Clinical use of amyloid‐positron emission tomography neuroimaging: Practical and bioethical considerations

Witte, Michael M.; Foster, Norman L.; Fleisher, Adam; Williams, Monique; Quaid, Kimberly A.; Wasserman, Mark; Hunt, Gail; Roberts, J. Scott; Rabinovici, Gil D.; Levenson, James L.; Hake, Ann Marie; Hunter, Craig A.; Campen, Luann E. Van; Pontecorvo, Michael J.; Hochstetler, Helen; Tabas, Linda B.; Trzepacz, Paula T.

doi:10.1016/j.dadm.2015.06.006

Cited by 37 publications

(37 citation statements)

References 54 publications

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“…In the AD patients, senile plaques were detected in the hippocampus (Sabri et al, 2015; Witte et al, 2015). Accumulating evidences have shown that 9-month-old APP/PS1 transgenic mice exhibited the formation of senile plaques which gradually increased with age (Bibari et al, 2013; He et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Icariside II Effectively Reduces Spatial Learning and Memory Impairments in Alzheimer’s Disease Model Mice Targeting Beta-Amyloid Production

et al. 2017

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Icariside II (ICS II) is a broad-spectrum anti-cancer natural compound extracted from Herba Epimedii Maxim. Recently, the role of ICS II has been investigated in central nervous system, especially have a neuroprotective effect in Alzheimer’s disease (AD). In this study, we attempted to investigate the effects of ICS II, on cognitive deficits and beta-amyloid (Aβ) production in APPswe/PS1dE9 (APP/PS1) double transgenic mice. It was found that chronic ICS II administrated not only effectively ameliorated cognitive function deficits, but also inhibited neuronal degeneration and reduced the formation of plaque burden. ICS II significantly suppressed Aβ production via promoting non-amyloidogenic APP cleavage process by up-regulating a disintegrin and metalloproteinase domain 10 (ADAM10) expression, inhibited amyloidogenic APP processing pathway by down-regulating amyloid precursor protein (APP) and β-site amyloid precursor protein cleavage enzyme 1 (BACE1) expression in APP/PS1 transgenic mice. Meanwhile, ICS II attenuated peroxisome proliferator-activated receptor-γ (PPARγ) degradation as well as inhibition of eukaryotic initiation factor α phosphorylation (p-eIF2α) and PKR endoplasmic reticulum regulating kinase phosphorylation (p-PERK). Moreover, phosphodiesterase type 5 inhibitors (PDE5-Is) have recently emerged as a possible therapeutic target for cognitive enhancement via inhibiting Aβ levels, and we also found that ICS II markedly decreased phosphodiesterase-5A (PDE5A) expression. In conclusion, the present study demonstrates that ICS II could attenuate spatial learning and memory impairments in APP/PS1 transgenic mice. This protection appears to be due to the increased ADAM10 expression and decreased expression of both APP and BACE1, resulting in inhibition of Aβ production in the hippocampus and cortex. Inhibition of PPARγ degradation and PERK/eIF2α phosphorylation are involved in the course, therefore suggesting that ICS II might be a promising potential compound for the treatment of AD.

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Section: Discussionmentioning

confidence: 99%

Icariside II Effectively Reduces Spatial Learning and Memory Impairments in Alzheimer’s Disease Model Mice Targeting Beta-Amyloid Production

et al. 2017

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“…Amyloid imaging increases the level of information available to clinicians and may also aid in prognostication [31]. Few data are available to guide the clinical interaction around amyloid imaging, however, beyond the proposed appropriate use criteria [11, 32] and initial recommendations for communicating scan results [33, 34](Grill et al, submitted ). To examine how amyloid imaging affects the diagnostic experience for patients and families, we performed a telephone interview study with patients and caregivers who received clinical care at an academic tertiary memory disorders clinic.…”

Section: Introductionmentioning

confidence: 99%

Patient and caregiver reactions to clinical amyloid imaging

Grill

Cox

Kremen

et al. 2017

Alzheimer's & Dementia

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INTRODUCTION Amyloid imaging is a tool that has recently become available to dementia specialists evaluating patients with possible Alzheimer’s disease. Studies have assessed the impact of amyloid imaging on diagnostic and treatment decisions, but patient and family perspectives have received less attention. METHODS To examine how amyloid imaging affects the diagnostic experience for patients and families, we interviewed members of 26 patient-caregiver dyads with whom a neurologist discussed the option of amyloid PET. RESULTS Most participants who chose to undergo amyloid imaging would choose to do so again. Regardless of the scan outcome, patients and caregivers commonly expressed relief upon learning the scan results. Some participants expressed expectations that were beyond scan capabilities. DISCUSSION Amyloid imaging may provide information that patients and their families find useful. Clinicians must set correct expectations and ensure that families understand the limitations of amyloid imaging.

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“…It will also be necessary to investigate the impact of special education for clinicians who handle amyloid imaging information, an important topic as recently pointed out by different groups (50)(51)(52). This education should contain lines of arguments on why there is clinical utility to both PET imaging outcome scenarios (amyloid positivity and negativity).…”

Section: Future Perspectivesmentioning

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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Clinical use of amyloid‐positron emission tomography neuroimaging: Practical and bioethical considerations

Cited by 37 publications

References 54 publications

Icariside II Effectively Reduces Spatial Learning and Memory Impairments in Alzheimer’s Disease Model Mice Targeting Beta-Amyloid Production

Icariside II Effectively Reduces Spatial Learning and Memory Impairments in Alzheimer’s Disease Model Mice Targeting Beta-Amyloid Production

Patient and caregiver reactions to clinical amyloid imaging

Clinical Use and Utility of Amyloid Imaging

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