New IDEAS: Imaging Dementia-Evidence for Amyloid Scanning Study

Study Overview
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Brief Summary
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New IDEAS is an observational, open-label, longitudinal cohort study designed to address the requirements of the CED provisions of the NCD on beta-amyloid PET. Building on the initial Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) study, New IDEAS will evaluate the association between amyloid PET and patient-centered outcomes in an expanded and more ethnoracially and clinically diverse group of Medicare participants presenting with cognitive impairment.

Detailed Description
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A total of 7,000 Medicare beneficiaries meeting the study's eligibility criteria will be consented and enrolled over 30 months at sites throughout the United States. To ensure diversity, the study will enroll at least 2,000 Blacks/African Americans, at least 2,000 Latinos/Hispanics, and up to 3,000 additional participants from other racial and ethnic backgrounds. Based on disease stage prior to PET, all participants will be classified as having MCI or dementia as their disease stage. Based on their clinical presentation prior to PET, all participants will be classified as having typical (i.e. progressive amnestic) or atypical clinical presentations of AD as the potential cause of dementia or MCI. Dementia specialists will team with PET facilities that have trained radiologists/nuclear medicine physicians and access to perform amyloid PET. All participating physicians and study staff will complete comprehensive training to ensure adherence of data requirements and study timelines. Amyloid PET will be performed and interpreted at each facility with results provided to the ordering dementia specialist for support in further decision making. The dementia specialists will record their diagnosis and intended management plan based on the current clinical and diagnostic information, and assuming no future access to amyloid PET at the Pre-PET visit. This represents a thought experiment documenting the management plan that would be recommended by the specialist if the participant were not enrolling in New IDEAS and thus had no access to amyloid PET. PET results will be disclosed to patients and any consequent changes in management (if any) will be recommended at the PET disclosure visit. Patients will return 90 ± 30 days following PET for an in person Post-PET visit. At this final visit, the dementia specialists will record the diagnosis and implemented management plan, incorporating amyloid PET into clinical decision making. Medicare claims data will be collected directly from CMS for 12 months prior to the PET imaging and 12 months after the PET imaging, for each participant. Aim 1 utilizes Medicare claims data to compare 12-month claims-derived outcomes in amyloid PET-positive versus amyloid PET-negative individuals with MCI and dementia across the entire cohort. Aims 2 and 3 investigate these associations in sub-groups of study participants based on self-identified race and ethnicity (Aim 2) and clinical presentation (Aim 3). Aims 2 and 3 additionally evaluate changes in management between the pre- and post-PET visits in the relevant sub-groups, to test whether benefits in health outcomes are mediated by changes in clinical management. The investigator's over-arching hypothesis, supported by preliminary data from the first IDEAS study, is that amyloid PET results will be associated with changes in clinical management, which in turn will translate into improved health outcomes in patients with amyloid PET-positive scans in comparison with patients with amyloid PET-negative scans. We further hypothesize that these effects will be seen across patients of different ethnoracial backgrounds, clinical presentations and disease stages (MCI and dementia). Optional components of the study include the collection and archival of participant's amyloid PET images, and blood plasma. These repositories will serve as a resource to the field, enabling the testing and validation of emerging genetic and blood biomarkers. Separate consent will be obtained for participation in these components.

Official Title
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New IDEAS: Imaging Dementia-Evidence for Amyloid Scanning Study - A Study to Improve Precision in Amyloid PET Coverage and Patient Care

Conditions
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Alzheimer's Disease, Dementia, Mild Cognitive Impairment

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Medicare beneficiary with Medicare as primary insurance; Meets clinical criteria for Mild Cognitive Impairment (MCI) or Dementia as defined by the 2018 National Institute on Aging - Alzheimer's Association Research Framework Brain 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; Neuropsychiatric syndrome can be classified into clinically typical or clinically atypical categories Exclusion Criteria: Normal cognition or subjective complaints that are not verified by cognitive testing or key informant. 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. Amyloid status already known to patient or referring clinician based on prior amyloid imaging or cerebrospinal fluid analysis. Current or previous enrollment in an anti-amyloid therapeutic trial. Scan is being ordered solely based on a family history of dementia, presence of apolipoprotein E (ApoE) 4, 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. Currently pregnant or planning to become pregnant within 90 days of registration. Life expectancy less than 24 months based on medical co-morbidities. Residence in a skilled nursing facility (assisted living facility is not an exclusion criterion).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Amyloid PET-Positive<br>Those for whom a beta amyloid PET scan is consistent with underlying AD as causing or contributing to cognitive impairment | |
| Amyloid PET-Negative<br>Those for whom a beta amyloid PET scan has ruled out AD (i.e. not consistent with underlying AD as causing or contributing to cognitive impairment) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aim 1: Health outcomes in amyloid PET-positive versus amyloid PET-negative | To compare 12-month claims-derived health outcomes in amyloid PET-positive versus amyloid PET-negative individuals presenting with MCI and dementia in the entire study cohort of diverse Medicare beneficiaries. | 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aim 2: Changes in patient management and health outcomes among various ethnoracial groups | To describe the association of amyloid PET findings with changes in patient management and 12-month claims-derived health outcomes among Blacks/African Americans, Latinos/Hispanics and Whites/Caucasians presenting with MCI and dementia. | 12 Months |