Alzheimer Disease Tests

AB09004 study
Training for Alzheimer disease tests and

questionnaires
December 2011 AB09004 training 1

Agenda
Introduction
Training on co-primary endpoints of AB09004 study

ADAS-Cog
ADCS-ADL
Quiz on ADAS-Cog and ADCS-ADL
Investigator training on secondary endpoints

MMSE
NPI
CDR-SB
CIBIC plus

Agenda
Introduction

ADAS-Cog
ADCS-ADL

MMSE
NPI
CDR-SB
CIBIC plus

Objectives of the training
Provide the general background and conventions for rating the relevant scale
Review general anchor points, essentials and caveats of individual scale items
ADAS-Cog and ADCS-ADL are primary criteria for study AB09004

very important for study reliability that persons who will assess these
neuropsychological tests are well trained
These standardized instructions are provided to ensure that all the tests are
administered in a standardized manner, regardless of the examiners prior
experience.
important to guarantee an homogeneous assessment by all the raters

Who?
Neuropsychological
Examiner qualification
test
ADAS-Cog MD or psychologist
ADCS-ADL MD or psychologist
MMSE MD
NPI MD
CRD-SB Preferably an independent MD
CIBIC-plus Independent MD
All examiners should be used to conduct neuropsychological tests

MD = medical doctor

How?
Order of tests:
All tests and questionnaires should be administrated in the same order
during the whole study, with ADAS-Cog at first.
Examiner throughout the study:

The same person should administrate each scale at all visits (see previous
slide), at the same time of the day
Caregiver / informant
The interviewed caregiver (ADCS-ADL, NPI, CDR-SB and CIBIC-plus tests)
should remain the same during the whole study

When?
Every 12 Final
Test Screening Baseline W4 W8 W12 W24
weeks visit
ADAS-Cog A* B C A B,C,A X
ADCS-ADL X X X X X X
MMSE X X X X X X
NPI X X X X
CDR-SB X X X X
CIBIC-plus X X X X X
*form of ADAS-Cog test to be administered

Practical aspects
Printed questionnaires / interview guide will be provided in local language.
ADAS-Cog and ADCS-ADL are printed in duplicate.

Original pages will be collected by the CRA
Scores will be entered in eCRF at each visit
MMSE, NPI, CDR-SB and CIBIC-plus are single-printed.

They should remain on site as source data and will be monitored
Scores will be entered in eCRF at each visit
ADAS-Cog material will be provided.

Agenda
Introduction
Training on co-primary endpoints of study AB09004

ADAS-Cog
ADCS-ADL

MMSE
NPI
CDR-SB
CIBIC plus

ADAS-Cog - introduction
The ADAS-Cog is a commonly used objective measure of cognitive change. There

are several versions of this test.
The version used in this study is the basic ADAS-Cog with 11 items: it was
designed to measure cognitive areas commonly seen to decline in Alzheimers
disease (AD), specifically learning (word list), naming (objects), following
commands (1 to 5 elements), ideational praxis (mail a letter), constructional
praxis (copy 4 figures), orientation (person, time and place), recognition memory
(from a second word list), and remembering test instructions (from the
recognition subtest)
The test includes three additional subjective scales containing assessment of

spoken language ability, word finding difficulty, and comprehension
This test takes about 30 minutes
The ADAS-Cog is scored from 0 to 70: higher score indicates greater cognitive
impairment

ADAS-Cog in AB09004 study
In AB09004 study, ADAS-Cog record form will be provided in your local

language.
Three different record forms: A, B, C, corresponding to different word
lists for Word recognition task.
You should alternate forms between visits (see flow-chart slide 6)
Material necessary for ADAS-Cog tests:

Suitcase with 10 objects*
Booklets of words (10 words + 12 words)*
Pencil
Envelopes
Paper sheet
* Provided by AB Science

ADAS-Cog - contents
1. Spoken language ability * (0-5 points)

2. Comprehension * (0-5 points)
3. Word finding difficulty in spontaneous speech *(0-5 points)
4. Word Recall Task (0-10 points)
5. Naming objects and fingers (0-5 points)
6. Orientation (0-8 points)
7. Commands (0-5 points) Total score range 0-70
8. Ideational Praxis (0-5 points)
9. Constructional Praxis (0-5 points)
10. Word recognition task (0-12 points)
11. Remembering test instructions (0-5 points)
* Involve subjective ratings

ADAS-Cog - procedures (1)
General Testing Principles

Test patient in a quiet room, preferably consistent from visit to visit
Room should be free of clocks, calendars.
Use Do Not Disturb signs
Face-to-face across testing table preferred, diagonal okay, the subject
should not see you scoring
Test will be administrated always on an empty table or desk (all the test
material should remain behind, or on a chair by the examiner)
ADAS-Cog should be the first test to be administrated

Overarching Principle: Obtain the best performance the patient is capable

of (without altering administration procedures)
Establish good rapport
Encourage subject as needed
Provide positive feedback (without info as to response accuracy)

Overarching Principle: Obtain the best performance the patient is capable

of (without altering administration procedures)
Establish good rapport
Encourage subject as needed
Provide positive feedback (without info as to response accuracy)
A subject can never perform better than his allowed abilities on

neurocognitive tests, but he can always perform worse!

ADAS-Cog components
Initial interview/conversation (item 1-3)

Every testing session should begin with a 5-10 minutes conversation,
open-ended questions on neutral topics, such as the weather, recent
events, etc.
Avoid talking about the study, patients health, or any negative or
distressing topics
This conversation is used for following purposes:

Putting patients at ease with examiner and testing situation
Rating patients on language measures (items 1-3)

ADAS-Cog - Spoken language ability (1)
Spoken language ability (item 1)

Rating refers to the global quality of the patients expressive
communication: how much it is difficult to understand the patient
0= no instances where it is difficult to understand the patient

1= very mild; one instance where it is difficult to understand the patient
2= mild; difficulty <25% of the time
3= moderate; difficulty 25-50% of the time
4= moderately severe; difficulty >50%
5= severe; mute or max 1-2 word utterances, or extremely paraphasic
language

ADAS-Cog - Spoken language ability (2)
Record form:
Scoring from 0 to 5 points

ADAS-Cog - Comprehension (1)
Comprehension (item 2)
Rating refers to the patients ability to understand the examiner during
the initial interview or during explanation of tasks- do not base this on
performance during Commands
0=no evidence of poor comprehension

1= very mild; one instance of misunderstanding
2= mild; 3-5 instances of misunderstanding
3= moderate; requires several repetitions and rephrasing
4= moderately severe; subject only occasionally responds correctly;
i.e., to yes/no questions
5= severe; subject rarely responds to questions correctly due to lack
of understanding

ADAS-Cog - Comprehension (2)
Record form:

ADAS-Cog - Word finding difficulty (1)
Word finding difficulty in spontaneous speech (item 3)

Rating also refers expressive communication, but here we are interested
specifically in word-finding difficulties, whereas item #1 was a more
global rating
0= no evidence of word finding difficulty in spontaneous speech

1=very mild; 1-2 instances, not clinically significant
2=mild; notable circumlocution/synonym substitution
3= moderate; loss of words without compensation on occasion
4= moderately severe; frequent loss of words without compensation
5= severe; nearly total loss of content words; speaks empty sounds; 1-
2 word utterances

ADAS-Cog - Word finding difficulty (2)
Record form:

ADAS-Cog - Word recall task (1)
Word recall task (item 4)

Material: booklet with 10 words
The patient reads aloud 10 words, presented on cards and tryes to
remember them
If the patient cannot read word, examiner reads word aloud and the
subject has to repeat : this can occur for all words if necessary
Words are presented for approximately 2 seconds each
After reading all 10, immediate recall tested
Give patient adequate time to recall as many words as possible
Three consecutive trials are proposed, the order of words is different at

each trial

ADAS-Cog - Word recall task (2)
Record form:
Score (0 - 10 points) = mean of number of words NOT recalled at the 3 trials

ADAS-Cog - Naming objects and fingers (1)
Naming objects and fingers (item 5)

Material: 10 objects (suitcase)
Objects
Show the subject each object, dont let them handle
Accept culturally correct variations on names
Give the clue only if patient does not respond
Dont give the subject the name if they dont know it
Objects can be presented in any order

Naming objects and fingers (item 5) continued

Fingers
Use fingers of patients dominant hand
Follow order: thumb to little
Accept culturally correct variations on names, but do not accept

numbers- if given number, ask for name
Score = number of incorrect items (from 0 to 5)

Record form:
Score (0-5 points) 0= 0-2 items named incorrectly; 1= 3-5 items named
incorrectly; 2= 6-8 items named incorrectly; 3= 9-11 items named incorrectly;
4= 12-14 items named incorrectly; 5= 15-17 items named incorrectly
ADAS-Cog - Orientation (1)
Orientation (item 6)
Questions (8 questions) can be asked twice. If the patient does not
respond at all after 10 seconds, the next question should be asked.
No clocks, watches, calendars or newspapers should be visible in testing

room
Do not allow patient to look at his watch
Date correct if within +/- one day; time +/- one hour
Season correct if named season is beginning within one week or less or
ended two weeks or less previously
Seasons determined per local custom
Place name requirement should be consistent

ADAS-Cog - Orientation (2)
Record form:
Score (0-8 points) = number of incorrect answers

ADAS-Cog - Commands (1)
Commands (item 7)
Material: pencil, watch, postcard
Give command in clear, sufficiently loud voice

If patient does not respond or makes an error, command is repeated once
Commands always given in its entirety
Prevent patient from beginning to respond before command is complete
Remove pencil, watch, and card before command #5 to prevent
distraction
Scoring: 0-5; number incorrectly performed

ADAS-Cog - Commands (2)
Record form:
Scoring (0-5 points) = number of commands incorrectly performed

ADAS-Cog - Ideational Praxis (1)
Ideational Praxis (item 8)

Material: sheet of paper (about 21 x 30 cm), a long envelope and a pencil
The examiner asks the patient to pretend that he has written a letter to
himself: the patient has to fold the letter, put it into the envelope, seal
the envelope, address the envelope to himself, and indicate location of
stamp.
Warning:
This is not a test of memory: if patient forgets a component, remind
him- one reminder per component
Address is considered correct if there is reasonable chance that postal
service could deliver the letter
Stamp should be in right top corner of envelope on the side of
address location
Order of task completion is not important, steps are individually
scored
ADAS-Cog - Ideational Praxis (2)
Record form:
Score (0-5 points) = number of components INCORRECTLY performed

ADAS-Cog - Constructional Praxis (1)
Constructional Praxis (item 9)

Subjects should be given the four following drawings to copy:
Erasing and re-drawing are allowed

A second attempt is allowed if 1st is incorrect
Encourage best effort, but drawings dont have to be perfect to pass
(see next slide)
Small gaps between lines do not count as errors
Changes in size do not count as errors
Refer to scoring criteria for additional information/clarification

Circle: A closed curved figure.
Overlapping Rectangles: Forms must be four-sided

and overlap and must be similar to presented form.
Diamond: Figure must be four-sided, oriented so that

points are at the top and bottom and sides of equal
length (longest side less than 1.5 times the length of
shortest side)
Cube: Form is three-dimensional, with front face in
the correct orientation, internal lines drawn correctly
between corners. Opposite sides of faces should be
approximately parallel.

Record form:
Score (0-5 points):

0= all 4 drawings correct
1 (resp. 2 or 3)= 1 (resp. 2 or 3) form(s) drawn incorrectly
4= 4 forms drawn incorrectly or one closing in
5= no figures drawn, scribbles, parts of form; words instead of forms

ADAS-Cog - Word recognition task (1)
Word recognition task (item 10)

Patient reads aloud 12 words, presented successively during 2 seconds
If patient fails to read word, read aloud and have him repeat
Then these 12 words are mixed with 12 new words and presented to the
patient. For each of the 24 words, the patient has to answer YES if the
word was presented before to him and by NO in opposite case. The
examiner writes on the form the answer given by the patient
Instructions:
first two test trials: Is this one of the words that I showed you before,
yes or no
remaining 22 trials: How about this one?
For AB09004 study, only one trial of recognition will be performed

Word Recognition task - continued

If patient clearly loses track of task demand (reads words or indicates
they are confused), re-orientate him. Record the number of reminders
given (used in scoring later)
If you feel that a patient has lost track of task and fallen into a
stereotyped response set (e.g., responding no to all stimuli), also
remind him of task demand, and count this as a reminder.
Requires clinical judgment- not using set cut-off #
If patient is uncertain of response for an item, encourage him to guess

(but do not count this as a reminder)

Record form:
Score (0-12 points)= number of INCORRECT responses at trial 1 (trial 2 is

NOT performed in this study)
ADAS-Cog - Remembering test instructions (1)
Remembering test instructions (item 11)

Refers specifically to the Word recognition task first trial only
Score based upon number of reminders needed during that task; i.e., the
number of times that the patient forgets the nature of the word
recognition task demands (during the recognition task after the 2 first
words)

ADAS-Cog - Remembering test instructions (2)
Record form:
Score (0-5 points):

0= patient never needs extra reminders or instructions
1= very mild, forgets once
2= mild- must be reminded twice
3= moderate- must be reminded 3 or 4 times
4= moderately severe - must be reminded 5 or 6 times
5= severe - must be reminded 7 or more times
ADAS-Cog Score total = sum of all items
1. Spoken language ability /5
2. Comprehension /5
3. Word finding difficulty in spontaneous speech /5
4. Word recall task / 10
5. Naming objects and fingers /5
6. Orientation /8
7. Commands /5
8. Ideational praxis /5
9. Constructional praxis /5
10. Word recognition task / 12
11. Remembering test instructions /5
Total score : ,/ 70
To be recorded in study eCRF

Agenda
Introduction

ADAS-Cog
ADCS-ADL

MMSE
NPI
CDR-SB
CIBIC plus

ADCS ADL: introduction
The ADCS - ADL Inventory measures basic activities of daily living (referred as
ADL) such as dressing, eating, bathing and traveling
In a structured interview format, informants (caregiver) are queried as to

whether patients attempted each of all items in the inventory during the
prior 4 weeks and their level of performance
The questionnaire should not be filled out by the informant directly
ADCS-ADL uses a scale from 78 to 0, with lower scores indicating declining

ability
This test takes about 15 minutes

ADCS ADL: format of questions (1)
For each basic ADL (questions 1-5, 6A), there is a forced choice of best
response
Example:

All other ADL consist of a main question followed by sub-questions

(descriptors)
Sub-questions are arranged in hierarchical fashion, starting with the highest
(most independent) level of ADL performance and ending with the lowest

For each ADL, the initial response to the main questions is yes, no or
don't know
If an informant gives 4 or more don't know responses, it is worth trying
to identify an alternative informant
After a no or don't know response, the sub-questions are disregarded

unless specific instructions indicate otherwise. No or don't know act as
fast forward cues to proceed to the next ADL

After a yes response, there are 2 possible paths:

1. From several descriptors, the informant chooses the one that best
matches the patient's performance (e.g., question 7 b). The informant
should be offered as many descriptors as necessary to describe the
patient's ADL ability, starting from the highest level and proceeding
downwards
2. OR the informant makes a yes or no choice for each sub question.
There is a reminder in these cases to ask every question after an initial "yes"
(e.g., question 8)

Administering the ADCS ADL Inventory
Standardizing ratings for independently, with supervision, and with

help:
For many ADL, the hierarchy depends on how much intervention is needed by
the informant or others to enable the patient to perform the ADL
Independently = the patient completed the ADL without physical help, and at
most with reminders to do the task, or a brief prompt during the ADL
With supervision = the patient required verbal reminders and instructions
while doing the ADL; this occupied the caregiver's (or informant's) time
With help = the patient was given some degree of physical assistance by
another person to perform the ADL

Usual performance of ADL
Patients may vary from day to day in their ADL performance
If an informant responds that a patient sometimes performs ADL at one level

and sometimes at another, the interviewer should ask him/her to choose the
most commonly applicable level/descriptor
When in doubt about a higher or lower level of ability, rate the higher one if
the patient does manage to perform at that level fairly consistently

Comments on specific questions in the Inventory (1)
1. Eating: self-explanatory
2. Walking: we are interested in mobility, not specifically walking. If the

patient uses a walker or wheelchair, but is mobile outside of home without
help, he is independent
4. Bathing: minor physical help includes actions such as washing hair, help
with drying, running the water or adjusting its temperature. More extensive
help should be scored as needing to be bathed
5. Grooming: nail cutting is not rated since physical difficulty may impede this
aspect of grooming, even in cognitively normal patients
6A. Selecting clothes: implies active participation by the patient. This may
involve physically selecting clothes, or providing input to the caregiver about
wishes or preferences. It is rated separately from physically getting dressed

6B. Dressing: the 3rd and 4th levels are similar

The intention is that help only for buttons, clasps or shoelaces implies
only a minor contribution from the caregiver, i.e. the patient performs
some degree of fastening, zipping or tying
Using "clothes needing no fastening or buttoning" implies that these have
been completely abandoned. Velcro counts as a fastener
7. Telephone: reminders or supervision are allowable but not help,

e.g.: a patient can be prompted to dial directory assistance, or told the
number and still score at the highest level
If the patient makes calls only if the numbers are dictated by the
caregiver, or if the telephone is set up to automatically dial one of a
preselected group of numbers on pressing a single button, the patient
scores 2 points

8. Television:
If the patient sits in front of a television screen without demonstrating
awareness or recollection of something he sees, then all sub questions
will be answered as no
Talk about the content of a program should be interpreted fairly
broadly; the patient does not need to initiate the conversation, but
should require more than a yes or no answer to a question like Did
you enjoy the program?
9. Conversation: pay attention to conversation or small talk implies more

than being present and seemingly alert during a conversation. The patient
must participate verbally. Since it is difficult to judge whether nonverbal
participation in a conversation is meaningful, it is not an option among the
descriptors

10. Clear dishes from a table:

the patient does not have to clear the table entirely, but should
participate enough to make a useful contribution
Clearing items other than dishes (e.g.: glasses or utensils) are acceptable
as alternatives
11. Finds personal belongings: it may be helpful to give examples such as

clothing, glasses, wallet, keys, etc.
12. Beverage: getting or preparing a beverage after instructions or a

reminder counts as no physical help

13. Meal or snack

if the patient required supervision to cook or microwave, but functioned
without physical help, score as the highest level
Mixing or combining items without cooking can also include supervision.
An example of the lowest level of a yes response is the patient who
finds and eats food pre prepared by someone else
14. Dispose of garbage or litter: does not only refer to major household
garbage produced in a kitchen. Disposing of any trash in an appropriate
container qualifies for a yes response

15. Travel: intends to cover the patient's ability to remain oriented, not get
lost and be able to venture beyond home
It does not matter whether the patient walked, drove, took public
transport or was a passenger in a car. The distance of 1 mile is arbitrary
and implies travel beyond sight of home
16. Shopping: shopping is a complex activity. We have focused on the two

most essential aspects (after getting to the shop, covered by question 15),
choosing items and paying
If the patient goes shopping with a prewritten list and a sum of money
provided by someone else, that should be scored as without supervision,
provided the patient selected the items on the list
Paying for items could involve cash, check or credit; the issue is whether
supervision or help is needed

17. Keep appointments or meetings: mainly aimed at monitoring memory

An appointment/meeting may be liberally interpreted to include almost
any kind of preplanned meeting, outing or excursion
It does not matter who made the appointment or whether the patient
traveled alone or with somebody else
The highest level implies the patient remembered the appointment on his
own, memory aids are acceptable
18. Left alone: if the patient was left alone for an hour or longer at home,
then they automatically will score a yes for descriptor c, less than 1 hour at
home.

19. Talk about current events:

The patient does not need to initiate conversation about current events,
but must demonstrate awareness or recollection by providing details of
the event(s)
Merely agreeing or disagreeing with other people by saying yes or no
is not sufficient to display knowledge/recall of current events
Patients who are severely aphasic will score no for talking about current
events

20. Reading: looking at a book, magazine or newspaper and turning the pages
for more than 5 minutes on end may equal reading
Unless the patient communicates the content of what he/she reads to
someone else, it is not possible to judge whether he actually reads or not,
in a way that shows elements of comprehension and retention of
information
The informant should be encouraged to interact with the patient to be
able to make an accurate judgment
21. Writing: short notes or messages can be either spontaneous or written to

dictation. A shopping list, to do list, or taking an intelligible telephone
message would qualify

22. Pastime, hobby or games: the menu of hobbies or games is to help the
informant and may provide us with secondary information if complex hobbies
are lost and replaced by simpler ones. A hobby should involve element(s) of
concentration, knowledge and memory, and manual skills. If hobbies other
than those in the menu are offered, try to describe what the patient does in
some detail so that we can monitor this
23. Household appliance: an appliance is defined as a device with one or

more switches or controls, usually (though not necessarily) with an electrical
or other power source, used to do chores
For men: tools with controls or switches would qualify, but not a
screwdriver, hammer or saw
Again, if the patient needs only minimal verbal prompting to operate the
appliance, press a switch, or operate a control, the highest level is scored

Agenda
Introduction

ADAS-Cog
ADCS-ADL

MMSE
NPI
CDR-SB
CIBIC plus

MMSE: Mini-Mental State Examination
Administered by a physician with patient
To assess the cognitive deficit: severity of Alzheimer disease (AD)
30 questions in 6 categories: 30-point score

Orientation
Registration
Attention / calculation
Recall
Language
Copying

MMSE: Orientation (1)
Orientation to time: What is the

year?
season ?
month of the year?
day of the week?
date?
Orientation to place : Where are you now? What is the

state (province)?
county (or city/town)?
city/town (or part of city/neighborhood)?
building (name or type)?
floor of the building

MMSE: Orientation (2)
Allow 10 seconds for each question. If the patient does not reply, give the
answer.
For season , naming an upcoming season within one week prior to its
onset, or naming a previous season for two weeks after its termination is
acceptable.
For floor , the patient may give an answer such as ground floor or first
floor. Others answers may be accepted so long as it is clear that the patient is
correctly oriented.
For town , accept one exact response.

MMSE: Registration
The rater says 3 words.
Give the names at one second intervals.
Allow 20 seconds for the response.
The order in which the three items are named is unimportant.

MMSE: Attention and calculation
The patient has to subtract 7 from 100 and then keep subtracting 7 from each
answer.
In the event of difficulty, each subtraction may be prompted e.g. 93-7= ?.
If mistakes are made, ask Are you sure ?
If the patient corrects the answer, include the point in the score.
You must not indicate if the answer was too high or too low.
Stop after two 2 errors. Allow 10 seconds for each reply.
Score one point for each correct subtraction.
Alternative item (WORLD backward) should only be administered if the

examinee refuses to perform the Serial 7s task.
Ask the patient to spell WORLD forward, then backward.
Correct forward spelling if misspelled, but score only the backward
spelling. (D = 1) (L = 1) (R = 1) (O = 1) (W = 1) (0 to 5)

MMSE: Recall
The patient has to give back the 3 words from registration test.
Allow 10 seconds for each response
1 point for each correct response

MMSE: Language (1)
Allow 10 seconds for each response
Naming: the patient has to identify objects:

What is this? [Point to a pencil or pen.]
What is this? [Point to a watch.]
Score one point for each correct answer
Repetition:
Ask the patient to repeat no ifs, ands, or buts.
Repeat up to 5 times, but score only the first trial (one point)
Three stage command:

Ask the patient to take a paper in his right hand [pause], fold it in half [pause],
and put it on the floor (or table).
No reminders are allowed. If the patients stops and asks what to do next,
reply: that which I first told you. Score one point for each action correctly
executed.
MMSE: Language (2)
Reading: the patient has to read words on the stimulus form and do what it
says.
Score 1 point for correct reading
Writing: The patient has to write a sentence.

If examinee does not respond, say: Write about the weather.
The sentence must have a subject and a verb and make sense.
If the writing is illegible but the patient reads out and it makes sense, it is
acceptable.
If the patient does not write a complete sentence, ask is this a
sentence? and allow him to correct.
Maximum time is 30 seconds.
Score 1 point for acceptable sentence

MMSE: Copying
Ask the patient to copy a design.
Score one point if the drawing consists of two 5-sided figures that intersect to
form a 4-sided figure.
All the 10 angles must be present and the figures must overlap. The patient
may restart if he asks to but the investigator must not prompt them to do
this.

MMSE: Scoring
Total : score all items
Orientation Score : ________ /10

Registration Score : ________ / 3
Attention Score : ________ / 5
Recall Score : ________ / 3
Language Score : ________ / 8
Copying Score : ________ / 1
TOTAL SCORE: ___________ / 30

Agenda
Introduction

ADAS-Cog
ADCS-ADL

MMSE
NPI
CDR-SB
CIBIC plus

NPI: Introduction
NPI = neuropsychiatric inventory
Purpose of the NPI:

Obtain information on the presence of psychopathology in patients with
brain disorders
Ten behavioral and neuro-vegetative areas are included.
NPI based on responses from the caregiver

Interview conducted with the caregiver in the absence of the patient to
facilitate an open discussion of behaviors that may be difficult to describe
with the patient presence

NPI: Generalities (1)
The questions pertain to changes in the patients behavior that have

appeared since the onset of the illness.
Behaviors that have been present throughout the patients life and have not
changed in the course of the illness are not scored even if they are abnormal
(e.g., anxiety, depression).
Behaviors that have been present throughout life but have changed since the
illness are scored (e.g., the patient has always been apathetic but there has
been a notable increase in apathy during the period of inquiry).
The NPI is typically used to assess changes in the patients behavior that have
appeared in a defined period of time (e.g., since last clinic visit )

NPI: Generalities (2)
Several points should be made when you introduce the NPI interview to the
caregiver:
Purpose of the interview
Answers apply to behaviors that are new since the onset of the disease
and have been present for the past four weeks or other defined period
Ratings: After answering all questions referring to a behavior, the
caregiver will have to rate this behavior in frequency, severity and
distress.
Questions can usually be answered with yes or no and responses
should be brief. If the caregiver lapses into elaborate responses that
provide little useful information, he/she may be reminded of the need to
be brief.
Questions should be asked exactly as written. Clarification should be provided

if the caregiver does not understand the question.
NPI: during the interview (1)
A screening question is asked for each behavior.
If the answer to the screening question is negative, the interviewer proceeds

to the next screening question without asking the sub-questions.
If the answer to the screening question is positive or any inconsistencies

between the response and other information known by the clinician (e.g. the
caregiver responds negatively to the euphoria screening question but the
patient appears euphoric to the clinician), the category is marked YES and is
explored in more depth with the sub-questions.
If the sub-questions confirm the screening question, the severity and

frequency of the behavior are determined according to the criteria provided
with each behavior.

NPI: during the interview (2)
In some cases, the caregiver will provide a positive response to the screening
question and a negative reply to all sub-questions.
If this happens, ask the caregiver to expand on why he/she responded

affirmatively to the screen.
If he/she provides information relevant to the behavioral domain but
in different terms, the behavior should be scored for severity and
frequency as usual.
If the original affirmative response was erroneous, leading to a failure
to endorse any sub-questions, then the behavior is changed to NO
on the screen.

NPI: example of screening question

NPI: example of sub-questions

NPI: scoring (1)
Frequency rated as:

1. Occasionally - less than once per week
2. Often - about once per week
3. Frequently - several times per week but less than every day
4. Very frequently - daily or essentially continuously present
Severity rated as:

1. Mild - produces little distress in the patient
2. Moderate - more disturbing to the patient but can be redirected by the
caregiver
3. Severe - very disturbing to the patient and difficult to redirect
Score for each domain= frequency x severity

NPI: scoring (2)
Caregiver distress scored as:

0 No distress
1 Minimal
2 Mild
3 Moderate
4 Moderately severe
5 Very severe or extreme
For each behavioral domain, there are four scores: frequency, severity,
total (frequency x severity), caregiver distress
Total NPI score: calculated by adding the scores of the first 10 domain scores

NPI: scoring record sheet
Date of exam: |___|___| |___|___| 20|___|___|

Agenda
Introduction

ADAS-Cog
ADCS-ADL

MMSE
NPI
CDR-SB
CIBIC plus

CDR-SB: Introduction (1)
CDR-SB = Clinical Dementia Rating - Sum of the boxes
Administered by a physician
Separated interview with patient and caregiver
Semi structured interview
To assess the severity of dementia with 5 scores:

CDR-0 = no cognitive impairment
CDR-0.5 = very mild dementia
CDR-1 = mild
CDR-2 = moderate
CDR-3 = severe
CDR-SB: Introduction (2)
Patients performance is assessed in six domains:

Memory
Orientation
Judgment/ problem solving
Community activities
Home and hobbies
Personal care
The six domains used to construct the overall CDR table are each scored
individually

CDR-SB: General principles
The patients suffering from AD deny or usually minimize their handicap. So

information obtained from caregiver must be considered as the most reliable
information source.
The structured conversations are of use as base to the evaluation. Be free to

ask additional questions to clarify the level of functioning to attribute a
quotation
IMPORTANT: if in a domain you hesitate between two quotations, attribute

the highest quotation (corresponding to the most important deficit)
During the structured interview:

the caregiver is questioned about 6 domains
the patient is questioned / tested only for: Memory, Orientation,
Judgment/ problem solving
CDR-SB: Rating example for memory
For every category , a descriptive text is presented with further information

to facilitate the scoring example with memory
0 = No memory loss or slight inconstant forgetfulness. This group corresponds

to the patients without evident signs of regular problems of memory with
short term
0,5 = Mild consistent forgetfulness; partial recollection of events; benign

forgetfulness. Moderate forgetting. Tendency to forget the details of
conversations, events; can repeat questions. Small impact on the activities of
the everyday life.
1 = Moderate memory loss, more marked for recent events; defect interferes
with everyday activities. A regular change of the memory for the details of
the recent events, the conversations. The deficit disturbs the activities and
the habits of the everyday life.

CDR-SB: Rating example for memory
2 = Severe memory loss; only highly learned materials retained; new material
rapidly lost. Severe / substantial loss of the capacity to memorize new
information or recent events. The former memories become inconsistent.
The chronology of the former events is often confused.
3 = Severe memory loss; only fragments remain. The new learning / the
recent memory are, for the main part, non-existent. Loss of substantial
memory of the former facts, including loss of memory important for
numerous events of the life.

CDR-SB in AB09004 study
After the scoring of each domain, there is a global scoring: use the calculator
http://www.biostat.wustl.edu/~adrc/cdrpgm/index.html
This score will be reported in the e-CRF.

Agenda
Introduction

ADAS-Cog
ADCS-ADL

MMSE
NPI
CDR-SB
CIBIC plus

CIBIC-plus
Clinicians Interview Based Impression of Change-plus (CIBIC-plus)

Administered by independent clinician with patient and caregiver.
It has to be assessed by the same assessor throughout the study, this
assessor should be experienced in evaluating patients with dementia.
(MD)
To assess the clinical condition change from baseline
7-point categorical rating, ranging from a score of 1, indicating markedly

improved, to a score of 4, indicating no change to a score of 7,
indicating markedly worse
It takes 30 to 45 minutes.

CIBIC-plus: Rating
The CIBIC must be completely based on the information collected during a

semi-structured interview with the patient and the caregiver.
The CIBIC-plus allows to estimate the condition of the patient and his
modification in 13 fields of activity allowing to quote four main trunk parts of
functioning:
the cognitive and mental functioning,
the behavior,
the activities of the everyday life,
and a general impression of functioning.
The examiner has a sheet with questions of examination which is used as a

guide to question the patient, in a free order. The sheet specifies for every
domain the activities that must be investigated.

CIBIC-plus: Interpretation
The examiner has to remain independent and cannot question other study
participant.
Before the initial interview, the examiner has to get acquainted with all the
accessible information sources on the behavior of the patient, including the
history, the data of the clinical examination, the results of the tests
After the initial interview, the examiner cant anymore consult patient data.

CIBIC-plus: Record form

CIBIC-plus: Results
Based on the evaluation of change of the patient by confronting the day

impression to the initial examination
Not assessed 0
Marked improvement 1
Moderate improvement 2
Minimal improvement 3
No change 4
Minimal worsening 5
Moderate worsening 6
Marked worsening 7

Thanks for your attention!

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AB09004 study

Training for Alzheimer disease tests and

December 2011 AB09004 training 1

Training on co-primary endpoints of AB09004 study

Quiz on ADAS-Cog and ADCS-ADL

Investigator training on secondary endpoints

December 2011 AB09004 training 2

Training on co-primary endpoints of AB09004 study

Quiz on ADAS-Cog and ADCS-ADL

Investigator training on secondary endpoints

December 2011 AB09004 training 3

ADAS-Cog and ADCS-ADL are primary criteria for study AB09004

December 2011 AB09004 training 4

All examiners should be used to conduct neuropsychological tests

December 2011 AB09004 training 5

Examiner throughout the study:

December 2011 AB09004 training 6

*form of ADAS-Cog test to be administered

December 2011 AB09004 training 7

Printed questionnaires / interview guide will be provided in local language.

ADAS-Cog and ADCS-ADL are printed in duplicate.

MMSE, NPI, CDR-SB and CIBIC-plus are single-printed.

ADAS-Cog material will be provided.

December 2011 AB09004 training 8

Training on co-primary endpoints of study AB09004

Quiz on ADAS-Cog and ADCS-ADL

Investigator training on secondary endpoints

December 2011 AB09004 training 9

The ADAS-Cog is a commonly used objective measure of cognitive change. There

The test includes three additional subjective scales containing assessment of

This test takes about 30 minutes

December 2011 AB09004 training 10

In AB09004 study, ADAS-Cog record form will be provided in your local

Material necessary for ADAS-Cog tests:

December 2011 AB09004 training 11

1. Spoken language ability * (0-5 points)

* Involve subjective ratings

December 2011 AB09004 training 12

General Testing Principles

December 2011 AB09004 training 13

Overarching Principle: Obtain the best performance the patient is capable

December 2011 AB09004 training 14

Overarching Principle: Obtain the best performance the patient is capable

A subject can never perform better than his allowed abilities on

December 2011 AB09004 training 15

Initial interview/conversation (item 1-3)

This conversation is used for following purposes:

Rating patients on language measures (items 1-3)

December 2011 AB09004 training 16

Spoken language ability (item 1)

0= no instances where it is difficult to understand the patient

December 2011 AB09004 training 17

Scoring from 0 to 5 points

December 2011 AB09004 training 18

0=no evidence of poor comprehension

December 2011 AB09004 training 19

Scoring from 0 to 5 points

December 2011 AB09004 training 20

Word finding difficulty in spontaneous speech (item 3)

0= no evidence of word finding difficulty in spontaneous speech

December 2011 AB09004 training 21

Scoring from 0 to 5 points

December 2011 AB09004 training 22

Word recall task (item 4)