Follow-up · Neuropsychiatric Inventory NPI (12 item) Functional Assessment Questionnaire Symptoms Checklist Adverse Events - Hospitalizations (1) Adverse Events - Hospitalizations

Case Report Form WP5 / P001 / _ _ / _ _ / T_ _

Follow-up

Barcelona

Brescia

Duisburg-Essen

Leipzig

Lille

Marseille

Toulouse

CENTRE:

Investigator name:

Patient number:

Date:

D D M M Y Y

2 / 62


3 / 62


Index

Continue or withdrawal

Cognitive History

Medical History

Concomitant medications for symptomatic treatment of dementia

Psychotropic Medications

Other Concomitant Medications

Vital Signs

Physical Examination

Neurological Examination

Geriatric Depression Scale

Clinical Dementia Rating (CDR)

Neuropsychiatric Inventory NPI (12 item)

Functional Assessment Questionnaire

Symptoms Checklist

Adverse Events - Hospitalizations (1)

Adverse Events - Hospitalizations (2)

Comments

Neuropsychological assessment

Biomarker collection

Diagnostic summary

Early Discontinuation / End of Study

Appendix - Excluded medications

Appendix - Adverse event recording

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14

42

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54

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59

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New symptoms at the follow-up

Symptoms in chronological orderSign 1,2,3...

__ __ __ __ __ __ __ __ __

Current symptoms

Memory deficitOther cognitive deficit (specify: ___________________________________________)Personality changeTopographic disorientationApraxiaBradycinesiaGait disturbanceFallsOther (specify: ___________________________________________)



Cognitive history

Continue or withdrawal

Does the patient continue the study?

if no, detail the reason in the End of Study section

yesno

5 / 62


Is there a change relative to the previous visit?

If yes, fill in the pertinent items

Psychiatric:

______________________________

Neurologic (other than MCI):

______________________________

Depression (date of first episode)

Head, Eyes, Ears, Nose and Throat:

______________________________

Cardiovascular:

______________________________

Hypercholesterolemia

Hypertension

Ischaemic heart disease

Respiratory:

______________________________

Hepatic:

______________________________

Dermatologic-Connective Tissue:

______________________________

Muscoloskeletal:

______________________________

Endocrine-Metabolic:

______________________________

Gastrointestinal:

______________________________

Hematopoietic-Lymphatic:

______________________________

__ __ __ __

__ __ __ __

__ __ __ __

__ __ __ __

__ __ __ __

__ __ __ __

__ __ __ __

__ __ __ __

__ __ __ __

__ __ __ __

__ __ __ __

__ __ __ __

__ __ __ __

__ __ __ __

__ __ __ __

yes no

yes no

yes no

yes no

yes no

yes no

yes no

yes no

yes no

yes no

yes no

yes no

yes no

yes no

yes no

yes no

yes no

yes no

yes no

yes no

yes no

yes no

yes no

yes no

yes no

yes no

yes no

yes no

yes no

yes no

Medical history

Year of diagnosisArea/medical condition Ongoing Stable

yesno

6 / 62


Renal-Genitourinary:

______________________________

Allergies or drug sensitivies:

______________________________

Alcohol Abuse

Drug abuse:

______________________________

Malignancy:

______________________________

Other:

______________________________

__ __ __ __

__ __ __ __

__ __ __ __

__ __ __ __

yes no

yes no

yes no

yes no

yes no

yes no

yes no

yes no

Year of diagnosisArea/medical condition Ongoing Stable

Medical history

__ __ __ __

__ __ __ __

yes no

yes no

yes no

yes no

Concomitant medications for symptomatic treatment of dementia

Drug name (trade)

________________

Drug name (trade)

________________

Drug name (trade)

________________

Drug name (trade)

________________

Dose

________________

Dose

________________

Dose

________________

Dose

________________

Start Date

__ __ __ __ __ __

Start Date

__ __ __ __ __ __

Start Date

__ __ __ __ __ __

Start Date

__ __ __ __ __ __

D

D

D

D

D

D

D

D

M

M

M

M

M

M

M

M

Y

Y

Y

Y

Y

Y

Y

Y

End Date

__ __ __ __ __ __

End Date

__ __ __ __ __ __

End Date

__ __ __ __ __ __

End Date

__ __ __ __ __ __

D

D

D

D

D

D

D

D

M

M

M

M

M

M

M

M

Y

Y

Y

Y

Y

Y

Y

Y

Is there change in the medication since the last visit? If yes, fill in the pertinent items.

Yes No

If medication is ongoing, leave end date blank

7 / 62


Other Concomitant Medications

Drug name (trade)

________________

Drug name (trade)

________________

Drug name (trade)

________________

Drug name (trade)

________________

Drug name (trade)

________________

Drug name (trade)

________________

Indication

________________

Indication

________________

Indication

________________

Indication

________________

Indication

________________

Indication

________________

Psychotropic medications

Drug name (trade)

________________

Drug name (trade)

________________

Drug name (trade)

________________

Drug name (trade)

________________

Indication

________________

Indication

________________

Indication

________________

Indication

________________

Start Date

__ __ __ __ __ __

Start Date

__ __ __ __ __ __

Start Date

__ __ __ __ __ __

Start Date

__ __ __ __ __ __

D

D

D

D

D

D

D

D

M

M

M

M

M

M

M

M

Y

Y

Y

Y

Y

Y

Y

Y

Start Date

__ __ __ __ __ __

Start Date

__ __ __ __ __ __

Start Date

__ __ __ __ __ __

Start Date

__ __ __ __ __ __

Start Date

__ __ __ __ __ __

Start Date

__ __ __ __ __ __

D

D

D

D

D

D

D

D

D

D

D

D

M

M

M

M

M

M

M

M

M

M

M

M

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

End Date

__ __ __ __ __ __

End Date

__ __ __ __ __ __

End Date

__ __ __ __ __ __

End Date

__ __ __ __ __ __

D

D

D

D

D

D

D

D

M

M

M

M

M

M

M

M

Y

Y

Y

Y

Y

Y

Y

Y

End Date

__ __ __ __ __ __

End Date

__ __ __ __ __ __

End Date

__ __ __ __ __ __

End Date

__ __ __ __ __ __

End Date

__ __ __ __ __ __

End Date

__ __ __ __ __ __

D

D

D

D

D

D

D

D

D

D

D

D

M

M

M

M

M

M

M

M

M

M

M

M

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Is there change in the medication since the last visit? If yes, fill in the pertinent items. If medication is ongoing, leave end date blank.

Yes No

Is there change in the medication since the last visit? If yes, fill in the pertinent items. If medication is ongoing, leave end date blank.

Yes No

8 / 62


01

02

03

04

05

06

07

08

09

10

11

12

Weight

Height

Blood pressure (supine)

Systolic

Diastolic

Pulse (supine)

One leg balance:Is the patient able to stand at least 5 seconds on one leg? (leg of his/her choice).The patient must keep eyes open and shoes on.



General appearance

Head, Eyes, Ears,Nose and Throat

Neck

Chest

Heart

Abdomen

Extremities

Edema

Peripheral vascular

Skin and Appendages

Muscoloskeletal

Other

Vital signs

Physical examination

YesNo

__ __ __ Kg

__ __ __ cm

__ __ __ /min

__ __ __ mm Hg

__ __ __ mm Hg

abnormal Details: ________________________________normal












yesno

9 / 62


01

02

03

04

05

06

07

08

09

10

11

12

13

14



Significant Visual Impairment

Significant Auditory Impairment

Tremor

Level of consciousness

Cranial nerves

Motor strength

Cerebellar - Finger to Nose

Cerebellar - Heel to Shin

Sensory

Deep tendon reflexes

Plantar reflexes

Gait

Parkinsonism signs

Other

Neurological examination

abnormal Details: ______________________________normal

present Details: ______________________________absent










abnormal

present

present

Details: ______________________________

Details: ______________________________

Details: ______________________________

normal

absent

absent

yesno

10 / 62


01

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29

30

InstructionsInstruct the subject: “in the next part of this interview, I will ask you questions about your feelings. Some of the questions I will ask you may not apply, and some may make you feel uncomfortable. For each question, please answer “yes” or “no”, depending on how you have been feeling in the past week, including today.”

Are you basically satisfied with your life?

Have you dropped many of your activities and interests?

Do you feel that your life is empty?

Do you often get bored?

Are you hopeful about the future?

Are you bothered by thoughts you can’t get out of your head?

Are you in good spirits most of the time?

Are you afraid that something bad is going to happen to you?

Do you feel happy most of the time?

Do you often feel helpless?

Do you often get restless and fidgety?

Do you prefer to stay at home, rather than going out and doing new things?

Do you frequently worry about the future?

Do you feel you have more problems with memory than most?

Do you think it is wonderful to be alive now?

Do you often feel downhearted and blue?

Do you feel pretty worthless the way you are now?

Do you worry a lot about the past?

Do you find life very exciting?

Is it hard for you to get started on new projects?

Do you feel full of energy?

Do you feel that your situation is hopeless?

Do you think that most people are better off than you are?

Do you frequently get upset over little things?

Do you frequently feel like crying?

Do you have trouble concentrating?

Do you enjoy getting up in the morning?

Do you prefer to avoid social gatherings?

Is it easy for you to make decisions?

Is your mind as clear as it used to be?

Geriatric depression scale

Symptoms YES NO

0 1

1 0

1 0

1 0

0 1

1 0

0 1

1 0

0 1

1 0

1 0

1 0

1 0

1 0

0 1

1 0

1 0

1 0

0 1

1 0

0 1

1 0

1 0

1 0

1 0

1 0

0 1

1 0

0 1

0 1

TOTAL SCORE

11 / 62


Clinical Dementia Rating (CDR)

Indicate the appropriate level for each domain

none0

questionable0.5

mild1

moderate2

severe3

Memory

No memory loss or slight inconsistent forgetfulness.

Consistent slight forget-fulness; partial recollec-tion of events; “benign” forgetfulness.

Moderate memory loss; more marked for recent events; defect interferes with everyday activities.

Severe memory loss; only highly learned material retained; new material rapidly lost.

Severe memory loss;only fragments remain.

Orientation

Fully oriented. Fully oriented except for slight difficulty with time relationships.

Moderate difficulty with time relationships; oriented for place at examination; may have geographic disorienta-tion elsewhere.

Severe difficulty with time relationships; usu-ally disoriented to time, often to place.

Oriented to person only.

Judgment & Problem Solving

Solves everyday problems & handles business & financial affairs well; judgment good in relation to past performance.

Slight impairment in solv-ing problems, similarities, and differences.

Moderate difficulty in handling problems, simi-larities, and differences; social judgment usually maintained.

Severely impaired in handling problems, simi-larities, and differences; social judgment usually impaired.

Unable to make judg-ments or solve problems.

Community Affairs

Independent function at usual level in job, shopping, volunteer and social groups.

Slight impairment in these activities.

Unable to function independently at these activities although may still be engaged in some; appears normal to casual inspection.

No pretence of independ-ent function outside home. Appears well enough to taken to func-tions outside a family home.

No pretence of independ-ent function outside home.Appears too ill to be taken to functions out-side a family home.

Home & Hobbies

Life at home, hobbies, and intellectual interests well maintained.

Life at home, hobbies, and intellectual interests slightly impaired.

Mild but definite impair-ment of function at home; more difficult chores abandoned; more complicated hobbies and interests abandoned.

Only simple chores preserved; very restricted interests, poorly maintained.

No significant function in home.

Personal Care

Fully capable of self-care. Needs prompting. Requires assistance in dressing, hygiene, keep-ing of personal effects.

Requires much help with personal care; frequent incontinence.

Fully capable of self-care

TOTAL SCORE:

12 / 62


Delusions

Hallucinations

AgitationAgression

DepressionDysphoria

Anxiety

ElationEuphoria

ApathyIndifference

Disinhibition

IrritabilityLability

Aberrant motorbehaviour

Sleep

Appetite andeating disorders

TOTAL SCORE: __ __

Scoring Summary

For each domain:If a domain is absent, tick the “0”. If a domain is present, tick one score each for Frequency and Severity.Tick one score for Distress.

Neuropsychiatric Inventory NPI (12 item)

n/a absent frequency severity distress

10 1 12 2 23 3 3 4 54

13 / 62


Writing checks, paying bills,or balancing checkbook

Assembling tax records,business affairs, or other papers

Shopping alone for clothes,household necessities, or groceries

Playing a game of skill such as bridge or chess, working on a hobby

Heating water, making a cup of coffee,turning off the stove

Preparing a balanced meal

Keeping track of current events

Paying attention to andunderstanding a TV program,book, or magazine

Remembering appointments,family occasions, holidays,medications

Travelling out of the neighbourhood,driving, or arranging to takepublic transportation

TOTAL SCORE: __ __

Instructions:Select the most accurate representation of the participant’s level of ability to perform each activity over the preceding four weeks, based on the Study Partner’s assessment.

Functional Assessment Questionnaire

0 normal0 never did, but could do now

1 never did, would have difficulty now1 has difficulty, but does by self

2 requires assistance3 dependent

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InstructionsConsidering the preceding six months, check “Absent” or “Present” for each symptom listed below.If “Present,” in the “Details” provide the required information.

Nausea

Description of Symptom

_______________________________________________________

Severity

Chronicity

Date of OnsetIf Month and/or Day is unknown, enter ‘ - - ’ in their place. A valid year must be provided.

__ __ __ __ __ __ __ __

Is the symptom ongoing?

Symptoms Checklist

01

AbsentPresent

YesNo

Date CeasedIf Month and/or Day is unknown, enter ‘ - - ’ in their place. A valid year must be provided.If Event is ongoing, leave Cease Date blank.

__ __ __ __ __ __ __ __

MildModerateSevere

Single occurrenceIntermittentPersistent

Day

Day

Month

Month

Year

Year

15 / 62


Vomiting


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


02

AbsentPresent

YesNo


__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

16 / 62


Diarrhoea


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


03

AbsentPresent

YesNo


__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

17 / 62


Constipation


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


04

AbsentPresent

YesNo

Date CeasedIf Month and/or Day is unknown, enter ‘ - - ’ in their place.A valid year must be provided.If Event is ongoing, leave Cease Date blank.

__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

18 / 62


Abdominal discomfort


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


05

AbsentPresent

YesNo


__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

19 / 62


Sweating


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


06

AbsentPresent

YesNo


__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

20 / 62


Dizziness


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


07

AbsentPresent

YesNo


__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

21 / 62


Low energy


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


08

AbsentPresent

YesNo


__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

22 / 62


Drowsiness


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


09

AbsentPresent

YesNo


__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

23 / 62


Blurred vision


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


10

AbsentPresent

YesNo


__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

24 / 62


Headache


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


11

AbsentPresent

YesNo


__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

25 / 62


Dry mouth


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


12

AbsentPresent

YesNo


__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

26 / 62


Shortness of breath


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


13

AbsentPresent

YesNo


__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

27 / 62


Coughing


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


14

AbsentPresent

YesNo


__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

28 / 62


Palpitations


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


15

AbsentPresent

YesNo


__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

29 / 62


Chest pain


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


16

AbsentPresent

YesNo


__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

30 / 62


Urinary discomfort (e.g. burning)


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


17

AbsentPresent

YesNo


__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

31 / 62


Urinary frequency


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


18

AbsentPresent

YesNo


__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

32 / 62


Ankle swelling


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


19

AbsentPresent

YesNo


__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

33 / 62


Muscoloskeletal pain


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


20

AbsentPresent

YesNo


__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

34 / 62


Rash


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


21

AbsentPresent

YesNo


__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

35 / 62


insomnia


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


22

AbsentPresent

YesNo


__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

36 / 62


Depressed mood


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


23

AbsentPresent

YesNo


__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

37 / 62


Crying


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


24

AbsentPresent

YesNo


__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

38 / 62


Elevated mood


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


25

AbsentPresent

YesNo


__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

39 / 62


Wandering


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


26

AbsentPresent

YesNo


__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

40 / 62


Fall


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


27

AbsentPresent

YesNo


__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

41 / 62


Other


_______________________________________________________

Severity

Chronicity


__ __ __ __ __ __ __ __


28

AbsentPresent

YesNo


__ __ __ __ __ __ __ __

MildModerateSevere


Day

Day

Month

Month

Year

Year

Symptoms Checklist

42 / 62


InstructionsThe following should be reported as Adverse Events: New symptoms. Previous symptoms that have worsened in chronicity or severity. If a diagnosis has been made, enter the diagnosis name under Event. Any symptoms associated with the diagnosis should be recorded in the Comments section of this form. Do not record associated symptoms as separate Adverse Events. At each visit, the Participant should be asked about the status of each Adverse Event.If no adverese events are reported, leave this section blank.Print more copies of this section if necessary.

AE N° Examination date

__ __ __ __ __ __ __ __ __ __ __

Event (Diagnosis or Symptom if diagnosis is not known)If a diagnosis is reported here, DO NOT report the associated symptoms as separate Adverse Events. Record associated symptoms under the Comments section of this form. * If an event description can be clarified with a keyword, please include that in parenthesis in the Event field (Example: “repeatedly combs hair (behaviour)”)

(_______________________________________________________________________________________________)

Check here if:

Onset DateIf Month and/or Day are unknown, enter ‘--’ in their place. A valid year must be provided.

__ __ __ __ __ __ __ __

Is the event ongoing?

Is the event a worsening of previous symptoms?

Severity Chronicity

YesNo


__ __ __ __ __ __ __ __

YesNo

MildModerateSevere


Month

Day

Day

Day

Month

Month

Year

Year

Year

Adverse Events - Hospitalization

this symptom was reported on the Baseline Symptoms Checklist,but has worsened in chronicity or severity.

43 / 62



Serious?If yes, refer to SOP GEST06 Management of SAE and send the SAE form within 24h of SAE occurrence to the sponsor by fax (in Italy IRCCS-FBF: number ++39303501592, in other countries Qualissima: number 0033488151440)

Serious Adverse Event Reported By:

__________________________________________________________________

Reason for Qualifying as Serious Adverse Event:

__________________________________________________________________

Life-threatening?If Yes, Serious must also be answered Yes.

Related to Imaging Procedure?

Related to Lumbar Puncture?

Related to other procedures of the study? (specify: _________________________________________________)

Concurrent Medication Prescribed or Changed?If Yes, update other concomitant medication section and put the AE number as treatment indication.

Did this event occur while the participant was being hospitalized for another event?

If Yes, did this event prolong hospitalization?If Yes, Serious must also be answered Yes.

YesNo

YesNo

YesNo

DefinitelyPossiblyNot Related



YesNo

YesNo

No Yes - OutpatientYes - Inpatient

If No, did this event require hospitalization?If Inpatient, Serious must be answered Yes.NOTE: All medications received during hospitalization must be reported on the Other Concomitant Medication section.

44 / 62


YesNo

Date of death

__ __ __ __ __ __ __ __

If Outpatient, provide the date of visit

__ __ __ __ __ __ __ __

If Inpatient, provide the date of hospitalization

Admit Date

__ __ __ __ __ __ __ __

Admit Diagnosis

________________________________________________________________________________________________

Discharge Date

__ __ __ __ __ __ __ __

Discharge Diagnosis

________________________________________________________________________________________________

Did this event result in death?If Yes, Serious must also be answered Yes


Day

Day

Day

Month

Month

Month

Year

Year

Year

Day Month Year

Cause of death:

____________________________________________________________________________________________________________________________________________________________________________________

45 / 62



InstructionsThe following should be reported as Adverse Events: New symptoms. Previous symptoms that have worsened in chronicity or severity. If a diagnosis has been made, enter the diagnosis name under Event. Any symptoms associated with the diagnosis should be recorded in the Comments section of this form. Do not record associated symptoms as separate Adverse Events. At each visit, the Participant should be asked about the status of each Adverse Event.If no adverese events are reported, leave this section blank.Print more copies of this section if necessary.

AE N° Examination date

__ __ __ __ __ __ __ __ __ __ __

Event (Diagnosis or Symptom if diagnosis is not known)If a diagnosis is reported here, DO NOT report the associated symptoms as separate Adverse Events. Record associated symptoms under the Comments section of this form. * If an event description can be clarified with a keyword, please include that in parenthesis in the Event field (Example: “repeatedly combs hair (behaviour)”)

(_______________________________________________________________________________________________)

Check here if:

Onset DateIf Month and/or Day are unknown, enter ‘--’ in their place. A valid year must be provided.

__ __ __ __ __ __ __ __

Is the event ongoing?

Is the event a worsening of previous symptoms?

Severity Chronicity

YesNo


__ __ __ __ __ __ __ __

YesNo

MildModerateSevere


Month

Day

Day

Day

Month

Month

Year

Year

Year

this symptom was reported on the Baseline Symptoms Checklist,but has worsened in chronicity or severity.

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Serious?If yes, refer to SOP GEST06 Management of SAE and send the SAE form within 24h of SAE occurrence to the sponsor by fax (in Italy IRCCS-FBF: number ++39303501592, in other countries Qualissima: number 0033488151440)

Serious Adverse Event Reported By:

__________________________________________________________________

Reason for Qualifying as Serious Adverse Event:

__________________________________________________________________

Life-threatening?If Yes, Serious must also be answered Yes.

Related to Imaging Procedure?

Related to Lumbar Puncture?

Related to other procedures of the study? (specify: _________________________________________________)

Concurrent Medication Prescribed or Changed?If Yes, update other concomitant medication section and put the AE number as treatment indication.

Did this event occur while the participant was being hospitalized for another event?

If Yes, did this event prolong hospitalization?If Yes, Serious must also be answered Yes.

YesNo

YesNo

YesNo




YesNo

YesNo

No Yes - OutpatientYes - Inpatient

If No, did this event require hospitalization?If Inpatient, Serious must be answered Yes.NOTE: All medications received during hospitalization must be reported on the Other Concomitant Medication section.

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YesNo

Date of death

__ __ __ __ __ __ __ __

If Outpatient, provide the date of visit

__ __ __ __ __ __ __ __

If Inpatient, provide the date of hospitalization

Admit Date

__ __ __ __ __ __ __ __

Admit Diagnosis

________________________________________________________________________________________________

Discharge Date

__ __ __ __ __ __ __ __

Discharge Diagnosis

________________________________________________________________________________________________

Did this event result in death?If Yes, Serious must also be answered Yes


Day

Day

Day

Month

Month

Month

Year

Year

Year

Day Month Year

Cause of death:

____________________________________________________________________________________________________________________________________________________________________________________

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Use comments section to clarify vague or problematic symptoms such as dizziness, chest pain, abdominal discomfort or the circumstances surrounding falls and trauma. If the circumstances of a fall or trauma reveal additional AEs or symptoms such as light-headedness, poor balance, visual disturbance, etc., record these as additional AEs and briefly describe the scenario in the comments section under one of the related symptoms.

Comments

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DOA: date of administration - TOB: time of beginning - TOE: time of end


ADAS-COG DOA: __ __ / __ __ / __ __ __ __ TOB: __ __ : __ __ TOE: __ __ : __ __

Word recall trial 1

Word recall trial 2

Word recall trial 3

Command

Constructional praxis

Delayed Word-recall

Naming Objects/Fingers

Ideational Praxis

Orientation

Word Recognition

sco

re Remembering test instructions

NoneVery mildMildModerateModerately severeSevere

Word finding difficulty


Comprehension


Spoken language ability


If the test or a subtest has not been administered, sign N.A. in the corresponding score box and check one:

Not done (for reasons other than physical/cognitive)Patient refusedPatient unable for physical reasonsPatient unable for cognitive reasons

Number cancellation

Number of targets hit

Number of errors

Number of times reminded of task

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AVLT DOA: __ __ / __ __ / __ __ __ __ TOB: __ __ : __ __ TOE: __ __ : __ __

Immediate recall

Delayed recall

Recognition

Clock Drawing Test DOA: __ __ / __ __ / __ __ __ __ TOB: __ __ : __ __ TOE: __ __ : __ __

Clock drawing

Clock copying

Trail Making Test DOA: __ __ / __ __ / __ __ __ __ TOB: __ __ : __ __ TOE: __ __ : __ __

Score

Errors of Commission

Errors of Omission

Score

Errors of Commission

Errors of Omission






pa

rt A

pa

rt B

score

raw score corrected score




score

score

score

score

sco

re

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WAIS-R Digit Symbol Substitution Test DOA: __ __ / __ __ / __ __ __ __ TOB: __ __ : __ __ TOE: __ __ : __ __

Total score

Boston Naming Test DOA: __ __ / __ __ / __ __ __ __ TOB: __ __ : __ __ TOE: __ __ : __ __

Total score

Digit Span Forward DOA: __ __ / __ __ / __ __ __ __ TOB: __ __ : __ __ TOE: __ __ : __ __

Total score

Digit Span Backward DOA: __ __ / __ __ / __ __ __ __ TOB: __ __ : __ __ TOE: __ __ : __ __

Total score














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Category fluency test DOA: __ __ / __ __ / __ __ __ __ TOB: __ __ : __ __ TOE: __ __ : __ __

Total score

Letter fluency test DOA: __ __ / __ __ / __ __ __ __ TOB: __ __ : __ __ TOE: __ __ : __ __

Total score raw score corrected score









Mini Mental State Examination DOA: __ __ / __ __ / __ __ __ __ TOB: __ __ : __ __ TOE: __ __ : __ __

Orientation

Immediate recall

Attention and calculation

Delayed recall

Naming

Repetition

Command

Reading

Writing

Construction

TOTAL SCORE

sco

re

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CANTAB DOA: __ __ / __ __ / __ __ __ __ TOB: __ __ : __ __ TOE: __ __ : __ __

Motor Control Task (MOT) - doa: __ __ / __ __ / __ __ __ __ tob: __ __ : __ __ toe: __ __ : __ __

Reaction Time (RTI) - doa: __ __ / __ __ / __ __ __ __ tob: __ __ : __ __ toe: __ __ : __ __

Five choice movement time

Five choice reaction time

Delayed Matching to Sample (DMS) - doa: __ __ / __ __ / __ __ __ __ tob: __ __ : __ __ toe: __ __ : __ __

Percent correct (all delays)

Percent correct (simultaneous)

Prob error given error

Paired Associate Learning (PAL) - doa: __ __ / __ __ / __ __ __ __ tob: __ __ : __ __ toe: __ __ : __ __

Total errors (adjusted)

Total errors (6 shapes, adjusted)

Spatial Working Memory (SWM) - doa: __ __ / __ __ / __ __ __ __ tob: __ __ : __ __ toe: __ __ : __ __

Between errors

Strategy

Rapid Visual Information Processing (RVP) - doa: __ __ / __ __ / __ __ __ __ tob: __ __ : __ __ toe: __ __ : __ __

Score

Pattern Recognition Memory (PRM) - doa: __ __ / __ __ / __ __ __ __ tob: __ __ : __ __ toe: __ __ : __ __

immediate - percent correct

delayed - percent correct

Spatial Recognition Memory - doa: __ __ / __ __ / __ __ __ __ tob: __ __ : __ __ toe: __ __ : __ __

Percent correct

Logical Memory DOA: __ __ / __ __ / __ __ __ __ TOB: __ __ : __ __ TOE: __ __ : __ __

Immediate recall total score

Delayed recall total score



sco

resc

ore

sco

resc

ore

sco

re

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Biomarker collection

MR scan

Done

Not done Reason: ______________________________________________

Not scheduled because of visit

Not scheduled because of centre

Blood

Done ID: _ / _ _ _ / _ _ / _ / _ _ / _ _ _ / _ _ _ / _ _ / _ _ _ _

Not done Reason: ______________________________________________



CSF

Done ID: _ / _ _ _ / _ _ / _ / _ _ / _ _ _ / _ _ _ / _ _ / _ _ _ _

Not done Reason: ______________________________________________



EEG

Done

Not done Reason: ______________________________________________



Actigraphy

Done

Not done Reason: ______________________________________________



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01

02

Instructions:This form should be completed by a physician at every in-clinic visit to confirm the participant’s current diagnosis and whether a conversion has occurred.

Date form completed

__ __ __ __ __ __ __ __

Has there been a conversion to dementia?

In the case of patient discontinuation from the study, detail the reason:

In case of early discontinuation, fax this leaf to YOUR sponsor:

In Italy, address it to IRCCS-FBF (fax number 0039 030 350 159 2)

In other countries, address to Qualissima (fax number 0033 488 151 440)

Diagnostic summary

Early Discontinuation / End of Study

YesNo

Day Month Year

If Yes

Withdrawal of consent(in this case, refer to SOP GEST08 Human sample management to manage biological samples of patient)

Withdrawal because of investigator decisiondetail reason: ____________________________________________________________________________

Occurrence of an adverse event which need the stop of study(fill in the AE/SAE section)

Occurrence of an exclusion criteriadetail: __________________________________________________________________________________

Progression to dementia (fill in the Diagnostic summary section)

Otherdetail: __________________________________________________________________________________

Scheduled/normal end of the study

Date of patient discontinuation:

__ __ __ __ __ __ __ __

Alzheimer’s diseaseother dementia (____________________________________________)

Day Month Year

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EXCLUDED MEDICATIONS

PERMITTED MEDICATIONS

Change in Medication After Enrolment

Antidepressants with anti-cholinergic properties are excluded.Regular use of narcotic analgesics (>2 doses per week) within 4 weeks of screening.Use of neuroleptics with anti-cholinergic properties (e.g., chlorpromazine, thioridazine) within 4 weeks of screening.Chronic use of other medications with significant central nervous system anticholinergic activity within 4 weeks of screening (e.g., diphenhydramine).Use of Anti-Parkinsonian medications (including Sinemet, amantadine, bromocriptine, pergolide, selegeline) within 4 weeks of screening.Participation in any other investigational drug study within 4 weeks of screening (individuals may not participate in any drug study while participating in this protocol).Diuretic drugs should not be started or discontinued within 4 weeks prior to screening. Any change in diuretic medication during the study should be reported.

Cholinesterase inhibitors and memantine are permitted if the dose is stable for 4weeks prior to screening.Use of estrogen and estrogen-like compounds is allowed if the dose has been stable for 4 weeks prior to screening.Use of vitamin E is allowed if the dose has been stable for 4 weeks prior to screening (no cap on amount allowed).

Exceptions to these criteria may be considered on a case-by-case basis at the discretion of the Protocol PI (Dr. Frisoni).

Any change in medication (including dose or frequency) should be recorded on the ‘Concurrent Medications Log’ for the visit it is reported. If a subject begins an excluded medication, the site must document this by requesting an exception from the Protocol PI (Dr. Frisoni). If a subject begins a cholinesterase inhibitor or memantine after being approved for enrolment into the study, this should be documented by completing an additional comment form describing the reason for the protocol deviation.


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Please note: This is not a complete list of excluded medications.For drugs not on this list, query the Study PI (Dr. Frisoni).

NARCOTIC ANALGESICS: Not allowed within 4 weeks prior to screening

General name:

NEUROLEPTICS: Not allowed within 4 weeks prior to screening

General name:

ANTICHOLINERGIC AGENTS: Not allowed within 4 weeks prior to screening

General name:

ANTIPARKINSONIAN MEDICATIONS: Not allowed within 4 weeks prior to screening

General name:

Oxycodone/AcetaminophenOxycodone/AspirinPropoxyphene Darvon and its variationsNarcotics that contain codeine or morphine

ChlorpromazineFluphenazineLoxapinePerphenazineThioridazineThiothixeneTrifluoperazineClozapineHaloperidol

Use of followings is permitted if dose is stable for 4 weeks prior to visit

AripiprazoleOlanzapineQuetiapineRisperidone (up to 2 mg/die)Ziprasidone

AmantadineBenztropineCyproheptadineDicyclomineDiphenhydramineDiphenoxylate with atropineHydroxyzineHyoscyamineMeclizineProchlorperazineTrihexyphenidylTrimethobenzamide

BromocriptineSelegilineLevodopaPergolidePramipexole


LIST OF EXCLUDED MEDICATIONS

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INVESTIGATIONAL DRUGS: Not allowed within 4 weeks prior to screening

SEDATIVES / BENZODIAZEPINES: Not allowed within 4 weeks prior to screening

General name:

ANTIHYPERTENSIVE AGENTS WITH FREQUENT CNS SIDE-EFFECTS:Not allowed 4 weeks prior to screening

General name:

ANTIDEPRESSANTS: Not allowed within 4 weeks prior to screening

General name:

ChlordiazepoxideClonazepamDiazepamFlurazepamMeprobamateTriazolam

Allowed if on stable doses 4 weeks prior to screening:

AlprazolamBuspironeChloral HydrateLorazepamOxazepamTemazepamTrazodoneZaleplonZolpidem

Clonidine

AmitriptylineAmoxapineClomipramineDesipramineDoxepinImipramineIsocarboxazideLithiumMaprotilineNortriptylinePhenelzineProtriptylineTranylcypromineTrimipramine

Use of the following is permitted if dose is stable 4 weeks prior to screening:

BupropionWellbutrinCitalopramDuloxetineEscitalopramFluoxetineMirtazapineNefazodoneParoxetineSertralineTrazodoneVenlafaxine


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AE - Definition of Severity:

AE - Relationship to Study Procedure:

SAE - A Serious Adverse Event is one that meets any of the following criteria:

Definition of Life-Threatening Event.An adverse experience is life threatening if, in the view of the investigator, the patient was at immediate risk of death from the reaction as it occurred.Hospitalization.When a patient is hospitalized in an acute care facility, the diagnosis or symptom that prompted hospitalization should be recorded on the serious Adverse Event Form. Visits to the emergency room that do not result in hospital admission should not be recorded as “inpatient.” Serious must always be answered ‘Yes’ when an event requires or prolongs hospitalization.Definition of Disabling / Incapacitating Event. An adverse event is incapacitating or disabling if the event results in a substantial and/or permanent disruption of the patient’s ability to carry out normal life functions.

Mild: Discomfort noticed, but no disruption of normal daily activity. Moderate: Discomfort sufficient to reduce or affect the normal daily activity.Severe: Incapacitating, with inability to work or perform normal daily activity.

Not Related: This category is applicable to those adverse events which, after careful medical consideration at the time of evaluation, are judged to be clearly, and beyond a reasonable doubt, due to extraneous causes (disease, environment, etc.). Additionally, the event does not meet the criteria for relationship to procedures as listed under Possibly Related or Definitely Related.

Possibly Related: This category applies to those adverse experiences in which the connection with the study procedure appears possible and cannot be ruled out with certainty. To be considered Possibly Related, the adverse experience should meet the following two criteria:

Definitely Related: This category applies to those adverse experiences which, after careful medical consideration at the time they are evaluated, are considered, beyond a reasonable doubt, to be related to the study procedure. To be considered Definitely Related, the adverse experience should meet the following criteria:

Fatal or immediately life-threateningCauses permanent or substantial disabilityRequires or prolongs inpatient hospitalization (acute)Congenital anomaly/birth defectIs a cancerSuggests any significant hazard, contraindication, side effect or precaution that may be associated with the use of a study procedureRegarded by the investigator as serious

It follows a reasonable temporal sequence from initiating the procedure. It could not be reasonably explained by the known characteristics of the patient’s clinical state, environmental or toxic factors, or modes of therapy administered (when applicable).

It follows a reasonable temporal sequence from initiating the procedure. It could not be reasonably explained by the known characteristics of the patient’s clinical state, environmental or toxic factors, or modes of therapy administered (when applicable).It follows a known pattern of response to the suspected procedure.

Appendix - Adverse event recording

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Documents

Follow-up · Neuropsychiatric Inventory NPI (12 item) Functional Assessment Questionnaire Symptoms Checklist Adverse Events - Hospitalizations (1) Adverse Events - Hospitalizations