Implications for Management of PET Amyloid Classification Technology

The primary purpose of this prospective, observational study is to examine the benefit of
[18F]Flutemetamol PET/CT scan in clinical practice for early diagnosis of cognitive
impairment and identifying Alzheimer's disease (AD) pathology. To accomplish this, when a
clinician has ordered an amyloid positron emission tomography (PET) scan, the investigators
will assess the impact of [18F]Flutemetamol PET/CT scans on 1) physician diagnosis and
management as it relates to care practices and drug management, and 2) patient reported
outcomes in patients evaluated in the Cognitive Disorders Clinic at the University of Utah
and meeting Appropriate Use Criteria (AUC) for clinical amyloid PET/CT scans. A secondary
purpose is to compare the semi-quantitative assessment of amyloid plaque burden using vendor
supplied software and standard visual assessment of amyloid positivity.

The primary hypothesis is that, in diagnostically uncertain cases, knowledge of amyloid
status as determined by amyloid PET/CT scans may alter patient diagnosis and management and
lead to significant changes in patient and family reported outcomes. A secondary hypothesis
is that vendor supplied semi-quantitative assessment of amyloid plaque positivity will be
superior to standard visual criteria assessments.

Aims:

Aim 1: To assess the change in diagnosis and management including both care practices and
drug management of adult patients being evaluated for cognitive deficits and meeting
Appropriate Use Criteria (AUC).

Aim 2: To assess the change of amyloid PET/CT scans on patient-reported outcomes involving
care partner confidence and satisfaction.

Aim 3: To assess the confidence of visual interpretation by using vendor supplied
semi-quantitative software to assess amyloid plaque burden.

Hypotheses to be Tested - Synopsis The hypothesis is that to aid early diagnosis, individuals
with a diagnostically uncertain etiology for their dementia will benefit from knowledge of
amyloid plaque burden status through an alteration of patient diagnosis and management, which
will lead to significant changes in patient and care partner reported outcomes.

Aim 1

1. Amyloid PET will change physician judgment of the likelihood of AD

2. Amyloid PET will change the leading diagnosis in more than 25% of cases

3. Amyloid PET will increase physician diagnostic confidence in the leading diagnosis

4. Amyloid PET will change more than 25% of care practice options from pre-scan management

5. Amyloid PET will change more than 25% of drug management options

Aim 2

1. Care partners are more confident in the diagnosis after the scan than before the scan

2. Care partners will be more satisfied with multidisciplinary cognitive specialty team
evaluation than previous evaluation

3. Care partners will be more satisfied with multidisciplinary cognitive specialty team
evaluation with amyloid PET than than the evaluation non-specialists performed without
amyloid PET

4. Care partners will find amyloid PET not very burdensome if the doctor finds a scan
helpful

5. Based upon their experience with the amyloid PET scan, a majority of the care partners
would still agree to have an amyloid PET scan performed if it were requested by the
specialist

6. Care partners will find that amyloid PET did not cause an increase in adverse reactions
(scan visit) than standard routine clinic visit (post-scan visit)

7. Care partners will find that the diagnostic clinic visit (post-scan visit) did not cause
an increase in adverse reactions than the first clinic visit (pre-scan visit)

Aim 3:

1. Confidence of radiologist / nuclear medicine physician interpretation of scans increases
after adding quantitative analysis as compared to qualitative analysis alone

This study will use [18F]Flutemetamol-PET imaging to assess and quantify the amyloid plaque
burden in patients with mild cognitive impairment (MCI) or dementia of unclear etiology,
according to Diagnostic Statistical Manual-IV (DSM-IV) and/or National Institutes of
Aging-Alzheimer's Association criteria, verified by a dementia specialist within 24 months.

The [18F]Flutemetamol-PET scans of these study participants will then be assessed using a
General Electric (GE) software databases (NeuroMarQ) which contain scan data from healthy
control individuals to evaluate for abnormalities in amyloid plaque burden differing from the
values expected for individuals in their age range.

Inclusion Criteria:

- Patients must be 45 to 90 years of age for inclusion in this research study.

- Confirmed diagnosis of MCI or dementia of unclear etiology, according to DSM-IV and/or
National Institutes of Aging-Alzheimer's Association criteria, verified by a dementia
specialist within 24 months.

- Meets Appropriate Use Criteria (AUC)

- Cognitive complaint verified by objectively confirmed cognitive impairment;

- The etiologic cause of cognitive impairment is uncertain after a comprehensive
evaluation by a dementia specialist, including general medical and neurological
examination, mental status testing including standard measures of cognitive
impairment, laboratory testing, and structural neuroimaging as below;

- Alzheimer's disease is a diagnostic consideration;

- Knowledge of amyloid PET status is expected to alter diagnosis and management.

- MRI and/or CT of the brain within 12 months prior to enrollment;

- Clinical laboratory assessment within the 12 months prior to enrollment: complete
blood count (CBC), standard blood chemistry profile, thyroid stimulating hormone
(TSH), vitamin B12;

- Patient must agree to have clinical and radiographic endpoints and the results of and
other laboratory information entered into a research database, as evidenced by signing
the informed consent form.

- Patient must be postmenopausal for a minimum of one year, surgically sterile, or has
been confirmed not to be pregnant by serum pregnancy test performed within 24 hours
prior to research PET imaging.

- All patients, or their legal guardians, must sign a written informed consent and HIPAA
authorization in accordance with institutional guidelines.

Exclusion Criteria:

- Patients with known allergic or hypersensitivity reactions to previously administered
radiopharmaceuticals. Patients with significant drug or other allergies or autoimmune
diseases may be enrolled at the Investigator's discretion.

- Adult patients who require monitored anesthesia for PET scanning.

- Patients who are too claustrophobic to undergo PET imaging.

- Prior participation in an amyloid vaccination clinical study at any time in the past
or completion of a passive amyloid vaccination study within 6 months before screening.

- Patients with Normal cognition or subjective complaints that are not verified by
cognitive testing.

- Subject's scans being ordered for one of the following reasons:

- Scan is being ordered solely based on a family history of dementia, presence of
apolipoprotein E, or in lieu of genotyping for suspected autosomal mutation
carriers;

- Scan being ordered for nonmedical purposes (e.g., legal, insurance coverage, or
employment screening)

- Currently pregnant

- Patients who are unwilling to know the results of their PET imaging scan.