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      Added value of amyloid PET in individualized risk predictions for MCI patients

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          Abstract

          Introduction

          To construct a prognostic model based on amyloid positron emission tomography (PET) to predict clinical progression in individual patients with mild cognitive impairment (MCI).

          Methods

          We included 411 MCI patients from the Alzheimer's Disease Neuroimaging Initiative. Prognostic models were constructed with Cox regression with demographics, magnetic resonance imaging, and/or amyloid PET to predict progression to Alzheimer's disease dementia. The models were validated in the Amsterdam Dementia Cohort.

          Results

          The combined model (Harrell's C = 0.82 [0.78–0.86]) was significantly superior to demographics (β = 0.100, P < .001), magnetic resonance imaging (β = 0.037, P = .011), and PET only models (β = 0.053, P = .003).The models can be used to calculate individualized risk, for example, a female MCI patient (age = 60, APOE ε4 positive, Mini-Mental State Examination = 25, hippocampal volume = 5.8 cm 3, amyloid PET positive) has 35% (19–57) risk in one year and 85% (64–97) risk in three years. Model performances in the Amsterdam Dementia Cohort were reasonable.

          Discussion

          The present study facilitates the interpretation of an amyloid PET result in the context of a patient's own characteristics and clinical assessment.

          Highlights

          • Our models facilitate amyloid PET–based prognosis in light of patient characteristics.

          • Amyloid PET is the key player in our prognostic models.

          • Our models are easy to use and can guide clinical decision making.

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          Most cited references19

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          Imaging beta-amyloid burden in aging and dementia.

          To compare brain beta-amyloid (Abeta) burden measured with [(11)C]Pittsburgh Compound B (PIB) PET in normal aging, Alzheimer disease (AD), and other dementias. Thirty-three subjects with dementia (17 AD, 10 dementia with Lewy bodies [DLB], 6 frontotemporal dementia [FTD]), 9 subjects with mild cognitive impairment (MCI), and 27 age-matched healthy control subjects (HCs) were studied. Abeta burden was quantified using PIB distribution volume ratio. Cortical PIB binding was markedly elevated in every AD subject regardless of disease severity, generally lower and more variable in DLB, and absent in FTD, whereas subjects with MCI presented either an "AD-like" (60%) or normal pattern. Binding was greatest in the precuneus/posterior cingulate, frontal cortex, and caudate nuclei, followed by lateral temporal and parietal cortex. Six HCs (22%) showed cortical uptake despite normal neuropsychological scores. PIB binding did not correlate with dementia severity in AD or DLB but was higher in subjects with an APOE-epsilon4 allele. In DLB, binding correlated inversely with the interval from onset of cognitive impairment to diagnosis. Pittsburgh Compound B PET findings match histopathologic reports of beta-amyloid (Abeta) distribution in aging and dementia. Noninvasive longitudinal studies to better understand the role of amyloid deposition in the course of neurodegeneration and to determine if Abeta deposition in nondemented subjects is preclinical AD are now feasible. Our findings also suggest that Abeta may influence the development of dementia with Lewy bodies, and therefore strategies to reduce Abeta may benefit this condition.
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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

            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 In an attempt to understand if amyloid PET imaging improves the care of patients with MCI or dementia, this cohort study investigates associations between information provided by amyloid PET scan and change in clinical management, defined as a composite of change in drug therapy or counseling about safety and future planning.
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              Appropriate use criteria for amyloid PET: a report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer's Association.

              Positron emission tomography (PET) of brain amyloid β is a technology that is becoming more available, but its clinical utility in medical practice requires careful definition. To provide guidance to dementia care practitioners, patients, and caregivers, the Alzheimer's Association and the Society of Nuclear Medicine and Molecular Imaging convened the Amyloid Imaging Taskforce (AIT). The AIT considered a broad range of specific clinical scenarios in which amyloid PET could potentially be used appropriately. Peer-reviewed, published literature was searched to ascertain available evidence relevant to these scenarios, and the AIT developed a consensus of expert opinion. Although empirical evidence of impact on clinical outcomes is not yet available, a set of specific appropriate use criteria (AUC) were agreed on that define the types of patients and clinical circumstances in which amyloid PET could be used. Both appropriate and inappropriate uses were considered and formulated, and are reported and discussed here. Because both dementia care and amyloid PET technology are in active development, these AUC will require periodic reassessment. Future research directions are also outlined, including diagnostic utility and patient-centered outcomes.
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                Author and article information

                Contributors
                Journal
                Alzheimers Dement (Amst)
                Alzheimers Dement (Amst)
                Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring
                Elsevier
                2352-8729
                29 July 2019
                December 2019
                29 July 2019
                : 11
                : 529-537
                Affiliations
                [a ]Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands
                [b ]Department of Epidemiology and Biostatistics, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands
                [c ]Department of Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands
                Author notes
                []Corresponding author. Tel.: +31204440816; Fax: +31204448529. i.vanmaurik@ 123456vumc.nl
                [1]

                Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database ( adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

                Article
                S2352-8729(19)30040-5
                10.1016/j.dadm.2019.04.011
                6667768
                31388557
                2412457d-cf45-497f-8540-8caf3ac88396
                © 2019 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Categories
                Neuroimaging

                biomarkers,amyloid positron emission tomography,mci,progression,alzheimer's disease

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