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Association of Amyloid Positron Emission Tomography With Subsequent Change in Clinical Management Among Medicare Beneficiaries With Mild Cognitive Impairment or Dementia

Educational Objective
To learn the association between the use of amyloid PET and subsequent change in clinical management of patients with cognitive impairment.
1 Credit CME
Key Points

Question  Is use of amyloid positron emission tomography (PET) associated with subsequent change in the management of patients with mild cognitive impairment (MCI) or dementia of uncertain etiology?

Findings  In this longitudinal study that included 11 409 participants with MCI or dementia of uncertain cause, patient management 90 days after amyloid PET changed (compared with the pre-PET plan) in 60.2% of patients with MCI and 63.5% of patients with dementia.

Meaning  Amyloid PET was associated with changes in the subsequent management of diagnostically challenging patients with cognitive disorders.


Importance  Amyloid positron emission tomography (PET) detects amyloid plaques in the brain, a core neuropathological feature of Alzheimer disease.

Objective  To determine if amyloid PET is associated with subsequent changes in the management of patients with mild cognitive impairment (MCI) or dementia of uncertain etiology.

Design, Setting, and Participants  The Imaging Dementia—Evidence for Amyloid Scanning (IDEAS) study was a single-group, multisite longitudinal study that assessed the association between amyloid PET and subsequent changes in clinical management for Medicare beneficiaries with MCI or dementia. Participants were required to meet published appropriate use criteria stating that etiology of cognitive impairment was unknown, Alzheimer disease was a diagnostic consideration, and knowledge of PET results was expected to change diagnosis and management. A total of 946 dementia specialists at 595 US sites enrolled 16 008 patients between February 2016 and September 2017. Patients were followed up through January 2018. Dementia specialists documented their diagnosis and management plan before PET and again 90 (±30) days after PET.

Exposures  Participants underwent amyloid PET at 343 imaging centers.

Main Outcomes and Measures  The primary end point was change in management between the pre- and post-PET visits, as assessed by a composite outcome that included Alzheimer disease drug therapy, other drug therapy, and counseling about safety and future planning. The study was powered to detect a 30% or greater change in the MCI and dementia groups. One of 2 secondary end points is reported: the proportion of changes in diagnosis (from Alzheimer disease to non–Alzheimer disease and vice versa) between pre- and post-PET visits.

Results  Among 16 008 registered participants, 11 409 (71.3%) completed study procedures and were included in the analysis (median age, 75 years [interquartile range, 71-80]; 50.9% women; 60.5% with MCI). Amyloid PET results were positive in 3817 patients with MCI (55.3%) and 3154 patients with dementia (70.1%). The composite end point changed in 4159 of 6905 patients with MCI (60.2% [95% CI, 59.1%-61.4%]) and 2859 of 4504 patients with dementia (63.5% [95% CI, 62.1%-64.9%]), significantly exceeding the 30% threshold in each group (P < .001, 1-sided). The etiologic diagnosis changed from Alzheimer disease to non–Alzheimer disease in 2860 of 11 409 patients (25.1% [95% CI, 24.3%-25.9%]) and from non–Alzheimer disease to Alzheimer disease in 1201 of 11 409 (10.5% [95% CI, 10.0%-11.1%]).

Conclusions and Relevance  Among Medicare beneficiaries with MCI or dementia of uncertain etiology evaluated by dementia specialists, the use of amyloid PET was associated with changes in clinical management within 90 days. Further research is needed to determine whether amyloid PET is associated with improved clinical outcomes.

Trial Registration  ClinicalTrials.gov Identifier: NCT02420756

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Article Information

Corresponding Author: Gil D. Rabinovici, MD, Memory and Aging Center, Department of Neurology, University of California, San Francisco, 675 Nelson Rising Ln, Ste 190, San Francisco, CA 94158 (Gil.Rabinovici@ucsf.edu).

Accepted for Publication: February 21, 2019

Author Contributions: Drs Rabinovici and Gatsonis had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Rabinovici, Gatsonis, Gareen, Hillner, Siegel, Whitmer, Carrillo.

Acquisition, analysis, or interpretation of data: Rabinovici, Gatsonis, Apgar, Chaudhary, Gareen, Hanna, Hendrix, Hillner, Olson, Lesman-Segev, Romanoff, Siegel, Carrillo.

Drafting of the manuscript: Rabinovici, Gatsonis, Hendrix, Olson, Lesman-Segev, Romanoff, Siegel, Whitmer, Carrillo.

Critical revision of the manuscript for important intellectual content: Rabinovici, Gatsonis, Apgar, Chaudhary, Gareen, Hanna, Hendrix, Hillner, Lesman-Segev, Romanoff, Siegel, Carrillo.

Statistical analysis: Gatsonis, Gareen, Hanna, Hillner, Romanoff, Whitmer.

Obtained funding: Rabinovici, Gatsonis, Apgar, Olson, Carrillo.

Administrative, technical, or material support: Gatsonis, Apgar, Chaudhary, Hanna, Hendrix, Olson, Lesman-Segev, Siegel, Carrillo.

Supervision: Rabinovici, Hendrix, Siegel, Whitmer, Carrillo.

Conflict of Interest Disclosures: Dr Rabinovici reported receiving grants from the American College of Radiology, the Alzheimer's Association, Avid Radiopharmaceuticals Inc, GE Healthcare, Life Molecular Imaging, and Eli Lilly and receiving personal fees from Eisai, Piramal Imaging, Merck, and Genentech. Dr Gatsonis reported receiving grants from the American College of Radiology. Dr Gareen reported receiving grants from the American College of Radiology Foundation. Ms Hanna reported receiving grants from the American College of Radiology. Dr Hillner reported receiving grants from the Alzheimer's Association. Dr Siegel reported receiving grants from American College of Radiology, Blue Earth Diagnostics, and Progenics Pharmaceuticals and receiving personal fees from GE Healthcare, Blue Earth Diagnostics, Avid Radiopharmaceuticals Inc, BTG Management Services, Capella Imaging, Curium Pharma, Merrimack Pharmaceuticals, and Siemens Healthineers. No other disclosures were reported.

Funding/Support: The trial was funded by the Alzheimer’s Association, the American College of Radiology, Avid Radiopharmaceuticals Inc (a wholly owned subsidiary of Eli Lilly and Company), General Electric Healthcare, and Life Molecular Imaging (formerly Piramal Imaging).

Role of the Funder/Sponsor: The funders/sponsors participated in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The Alzheimer’s Association and American College of Radiology additionally participated in the decision to submit the manuscript for publication but did not have the right to veto submission or to require submission to a particular journal. The Centers for Mediare & Medicaid Services provided coverage for amyloid PET scans under coverage with evidence development.

Additional Contributions: We acknowledge the following individuals for their contributions to study planning, operations, and participation in study committees: Daniel Caños, PhD, Rosemarie Hakim, PhD (Centers for Medicare & Medicaid Services); Niles Frantz, BA, Meredith McNeil, MA, Joanne Pike, DrPH, April Ross, PhD (Alzheimer’s Association); Anna Boyle, MS, Val Castle, MBA, Tifani Dawson, BA, Alexis Dickens, HS Diploma, Kieona Fairley, BA, Shawn Farley, MS, Alycia Ford, BS, Glenna Gabrielli, BS, Viral Kamdar, MS, KingSum Lo, MS, Donald Rosen, MD, Leslie Sears, LPN, Josephine Schloesser, BS, Maryann Verrillo, BA, Denise Woods, MA (American College of Radiology); Brian Carey, JD (Foley Hoag LLP); Adam Fleisher, MD, Marybeth Howlett, MEM, Mark Mintun, MD (Avid Radiopharmaceuticals Inc, a wholly owned subsidiary of Eli Lilly and Company); Kathyrn Hoffman, MPH, PhD, Meridith Johnson, MSc, Ben Newton, PhD (GE Healthcare); William Abbott, MS, Nicole Fletcher, BA, Cynthia Herring, MHA, Robert Sgroi, MS, Susan DeSanti, PhD (Life Molecular Imaging Inc, formerly Piramal Imaging); Susan Bunning, MA, Terri Wilson, MBA (Medical Imaging and Technology Alliance); Denise Merlino, MBA (Merlino Healthcare Consulting Corporation); Ashley Mensing, BS, Laurel Skurko, MBA (University of California, San Francisco); Philip Scheltens, MD, PhD (VU University Medical Center, Amsterdam, the Netherlands); Linda Budzinski, BA; and Ann Latham, BA (Society of Nuclear Medicine and Molecular Imaging). Dr Ross, Mss Boyle, Castle, Dawson, Dickens, Fairley, Ford, Gabrielli, Sears, Schloesser, Woods, and Mensing, and Mssrs Kamdar, Lo, and Carey received salary support specifically for their roles in this study. We thank Kevin Donohoe, MD (Beth Israel Deaconess Medical Center), Norman Foster, MD (University of Utah), Peter Herscovitch, MD (National Institutes of Health), Jason Karlawish, MD (University of Pennsylvania), Keith Johnson, MD (Massachusetts General Hospital), Satoshi Minoshima, MD, PhD (University of Utah), and Stephen Salloway, MD (Brown University), for their critical contributions to developing the IDEAS protocol; Lisa Bain, MA, for assistance with manuscript drafting; and all dementia specialists, imaging specialists, and patients who participated in the study.

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