeks, 2.0 
g  .  Further, it should be reduced according to symptoms.  
 Dry syrup: usually, once a day for adults 0. 3 g  It starts from 
0 after one to two weeks. 5 g  And orally administered.  The high 
degree of Alzheimer-type dementia, 0. 5 g  In 4 weeks or more, 1. 
0 g  .  Further, it should be reduced according to symptoms.  
 Test method  
 Clinical research personnel to query the allocation group to 
promptly clinical research secretariat after consent from the subject 
has been acquired ( "informed consent file" in due strengthening 
leadership group / Normal leadership group), the administration of 
Aricept ® Start.  Among the study period of between 48 weeks, the 
subjects required date to visit (2 weeks, 12 weeks, 24 weeks, 48 
weeks, increase the time from the donepezil hydrochloride 5 mg to 
10 mg), examination of the provisions · Perform observation 
( compliance with medication, cognitive function test, adverse 
events , concomitant medication ).  
 Enhanced leadership group due to "informed consent file", 
intends line medication guidance using the "informed consent file" 
to the required date to subject himself and family or caregiver.  
 If you stop taking Aricept ® medication, investigate until the 
reason is clear .  
 Evaluation 
items  
 Key evaluation items  
 - Aricept ® medication continuation rate when medication after 
48 weeks  
- Aricept ® medication discontinuation at the time of reason  
  
 Secondary endpoint  
- Aricept ® factor analysis of the impact on the medication 
continued  
 analysis  
 Aricept ® medication continuation rate of 48 weeks compared 
with strengthening leadership group and the normal guidance 
group due to "informed consent file".  Aggregates the reason at 
the time of Aricept ® medication discontinuation, to compare the 
reason for terminating between groups.  In addition, the factors 
that affect the Aricept ® medication continuously analyzed by 
logistic regression analysis.  
 Medical 
institutions  
 15 facilities  
 Research period   After the Joint Ethics Committee approval to 2017 Dec.  
 
 

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 table of contents  
 1.                Background · Preface  
 2.                Purpose of clinical research  
 3.                Object  
 3.1.                Selection criteria  
 3.2.                Exclusion criteria  
 3.3.                Definition of cancellation example  
 3.4.                Additional Supplementary Items in Canceled Example  
 Four.                Explain to the subject and obtain consent  
 Five.                Clinical research method  
 5.1.                Clinical research design  
 5.2.                Test outline  
 5.3.                Study participation schedule period of subjects  
 5.4.                Drug information  
 5.5.                Dose / administration method and administration period / method of use  
 5.6.                Assignment method  
 5.7.                Regulations on concomitant medication (therapy)  
 6.                Evaluation item  
 6.1.                Key evaluation items  
 6.2.                Secondary purpose  
 7.                Observation / inspection items and schedule  
 7.1.                Observation and inspection schedu  
 7.2.                Observation and inspection items  
 8.                End of research, suspension and suspension  
 8.1.                End of research  
 8.2.                Stop / stop research  
 9.                Adverse events and pregnancy information, other events  
 9.1.                Definition  
 9.2.                Record of adverse events  
 9.3.                Report of serious adverse events  
 9.4.                Report on pregnancy information  
 9.5.                Report of other events  
 9.6.                Expected adverse events  
 9.7.                Report to the manufacturer of the drug  
 Ten.                Implementation period  
 11.                Statistical analysis  
 11.1.                Analysis target group  
 11.2.                Analysis of main evaluation items  
 11.3.                Analysis of secondary evaluation items  
 11.4.                Safety analysis  
 11.5.                Other  
 12.                Target case number and setting rationale  
 13.                Ethical matters  
 13.1.                Rules to observe  
 13.2.                Creation and revision of explanatory documents / consent documents  
 13.3.                Ethics committee review  

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 13.4.                audit  
 14.                Money payment and health damage compensation, financial resources for 
clinical research  
 14.1.                Medical expenses during this clinical study  
 14.2.                Money payment to subjects  
 14.3.                Funding sources and conflicts of interest in clinical research  
 14.4.                compensation  
 15.                About personal information and other rights  
 15.1.                Protection of privacy  
 15.2.                By signing a consent form, you will approve browsing  
 15.3.                About cases where intellectual property rights etc. arise  
 15.4.                About browsing of source material  
 16.                Preservation of materials  
 16.1.                Anonymize materials  
 16.2.                Storage of documents  
 17.                Publication of research results  
 18.                Clinical research implementation system  
 19.                References  
 1  
  

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 1.           Background · Preface  
 Alzheimer type dementia ( AD ) is a progressive neurodegenerative disorder, with a 
decline in cognitive and memory ability, progressive disorder in daily living behavior, 
various symptoms of mental symptoms and behavior disorder 1) .  Along with the rapid 
aging, the prevalence of dementia in Japan is increasing, according to the announcement 
of the Ministry of Health, Labor and Welfare study group in May 2013 (Representative 
Takashi Asada Tsukuba University), 65 years of age or older The prevalence of dementia 
among elderly people is estimated at 15 % , which is said to be 4.62 million at 2012 .  AD 
is pathologically characterized by generalized cerebral atrophy and senile plaques of the 
cerebral cortex and neurofibrillary tangles.  In addition, neurochemical studies have 
reported reduction of acetylcholine ( ACh ) mainly in forebrain and decreased activity of 
choline acetyltransferase which is ACh synthase, and the functional deterioration itself 
in intracerebral cholinergic nerve itself is the most essential "Choline hypothesis" to be 
said to be a pathological condition began to be cast.  
 Aricept ® (generic name: donepezil hydrochloride) is an acetylcholinesterase ( AChE ) 
inhibitor created by Eisai Co., Ltd. It is an AD therapeutic agent having an action of 
increasing ACh concentration in the brain .  In Japan, in October 1999 tablets ( 3 mg , 
5 mg ) were approved for the suppression of the progress of cognitive symptoms in mild 
and moderate AD, and in tablets ( 3 mg , 5 mg ) as approval, in August 2007 irrespective 
of severity, Suppression of progress of cognitive symptoms in all AD was recognized as 
efficacy and effect.  With respect to the dosage form additional, fine granules in March 
2001, orally disintegrating in February 2004 (D) Tablets (3 m g, 5 mg) , with the change 
of dosage regimen in August 2007, tablets ( 10 mg ), D tablet ( 10 mg ), oral jelly ( 3 mg , 
5 mg , 10 mg ) in July 2009 , and dry syrup in February 2013 .  
 Aricept ® once, suspended (6 weeks or 4-8 weeks) Then, the case of no treatment 
cognitive function that is equivalent reported 2), compliance continuation rate of Aricept 
® under the actual clinical, low values (Table - 1).  According to the report 3) of 
Watanabe et al., When carried out understanding of drug therapy with pathology and 
Aricept ® of AD, medication instruction classroom with the aim to improve the 
medication adherence of the (Aricept classroom 4)) to the patient and family, medication 
continuation rate although the improvement of is Ru recognized, yet, a patient of about 
30% in one year has led to discontinuation.  In addition, the reason that lead to 
medication discontinuation of Aricept ®, the details are to grasp the unknown is often a 
(eg. Visits and the like that are no longer), the reason for terminating also in order to 
address the measures for medication continuation rate improved details There is a need.  

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 Table - 1 medication continuation rate of Aricept ® under real clinical  
  
 Specific usage record 
survey A 5 )  
 Specific 
usage 
record 
survey B 6 )  
 Watanabe 's report 
3)  
 Object  
 Mild  
 Height  
 Mainly 
mild, 
moderate  
 Example 
number  
 640 cases  
 824 cases  
 About 50 cases  
 period  
 3 months  
 6 
months 
 1 year   2 
years  
 1 year  
 Drug 
continuation 
rate  
 59.7 %  
 
83.7 %  
 
68.9 %  
 
50.9 %  
 49.2 %  
 Aricept 
Classroom  
 Drug 
continuation 
rate at the time 
of 
implementation  
  
 73.1 %  
  
 Eisai Co., Ltd., has been created with the patient and family that medication Aricept 
® a description for the tool for caregivers "informed consent file".  This tool explains the 
pathology of AD , the significance of medication by Aricept ® , side effects, etc. , and aims 
to improve the continuation rate of Aricept ® medication by deepening the 
understanding of patients and their families and carers .  
 In the present study, strengthening of medication instruction using the tool to verify 
the impact on the Aricept ® medication continuation rate.  In addition, in subjects 
medication of Aricept ® has reached the stop, investigate the reason for discontinuation 
in more detail, you analyze the background factor.  
 As a result of this study, we hope to build a standard dosing guidance method for 
drug treatment of Alzheimer type dementia and accumulate useful information for 
measures to improve the medication continuity rate .  
  
  

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 2.           Purpose of clinical research  
The purpose of this study is to examine the influence of the instruction on the use of 
Aricept with educational brochure on the 48-week medication persistence and to assess 
the reasons for discontinuation. To examine the influence of the instruction on the use 
of Aricept with educational brochure comparing to the ordinary instruction on the 48-
week medication persistence and to assess the reasons for discontinuation. 
  
 3.           Object  
 Alzheimer disease patients  
  
 3.1.           Selection criteria  
 Target patients who meet all of the following criteria  
 1)           Patients conforming to the diagnostic criteria for Alzheimer type dementia 
by DSM - IV  
 2)           Patients who agreed with this research (consent from patients should be 
acquired as much as possible and consent from substitute is essential)  
 3)           We agreed to cooperate with this research, provide subject information 
necessary for this research, patients with families or caregivers who can accompany 
at the regular visit date  
 Four)           Outpatient from home  
  
 3.2.           Exclusion criteria  
 Patients who conflict with any of the following will not be included in this clinical 
study  
 1)           Patients AChE inhibitor within 4 weeks prior informed consent (donepezil, 
galantamine, rivastigmine), and are receiving medical NMDA receptor antagonists 
(memantine)  
 2)           Patients with dyspepsil hydrochloride preparations or hypersensitivity to 
piperidine derivatives  
 3)           Patients are also other test drug which has received the administration of 
investigational drugs within 12 weeks before the start of administration of study 
drug  
 Four)           Other patients whose clinical research doctor deemed inappropriate as 
subjects  
  
 [ Rationale for setting ]  

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 1)    Because there is concern about the influence on the evaluation of drug 
continuation rate , 2 ) to 3 ) for safety consideration  
 4 )    In order to leave room for clinical research doctors to consider whether to 
participate in this clinical study considering the safety of the subject taking the general 
factors other than those mentioned above into consideration  
  
 3.3.           Definition of cancellation example  
 During the clinical study period ,  Medication of Aricept ® If you need to abort occurs, 
if it is found that to stop the medication of Aricept ®, or when it becomes the patient was 
transferred, non-visit by the institutionalization and hospitalization, etc., the case 
became untraceable It is handled as a discontinued example.  In addition, even if you 
change the Aricept ® to generic drugs handled as a discontinued example.  
 In addition, we are dealing with a subject that is not called off example with a 
"medication continue".  
 The doctor in charge of clinical research investigates the reasons for suspension 
( classification ① and classification ② below ) until the reason becomes clear in the 
discontinued example and records it in the case report.  
  
 [Reason classification of ①] (1 only one selection)  
 1)           Doctor's judgment  
 2)           Hope and judgment of the subject himself / herself  
 3)           Hope , judgment of family member or carer  
  
 [Reason classification of ②] (select one or more)  
 1)           Adverse event  
 2)           Insufficient effect  
 ( A )       Effect on cognitive function  
 (B)       Effect on ADL  
 ( C )       Effect on psychological symptoms  
 ( D )       Other: Free description  
 3)           Change to other oral preparations (galantamine, memantine) ( 1) 2) Reason 
for change other than 12) : Free description)  
 Four)           Change to patch agent (rivastigmine) ( 1) 2) Reason for change other 
than 12) : Free description)  
 Five)           Change to generic drug  

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 6)           Aricept ® drug discontinuation due to hospital entry, ward hospitalization 
(entry to nursing home health care facility, hospitalization of comprehensive 
medical system etc )  
 7)           Withdrawal of treatment due to visiting difficulties (eg family members or 
carers were absent)  
 8)           Discontinuation of therapy due to medication assistance burden increase  
 9)           Refusal (if the subject refuses to take the test medicine and the reason is 
unclear)  
 10)       Transfer , facility entry , inpatient due to hospitalization  
 11)       Others: it corresponds to the freedom described (12 if the reason is unclear))  
 12)       Unknown (When it becomes impossible pursuit, reason is unclear etc.)  
  
 3.4.           Additional Supplementary Items in Canceled Example  
 Investigate the date of discontinuation and state it in the case report.  
 Even after discontinuation, when continuing medication for Aricept ® (for example, 
in case of inability to visit by transfer, facility entry , hospitalization, etc) , follow up will 
take place at the prescribed visit points ( 2 weeks, 12 weeks, 24 weeks, 48 weeks) At the 
time of the period, investigate the medication situation of Aricept ® by phone etc. and 
describe it in the case report.  
 If there is use of Alzheimer's type dementia treatment drug (including generic drugs) 
after discontinuation, as follow up, investigate the medication situation of the 
therapeutic medicine on the telephone etc. at 48 weeks and describe the contents in the 
case report .  
  
  
 4.           Explain to the subject and obtain consent  
 This doctor in charge of clinical research will fully explain the content of this clinical 
study etc. to subjects and substitutes .  Give subjects and substitutives enough time to 
ask questions and whether to participate in this clinical study or not before confirming 
that we have understood the content of this clinical study well and before starting Obtain 
written consent from the principal (as far as possible) and from the substitute for free 
participation in participation in this clinical study .  
 The consent document, describes the clinical research physician and agreed subjects 
(as possible) was carried out, Daidaku's signed or serial name seal, dating.  In addition, 
if the CRC · pharmacist etc complementarily explained, the cooperating person also signs, 

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signs, signs, and writes dates.  One copy of the original shall be kept in the chart and 
the copy shall be given to the subject.  
 During this clinical study period, it can affect the willingness of subjects and 
Daidaku's about whether you want to join to continue to subject and Daidaku's new 
important information may be related to the consent of, or this clinical study, If sexual 
information is obtained, the clinical research representative promptly revises the 
consent explanation document based on the information and obtain approval from the 
joint ethics committee.  Clinical research representatives will provide clinical research 
physicians with a revised consent statement .  The doctor in charge of clinical research 
should promptly explain the information to the subject and the substitute, obtain the 
reconsideration by free will about the continuing participation in this clinical study, copy 
the copy of the consent form and the revised explanatory document to the subject .  
 In addition, subjects and substitutes can withdraw their consent at any time even 
after agreeing to participate in this clinical study, and shall not suffer any disadvantage 
due to withdrawal of consent .  
  
  
 5.           Clinical research method  
 5.1.           Clinical study design  
 Multicenter joint randomized parallel group comparison study comparative study  
   
 5.2.           Test outline  
  
  
 Reinforcement guidance group by "informed consent file" 
( 75 cases)  
  
  
 Aricept ® administration period ( 48 weeks)  
  
  
Acquisition 
consent  
 Random  
allocation  
 Regular teaching group ( 75 cases)  
  
1)           Taking medication by "Informed consent file" (Attachment 2 )  
 In strengthening leadership group due to "informed consent file", during the visit 
of the provisions (the second week [at the time increased from donepezil 
hydrochloride 3 mg to 5 mg], 12 weeks, 24 weeks, 48 weeks, and the increase at the 
time) from the donepezil hydrochloride 5 mg to 10 mg, use the "informed consent 

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file", the pathology of AD, the significance of drug therapy with Aricept ®, side 
effects, etc. to the subject himself and family or caregiver explain.  
  
 2)           Confirmation of reason for canceling medication  
 If medication is stopped , confirm the reason .  If you did not visit the clinical 
research physician, CRC · pharmacist or the like to perform the investigation until 
the clear reason by telephone or the like.  
  
 5.3.           Study participation schedule period of subjects  
    48 weeks  
  
 5.4.           Drug information  
 Aricept ® products [ Eisai Co., Ltd. ]  
 1)           Tablets 3 mg , tablets 5 mg , tablets 10 mg ( containing 3 mg , 5 mg , 10 mg 
of donepezil hydrochloride in 1 tablet )  
 2)           Fine grain 0.5 % ( 1.0  g contains 5 mg of donepezil hydrochloride )  
 3)           D Tablets 3 mg, D Tablets 5 mg, (containing donepezil hydrochloride 3 mg 
in 1 tablet, 5 mg, 10 m g) D Tablets 10 mg  
 4)           Oral jelly 3 mg, oral jelly 5 mg, (containing donepezil hydrochloride 3 mg, 
5 mg, 10 mg in 1) oral jelly 10 mg  
 5)           Dry syrup 1% ( containing 1 mg of donepezil hydrochloride in 1.0 g )  
 It is possible to change the dosage form during the research period .  When changing 
the dosage form, describe its contents in the case report.  
  
 Storage and Storage Conditions  
 · Storage at room temperature  
 · Before opening the fine grained bulk package, shield the light and preserve it.  
 · D tablet After opening the aluminum bag, PTP packing should be stored avoiding 
moisture.  Rose packaging should be stored after opening the aluminum bag, 
shielding light and avoiding dampness.  
  
 For details see Aricept ® package insert  
  
 5.5.           Dose / administration method and administration period / method of use  
 There line the administration of the following drug agents, to continue 48 weeks.  

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 Once a day as donepezil hydrochloride 3 mg  Starting from 1 to 2 weeks 5 mg  And 
orally administered.  For advanced Alzheimer's type dementia patients, 5 mg  In 4 
weeks or more, 10 mg  .  Further, it should be reduced according to symptoms.  
 Fine: Normal, for adults once a day 0.6 g  Starting from 1 to 2 weeks 1.0 g  And 
orally administered.  For advanced Alzheimer type dementia patients, 1.0 g  In after 
more than 4 weeks, 2.0 g  .  Further, it should be reduced according to symptoms.  
 Dry syrup: usually, once a day for adults 0. 3 g  It starts from 0 after one to two 
weeks. 5 g  And orally administered.  The high degree of Alzheimer-type dementia, 0. 
5 g  In 4 weeks or more, 1. 0 g  .  Further, it should be reduced according to symptoms.  
  
   In addition, if the dose of donepezil hydrochloride is increased or decreased in the 
range up to 10 mg at the discretion of the doctor in charge of clinical research , the study 
is continued .  
   
 5.6.           Assignment method  
   Assignment managers prepare subject individually allocated envelopes of random 
assignment of 240 cases of study treatment ( including 90 preliminary cases ) beforehand 
and provide them to the clinical research secretariat .  Clinical research staff will 
promptly refer to the clinical research secretariat to allocate examination treatment of 
the subject in the registration form after consent from the subject is acquired .  Clinical 
research Secretariat, in advance based on the allocation table that was created, and 
notifies the allocation group that is described in the allocation table by young turn to 
clinical research personnel.  When notifying the assignment, the Clinical Research 
Secretariat promptly transmits " registration date ", " date of consent acquisition", 
"subject identification code", "facility name", " name of clinical research staff who made 
the notification " fill in the allocation record file, stores.  
 After the subject of allocation query, clinical research personnel, for subjects having 
acquired the consent, store to create a subject identification code table.  In the subject 
ID code table, fill in the subject name, gender, consent acquisition date, medical record 
number, subject ID code.  The assignment treatment group notified from the clinical 
research secretariat shall be entered in the subject identification code table promptly 
after notification .  
  
 5.7.           Regulations on concomitant medication (therapy)  
 1) Concomitant medication (therapy)  
 Not applicable  

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 2) Combination prohibited drug (therapy)  
   · AChE inhibitors (galantamine , rivastigmine )  
  
 3) combination restriction drug (therapy)  
   Not applicable  
  
 4) Combination caution drug (therapy)  
 Use it with caution when using it.  
 · Sucamethonium chloride hydrate  
 It may potentiate muscle relaxant action.  
 · Choline activator, cholinesterase inhibitor  
 There is a possibility that the choline stimulating action such as the vagus nerve 
stimulating action is enhanced.  
 · Itraconazole, erythromycin, etc., quinidine sulfate hydrate etc.  
 It may inhibit the metabolism of this drug and potentiate its action.  
 · Carbamazepine, dexamethasone, phenytoin, phenobarbital, rifampicin etc.  
 It may promote the metabolism of this drug and reduce its action.  
 · Central anticholinergic agent, atropine anticholinergic agent  
 This drug and anticholinergic agent may interfere with each other and reduce the 
respective effects.  
 Non-steroidal anti-inflammatory analgesics  
 It may cause peptic ulcers.  
  
 For details see Aricept ® package insert  
  
  
 6.           Evaluation item  
 6.1.           Key evaluation items  
 1 )      Compliance continuation rate when Aricept ® administration after 48 weeks  
 2 )      The reason at the time of Aricept ® medication discontinuation  
  
 6.2.           Secondary objectives  
 1)           In each group, the analysis of the factors that affect the Aricept ® medication 
continues  

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 [ Subject background factor ]  
 - years of education (number of years)  
 · Same residence family (Yes No)  
 · Caregiver background (relationship, sex, age, nursing care experience, watch over 
/ day)  
 · Nursing care classification ( 7 categories)  
 · In-home service (availability, type [free description] , frequency / month)  
 · Severity : FAST ( 7 steps)  
 · MMSE-J total score  
 · MMSE-J item scores  
 · Daily independence degree of elderly with dementia ( 9 ranks)  
 · 
Concomitant 
medications 
(antipsychotic 
drugs, 
antiepileptic 
drugs, 
antidepressants, sleep inducing drugs, Chinese herbal medicines etc. )  
 · Number of concomitant drugs (number)  
 · BPSD ( delusions, hallucinations, excitement, depression · discomfort, anxiety, 
euphoria, irresponsible · indifference, depression suppression, irritability · 
instability, presence or absence of abnormal behavior )  
  
 [ Factors after commencement of research ]  
 · MMSE-J total score change  
 · MMSE-J The amount of change in each item score  
 · Average compliance ( 90 % or more, 70 % or more and less than 90 % , 30 % or 
more and less than 70 % , 10 % or more and less than 30 %, less than 10 % )  
 · Addition (presence or absence) of antipsychotic drugs, antiepileptic drugs, 
antidepressants, sleep inducing drugs, Chinese herbal medicines etc. during the 
research period  
 · Addition of memantine during the research period (presence / absence)  
  
 2)           Safety assessment  
 · Adverse events  
 Side effects  
  
  

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 item  
 
Clinical  
 the 
study  
 start 
date  
 
Administration  
 start date  
 2 
weeks  
 ※ 1  
 12 
weeks  
 ※ 2  
 24 
weeks  
 ※ 2  
 48 
weeks ※ 
2  
 Or  
 
Canceled 
※ 4  
 Donepezil 
hydrochloride 
when 
increasing from 
5 mg to 10 mg * 
5  
 
Acquisition 
consent  
 ○  
  
  
  
  
  
  
 Subject 
background  
 ○  
  
  
  
  
  
  
 Medication  
 compliance  
  
  
 ○  
 ○  
 ○  
 ○  
 ○  
 Medication 
instruction 
by 
'informed 
consent file' 
※ 3  
  
 ○  
 ○  
 ○  
 ○  
  
 ○  
 Cognitive 
function 
test * 6  
 ( MMSE-
J )  
  
 △  
  
 △  
 △  
 △  
 △  
 Adverse 
event  
  
  
 ○  
 ○  
 ○  
 ○  
 ○  
 Use of 
concomitant 
medication  
  
 ○  
 ○  
 ○  
 ○  
 ○  
 ○  

Version_2013.Sept.5 
 
  
 7.           Observation / inspection items and schedule  
 7.1.           Observation and inspection schedu  
 Table - 2 Administration and Inspection Schedule  
 ※ 1    Increase from 3 mg to 5 mg of donepezil hydrochloride .  The week 
before the allowable range.  
 ※ 2 Allow 2 weeks before and after .  
 ※ 3    It is implemented in the reinforcement guidance group by "informed 
consent file" .  (Attachment 2 )  
 * 4 Detailed confirmation of the reason for termination is carried out .  If you do 
not visit the hospital, doctor in charge of clinical research, CRC · pharmacist etc 
investigate until the reason is clarified by telephone etc.  
 ※ 5    It is carried out in advanced Alzheimer's type dementia.  From donepezil 
hydrochloride 5 mg to 10 mg  
 Is increased.  
 * 6 When implementation is possible, at the start of administration and at 12 weeks.  
Furthermore, it is also carried out to the extent possible, at 24 week, 48 week, 
when stopping, and when increasing from 5 mg to 10 mg of donepezil 
hydrochloride .  
  
 7.2.           Observation and inspection items  
 7.2.1.           Subject background  
 Investigate the following items at the start of clinical research and fill in the case 
report.  
 · Subjects Background: gender, date of birth or age, years of education (number of 
years), family member (presence or absence), caregiver background 
(relationship, gender, age, presence or absence of nursing experience, 
watching time / day), requiring long-term care division ( 7 categories) , 
in- home service (presence / absence, type [ free description ] , 
frequency / month)  
 · Consent of examinee and substitutee : date of consent acquisition , subject 
identification code  
 · Disease period: morbidity period, severity FAST Attachment 3) ( 7th step ) , Daily life 
independence of elderly people with dementia Attachment 4) ( 9 ranks) ,  
 Total score of each MMSE-J and each item score, BPSD (delusions, 
hallucinations, excitement, depression · discomfort, anxiety, euphoria, 

Version_2013.Sept.5 
 
excitement / indifference, depression suppression, irritation / instability, 
abnormal behavior)  
 · Complications: Name of the afflicted disease at acquiring consent  
 · Concomitant medication: drug name  
  
 7.2.2.           View  
 When administered after 2 weeks, when 12 weeks, at week 24, at 48 weeks or when 
stopped, and examined the following items during increase from donepezil hydrochloride 
5 mg to 10 mg, to fill in the case report form.  
 1)           Medication compliance  
 The doctor in charge listens to subject compliance and evaluates in the following 
five stages.  
 ① medication 90 % or more ② medication 70 % or more and less than 90 % ③ 
medication 30 % or more and less than 70 %  
 ④ medication 10 % or more and less than 30 %    ⑤ medication taking less than 
10 %  
 2)           Cognitive function test  
 Examine the total score and each item score of MMSE- J .  If practicable, perform 
at the beginning of administration and at 12 weeks.  Furthermore, it is also carried 
out to the extent possible, at 24 week, 48 week, when stopping, and when increasing 
from 5 mg to 10 mg of donepezil hydrochloride .  
 3)           Adverse event  
 9.2 See record of adverse events  
 Four)           Use of concomitant medication  
 Investigate the drug name.  For memantine, we investigate dose and dosing 
period.  
  
  
 8.           End of research , suspension and suspension  
 8.1.           The end of the study  
   Regarding treatment after completion of this clinical study, we will leave it to the 
judgment of the attending physician based on the state of the subject .  
   In the case where the clinical study has been completed in the exemplary medical 
institutions, research responsible physician based on the provisions of the medical 
institution, the length and Tokushukai group Co Ethics Committee schematic and 
terminated that the medical institutions of this clinical study results .  

Version_2013.Sept.5 
 
  
 8.2.           Stop-interruption in the research  
 During this clinical study progresses, if it is forced to change, such as stop-interrupted 
or this clinical study implementation plan of the clinical studies for the following reasons, 
research investigators length of quickly its contents and the reasons of medical 
institutions Contact.  The responsible physician shall promptly report the relevant 
information to the head of the medical institution and the Joint Ethics Committee in 
writing.  
 1)           If drug safety agent used, the critical information on the effectiveness 
obtained  
 2)           When it is judged that it is necessary to change this clinical study 
implementation plan due to the occurrence of serious adverse event  
 3)           When it is judged that recruitment of subjects is difficult and it is obviously 
difficult to achieve the number of cases planned  
  
  
 9.           Adverse events and pregnancy information , other events  
 9.1.           Definition  
   Definitions of adverse events ( AE ) and serious adverse events ( SAE ) are shown 
below.  
 9.1.1.           Adverse event ( AE )  
 The adverse event occurs during this clinical study period to a subject in medicine 
agent is administered, (including abnormal abnormal laboratory values) any 
undesirable or unintended sign is that the event, and this clinical study Whether or 
not there is a cause-and-effect relation does not matter.  Including worsening of the 
original disease, deterioration of complications.  
  
 9.1.2.           Serious adverse events (Serious adverse event: SAE)  
 The serious adverse events, of any medical events that occur when drug agent is 
administered (both doses), refers to the following event.  
 1)         Those that resulted in death  
 2)         Threatening life  
 3)         Those in need of extension of hospitalization or hospitalization / 
treatment period  
 4)         Persistent or serious malfunction  
 5)        Congenital abnormality has come  

Version_2013.Sept.5 
 
 6)        Other serious medical events  
Medical judgment that medical or surgical treatment is required to expose subjects to 
crisis or not to result in any of the above, even if death, life-threatening events, or events 
requiring hospitalization are not occurred Is considered a serious adverse event.  
  
9.2. Record of adverse events          
Clinical research physician is, this clinical study for a new adverse events occurring 
after the start, the event name , serious category (serious, non-serious), severity (mild, 
moderate, severe) , the expression date, treatment , outcome date (or outcome date 
confirmed) , outcome ( recovery, there has been recovery sequelae, light, non-recovery, 
death, unknown) and this clinical study causal relationship between (no relation, related 
Oh might Rukamo , probably related Yes ) In the case report.  
For abnormal variations in clinical laboratory values judged clinically important by a 
doctor in charge of clinical research , fill out the case report along with the basis.  
Regarding the causal relationship between adverse events and this clinical study , fill 
in the case report the basis of the judgment.  
  
 (1)   Causality relationship with this clinical study  
1 ) No relation:  
There is no reasonable causal relation between this drug administration 
and adverse event. (There is no temporal rationality between this drug 
administration and adverse events, or it is thought that the factors of 
patients, such as concomitant drugs and original diseases and 
complications, are greatly influenced by patients.)  
2 ) There may be relevance :  
There is a possibility of a reasonable causal relationship between this 
drug administration and an adverse event. (There is temporal rationality 
between this drug administration and the adverse event expression and 
the possibility of a causal relationship with this drug is considered even 
when considering factors of patients such as concomitant drugs and 
original diseases and complications Conceivable.)  
3 ) Probably related :  
There is a high possibility of a reasonable causal relationship between 
this drug administration and an adverse event. (There is temporal 
rationality between this drug administration and the adverse event 
expression and the possibility of a causal relationship with this drug is 

Version_2013.Sept.5 
 
considered even when considering factors of patients such as concomitant 
drugs and original diseases and complications A similar adverse event is 
admitted by re - administration.  
  
 (2)   Severity of Adverse Events  
1 ) Mild: degree of discomfort, but not affecting normal daily activities  
2 ) Moderate: degree of disruption to normal daily activities due to discomfort  
3 ) High level : incapacity or enough to normal daily activities becomes 
impossible, it was deprived of the activity capacity state  
  
If the severity of an adverse event changes, record the heaviest one.  
  
9.3. Report of serious adverse events          
This clinical study regardless of presence or absence of a causal relationship between, 
if serious adverse events were expressed, investigator physician , after taking prompt 
and appropriate treatment of safety in the first priority, immediately the medical Report 
to the chief of the institution.  
  Brief description of the adverse events, the reason is judged to be severe , the test 
subject identification code , investigator physician , clinical research name and day 1 of 
administration , causality ( drug agents and clinical studies determined steps) shall 
describe . In addition, the adverse event will be notified to the joint clinical research 
institution.  
In addition, prepare a serious adverse event report and contact the clinical research 
secretariat (submission of a copy) . In addition, when unexpected serious adverse events 
related to this clinical study occur, the status and results of response will be announced 
and reported to the Minister of Health, Labor and Welfare, etc.  
  
9.4. Reporting of pregnancy information          
If you perceive the information about the pregnancy is , the study investigators report 
on pregnancy and to create, clinical research secretariat to contact the (Submission of 
copy) . Study principal investigator, and follow-up to the outcome of birth, spontaneous 
abortion, abortion, etc. pregnancy is known, after the proven outcomes of pregnancy, to 
create a report on the outcome of pregnancy, clinical research secretariat to contact the 
(A copy of the Submit) . If the outcome of pregnancy is spontaneous abortion, abortion, 
congenital anomaly, perinatal mortality, treat it as a serious adverse event, in addition 

Version_2013.Sept.5 
 
to a report on the outcome of pregnancy, together with a serious adverse event report 
create.  
  
9.5. Report of other events          
  Excessive amount of administration If you perceive the information related to the 
research principal investigator excessive amount of administration report on the Create, 
clinical research secretariat to contact the (Submission of copy) .  
  
9.6. Expected adverse events          
Please refer to the Aricept ® package insert for the content and rate of occurrence of 
anticipated adverse events .  
9.7. Report to the manufacturer of the drug concerned          
The clinical research secretariat submits the following report ( copy ) to Eisai Co., Ltd., 
the manufacturer of the drug.  
· Serious adverse event report  
· Report on pregnancy and report on pregnancy outcome  
· Report on overdosage  
  
 Ten.      Implementation period  
  Joint Ethics Committee approval after ~ 201 5 years 6 May 3 1 day  
Registration period: Joint Ethics Committee approval later - 2014 years 3 Tsuki 31 
days  
    Patient Out Last : 2015 year 3 Tsuki 3 1 day  
   Statistical analysis: ~ 2015 years 5 May 3 1 day  
   Summary reporting: ~ 2015 years 6 May 3 0 days  
  
 11.      Statistical analysis  
11.1. Analysis target group       
  Obtaining informed consent to the procedure noncompliance with examples, all 
analyzes target excluded from. Aricept ® medication continuation rate , Aricept ® 
medication discontinuation at the time of the reason for the analysis of, the full analysis 
( Full Analysis Set : FAS ) and the target group which is adapted to study 
implementation plan ( Per Protocol Set : PPS ) providing a . FAS is also a one-time study 
drug is administered has been a subject of the population. PPS shall be a group excluding 
cases of inappropriate selection / exclusion criteria from FAS and examples of use of 

Version_2013.Sept.5 
 
prohibited concomitant medications . In addition, safety on the analysis is , even study 
drug was administered once a subject of the population.  
  
11.2. Analysis of main evaluation items       
  48 weeks Aricept between ® medication continuation rate the due to "informed 
consent file" strengthening leadership group and the normal guidance in group 2 
performs a comparison of rates between the groups (two-tailed test, the p-= 0.05 , with 
respect to the following statistical tests Similarly). We also compare intergroups 
independently in the medication continuation rate for each Visit [ 2 nd week, 12 th week, 
24 th week ] .  
  Aricept ® medication discontinuation during aggregates the reason of, between the 
groups stop reason to compare .  
  
11.3. Secondary assessment analysis of the item       
In each group, Aricept ® medication continues to affect the factors by logistic 
regression analysis to analyze ( Factors, 6.2 2 ) reference ). In addition, we compare the 
influence of factors among groups (points which are multiple selections are not 
considered) .  
  
11.4. Analysis of safety       
Subjects who are included in this clinical study and whose test drugs have been 
administered at least once are subject to safety analysis.  
All adverse events are indicated and serious adverse events are separately counted. 
Drugs agents adverse events observed after administration administration group by type 
of adverse events for each, categorical adverse events was calculated expression rate, a 
comparison between groups (adverse events by type, categorical statistical analysis 
Performed by the data center prior to) .  
11.5.        Other  
In addition to the predetermined analysis plan , additional exploratory analysis is 
performed as necessary, such as comparison between transition patterns of the clinical 
state after incorporation into the study , as necessary.  
  
12. Number of target cases and setting basis      
Total 150 cases  
  
[ Rationale for setting ]  

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In one year's observation results 3) , which showed the influence on the continuation 
rate of the medication instruction class (Aricept class) in patients with Alzheimer's type 
dementia 3) , the continuation rate of the group not taking medication instruction was 
0.49 ( 95% confidence limit 0.36 - 0.61 ), but in the advising instruction classroom the 
continuation rate was 0.73 ( 95% confidence limit 0.60 to 0.85 ). Point estimation of these 
continuation rate values the group to the detectability 0. 8 as when determining the 
number of necessary cases, 1 group 64 becomes example. Table 3 shows representative 
values within the confidence limits of the continuity rate of each group and the number 
of necessary cases for the point estimate. Based on the consideration of the number of 
these necessary cases and the number of new patients with Alzheimer type dementia in 
the Tokushu Association Hospital group, the number of target cases was set to 150 cases .  
  
Table - 3 Calculation of the number of necessary examples in the interval estimation 
range of the medication continuation rate of non-medication / guidance group 
(detection power = 0.8 )  
  
  
Medication instruction group  
  
  
 0.6 
 0.65 
0.7 
0.73 
0.75 
 0.8 
0.85 
Clothes  
agents  
non  
 finger  
Guiding 
 group  
0.35 
 62 
 43 
 31 
 26 
 
twenty 
four 
 18 
 14 
 0.4 
 97 
 62 
 42 
 35 
 31 
 
twenty 
three 
 17 
0.45 
 173 
 96 
 61 
 48 
 41 
 29 
 
twenty 
two 
0.49 
321 
150 
 85 
 64 
 54 
 37 
 26 
 0.5 
 388 
 170 
 93 
 70 
 58 
 39 
 27 
 0.55 
1534 
376 
 163 
 111 
 89 
 54 
 36 
 0.6 
 - 
1471 
356 
 206 
 152 
 82 
 49 
  
  
13. Ethical matters      
13.1. Rules to Observe       
  This all persons involved in the clinical study, "World Medical Association 
Declaration of Helsinki" ( 2008 year 10 May revised edition) and "Ethical Guidelines for 

Version_2013.Sept.5 
 
Clinical Research" (ending 20 years the Ministry of Health, Labor and Welfare 
Notification No. 415 in accordance with the issue).  
  
13.2. Creation and revision of explanatory documents / consent documents       
The research responsible doctor prepares agreement documents etc. to be used to 
obtain consent to participate in this clinical study from subjects and substitutes, and 
revises them if necessary. An agreement explanation document / agreement document 
that has been created or revised shall be used after review by the Joint Ethics Committee 
in advance .  
The consent document shall include the following items. However, do not describe such 
as to induce subjects intentionally.  
 1)        Participation in this clinical study is optional  
 2)        Do not accept disadvantageous response by not agreeing to participate in this 
clinical study  
 3)        Subject or substitute etc shall be able to retract the consent document given by 
himself without being disadvantaged at any time  
 Four)        Reason for being selected as a subject  
 Five)        Significance, purpose, method and duration of this clinical study  
 6)        Research responsibility doctor the name of such and job title  
 7)        It predicted the clinical study result of this clinical study expected benefit from 
participating in and Possible risks and entail unpleasant condition, the clinical study 
correspondence after completion  
 8)        Subject and by the hope of such Daidaku person, personal information 
protection and of other subjects this clinical study carried out of in that there is no 
hindrance to the range, this clinical study plan and this clinical study is possible to 
obtain or view the documentation on how to What you can do  
 9)        The possibility of providing the results of this clinical research to other agencies 
after judging by the Joint Ethics Committee about the handling of personal 
information, the name of the institution of the providing destination, reasonable use 
purpose at the destination, etc.  
 10)    This clinical study that there is a possibility that the intellectual property rights, 
such as is produced by the achievements of and in the case of intellectual property 
rights or the like has been produced of the right attribution  
 11)    The results of this clinical study may be published after making it impossible to 
identify subjects  
 12)    Method of storage and use of samples and storage period  

Version_2013.Sept.5 
 
13) this clinical research funding sources involved in, conflict of interest that may occur 
and research investigator relationships with related organizations such as    
14) Presence or absence of compensation accompanying this clinical study    
15) Information on inquiries, contact information of contacts such as complaints    
  
13.3. Ethics committee review       
Prior to the implementation of this clinical study , the Joint Ethics Committee , at the 
Joint Ethics Committee, the content of the clinical study implementation plan, consent 
explanation document, case report, other materials required by the Joint Ethics 
Committee, ethical, scientific and medical From the viewpoint of validity and 
investigative responsibility doctor 's eligibility etc, conduct the examination after the 
Joint Ethics Committee approves the implementation of clinical research .  
In addition, this clinical study throughout the period, the document which is the 
subject of a joint ethics committee of examination is added, updated or revised if it is 
(minor add, update or revised except for) , and year 1 times, the progress of clinical 
research as well as the occurrence of adverse events in with are also intended to be 
subject to review in the same way.  
  
13.4. Audit       
  If the audit by the Joint Ethics Committee and regulatory agencies is conducted 
before, during or after the completion of this clinical study , it shall be accepted.  
  
  
14. Money Payment and Health Damage Compensation , Funding Source for Clinical 
Studies      
14.1. Medical expenses during this clinical study       
This clinical study for the treatment to be performed on the subject during the 
participation period , is subject to the health insurance subject to join, the co-payment 
amount is the subject of the burden.  
  
14.2. Payment of money to subjects       
This clinical research by which to participate in the research, there is no possibility to 
receive the burden costs.  
  

Version_2013.Sept.5 
 
14.3. Funding sources and conflicts of interest in clinical research       
The source of contribution of this clinical research fund is Eisai Co. , Ltd. In addition, 
this clinical for the conflict of interest situation of the study investigator, line the 
information disclosure required in the Conflict of Interest Committee Joint Ethics 
Committee intends .  
  
14.4. Compensation       
If health damage occurs in this clinical study , health insurance will be used for 
treatment costs. To prepare for compensation and liability incurred in this clinical study, 
research researcher and research sharing doctor join clinical research insurance.  
  
  
15. About personal information and other rights      
 15.1.       Protection of privacy  
Joint Ethics Committee this ongoing clinical studies or after the end, documents 
related to the implementation, serious adverse events reports and case report form the 
investigation of such Kotogaa that is, this time, the contents of which can identify an 
individual offer It is not done .  
In addition, those who participate in this clinical research shall not leak information 
on the subject's privacy, which was learned by viewing the source material, to third 
parties .  
  
 15.2.       By signing a consent form, you will approve browsing  
This clinical study participants of, materials , etc. to view it is that, for these officials 
imposed a duty to protect the secrets are . Patients By signing this consent document, 
approved the view that the made .  
  
15.3. On cases where intellectual property rights etc. arise       
This clinical study if the from the results intellectual property rights or the like is 
generated, the rights Eisai Co., Ltd. belong to, this clinical study to participate in the 
participating institutions, such as research investigators, and the patient is not to have 
that right.  
  
15.4. About viewing original material       
This clinical study material about how the subject is hope and if, personal information 
protection and of other subjects this clinical study carried out of in that there is no 

Version_2013.Sept.5 
 
hindrance to the range, be obtained or browsing is possible . However, it desires to 
browse and since the protection of personal information described above , such as for a 
variety of procedures or clinical studies practitioner and clinical studies conference of 
the exemplary tissue lines the Ukoto . As a result, there are cases in which it takes time 
to present the material and only a part of the desired material is presented.  
  
  
16. Save the document      
16.1. Documents anonymity of       
Materials concerning this clinical study of all subjects who got consent shall be specified 
by concatenable anonymous subject identification code given at the time of registration . 
The correspondence table specifying the subject and the subject identification code is 
strictly managed by the research responsible doctor.  
  
16.2. Storage of documents       
  Essential documents related to the implementation of this clinical study (a copy of 
the application document, a notice from the hospital director, a copy of various 
applications and reports, a copy of the subject identification code list, consent form, case 
report etc, Documents or records necessary to ensure sexuality, etc.). Also, when 
discarding materials , they shall be made anonymous. Researchers should take steps to 
prevent these documents from being accidentally or promptly destroyed.  
Storage location : Each medical institution   
Responsible Officer: Research Researcher  
Retention period: 5 years after clinical study is over  
  
  
17. Publication of research results      
The results of this clinical study will be published as a paper or conference 
presentation. Also, at the time of publication, personal information of the subject shall 
not be leaked to a third party.  
  
  
18. Clinical research implementation system      
1) Clinical research representative  

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Kamei 
Toritome  
Shonan 
Fujisawa 
virtue 
Zhuzhou 
meeting hospital  
Nerve within 
the 
Department 
of  
Hospital 
length  
0466 - 35 - 1177  
[Operation] We will conduct this clinical study and oversee the whole clinical research.  
  
2) Collaborators  
Satoshi Takahashi Medical Law Humanities Association Tokyo Headquarters Drug 
Delegation  
[Operation] Perform adjustment work of participating facilities.  
  
3 ) Statistical analysis director / assignment manager  
Toru Uoi Director Aurolink Co., Ltd.  
[Operation] Perform statistical analysis and prepare analysis plan / analysis report. 
Specification design of the allocation table , creation / storage of the allocation table .  
  
4 ) Data center  
AUROLINK Inc.  
Yubinbango 101-0054 Nishikicho Kanda, Chiyoda-ku, Tokyo 3-21 Chiyoda Platform 
Square 1186  
  TEL : 03 - 6666 - 0018 FAX : 0 3 - 6666 - 0018    
[Operation] Implement data management.  
  
5 ) Clinical research secretariat  
  Future Medical Research Center, Inc.  
  Hiroyoshi Yamaji (Representative of the Research Bureau)  
Yubinbango 102 - 0083 Kojimachi, Chiyoda-ku, Tokyo 1-8-7 Eminabiru 3 floor   
  TEL : 03 - 3263 - 4801 FAX : 0 3 - 3263 - 4802    
[Operation] We perform general support activities of this clinical research , and central 
registration / assignment work .  
  
6 ) implementation facilities and research officer  
See Attachment 1  
  
  

Version_2013.Sept.5 
 
19. References      
 1)          Cummings JL. Alzheimer's disease. N Engl J Med. 2004 Jul 1; 351 (1): 56-67.  
 2)          Dement Geriatr Cogn Disord. Homma A , Imai Y, Tago H, et al. Long-term 
safety and efficacy of donepezil in patients with severe Alzheimer's disease: results 
from a 52 - week, open - label, multicenter, extension study in . 2009 ; 27 (3 ) : 232- 
23 9 .  
 3)          Watanabe N , Yamamura K , Suzuki Y, et al. Pharmacist-based Donepezil 
Outpatient Consultation Service to improve medication persistence. Patient Prefer 
Adherence. 2012 ; 6 : 605-611.  
 Four)          Keiko Yamamura Supervised Aricept Class Text  
Available from: http://www.aricept.jp/helpful/art_classroom.html  
 Five)          Akira Honma . Alzheimer's disease patients ADL respect of donepezil 
hydrochloride effective and discontinuations prognosis (Aricept special survey) . 
Geriatr Med. 2009 ; 47 ( 8 ): 1047-1059.  
 6)          Akira Honma . Advanced Alzheimer's disease donepezil hydrochloride for 10 
mg / safety and efficacy of daily administration (Aricept (R) specific-use results 
surveys) . Geriatr Med. 2013 ; 51 ( 3 ): 309-342.