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.

β-Amyloid plaques and tau-containing neurofibrillary tangles are the two neuropathological hallmarks of Alzheimer’s disease (AD) and are thought to play crucial roles in a neurodegenerative cascade leading to dementia. Both lesions can now be visualized in vivo using positron emission tomography (PET) radiotracers, opening new opportunities to study disease mechanisms and improve patients’ diagnostic and prognostic evaluation. In a group of 32 patients at early symptomatic AD stages, we tested whether β-amyloid and tau-PET could predict subsequent brain atrophy measured using longitudinal magnetic resonance imaging acquired at the time of PET and 15 months later. Quantitative analyses showed that the global intensity of tau-PET, but not β-amyloid–PET, signal predicted the rate of subsequent atrophy, independent of baseline cortical thickness. Additional investigations demonstrated that the specific distribution of tau-PET signal was a strong indicator of the topography of future atrophy at the single patient level and that the relationship between baseline tau-PET and subsequent atrophy was particularly strong in younger patients. These data support disease models in which tau pathology is a major driver of local neurodegeneration and highlight the relevance of tau-PET as a precision medicine tool to help predict individual patient’s progression and design future clinical trials.

based on the technology described in this manuscript. Drs. Klunk and Mathis are co-inventors of PIB and, as such, have a financial interest in this license agreement. GE Healthcare provided no grant support for this study and had no role in the design or interpretation of results or preparation of this manuscript.