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Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Alzheimer’s Disease Assessment
Scale – Cognitive (ADAS – Cog)
List - 1
Compound: MK-8931
Protocol: 019
Visit 1
Visit 9
Train
ing
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Alzheimer’s Disease Assessment Scale – Cognitive (ADAS – Cog)
Administration and Scoring Guidelines
INTRODUCTION:
Description
The subtests of the ADAS-Cog should be given in the order indicated. Following the objective testing, subjective clinical ratings of language ability and the ability to remember subtest instructions are recorded by the tester. These ratings are based on information gathered during the interview.
The ADAS-Cog is not a timed test. Subtests should be administered so that thesession moves smoothly and quickly, though the subject should not feel pressured to respond rapidly.
The overarching principle is to elicit the best possible performance from the subject, while closely following the administration and scoring guidelines outlined here and in tester training.
Feedback to the subject should be neutral and, usually, should not indicate whether or not the response was correct. Comments such as “That’s fi ne” or “You’re doing well” are appropriate as long as the subject is trying.
GENERAL GUIDELINES:
For each of the subtests of the ADAS–Cog, the set-up will be as follows:
The fi rst page (left facing page) will contain general administration guidelines.
The Case Report Form (right facing page) will contain the instructions to the subject (in bold).
Record subjects’ responses verbatim on the Case Report Form, where instructed to do so.
For each subtest place a tick mark in the appropriate boxes to indicate the subject’s response. If any subtest is not completed, the subtest cannot be scored. Indicate this by entering a “-1” in both the # Correct and the # Incorrect Total Boxes (or in the # Recalled and # Not Recalled depending on the subtest). This will result in missing data, however, so testers must make every effort to encourage subjects to continue and do the best that they can.
Testers need to be familiar with all instructions and scoring conventions as outlined here and in tester training before administering any subtests to the subject.
Train
ing
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Initial Conversation:
General Guidelines
At the start of the test session, before formal testing begins, engage the subject in a short, open-ended conversation about neutral topics (e.g., the weather, what the subject likes to do for exercise or entertainment, how the subject’s appetite has been lately).
This conversation has multiple purposes: • It helps to put the subject at ease before testing begins and builds rapport. • It gives the tester an opportunity to make an initial assessment of the subject’s expressive and receptive speech (i.e., how well the subject can use and understand language). This conversation, as well as the subject's speech throughout the ADAS-Cog testing, will be used to conduct the three clinical ratings of the subject's language ability.
Initial Conversation Notes on Page 3 must support the scoring of these clinical
ratings.
Train
ing
I confi rm this information is accurate. Staff Initials: Date:
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Compound Protocol Visit Randomization No.Screening No. (Site - Sequence No.)
__ __ __ __-__ __ __ __ __ __ __ __ __ __ __
AN EFFICACY AND SAFETY TRIAL OF MK-8931 IN SUBJECTS WITH PRODROMAL AD
MK-8931 019
A D A S - C O G I N I T I A L C O N V E R S AT I O N N O T E S
Possible topics include appetite, sleep, exercise or other areas.
1) Spoken Language
2) Word Finding
3) Comprehension
Testing Comments:
Was evaluation performed on visit date? or specify date: _______________DD-Mon-YYYY
Train
ing
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Word Recall:
General Guidelines
MATERIALS:
Use the appropriate Word Recall list for this visit as indicated on the study worksheet (facing page).
ADMINISTRATION:
On this subtest, the subject is given three trials to learn a list of 10 high-frequency, high-imagery nouns. The 10 words are printed in block letters on white cards and are presented one at a time. If the subject cannot read a word or is slow, the tester can say the word out loud and have the subject repeat it. In some cases (e.g., anopsia), the tester may have to say all of the words and have the subject repeat them. Regardless, make sure the subject looks at each word while repeating it.
Note: The presentation of each word is not timed.
Note: Encouragement can be given if the subject is nervous or appears to be giving
up.
Record the subject’s responses on the study worksheet.
SCORING:
For each trial, indicate the number of words recalled and not recalled. If a trial is completed as intended, then the total number recalled plus the total number not recalled must equal 10. Enter a “ -1” in both the # recalled (correct) and the # not recalled (incorrect) boxes if the trial is not completed by the subject.
Train
ing
I confi rm this information is accurate. Staff Initials: Date:
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Compound Protocol Visit Randomization No.Screening No. (Site - Sequence No.)
__ __ __ __-__ __ __ __ __ __ __ __ __ __ __
AN EFFICACY AND SAFETY TRIAL OF MK-8931 IN SUBJECTS WITH PRODROMAL AD
MK-8931 019
“Good, now tell me all of the words you remember that
were on the list.”
“Any others?”
“I am going to show you some words printed on these
white cards one at a time. Please read each word out
loud and try to remember it, because later, I will ask
you to try to remember all of the words I have shown
you. Ready, read the word and try to remember it.”
Trial 1: At the start of the fi rst trial, the tester gives instruction similar to the following:
1. WORD RECALL (List-1)
TRIAL 3
# RECALLED (Correct)
# NOT RECALLED(Incorrect)Reminder: count all unchecked boxes.
TRIAL 1 TRIAL 2
# RECALLED (Correct)
# NOT RECALLED(Incorrect)Reminder count all unchecked boxes.
# RECALLED (Correct)
# NOT RECALLED(Incorrect)Reminder: count all unchecked boxes.
ADASC1-12
Shore
Letter
Arm
Cabin
Pole
Ticket
Engine
Grass
Butter
Queen
Pole
Letter
Butter
Queen
Arm
Shore
Grass
Cabin
Ticket
Engine
Butter
Arm
Shore
Letter
Queen
Cabin
Pole
Ticket
Grass
Engine
DD-Mon-YYYY
“Now, I am going to show you that same list again.
Read each word out loud and try to remember it.”
After the presentation, the tester asks the subject to try to recall as many of the words as possible by saying:
Once the subject appears to have recalled as many words as possible, the tester can prompt with:
After presentation of the list is completed say:“Good, now tell me all of the words you remember that
were on the list.”
Time Ended :_____________________
As necessary, the tester can prompt with: “Read it out loud and try to remember it.”
Trials 2 and 3:
Say to the subject:
(24-hour clock)
A L Z H E I M E R ’ S D I S E A S E A S S E S S M E N T S C A L E – C O G N I T I V E
Specify completion date: ___________________
Train
ing
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Commands:
General Guidelines
MATERIALS:
A pencil, a watch and a card from the ADAS-Cog kit
ADMINISTRATION:
This subtest is designed to assess receptive speech. The subject is asked to carry out fi ve separate commands with one to fi ve steps per command.
All commands should be given to every subject. Speak in a clear voice with adequate volume. Each command should be read once. If the subject makes an error and recognizes that an error was made, the examiner says the entire command one more time. The subject may recognize that an error was made by requesting another attempt, stating that their fi rst attempt was not correct, or indicating that they are not satisfi ed with their fi rst attempt. If the subject does not recognize that they made an error, the examiner does not repeat the command.
If the subject has hearing or attentional difficulties, orient them prior to each command by saying: “Ready?” or “Now, I want you to…” prior to giving the command again.
Commands 3 and 4 require the use of stimulus materials (a pencil, a watch, and a card) that are placed on the table directly in front of the subject, in the specifi c order indicated on the facing page. There should be no other items (pens, paper, etc.) near these subtest materials during the commands, and the subtest materials should be removed before giving the last command (“Tap each shoulder…”).
SCORING:
Each command is scored as a whole (i.e., no partial credit is given). All components must be correct for the response to be scored as correct. Check each command performed correctly on the right facing page.
For this subtest, indicate the total number correct and the total number incorrect. If the subtest is completed as intended, then the total number correct plus the total number incorrect must equal 5. Enter a “ -1” in both the # correct and the # incorrect boxes if the subtest is not completed by the subject.
Train
ing
I confi rm this information is accurate. Staff Initials: Date:
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Compound Protocol Visit Randomization No.Screening No. (Site - Sequence No.)
__ __ __ __-__ __ __ __ __ __ __ __ __ __ __
AN EFFICACY AND SAFETY TRIAL OF MK-8931 IN SUBJECTS WITH PRODROMAL AD
MK-8931 019
“Now I am going to ask you to do a few things. First,…”
ALZHEIMER’S DISEASE ASSESSMENT SCALE – COGNITIVE (CONTINUED)
ADASC2-12
2. COMMANDS
Correct Incorrect “Make a fi st.”
From the patient’s left to right, line up a pencil, watch, and cardon the table, Say:
Remove the pencil, watch, and card from the table. Say:
“Tap each shoulder twice with two fi ngers, keeping your
eyes shut.”
“Put the watch on the other side of the pencil, then turn
over the card.”
“Put the pencil on top of the card, then put it back.”
“Point to the ceiling, then to the fl oor.”
Correct Incorrect
TOTAL # CORRECT:
TOTAL # INCORRECT:
Correct Incorrect
Correct Incorrect
Correct Incorrect
Train
ing
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Constructional Praxis:
General Guidelines
MATERIALS:
Worksheets containing the four geometric shapes and a pencil with an eraser.
ADMINISTRATION:
The tester should give the subject a pencil with an eraser and present each fi gure one at a time. The fi gures should be presented in the following order: Circle, Overlapping Rectangles, Diamond, Cube.
The subject is allowed to spontaneously erase and correct (without prompting from the tester). After the subject completes a drawing, a second attempt is allowed if the subject asks or indicates a problem with his/her drawing. The subject is allowed up to two attempts for each fi gure. If the subject indicates that the reproduction is poor after the fi rst attempt, query if they would like another try. When two attempts are made, ask the subject to indicate which one is best, and then score that attempt. The chosen fi gure needs to be clearly identifi ed on the page. If the subject cannot reproduce the fi gure in two attempts, the tester should go on to the next item.
If the subject draws on top of the printed fi gure, count this as one attempt and indicate that they should try again on an empty part of the page.
Note: When providing instructions, do not provide the name of the actual fi gure.
SCORING:
A drawing should be scored as correct if the subject has reproduced all of the essential geometric features of the original. Changes in size do not count as errors. Small gaps between lines do not indicate an error, as long as the fi gure has been correctly reproduced.
CIRCLE: A closed curved fi gure.
OVERLAPPING RECTANGLES:
The two fi gures must be four-sided and overlap in a similar manner to the presented stimulus.
DIAMOND:
The fi gure must be four-sided, oriented so that the points are at the top and bottom, and the sides are of approximately equal length (i.e., longest side is not >1.5 times the length of the shortest side).
CUBE:
The fi gure is 3-dimensional, with the front face in the correct orientation, and internal lines drawn correctly between corners. Opposite faces of the cube should be approximately parallel.
Examples of correct and incorrect drawings are shown on the next page.
For each fi gure, check “CORRECT”, “INCORRECT,” or “NO RECOGNIZABLE ATTEMPT.” A “RECOGNIZABLE ATTEMPT” means that the subject drew at least one line or section that reasonably represents a side or portion of the shape.
Train
ing
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
OVERLAPPING RECTANGLES
E X A M P L E S O F C O R R E C T A N D I N C O R R E C T D R A W I N G S :
Correct
CUBE
Incorrect
Correct
DIAMOND
Incorrect
Correct Incorrect
CIRCLES
Correct Incorrect
Train
ing
I confi rm this information is accurate. Staff Initials: Date:
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Compound Protocol Visit Randomization No.Screening No. (Site - Sequence No.)
__ __ __ __-__ __ __ __ __ __ __ __ __ __ __
AN EFFICACY AND SAFETY TRIAL OF MK-8931 IN SUBJECTS WITH PRODROMAL AD
MK-8931 019
ADASC3-12
3. Constructional Praxis
To begin testing, say: “On this piece of paper is a shape. Try to draw another one that looks just
like this, somewhere on the page.”
Note: The Constructional Praxis Total Score will be calculated, so there is no need to note it on the worksheet
Circle:
A closed curved fi gure.
Correct
Incorrect (at least one side/section of shape drawn).
No recognizable attempt at drawing any side/section of shape
Two overlapping rectangles:
Each shape must be four-sided and overlap must be similar to presented diagram.
Correct
Incorrect (at least one side/section of shape drawn).
No recognizable attempt at drawing any side/section of shape
Rhombus (Diamond):
Shape must be four-sided, oriented so that the points are at the top and bottom, and the sides approximately equal in length (i.e., longest side is not > 1.5 times the length of the shortest side).
Correct
Incorrect (at least one side/section of shape drawn).
No recognizable attempt at drawing any side/section of shape
Cube:
The shape is 3-dimensional, with front face in the correct orientation, and internal lines drawn correctly between corners. Opposite sides of faces should be approximately parallel.
Correct
Incorrect (at least one side/section of shape drawn)
No recognizable attempt at drawing any side/section of shape
ALZHEIMER’S DISEASE ASSESSMENT SCALE – COGNITIVE (CONTINUED)
Train
ing
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Delayed Word Recall:
General Guidelines
MATERIALS:
None
ADMINISTRATION:
Delayed free recall of the word list should be attempted approximately 5 minutes after trial 3 of the Word Recall Task. The interval should be fi lled by the ADAS Commands and Constructional Praxis items. If these tasks are completed in less than 5 minutes, the delay interval should be fi lled with the continuation of the interview to assess language, concentration, etc. before beginning delayed word recall.
Discontinue when there is no further response or if the subject indicates that he/she cannot recall any more words after prompting.
SCORING:
Indicate the number of words recalled and not recalled. The total number recalled plus the total number not recalled must equal 10. Enter a “ -1” in both the # recalled (correct) and the # not recalled (incorrect) boxes if the trial is not completed by the subject.
Train
ing
I confi rm this information is accurate. Staff Initials: Date:
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Compound Protocol Visit Randomization No.Screening No. (Site - Sequence No.)
__ __ __ __-__ __ __ __ __ __ __ __ __ __ __
AN EFFICACY AND SAFETY TRIAL OF MK-8931 IN SUBJECTS WITH PRODROMAL AD
MK-8931 019
YES NO
4. DELAYED WORD RECALL
Butter
Arm
Shore
Letter
Queen
Cabin
Pole
Ticket
Grass
Engine
TOTAL # CORRECT
TOTAL # INCORRECT
“A few minutes ago I had you read some words printed
on these cards (point to word list). Tell me all of the
words you can remember that were on the cards.”
Prompt with: “Any others?” as necessary.
Time Began: ________________ (24-Hour Clock)
ADASC4-12
ALZHEIMER’S DISEASE ASSESSMENT SCALE – COGNITIVE (CONTINUED)
Train
ing
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Naming Objects and Fingers:
General Guidelines
MATERIALS: 12 objects provided in the ADAS-Cog kit
ADMINISTRATION:
In this subtest, the subject is asked to name 12 randomly presented real objects and is then asked to name the fi ngers on his/her dominant hand (i.e., thumb, index fi nger [pointer/forefi nger], middle fi nger, ring fi nger, and pinky/little fi nger). The objects should be presented in random order. Show the objects to the subject but do not allow the subject to touch or handle the objects.
On the facing page, record the response given by the patient in the space provided
next to the corresponding object or fi nger’s name.
SCORING:
Check each object and fi nger named correctly. The hardest part of scoring the naming subtest is determination of the range of correct responses based on the subject’s cultural and geographical background. A response other than the name given on the response form should be scored as correct if it is a name that would be used by a cognitively healthy person with the same cultural background as the subject. For example, in some parts of the world, the Mask might be called a “false face”, the Wallet might be called a “billfold”, or the Harmonica might be called a “mouth organ”. Descriptions of the object, and semantic or phonemic paraphasic errors should not be scored as correct.
EXAMPLES OF INCORRECT RESPONSES: “listening thing” for Stethoscope, “cutter” for Scissors, or “prongs” for Tongs.
For this subtest, indicate the total number correct and the total number incorrect. If the subtest is completed as intended, then the total number correct plus the total number incorrect must equal 17. Enter a “ -1” in both the # correct and the # incorrect boxes if the subtest is not completed by the subject.Tra
inin
g
I confi rm this information is accurate. Staff Initials: Date:
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Compound Protocol Visit Randomization No.Screening No. (Site - Sequence No.)
__ __ __ __-__ __ __ __ __ __ __ __ __ __ __
AN EFFICACY AND SAFETY TRIAL OF MK-8931 IN SUBJECTS WITH PRODROMAL AD
MK-8931 019
OBJECTS
Flower (Clue: grows in a garden) Correct Incorrect Bed (Clue: used for sleeping in) Correct Incorrect Whistle (Clue: makes a sound when you blow on it) Correct Incorrect Pencil (Clue: used for writing) Correct Incorrect Rattle (Clue: a baby’s toy) Correct Incorrect Mask (Clue: hides your face) Correct Incorrect Scissors (Clue: cuts paper) Correct Incorrect Comb (Clue: used on hair) Correct Incorrect Wallet (Clue: holds your money) Correct Incorrect Harmonica (Clue: a musical instrument) Correct Incorrect Stethoscope (Clue: doctor uses it to listen to your heart) Correct Incorrect Tongs (Clue: picks up food) Correct Incorrect
FINGERS
Thumb Correct Incorrect Index/forefi nger/pointer Correct Incorrect Middle Correct Incorrect Ring Correct Incorrect Pinky/little Correct Incorrect
TOTAL # CORRECT:
TOTAL # INCORRECT:
ADASC5-12
If the subject does not respond, or makes an error, the tester must give the corresponding clue for that item. If the subject still does not respond or makes an error, go to the next object.
“Now I am going to show you some objects. I want you
to tell me what their names are. What is this called?” (present object)
“What is this called?” or “What is the name of this thing?”
“Yes, that’s what it does, but what is its name?”
Give the subject instructions similar to the following:
Continue to present objects in random order. The fi rst question about each object should be:
If the subject responds with the object’s function say:
“Now I am going to point to a part of your hand and I want
you to tell me what it’s called. What is this?”
“What is another name for this fi nger?”
Give the subject instructions similar to the following:
For the 4 fi ngers, if a query isnecessary, say:
5. NAMING OBJECTS AND FINGERS
Objects:
Fingers:
ALZHEIMER’S DISEASE ASSESSMENT SCALE – COGNITIVE (CONTINUED)
Train
ing
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Ideational Praxis:
General Guidelines
MATERIALS:
A standard envelope, a standard unlined sheet of paper, and a pencil with eraser
ADMINISTRATION:
Place the envelope, the sheet of paper, and the pencil in front of the subject.
If the subject forgets part of the subtest, or is having difficulty, the tester must repeat the instruction for the component of the subtest on which the subject is having difficulty. For example, if the subject stops after folding the paper and putting it into the envelope, the tester should give one reminder on the next component: “Now seal the envelope.” If the subject cannot do this part, move on and give one reminder for the next component: “Now
address the letter to yourself.” Only one additional reminder may be given for each component of the subtest. If the subject performs a step incorrectly after prompting, the tester must not correct the error or assist in any way.
Have the subject place an “X” on the envelope to indicate where the stamp goes. If the subject merely points to where the stamp goes, the tester should write the “X” on the envelope.
SCORING:
Check each component of the subtest correctly completed on the right facing page and indicate the total number correct and the total number incorrect. Any address which would enable a postal worker to deliver the envelope is considered correct.
If the subtest is completed as intended, then the total number correct plus the total number incorrect must equal 5. Enter a “ -1” in both the # correct and the # incorrect boxes if the subtest is not completed by the subject.Tra
inin
g
I confi rm this information is accurate. Staff Initials: Date:
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Compound Protocol Visit Randomization No.Screening No. (Site - Sequence No.)
__ __ __ __-__ __ __ __ __ __ __ __ __ __ __
AN EFFICACY AND SAFETY TRIAL OF MK-8931 IN SUBJECTS WITH PRODROMAL AD
MK-8931 019
6. IDEATIONAL PRAXIS
“I want you to pretend you have written yourself a letter. Take
this piece of paper, fold it so that it will fi t into the
envelope, and then put it into the envelope. Then, seal the
envelope, address the envelope to yourself, and show me
where the stamp goes.”
TOTAL # CORRECT:
TOTAL # INCORRECT:
ADASC6-12
Fold a letter Correct Incorrect
Put letter in envelope Correct Incorrect
Seal envelope Correct Incorrect
Address envelope Correct Incorrect
Place stamp on the envelope Correct Incorrect
ALZHEIMER’S DISEASE ASSESSMENT SCALE – COGNITIVE (CONTINUED)
Train
ing
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Orientation:
General Guidelines
MATERIALS:
None.
ADMINISTRATION:
Ask the subject each question on the next page one at a time. One restatement of each question is allowed (e.g., if subject confuses day and date). Make sure no watches, clocks, calendars, etc. are visible to the subject.
For the question pertaining to location, do not provide a clue about the location with questions such as: “What’s the name of this hospital?”
On the facing page, record the response given by the patient in the space provided
next to the corresponding question.
SCORING:
Check each item answered correctly on the right facing page. Guidelines regarding the range of appropriate correct responses and information about the seasons are provided below.
Full Name: Must be exact (only fi rst and last names are needed)
Month: Must be exact
Date: ± 1 day
Year: Must be exact
Day of week: Must be exact
Season: Within one week prior to onset or within two weeks of termination
Time: ± 1 hour
Place: Partial name acceptable (e.g., name of hospital, clinic or professional building), but generic terms are not acceptable (e.g., “hospital”, or “doctor’s office”).
Indicate the total number correct and the total number incorrect. If the subtest is completed as intended, then the total number correct plus the total number incorrect must equal 8. Enter a “ -1” in both the # correct and the # incorrect boxes if the subtest is not completed by the subject.
Train
ing
I confi rm this information is accurate. Staff Initials: Date:
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Compound Protocol Visit Randomization No.Screening No. (Site - Sequence No.)
__ __ __ __-__ __ __ __ __ __ __ __ __ __ __
AN EFFICACY AND SAFETY TRIAL OF MK-8931 IN SUBJECTS WITH PRODROMAL AD
MK-8931 019
1. Person “Can you tell me your full name?” Correct Incorrect
2. Day of the “Can you tell me what day of the Correct Incorrect Week week it is?”
3. Date “What is today’s date?” Correct Incorrect
4. Month “What month are we in?” Correct Incorrect
5. Year “What year are we in?” Correct Incorrect
6. Season “What season of the year is it?” Correct Incorrect
7. Time of Day “Without looking at your watch, Correct Incorrect can you tell me what time it is?”
8. Place “What is the name of the place Correct Incorrect where we are now?”
Total # Correct:
Total # Incorrect:
7. Orientation
COMPONENT QUESTION CORRECT INCORRECT
ADASC7-12
The tester asks the following questions, word for word, in this order:
ALZHEIMER’S DISEASE ASSESSMENT SCALE – COGNITIVE (CONTINUED)
Train
ing
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Word Recognition:
General Guidelines
MATERIALS:
Use the appropriate Word Recognition list for each visit as indicated on the study worksheet (next page).
ADMINISTRATION:
This subtest is presented sequentially in two parts, with the Learning Trial coming fi rst and the Recognition Trial coming second. In the Learning Trial, the subject is given one trial to learn a list of 12 words. In the Recognition Trial, the 12 words presented in the Learning Trial are mixed with 12 new words and the subject is asked to decide, for each word, whether or not it was one of the 12 original words.
In case of errors in reading, or no response on the Learning Trial, the tester reads the word for the subject and has them repeat it afterwards. The subject should look at each word card while repeating it.
On the Recognition Trial, the subject must be given the full reminder for the fi rst two words that are presented.
Note: The presentation of each word is not timed.
After the fi rst two words, if the subject does not remember the subtest instructions (e.g., reads the word rather than responding yes or no), the tester should repeat or rephrase the entire question and check “Reminder” indicating that the subject had to be reminded of the subtest instructions.
Likewise, if the subject appears to have fallen into a response set (i.e., saying “Yes” to every word or saying “No” to every word), the subtest instructions should be repeated. Place a checkmark in the “Reminder” column at each point when a reminder is given.
SCORING:
The tester should check the “yes” or “no” response made by the subject for each of the target and distractor items.
The number correct is equal to the number of checked, unshaded boxes in the ‘Yes’ column plus the number of checked, unshaded boxes in the ‘No’ column. The number incorrect is equal to the number of checked, shaded boxes in the ‘Yes’ column plus the number of checked, shaded boxes in the ‘No’ column.
The maximum number correct is 24 and the maximum number incorrect is also 24. If this subtest is completed as intended, then the total number correct plus the total number incorrect must equal 24.
Add the total number of checkmarks in the ‘Reminder Given’ column and record this number in the ‘Reminders’ box. The fi rst two reminders are mandatory and should not be counted towards the total. If the Word Recognition subtest was not completed or not attempted, then this item must not be scored. Instead, enter a “ -1” in both the # correct and the # incorrect boxes if the subtest is not completed by the subject.
Train
ing
I confi rm this information is accurate. Staff Initials: Date:
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Compound Protocol Visit Randomization No.Screening No. (Site - Sequence No.)
__ __ __ __-__ __ __ __ __ __ __ __ __ __ __
AN EFFICACY AND SAFETY TRIAL OF MK-8931 IN SUBJECTS WITH PRODROMAL AD
MK-8931 019
YES NO REMINDER GIVEN
ADASC8-12
8. WORD RECOGNITION (List-1)
At the start of the learning portion of the subtest,the tester gives the following instructions:
“I am going to show you some words printed on these
white cards. I want you to read each word out loud and
try to remember it, because later I will ask you to try to
remember all of the words I have shown you… Ready,
read the word and try to remember it.”
The tester can prompt, as necessary, with:
In the recognition portion of this subtest, thetester should say:
The tester shows the fi rst word and says either:
or:
The same instruction is given before the second subtest word. For the remaining subtest words the testershould say:
“Read it out loud and try to remember it.”
“Now I’m going to show you another set of words.
Some of the words were on the list I just showed you
and others are new. For each word I want you to tell
me whether it is one of the words I just showed you.”
“Is this one of the words I showed you before, yes or
no?”
“Did I show you this word before?”
“How about this one?”
If the subject indicates they are not sure, they may be encouraged with: “Just take your best guess.”
Nurse
Magazine
Wizard
Van
Leopard
Sale
Sea
Train
Coin
Ship
Institution
Map
Axe
Board
Carrot
Milk
Volume
Forest
Anchor
Gem
Cat
Fund
Edge
Cake
Total # CORRECT
Total # INCORRECT
Total # REMINDERS
ALZHEIMER’S DISEASE ASSESSMENT SCALE – COGNITIVE (CONTINUED)
Train
ing
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Remembering Word Recognition Subtest Instructions:
General Guidelines
ADMINISTRATION:
For this study, “Remembering Word Recognition Subtest Instructions” will be calculated automatically from the number of reminders given from the previous item. No action on the part of the tester is required.
Train
ing
I confi rm this information is accurate. Staff Initials: Date:
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Compound Protocol Visit Randomization No.Screening No. (Site - Sequence No.)
__ __ __ __-__ __ __ __ __ __ __ __ __ __ __
AN EFFICACY AND SAFETY TRIAL OF MK-8931 IN SUBJECTS WITH PRODROMAL AD
MK-8931 019
ADASC9-12
9. Remembering Word Recognition Subtest Instructions – NO ACTION REQUIRED
ALZHEIMER’S DISEASE ASSESSMENT SCALE – COGNITIVE (CONTINUED)
Train
ing
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Spoken Language Ability:
General Guidelines
ADMINISTRATION / SCORING:
This item is a global rating of the quality of the subject’s speech and their ability to communicate verbally (i.e., clarity, ability to make oneself understood).
In rating this item, the tester should consider all of the speech produced by the subject during the test session, including the opening conversation.
Quantity of speech and word-fi nding difficulty are not considered in the scoring of this item (i.e., circumlocutions would not be rated/evaluated on this item).
Ratings of “Moderately Severe” and “Severe” are reserved for subjects whose expressive language abilities are impaired to an extent that they seldom communicate without difficulty.
Train
ing
I confi rm this information is accurate. Staff Initials: Date:
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Compound Protocol Visit Randomization No.Screening No. (Site - Sequence No.)
__ __ __ __-__ __ __ __ __ __ __ __ __ __ __
AN EFFICACY AND SAFETY TRIAL OF MK-8931 IN SUBJECTS WITH PRODROMAL AD
MK-8931 019
No impairment – no instance of lack of understandability
Very mild – one instance of lack of understandability
Mild – subject has difficulty less than 25% of the time
Moderate – subject has difficulty 25-50% of the time
Moderately severe – subject has difficulty more than 50 % of the time
Severe – one or two word utterances; fl uent, but empty speech; mute
ADASC10-12
10. SPOKEN LANGUAGE ABILITY
ALZHEIMER’S DISEASE ASSESSMENT SCALE – COGNITIVE (CONTINUED)
Train
ing
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Word-Finding Difficulty:
General Guidelines
ADMINISTRATION / SCORING:
This item rates impairment in expressive speech, but it refers to word fi nding difficulty only. In contrast, the Spoken Language Ability item is more of a global rating of the subject’s ability to communicate verbally.
The tester rates the level of difficulty the subject had in fi nding desired words in spontaneous speech during the opening conversation and the test session (but it does NOT include the subject’s responses on the formal Naming Objects and Fingers tests).
Note: the subject may attempt to mask word fi nding difficulty by circumlocution (i.e., giving explanatory phrases or nearly satisfactory synonyms).
Instances when the tester has to infer the intended word from context should be rated here.
Train
ing
I confi rm this information is accurate. Staff Initials: Date:
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Compound Protocol Visit Randomization No.Screening No. (Site - Sequence No.)
__ __ __ __-__ __ __ __ __ __ __ __ __ __ __
AN EFFICACY AND SAFETY TRIAL OF MK-8931 IN SUBJECTS WITH PRODROMAL AD
MK-8931 019
11. WORD FINDING DIFFICULTY
No impairment in fi nding desired word in spontaneous speech
Very mild – 1 or 2 instances, not clinically signifi cant
Mild – noticeable circumlocution or synonym substitution
Moderate – loss of words without compensation on occasion
Moderately severe – frequent loss of words without compensation
Severe – nearly total loss of content words; speech sounds empty; 1-2 word utterances
ADASC11-12
ALZHEIMER’S DISEASE ASSESSMENT SCALE – COGNITIVE (CONTINUED)
Train
ing
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Comprehension of Spoken Language:
General Guidelines
ADMINISTRATION / SCORING:
This item evaluates the subject’s ability to understand speech.
To rate this item, the tester should consider how well the subject was able to understand the tester’s speech during the opening discussion and throughout the test session.
DO NOT include the subject’s responses on the Commands test in making this evaluation.
The tester should consider how frequently they had to repeat or rephrase communications to the subject in order for the subject to comprehend what the tester had communicated.
Repetitions or reminders due to memory problems should not be considered in the scoring of this test.
Train
ing
I confi rm this information is accurate. Staff Initials: Date:
Confi dential - Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USAPrinted in USA031302
US (English) (V1.0_00_2.0)
Compound Protocol Visit Randomization No.Screening No. (Site - Sequence No.)
__ __ __ __-__ __ __ __ __ __ __ __ __ __ __
AN EFFICACY AND SAFETY TRIAL OF MK-8931 IN SUBJECTS WITH PRODROMAL AD
MK-8931 019
12. COMPREHENSION OF SPOKEN LANGUAGE
No impairment – subject understands speech
Very mild – 1 or 2 instances of misunderstanding
Mild – 3-5 instances of misunderstanding
Moderate – requires several repetitions and rephrasing
Moderately severe – subject only occasionally responds correctly, i.e., to yes-no questions
Severe – subject rarely responds to questions appropriately; not due to poverty of speech
ADASC12-12
Used with permission from the NIA Alzheimer’s Disease Cooperative Study (NIA Grant AG10483). Mohs, R.; Knopman, D.; Petersen, R.; Ferris, S.; Ernesto, C.; Grundman, M.; Sano, M.; Bieliauskas, L.; Geldmacher, D.; Clark, C.; Thal, L.; and the ADCS. “Development
of Cognitive Instruments for Use in Clinical Trials of Antidementia Drugs: Additions to the Alzheimer’s Disease Assessment Scale That Broadens its Scope.” Alzheimer’s Disease and Associated Disorders, 1997, Volume 11 (S2): S13-S21.
ALZHEIMER’S DISEASE ASSESSMENT SCALE – COGNITIVE (CONTINUED)
Train
ing
Co
nfi
den
tial
- M
erc
k S
harp
& D
oh
me C
orp
.,
a s
ub
sid
iary
of
Merc
k &
Co
., I
nc.,
Whi
teho
use
Sta
tion,
New
Jer
sey,
US
AP
rinte
d in
US
A03
1302
US
(E
nglis
h) (
V1.
0_00
_1.0
)
NU
MB
ER
C
AN
CE
LL
AT
IO
N
Instr
ucti
on
s f
or
Exam
ple
:
Pla
ce th
e pr
actic
e fo
rm fa
ce u
p in
fron
t of t
he s
ubje
ct. S
ay, “
On
th
e to
p o
f th
is p
ag
e a
re tw
o n
um
bers
. O
n th
is p
ag
e y
ou
will fi
nd
th
ese n
um
bers
mix
ed
in
with
oth
er
nu
mb
ers
. I’d
lik
e y
ou
to
beg
in h
ere
...” (p
oint
to th
e b
egin
ning
of t
he li
ne)
“...a
nd
go
ing
acro
ss th
e lin
e, cro
ss o
ff e
ach
nu
mb
er
that m
atc
hes e
ith
er
of th
e tw
o n
um
bers
at th
e to
p o
f th
e p
ag
e.
Ple
ase w
ork
as q
uic
kly
as y
ou
can
.” D
isco
ntin
ue th
e ex
ampl
e af
ter 3
0 s
econ
ds.
Instr
ucti
on
s f
or
Task:
Pla
ce th
e fo
rm fa
ce u
p in
fron
t of t
he s
ubje
ct a
nd s
ay: “
On
th
e t
op
of
this
pag
e a
re t
wo
nu
mb
ers
.
Th
rou
gh
ou
t th
is p
ag
e y
ou
will fi
nd
th
ese n
um
bers
mix
ed
in
wit
h o
ther
nu
mb
ers
. I’d
lik
e y
ou
to
beg
in h
ere
...”
(poi
nt to
the
beg
inni
ng o
f the
fi rs
t lin
e), “
...a
nd
go
ing
acro
ss lin
e b
y lin
e, cro
ss o
ff t
he n
um
bers
th
at
matc
h t
he
nu
mb
ers
at
the t
op
of
the p
ag
e. P
lease w
ork
as q
uic
kly
as y
ou
can
.”
If th
e fi r
st c
ance
llatio
n do
ne b
y th
e su
bjec
t is
inco
rrect
, say
: “T
hese a
re th
e c
orr
ect n
um
bers
to
cro
ss o
ut,”
and
poi
nt to
the
targ
et n
umbe
rs a
t the
top
of th
e pa
ge. I
f the
sub
ject
bec
omes
con
fuse
d or
sto
ps w
hile
doi
ng th
e te
st, r
epea
t the
stan
dard
inst
ruct
ions
as
need
ed. D
isco
ntin
ue th
e te
st a
fter 4
5 s
econ
ds.
Train
ing
“6”
an
d “
1”
1 2
2 4
5 9
5 6
6 9
1 9
6 7
8 3
2 4
3 7
2 1
4 2
2 1
2 6
6 3
E
xam
ple
fo
r u
se w
ith
vers
ion
s A
, B
, an
d C
Train
ing
6 2
6 7
2 3
1 3
8 5
5 5
8 1
7 9
1 7
2 7
4 5
7 6
1 3
9 6
2 1
9 4
6 9
5 7
1 8
9 5
6 5
4 2
7 1
5 2
7 9
1 7
1 1
1 4
2 8
5 8
1 9
7 9
7 1
6 7
8 6
5 5
7 2
9 6
5 9
5 4
7 3
2 4
5 6
1 4
3 4
4 6
8 4
1 4
1 7
2 4
7 1
7 6
7 5
4 9
8 7
5 6
2 1
6 9
3 1
4 8
7 8
6 7
1 7
1 3
4 3
9 8
6 5
1 8
3 4
2 6
9 9
6 1
6 4
3 9
3 4
4 9
3 8
7 2
5 4
4 8
7 6
4 1
4 7
2 6
8 7
5 6
3 2
6 4
4 6
8 4
4 8
3 4
7 5
4 4
7 9
7 3
6 8
6 5
4 7
4 3
4 9
2 5
3 5
4 7
3 5
4 9
3 3
8 1
8 4
2 6
5 6
6 1
7 2
4 2
9 7
9 7
6 1
5 1
4 1
9 8
A
“2”
an
d “
8”
Train
ing
7
8 7
5
2 2
1
6 9
3
1 4
8
7
9
3
5
4
7
5
1 6
8
7
3
2
3
9 3
7
3 9
2 6
4 3
9
3
4
1
2
1
6
1
6
3
2
3
4
7
3 2
6
3
1
3
7
8 6
7
1
7
1
3
6
3
9
8
6
5
1
8 3
4
2
6
9
5
6
1 9
3
6
8
7
2
5
4
6
8
8
6
8
1
4
7
2
6
8
7
5
6 3
2
6
4
1
6
8
4
5 3
4
7
9 7
3
6 8
6
2 3
9
6
5
3
5
6
7
3
5
5
9 3
3
8
1
8
2
2
6
2 6
6
1
7
2
8
2 9
7 9
3
8 1
7
6
1
5
1
8 4
3
3
8
7
5 4
2
7
9 7
3
6
8
6 5
4
7
4
3 6
1
6 3
5
4 8
3
9
3
4
7
1
3 4
3
6
1
6
7
1 7
6
7
3
5
2
9
8
7 5
2
2
1
6
9
3
1
4
8
7
9
3
4
1
7
5
2
2
1
6
8
3
1
4
8
7
9
3
B
“4”
an
d “
9”
Train
ing
1 9
8
1 3
2 3
9 4
2 9
3 2
6 4
4 6
6 1
3 8
8 4
2 7
1 4
2 8
5
8 1
9 6
9
7
1 4
5
5
6
7
6
6 5
5
7
2
2
2
5
9
5
4
7
1 7
6
7 5
4 9
8 8
1 4
3 4
4 6
8 4
1 4
1 7
2 4
7 9
2 6
1 7
2 1
3 4
2 3
2 6
4 1
3 7
1 5
6 8
5 4
9 8
2 5
2 2
1 6
9 3
1 4
8 7
9 3
4 1
2 6
1 6
9 4
2 4
2 3
2 6
3 1
4 2
8 6
9 1
7 1
3 4
3 9
8 6
5 1
8 3
4 2
6 9
9 6
1 6
9 3
8 7
2 5
4 4
8 8
6 4
1 4
7 2
6 8
7 5
6 3
2 6
4 4
6 8
4 5
4 6
8 9
7 3
6 8
6 5
4 9
2 5
3 5
4 7
3 5
4 9
5 3
8 1
8 2
2 6
2 6
6 1
5 2
4 2
9 4
9 7
6 1
5 1
4 1
8 8
C
“3”
an
d “
7”
Train
ing
“2”
an
d “
9”
7 9
3 3
7 2
1 3
4 9
5 7
5 2
4 6
9 9
3 1
6 5
4 8
2 2
5 6
4 3
E
xam
ple
fo
r u
se w
ith
vers
ion
DTrain
ing
8 6
7 1
7 1
3 4
3 9
8 6
5 1
8 3
4 2
6 9
9 6
1 6
2 5
2 6
3 2
3 4
7 3
2 6
3 1
3 1
9 3
8 7
2 5
4 4
8 8
6 4
1 4
4 5
4 4
7 9
7 3
6 8
6 5
7 2
6 8
7 5
6 3
2 6
4 4
6 8
4 9
2 5
3 5
4 7
3 5
4 9
3 3
8 1
8 2
2 6
2 6
6 1
7 2
4 2
9 7
9 7
6 1
5 1
4 1
8 8
8 4
3 4
7 5
4 4
7 9
7 3
6 8
6 5
4 7
4 3
6 1
6 3
5 4
4 3
9 3
6 4
8 7
4 3
6 1
6 3
7 1
7 6
7 5
4 9
8 7
5 2
2 1
6 9
3 1
4 8
7 9
3 4
1 7
5 2
2 1
6 9
3 1
4 8
7 9
3 4
7 9
7 3
6 8
6 8
1 9
7 3
6 8
7 9
7 6
5 7
2 6
8 7
5 6
3 2
6 1
4 6
8 7
2 4
2 7
2 4
D
“1”
an
d “
5”
Train
ing
I co
nfi
rm t
his
info
rmat
ion
is a
ccu
rate
.
Sta
ff In
itial
s:
Dat
e:
Co
nfi
den
tial
- M
erc
k S
harp
& D
oh
me C
orp
.,
a s
ub
sid
iary
of
Merc
k &
Co
., I
nc.,
Whi
teho
use
Sta
tion,
New
Jer
sey,
US
AP
rinte
d in
US
A
AN
EF
FIC
AC
Y A
ND
SA
FE
TY
TR
IAL
OF
MK
-8931 IN
SU
BJE
CT
S W
ITH
PR
OD
RO
MA
L A
D
0313
02U
S (
Eng
lish)
(V
1.0_
00_1
.0)
C
ompo
und
Pro
toco
l V
isit
M
K-8
931
019
Ran
dom
izat
ion
No.
Scr
eeni
ng N
o. (
Site
- S
eque
nce
No.
)
__ _
_ __
__-
__ _
_ __
__
____
__
__ _
_ __
__
N
umbe
r of
targ
ets
hit (
tota
l of c
orre
ct n
umb
ers
cros
sed
off)
N
umbe
r of
err
ors
(tot
al o
f inc
orre
ct n
umb
ers
cros
sed
off)
N
umbe
r of
tim
es r
emin
ded
of ta
sk
NC
“U
SE
D W
ITH
PE
RM
ISS
ION
FR
OM
TH
E N
IA A
LZ
HE
IME
R’S
DIS
EA
SE
CO
OP
ER
AT
IVE
ST
UD
Y (N
IA G
RA
NT
AG
10
48
3)”.
MO
HS
, R
.; K
NO
PM
AN
, D
.; P
ET
ER
SE
N, R
.; F
ER
RIS
, S
.; E
RN
ES
TO
, C
.; G
RU
ND
MA
N, M
.; S
AN
O, M
.; B
IEL
IAU
SK
AS
, L
.; G
EL
DM
AC
HE
R, D
.; C
LA
RK
, C
.; T
HA
L, L
.; A
ND
TH
E A
DC
S. “
DE
VE
LO
PM
EN
T O
F C
OG
NIT
IVE
IN
ST
RU
ME
NT
S F
OR
US
E I
N C
LIN
ICA
L T
RIA
LS
OF
AN
TID
EM
EN
TIA
DR
UG
S: A
DD
ITIO
NS
TO
TH
E A
LZ
HE
IME
R’S
DIS
-
EA
SE
AS
SE
SS
ME
NT
SC
AL
E T
HA
T B
RO
AD
EN
S I
TS
SC
OP
E.”
A
LZ
HE
IME
R’S
DIS
EA
SE
AN
D A
SS
OC
IAT
ED
DIS
OR
DE
RS
, 19
97,
VO
LU
ME
11
(S
2):
S13
-S2
1.
NU
MB
ER
C
AN
CE
LL
AT
IO
N
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