Diagnostic impact of [18F]flutemetamol PET in early-onset dementia

Zwan, Marissa D.; Bouwman, Femke H.; Konijnenberg, Elles; Flier, Wiesje M. van der; Lammertsma, Adriaan A.; Verhey, Frans R.J.; Aalten, Pauline; Berckel, Bart N.M. van; Scheltens, Philip

doi:10.1186/s13195-016-0228-4

Cited by 106 publications

(123 citation statements)

References 29 publications

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“…2,3,10,17 Noting that changes in these biomarkers can already be identified when cognitive impairment is mild and in the absence of functional disability (so-called prodromal, or mild cognitive impairment -MCI -stage) 11 new diagnostic criteria incorporating biomarkers now allow for a diagnosis of AD before the development of full-blown dementia (Panel 2). 2,10,17,18 Biomarkers can also be used in the full-blown dementia stage for a more accurate aetiologic diagnosis 19,20 , and, potentially, to screen the general population for persons at high risk of entering the symptomatic stages. 18 Biomarker assessment -Absence of medial temporal (mainly hippocampal) atrophy on MRI in typical (memory) presentations makes AD less likely.…”

Section: The Clinical Context: the Diagnosis Of Prodromal Ad Requiresmentioning

confidence: 99%

Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers

Frisoni

Boccardi

Barkhof

et al. 2017

The Lancet Neurology

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Biomarkers sensitive to functional impairment, neuronal loss, tau, and amyloid pathology based on MR, PET, and CSF studies are increasingly used to diagnose Alzheimer's disease (AD), but clinical validation is incomplete, hampering reimbursement by payers, widespread clinical implementation, and impacting on health care quality. An expert group convened to develop a strategic research agenda to foster the clinical validation of AD biomarkers. These demonstrated sufficient evidence of analytical validity (phase I of a structured framework adapted from oncology). Research priorities were identified based on incomplete clinical validity (phases II and III), and clinical utility (phases IV and V). Priorities included: definition of the assays; reading procedures and thresholds for normality; performance in detecting early disease; accounting for the effect of covariates; diagnostic algorithms comprising combinations of biomarkers; and developing best practice guidelines for the use of biomarkers in qualified memory clinics in the context of phase IV studies. 5 GlossaryBiomarker. An objective measure of a biological or pathogenic process with the purpose of evaluating disease risk or prognosis, guiding clinical diagnosis or monitoring therapeutic interventions. While the term originally referred to traceable substances produced by or introduced into an organism, it later evolved to any measurable parameter, including those obtained via imaging procedures.Roadmap. Objective-oriented, structured, and efficient action plan. In science and technology also called "strategic research agenda".Alzheimer's disease (AD) dementia. Traditionally and according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria, Alzheimer's disease was defined as a syndrome with progressive cognitive impairment severe enough to impact on daily activities. A diagnosis of Alzheimer's disease could only be made after exclusion of other possible causes. 1 Sixty-five to 80% of cases of patients fulfilling these criteria have Alzheimer's pathology (plaques and tangles), the remainder having a range of other pathologies. In order to increase diagnostic certainty, contemporary criteria for AD dementia incorporate biomarker evidence for different aspects of Alzheimer's pathology, including imaging (magnetic resonance imaging -MRI -measures of atrophy; 18 F-fluorodeoxyglucose-positron emission tomography -FDG-PET -measures of cerebral hypometabolism; amyloid PET measures of fibrillar β-amyloid -A -deposition) and cerebrospinal fluid -CSF (decreased levels of A42, increased levels of tau and phospho-tau). 2,3 Alzheimer's disease process. Recognizing that AD pathology is present many years before symptoms emerge, new criteria classify the disease process on a continuum from asymptomatic to prodromal and finally to dementia stage. 4 Individuals at the asymptomatic stage can only be identified by biomarkers of Alzheimer's pathology. None...

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Section: The Clinical Context: the Diagnosis Of Prodromal Ad Requiresmentioning

confidence: 99%

Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers

Frisoni

Boccardi

Barkhof

et al. 2017

The Lancet Neurology

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511

480

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“…It is certainly necessary to further investigate this feature and to adapt the AUCs once new evidence on the usefulness or nonusefulness of amyloid imaging in certain scenarios emerges. For instance, Zwan et al (17) reported that patients might benefit from amyloid imaging even if diagnostic confidence does not increase. Further, given a certain likelihood that disease-modifying antiamyloid drugs will be available in the future, AUCs might need to be expanded to cases in which clinical testing reveals typical AD features ("probable AD dementia").…”

Section: Appropriate Use Criteria (Aucs) For Amyloid Imagingmentioning

confidence: 99%

“…Sixteen studies concerning the clinical utility of amyloid PET imaging were found in the literature (17,(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48). Supplemental Table 3 summarizes these studies.…”

Section: Clinical Utility Of Amyloid Imagingmentioning

confidence: 99%

Clinical Use and Utility of Amyloid Imaging

Barthel

Sabri

2017

J Nucl Med

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Currently, 3 amyloid PET tracers are approved and commercially available for clinical use. They allow for the accurate in vivo detection of amyloid plaques, one hallmark of Alzheimer disease. Here, we review the current knowledge on the clinical use and utility of amyloid imaging. Appropriate use criteria for the clinical application of amyloid imaging are established, and most currently available data point to their validity. Visual amyloid image analysis is highly standardized. Disclosure of amyloid imaging results is desired by many cognitively impaired subjects and seems to be safe once appropriate education is delivered to the disclosing clinicians. Regarding clinical utility, increasing evidence points to a change in diagnosis via amyloid imaging in about 30% of cases, to an increase in diagnostic confidence in about 60% of cases, to a change in patient management in about 60% of cases, and specifically to a change in medication in about 40% of cases. Also, amyloid imaging results seem to have a relevant impact on caregivers. Further, initial simulation studies point to a potential positive effect on patient outcome and to cost effectiveness of amyloid imaging. These features, however, will require confirmation in prospective clinical trials. More work is also required to determine the clinical utility of amyloid imaging specifically in subjects with mild cognitive impairment and in comparison with or in conjunction with other Alzheimer disease biomarkers. In summary, the clinical use of amyloid imaging is being studied, and the currently available data point to a relevant clinical utility of this imaging technique. Ongoing research will determine whether this accurate and noninvasive approach to amyloid plaque load detection will translate into a benefit to cognitively impaired subjects. Wi th the successful development and subsequent clinical approval of 18 F-florbetapir, 18 F-florbetaben, and 18 F-flutemetamol, the nuclear imaging community has a set of b-amyloid aggregatetargeting PET tracers in hand for clinical use. They allow the in vivo detection or exclusion of neuritic b-amyloid plaques, one histopathologic hallmark in the neocortex of patients with Alzheimer disease (AD), which previously could be diagnosed only histopathologically after death. Of note, brain b-amyloid accumulation is known to be an early event in this disease (1) and is considered by many as the initial trigger of a cascade of other pathobiochemical and pathophysiologic alterations finally leading to neurodegeneration and related cognitive decline in AD (2).The emergence of amyloid imaging technology is hoped to fill a relevant diagnostic gap in the clinic in cognitively impaired subjects and in AD in particular. Most people would like to get a diagnosis when cognitive symptoms are identified (3). Conversely, dementia diagnosis is often missed and delayed (4,5). With regard to the therapeutic implications of an AD diagnosis, it was reported that older people are willing to accept the relevant side effects of AD-modifying therap...

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“…The development of PET (positron emission tomography) imaging biomarkers that bind to fibrillar β-amyloid (Aβ), including Pittsburgh compound B ( 11 C-PiB) [13], florbetaben ( 18 F) [14], flutemetamol ( 18 F) [15], and florbetapir ( 18 F) [16,17], has made it possible to estimate whether or not a given patient has moderate-to-frequent neuritic amyloid plaques, a required feature for the pathological diagnosis of AD. At least five groups have now begun exploring the potential impact of amyloid PET imaging biomarkers on diagnosis and management in a clinical setting [18,19,20,21,22,23,24,25]. These studies have consistently reported that knowledge of the Aβ status could change the diagnosis in the direction of the scan result, improve physicians' confidence in their diagnosis, and change treatment.…”

Section: Introductionmentioning

confidence: 99%

Effectiveness of Florbetapir PET Imaging in Changing Patient Management

Pontecorvo

Siderowf

Dubois

et al. 2017

Dement Geriatr Cogn Disord

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Aims: To evaluate the impact of amyloid PET imaging on diagnosis and patient management in a multicenter, randomized, controlled study. Methods: Physicians identified patients seeking a diagnosis for mild cognitive impairment or dementia, possibly due to Alzheimer disease (AD), and recorded a working diagnosis and a management plan. The patients underwent florbetapir PET scanning and were randomized to either immediate or delayed (1-year) feedback regarding amyloid status. At the 3-month visit, the physician updated the diagnosis and recorded a summary of the actual patient management since the post-scan visit. The study examined the impact of immediate versus delayed feedback on patient diagnosis/management at 3 and 12 months. Results: A total of 618 subjects were randomized (1:1) to immediate or delayed feedback arms, and 602 subjects completed the 3-month primary endpoint visit. A higher proportion of patients in the immediate feedback arm showed a change in diagnosis compared to the controls (32.6 vs. 6.4%; p = 0.0001). Similarly, a higher proportion of patients receiving immediate feedback had a change in management plan (68 vs. 55.5%; p < 0.002), mainly driven by changes in AD medication. Specifically, acetylcholinesterase inhibitors were prescribed to 67% of the amyloid-positive and 27% of the amyloid-negative subjects in the information group compared with 56 and 43%, respectively, in the control group (p < 0.0001). These between-group differences persisted until the 12-month visit. Conclusion: Knowledge of the amyloid status affects the diagnosis and alters patient management.

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Diagnostic impact of [18F]flutemetamol PET in early-onset dementia

Cited by 106 publications

References 29 publications

Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers

Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers

Clinical Use and Utility of Amyloid Imaging

Effectiveness of Florbetapir PET Imaging in Changing Patient Management

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