Impact of Beta-Amyloid-Specific Florbetaben PET Imaging on Confidence in Early Diagnosis of Alzheimer’s Disease

Abstract

Background: Early diagnosis of Alzheimer’s disease (AD) may be corroborated by imaging of beta-amyloid plaques using positron emission tomography (PET). Here, we performed an add-on questionnaire study to evaluate the relevance of florbetaben imaging (BAY 949172) in diagnosis and consecutive management of probable AD patients. Methods: AD patients with a clinical diagnosis in accordance with the NINCDS-ADRDA criteria or controls were imaged using florbetaben. Referring physicians were asked on a voluntary basis about their confidence in initial diagnosis, significance of PET imaging results, and their anticipated consequences for future patient care. Results: 121 questionnaires for probable AD patients and 80 questionnaires for controls were evaluated. In 18% of patients who had initially received the diagnosis of probable AD, PET scans were rated negative, whereas in controls 18% of scans were positive. An increase in confidence in the initial diagnosis was frequently reported (80%). Imaging results had a significant impact on the intended patient care, as judged by the referring physicians; this was most prominent in those patients with a contradicting scan and/or a low confidence in the initial diagnosis. Conclusion: Florbetaben amyloid imaging increases the overall confidence in diagnosis of AD and may frequently influence clinical decisions and patient management.

Effect of Amyloid Imaging on the Diagnosis and Management of Patients with Cognitive Decline: Impact of Appropriate Use Criteria

“…The finding that the proportion of amyloid-positive cases increases with disease severity along the spectrum of suspected AD patients is consistent with an extensive literature [26,27,28,29]. This may explain the difference in the proportion of amyloid-positive cases and the difference in the proportion of cases with diagnostic change among previous studies that have compared scan effects in well-characterized, diagnosed subjects (e.g., AD vs. healthy controls [21] or AD vs. frontotemporal dementia [20]) and the effect in memory clinic patients [16,18,19]. The current finding that diagnostic change is also more likely in the diagnostically indeterminate AUC-like cases than in the more certain probable AD cases is also consistent with reports that change is more likely in situations of lower diagnostic confidence or greater uncertainty [19,20].…”

“…Because neuritic plaques are a required component of a pathological diagnosis of AD, PET-derived information regarding neuritic plaque density could be of value in the diagnosis of patients with cognitive impairment. Multiple studies have now investigated the impact of amyloid PET imaging on diagnostic decision-making [15,16,17,18,19,20,21], demonstrating that PET imaging information could lead to changes in diagnosis and diagnostic confidence. Further, the study by Grundman et al [17] demonstrated a change in intended management by study physicians in 87% of cases.…”

“…The patients selected for the studies above ranged from participants in a phase 2 clinical trial [21] to patients in clinical settings [16,18,19]. The study population used by Grundman et al [17] was designed to encompass what was, at that time, expected to be the likely population to receive amyloid PET once an agent was approved, i.e., patients undergoing or having recently completed evaluations for cognitive decline in clinical settings for whom there remained diagnostic uncertainty.…”

Clinical Use and Utility of Amyloid Imaging

“…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.…”

Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer’s disease

“…Among many other applications, amyloid-b imaging has been incorporated into diagnostic criteria for various stages of the disease (Albert et al, 2011;McKhann et al, 2011;Sperling et al, 2011;Dubois et al, 2014), has substantial impact on clinical decision-making (Ossenkoppele et al, 2013a;Sanchez-Juan et al, 2014) and patient management plans (Schipke et al, 2012;Grundman et al, 2013), and has shown potential as a surrogate outcome measure in clinical trials tailored to reduce cerebral amyloid-b plaque burden (Salloway et al, 2014;Liu et al, 2015). A yet unresolved issue after a decade of amyloid-b imaging research, however, is the disconnection between the diffuse distribution of amyloid-b pathology throughout the neocortex (Rabinovici et al, 2010;Wolk et al, 2012;Lehmann et al, 2013;Jung et al, 2015) and the selective patterns of brain atrophy and glucose hypometabolism that strongly correlate with clinical symptoms (Rabinovici et al, 2010;Ridgway et al, 2012;Lehmann et al, 2013;Madhavan et al, 2013).…”