Imaging Dementia—Evidence for Amyloid Scanning (IDEAS) Study

The IDEAS Study is an observational, open-label, longitudinal cohort study designed to assess
the impact of amyloid PET on patient-oriented outcomes in Medicare beneficiaries with mild
cognitive impairment (MCI) or dementia of uncertain etiology. The study falls under the
Centers for Medicare & Medicaid Services (CMS) Coverage with Evidence Development (CED)
policy. A total of 18,488 Medicare beneficiaries meeting Appropriate Use Criteria (AUC) for
amyloid PET will be enrolled over 24 months at sites throughout the United States. Dementia
specialists will team with PET facilities able to perform amyloid PET and with trained
radiologists/nuclear medicine physicians, all of whom will consent to completing the data
requirements and timelines for the study. Amyloid PET will be performed and interpreted at
each facility with results provided to the ordering physician for support in further clinical
decision making, which will be captured for the study.

Our over-arching hypothesis is that, in diagnostically uncertain cases, knowledge of amyloid
status as determined by amyloid PET will lead to significant changes in patient management,
and that this will translate into improved long-term outcomes. We will pursue two specific
aims:

Aim 1 investigates the impact of amyloid PET on short-term patient management, by comparing
pre-PET intended management (ascertained in a case report form [CRF] prior to PET) to
post-PET actual management 90-days post-PET). The primary objective will be to test whether
amyloid PET leads to a ≥ 30% change between intended and actual patient management within 90
days in a cumulative endpoint consisting of: Alzheimer's disease (AD) drug therapy, other
drug therapy, and counseling about safety and future planning. Secondary objectives will
assess the impact of amyloid PET results on clinical diagnosis and prevention of unnecessary
diagnostic procedures and treatments.

Aim 2 utilizes Medicare claims data to compare medical outcomes at 12 months for patients
enrolled in the longitudinal cohort (amyloid PET-known) with those for a matched control
cohort of patients who have never undergone amyloid PET imaging (amyloid PET-naïve). The
primary objective will be to determine if amyloid PET in the amyloid PET-known cohort of
patients is associated with a ≥ 10% reduction in hospitalizations and emergency room visits
in comparison to the matched amyloid PET-naïve patients. Secondary objectives will examine
whether knowledge of amyloid PET status reduces hospitalizations related to
ambulatory-sensitive conditions, whether the association between amyloid PET knowledge and
health outcomes varies by baseline cognitive status (MCI versus dementia) and amyloid status
(amyloid positive versus negative). The amyloid PET-naïve cohort will be identified via a
matching algorithm where each individual in the amyloid PET-known cohort will be matched to
one individual with similar dementia diagnosis, pre-scan dementia-related resource
utilization, age, race, gender, ethnicity, geographic location, and comorbid chronic
conditions likely to impact cognition or the outcomes of interest seen at the same time as
the amyloid PET-known patient (concurrent control).

In pursuing these Aims, we will generate valuable observational data on clinical utility that
will inform future use of this technology in diagnostic algorithms, and develop a cohort of
patients who undergo amyloid PET and can serve as a foundation to address future research
questions.

Inclusion Criteria:

- 65 and older;

- Medicare beneficiary;

- Diagnosis of MCI or dementia, according to DSM-IV and/or National Institutes of
Aging-Alzheimer's Association criteria, verified by a dementia specialist within 24
months (American Psychiatric Association. 2000; McKhann et al. 2011; Albert et al.
2011);

- Meets 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.

- Head MRI and/or CT within 24 months prior to enrollment;

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

- Able to tolerate amyloid PET required by protocol, to be performed at a participating
PET facility;

- English or Spanish speaking (for the purposes of informed consent);

- Willing and able to provide consent. Consent may be by proxy.

Exclusion Criteria:

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

- Knowledge of amyloid status, in the opinion of the referring dementia expert, may
cause significant psychological harm or otherwise negatively impact the patient or
family.

- 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).

- Cancer requiring active therapy (excluding non-melanoma skin cancer);

- Hip/pelvic fracture within the 12 months prior to enrollment;

- Body weight exceeds PET scanner weight limit;

- Life expectancy less than 24 months based on medical co-morbidities;

- Residence in a skilled nursing facility.