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Key Points

Question听 Is amyloid positron emission tomography (PET) scanning useful for the assessment of patients with cognitive impairment?

Findings听 In this multicenter study of 228 cognitively impaired adults undergoing amyloid PET, results inconsistent with previous diagnosis led to significant changes in diagnosis, diagnostic confidence, and therapeutic plan.

Meaning听 Amyloid PET has a significant effect on the evaluation of patients for cognitive impairment.

Importance听 Cerebral amyloidosis is a key abnormality in Alzheimer disease (AD) and can be detected in vivo with positron emission tomography (PET) ligands. Although amyloid PET has clearly demonstrated analytical validity, its clinical utility is debated.

Objective听 To evaluate the incremental diagnostic value of amyloid PET with florbetapir F 18 in addition to the routine clinical diagnostic assessment of patients evaluated for cognitive impairment.

Design, Setting, and Participants听 The Incremental Diagnostic Value of Amyloid PET With [¹⁸F]-Florbetapir (INDIA-FBP) Study is a multicenter study involving 18 AD evaluation units from eastern Lombardy, Northern Italy, 228 consecutive adults with cognitive impairment were evaluated for AD and other causes of cognitive decline, with a prescan diagnostic confidence of AD between 15% and 85%. Participants underwent routine clinical and instrumental diagnostic assessment. A prescan diagnosis was made, diagnostic confidence was estimated, and drug treatment was provided. At the time of this workup, an amyloid PET/computed tomographic scan was performed, and the result was communicated to physicians after workup completion. Physicians were asked to review the diagnosis, diagnostic confidence, and treatment after the scan. The study was conducted from August 5, 2013, to December 31, 2014.

Main Outcomes and Measures听 Primary outcomes were prescan to postscan changes of diagnosis, diagnostic confidence, and treatment.

Results听 Of the 228 participants, 107 (46%) were male; mean (SD) age was 70.5 (7) years. Diagnostic change occurred in 46 patients (79%) having both a previous diagnosis of AD and an amyloid-negative scan (P鈥�<鈥�.001) and in 16 (53%) of those with non-AD diagnoses and an amyloid-positive scan (P鈥�&濒迟;鈥�.001). Diagnostic confidence in AD diagnosis increased by 15.2% in amyloid-positive (P鈥�&濒迟;鈥�.001; effect size Cohen d鈥�=鈥�1.04) and decreased by 29.9% in amyloid-negative (P鈥�&濒迟;鈥�.001; d鈥�=鈥夆垝1.19) scans. Acetylcholinesterase inhibitors and memantine hydrochloride were introduced in 61 (65.6%) patients with positive scan results who had not previously received those drugs, and the use of the drugs was discontinued in 6 (33.3%) patients with negative scan results who were receiving those drugs (P鈥�&濒迟;鈥�.001).

Conclusions and Relevance听 Amyloid PET in addition to routine assessment in patients with cognitive impairment has a significant effect on diagnosis, diagnostic confidence, and drug treatment. The effect on health outcomes, such as morbidity and mortality, remains to be assessed.

Brain 尾-amyloid is a hallmark of Alzheimer disease (AD)^1-3 and is quantifiable in vivo through specific positron emission tomography (PET) radiotracers binding to 尾-amyloid with 96% to 97.8% sensitivity and 88.9% to 100% specificity.^4,5The F 18鈥搇abeled tracers (eg, [¹⁸F]-florbetapir, [¹⁸F]-flutemetamol, and [¹⁸F]-florbetaben) now overcome the limited clinical applicability of carbon 11鈥搇abeled Pittsburgh Compound B⁶ with their longer half-life (110 minutes). This evidence of analytical validity and feasibility makes amyloid PET a promising pathophysiologic marker for diagnosing AD according to most recent criteria.^7-9 However, the clinical utility of amyloid PET is still under investigation worldwide. The presence of brain amyloidosis in patients with clinically diagnosed AD or lack thereof in individuals without AD is not warranted. In a recent meta-analysis,¹⁰ the prevalence of positive scans was 88% in patients with AD, 51% in patients with dementia with Lewy bodies (DLB), 30% in those with cerebrovascular disease (CVD), 12% in patients with frontotemporal lobar degeneration (FTLD), 38% in those with corticobasal degeneration (CBD), and 24% in healthy elderly individuals serving as controls. Consequently, amyloid PET, although approved for clinical use, is still not reimbursed by national health care systems. In the United States, a wide collection of clinical cases using amyloid PET, funded by private and public sources,¹¹ perform amyloid PET scans in cases consistent with the pertinent Appropriate Use Criteria,^12,13 collecting quantitative evidence on the incremental value of the examination for a large sample. To date, the published evidence on the added value of amyloid PET has important limitations.

The aim of this study was to quantify the effect of amyloid PET on the routine clinical diagnostic assessment of a large set of patients evaluated for cognitive impairment in a naturalistic setting. At variance with the largest study published so far¹⁴ and similar to only preliminary evidence,^15-20 in our study the clinicians relied on amyloid PET for their final clinical diagnoses and identification of the most appropriate treatment.

The Incremental Diagnostic Value of Amyloid PET With [¹⁸F]-Florbetapir (INDIA-FBP) Study is an open-label, multicenter study in which patients were evaluated and underwent instrumental examination as routinely required in 18 AD evaluation units from eastern Lombardy, Northern Italy (EudraCT ). Most patients receiving care at memory clinics have cognitive symptoms and are referred by general practitioners. The coordinating centers, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy, and Azienda Socio Sanitaria Territoriale of Spedali Civili, Brescia, Italy, contributed patients from their internal memory clinics with the same procedure as the other memory clinics. The study was performed as illustrated in Figure 1. The study was approved by the local ethics committee (Comitato Etico delle Istituzioni Ospedaliere) and adhered to the Declaration of Helsinki.²¹ All participants or their representatives provided written informed consent before entering the study. Participants did not receive financial compensation. The study was conducted from August 5, 2013, to December 31, 2014.

During the first visit, the dementia expert (a neurologist or geriatrician) performed a cognitive, physical, and neurologic examination and made a preliminary evaluation of eligibility. Enrolled patients underwent the local routine diagnostic workup and ancillary examinations (eg, magnetic resonance imaging, computed tomography (CT), ¹⁸F-fludeoxyglucose-PET/CT, cerebrospinal fluid collection, and clinical and neuropsychological assessment), except amyloid PET, which is usually performed to achieve the final formulation of diagnosis and treatment plan in Italian memory clinics. Patients also underwent a standard clinical and neuropsychological assessment specific to this study (eMethods in the Supplement). The assessment includes 2 tests evaluating the global cognition: Mini-Mental State Examination (range: 0 [worse performance] to 30 [better performance])²² and Alzheimer鈥檚 Disease Assessment Scale鈥揅ognitive subscale (range 0 [better performance] to 70 [worse performance]).²³

When the local routine diagnostic workup was completed, physicians formulated their diagnosis, rated their confidence that cognitive impairment was due to AD on a scale of 0% to 100%, and prescribed drug treatment based on the workup (prescan assessment). Between the first visit and prescription of drug treatment, patients underwent the amyloid PET/CT; the results were communicated to physicians only after the workup was completed and the prescan assessment was formulated. After disclosure of the amyloid PET result, dementia experts were asked to revise patients鈥� diagnosis, diagnostic confidence, and drug treatment (postscan assessment). Thus, any changes before and after the scan can only be attributed to knowing such results.

Participants were consecutive patients receiving care at AD evaluation units for diagnosis of cognitive abnormalities and suspicion of AD. Inclusion criteria were cognitive abnormality, age between 50 and 85 years, availability of an informant (spouse, adult child, or other knowledgeable informant), and a prescan diagnostic confidence of AD between 15% and 85%. Exclusion criteria were having a score greater than 2 on the Clinical Dementia Rating scale at baseline (range, 0-3)²⁴; having clinically significant psychiatric conditions potentially preventing a PET scan; being a woman with childbearing potential unless receiving contraceptives; having a relevant history of severe drug allergy or hypersensitivity; previous participation in an experimental study using an amyloid-targeting agent, unless documented that the participant had received only placebo during the whole time of the study; receipt of investigational medications within the past 30 days; and having had radiopharmaceutical imaging or treatment within 7 days before the study imaging session. Based on an estimate from the 4 top-recruiting centers (amyloid PET requests on total number of new patients in the enrolling period), these criteria select 14% to 27% of new patients referred to Northern Italy memory clinics.

Outcome variables of this study were diagnosis, diagnostic confidence, and treatment plan. Throughout the study, dementia experts evaluated patients 3 times (Figure 1). The first time corresponded to the first visit. At time 2, diagnosis, diagnostic confidence, and treatment plan were based on clinical evaluation and ancillary examinations. At time 3, physicians received the amyloid PET result and reformulated the diagnosis, diagnostic confidence, and treatment plan based on the amyloid PET result. At each evaluation physicians uploaded information using a shared web portal.²⁵

At the beginning of the study, the project principal investigators and the study management team organized an in-person meeting with participating physicians from the memory clinics who were briefed on the latest scientific literature on amyloid imaging in humans and diagnostic criteria for AD and non-AD conditions (eMethods in the Supplement). At each time point of the study, physicians were asked to stage cognitive impairment (ie, mild cognitive impairment or dementia), express an etiologic diagnosis, and rate their diagnostic confidence (0%-100%) that the cognitive impairment was consistent with an AD etiology. Etiologic diagnoses were AD (eg, typical or atypical AD, mixed AD, or AD with comorbidity) or non-AD. The non-AD diagnoses were further grouped into FTLD and subcortical diseases (ie, CVD, DLB, CBD, Parkinson disease dementia, multiple system atrophy, progressive supranuclear palsy, and normal pressure hydrocephalus).

At all time points, physicians reported medication prescription as follows: (1) acetylcholinesterase inhibitors; (2) memantine hydrochloride; (3) anxiolytics, hypnotics, or antidepressants; and (4) antipsychotics or anticonvulsants. These drugs were further grouped as cognition specific (ie, acetylcholinesterase inhibitors and memantine) and non鈥揷ognition specific (ie, anxiolytics, hypnotics, antidepressants, antipsychotics, and anticonvulsants).

PET/CT scans with [¹⁸F]-florbetapir were acquired at Poliambulanza Foundation (Siemens Biograph 40 mCT; Siemens Healthineers) and at Azienda Socio Sanitaria Territoriale of Spedali Civili, Brescia, Italy (GE Discovery 690; GE Healthcare). A total of 370 MBq (10 mCi) of [¹⁸F]-florbetapir was injected as an intravenous bolus, and acquisition and reconstruction followed standard operating procedures.²⁶ One nuclear medicine physician per center (U.P.G. and B.P.) was trained to visually read scans and rate them as amyloid positive or amyloid negative following the procedures provided by the ligand manufacturer. Visual reading was performed independently by both readers for all scans, blinded to patients鈥� diagnosis and clinical information. Throughout the study, the readers evaluated visually, with a dichotomous output (positive or negative), 267 amyloid PET scans (including 241 patients and 26 healthy elderly controls). The readers had a concordance rate of 87% (Cohen 魏鈥�=鈥�0.74; SE, 0.042, indicating very good agreement), disagreeing in 34 cases, on the first round. The agreement converged over a second round of joint reading in 19 (56%) of these cases. The remaining 15 cases were read by a reference expert from the ligand manufacturer (Avid Radiopharmaceuticals).

The 26 persons serving as controls were cognitively intact and between ages 52 and 79 years. Those with amyloid-positive scan results were 4 persons aged 60, 66, 70, and 71 years (15% of the controls).

For each diagnosis we pooled patients with mild cognitive impairment and those with dementia. We assessed normality of data distribution through histogram inspection and the Shapiro-Wilk normality test. Because of nonnormal distribution of data, we performed nonparametric analyses (Mann-Whitney test and Wilcoxon signed rank test). For categorical variables, the 蠂² test (or Fisher exact test for small samples) was used. Effect size metrics were computed with Cohen d for continuous variables (0.20 [small], 0.50 [moderate], and 0.80 [large] effect sizes), or 桅 for categorical variables (0.10 [small], 0.30 [moderate], and 0.50 [large] effect sizes). The 1-sample proportions test was used to evaluate whether proportions of patients showing changes owing to amyloid PET are significantly different from 0.00001 (ie, virtually no change expected in the absence of amyloid PET). We assessed interrater agreement for amyloid PET scan visual reading between the 2 nuclear medicine physicians with the Cohen 魏 coefficient (0.20 [fair], 0.40 [moderate], 0.60 [good], and 0.80 [very good] strength of agreement) and the rate of concordance. All statistical analyses were performed with R, version 3.1.1 (R Foundation for Statistical Computing, ).

Of the 241 enrolled patients, 2 individuals were excluded owing to incomplete data and 11 were excluded because of prescan diagnostic confidence for AD of less than 15% or more than 85%; 228 patients were included in the analyses. Mean (SD) age was 70.5 (7) years. Clinical and sociodemographic features between patients initially diagnosed as having AD or non-AD were similar, with the exception of the prevalence of mild cognitive impairment syndrome, which was more frequent in patients with AD (蠂²鈥�=鈥�8.60, P鈥�=鈥�.003, 桅鈥�=鈥�0.20). By definition, non-AD cases had lower diagnostic confidence than AD cases (Mann-Whitney,鈥�10鈥�356, P鈥�<鈥�.001, Cohen d鈥�=鈥�3.69) (Table). Of the patients who had a prescan diagnosis other than AD, 37 had a diagnosis of FTLD and 26 had a diagnosis of subcortical diseases (CVD, 11; DLB, 5; CBD, 4; Parkinson disease dementia, 3; multiple system atrophy, 1; progressive supranuclear palsy, 1; and normal pressure hydrocephalus, 1). Diagnoses were equally represented among patients recruited by academic and nonacademic memory clinics. Moreover, the consensual reading used in this study led to the same results as single-rater visual reading.

The prevalence of positive scan results was greater for patients with a prescan diagnosis of AD than for those with non-AD diagnoses (蠂²鈥�=鈥�4.95, P鈥�=鈥�.03, 桅鈥�=鈥�0.16), but the latter was not negligible (Figure 2). A similar prevalence of positivity was found in the FTLD group (18 of 37 [48.6%]) and subcortical group (12 of 26 [46.2%]) (蠂²鈥�=鈥�0, P鈥�>鈥�.99, 桅鈥�=鈥�0.02).

As expected, the negative predictive value of amyloid scans had a greater effect on diagnostic change of patients with AD than on the positive predictive value in those without AD (46 [79%] vs 16 [53%]; 蠂²鈥�=鈥�5.22, P鈥�=鈥�.02, 桅鈥�=鈥�0.27) (Figure 2).

Among clinically diagnosed non-AD disorders, amyloid PET more frequently helped in the diagnosis of patients with an FTLD syndrome (change observed in 72% of patients with FTLD and positive scan results) than that of patients with subcortical disease (change observed in 25% patients with positive scan results); the difference was significant (蠂²鈥�=鈥�4.69, P鈥�=鈥�.02, 桅鈥�=鈥�0.46). When patients with FTLD had a diagnostic change resulting from a positive scan, this led invariably to an AD diagnosis. However, when the change was observed in patients diagnosed with AD before the scan, greater variability of the final diagnoses occurred in those with a negative scan result (eTable 1 in the Supplement). Overall, 123 of 137 patients (89.8%) with amyloid-positive results received a final diagnosis of AD, and 79 of 91 (86.8%) of those with amyloid-negative results received a final diagnosis of non-AD.

The availability of amyloid imaging positively affected diagnostic confidence both after positive (螖鈥�=鈥�15.2; SD, 15; Wilcoxon signed rank,鈥�165; P鈥�&濒迟;鈥�.001; Cohen d鈥�=鈥�1.04) and negative (螖鈥�=鈥夆垝29.9; SD, 24.1; Wilcoxon signed rank,鈥�2972.5; P鈥�&濒迟;鈥�.001; Cohen d鈥�=鈥夆垝1.19) scan results and for AD and non-AD diagnoses (Figure 3). The greater or negative 螖 values depicted in Figure 3B and C reflect diagnostic changes, with the figure representing confidence that cognitive impairment is due to AD. Significant increases in diagnostic confidence were also observed when the diagnosis did not change from before the scan to after the scan (Figure 3A and D) (P鈥�<鈥�.001 for both AD and non-AD diagnoses). Patients with a confirmed diagnosis of AD despite negative scan results had greater prescan diagnostic confidence than did patients with AD who had negative results and had their diagnosis changed (75.8% vs 67.9% respectively; Wilcoxon signed rank, 376.5; P鈥�<鈥�.05; Cohen d鈥�=鈥�0.63).

A relevant influence of amyloid PET was observed for treatment plans. A positive amyloid PET scan result led to introduction of cognition-specific medications in 61 (65.6%) of previously untreated patients, and negative results led to drug discontinuation in 6 (33.3%) of previously treated patients (P鈥�<鈥�.001) (Figure 4).

In this study, we estimated the incremental value of amyloid PET when added to the routine diagnostic procedures of largely nonacademic Italian AD evaluation units in eastern Lombardy. The population from which patients were recruited is representative of the Northern Italian population seeking specialist help for cognitive impairment. This kind of study is key to the assessment of the clinical utility of amyloid PET as an AD biomarker. We found significant changes in diagnosis, diagnostic confidence, and treatment for patients with amyloid-positive as well as those with amyloid-negative results. Changes were within the range of available evidence to date (eTable 2 in the Supplement). However, different from the largest study¹⁴ published so far in which the effect of intended use of amyloid PET was estimated retrospectively, in the present study, amyloid PET results were used for the definition of the final diagnosis and patient treatment plan, and our results provide a realistic estimate of the incremental value of the examination in routine clinical settings. This design qualifies it as a phase 4 study according to a 5-phase biomarker validation framework recently adapted to the AD field.²⁷

Among patients who had AD diagnosed before amyloid PET scans were performed, as many as 58 (35%) had a negative scan. This percentage is within the range reported by clinical studies (12%-38%)^14-18,28-30 (eTable 2 in the Supplement) and slightly higher than the percentage of patients with AD who had no more than sparse neuritic amyloid plaques at autopsy (14%-25%).^31,32 Among patients with a clinical non-AD diagnosis, as many as 48% had a positive scan result. This finding is consistent with the range of 12% to 51% positivity reported for non-AD diagnoses, such as DLB, CBD, CVD, and FTLD,¹⁰ as well as within the range observed for the previously available studies^14-18,28-30 on the incremental value of amyloid imaging (eTable 2 in the Supplement).

Inconsistent scan results led to diagnostic changes in a relevant proportion of cases: 46 (79%) of patients with clinically diagnosed AD with negative amyloid PET scan results had their diagnosis changed to non-AD diseases, confirming the important negative predictive value of amyloid imaging (Figure 2). Twelve patients, however, had their AD diagnosis confirmed. These 12 patients had a higher diagnostic confidence for AD before the amyloid PET scan than did patients with AD with a revised diagnosis, suggesting a more prototypical AD clinical picture. The fact that their diagnosis was not changed to suspected non-AD pathology (SNAP) may suggest that SNAP is not yet recognized as a clinical entity despite data suggesting slower progression than with amyloid-positive AD.³³ We should, however, consider that the sensitivity of [¹⁸F]-florbetapir in detecting brain amyloidosis is 92%⁴; thus, 12 patients with false-negative scan results can be expected in our sample.

Among patients with a previous diagnosis of AD and negative amyloid scan, a comparable proportion in the present study and in a previous study²⁰ (19% and 23.5%, respectively) had their diagnosis changed to FTLD. The other most common diagnosis in our sample was cognitive impairment due to CVD and as noted in depression; Rabinovici et al²⁰observed a larger amount of CBD after negative scans, which was possibly explained by more cases of rare dementia in his level III memory clinic.

Fourteen patients (47%) without AD did not have their diagnosis changed despite positive scan results, which is consistent with the known prevalence of brain amyloidosis in neurodegenerative diseases other than AD and with age-related asymptomatic brain amyloidosis in normal aging.^10,34 This finding also denotes that physicians use the positive predictive value of amyloid imaging in their diagnostic procedure, although its negative predictive value is considered the strongest source of added value.

As described above, inconsistent amyloid PET scans led to diagnostic changes in most patients. However, amyloid PET also showed clinical utility for cases with confirmed diagnoses, significantly increasing the diagnostic confidence that cognitive impairment was due to AD for confirmed AD cases and reducing such confidence for confirmed non-AD cases.

The treatment plan was also changed following amyloid PET scans, which was consistent with scan results and diagnostic changes. Although the current impact of amyloid PET is debatable owing to a lack of disease-modifying drugs, future therapies may need to leverage on amyloid PET results. At present, more accurate etiologic diagnosis and targeted drug treatment are justified by reports of adverse events in patients with FTLD treated with cholinesterase inhibitors^35-37 and of ineffectiveness for cognitive impairment of vascular etiology.³⁸ Additional advantages of this expensive examination consist of the formulation of a benign diagnosis in patients with mild cognitive impairment who have negative scan results, and undergoing such an examination provides more certain answers to patients with positive scans who require diagnosis. In these cases, earlier intervention can be started.³⁹ Recruitment in clinical trials and the possibility for patients and caregivers to make residence and financial arrangements at a time when patients are still able to express their preference may be considered when weighing costs and benefits. The rapid evolution of biomarkers⁴⁰ and treatment requires periodic revisions of the cost-benefit ratio.

Although the multicenter design can be considered a strength of this study, this is also the source of its limitations since patients did not follow a fully standardized procedure for their diagnostic assessment. The incremental value of amyloid PET may differ depending on the set of instrumental investigations conducted before the scan, which is an issue that warrants further investigation.

Physicians鈥� backgrounds may also have an effect in the study. In Italy, patients with cognitive impairment who present to memory clinics are assessed by neurologists or geriatricians who see patients with AD or related disorders for all or most of their working time.⁴¹ These experts have a similar background regarding the specificity of the examined disorders, and we provided a common background on all participants at the beginning of this study. However, differences among professional specialization, continuing medical education, or other variables, such as beliefs on the role of amyloid in AD pathogenesis,⁴² may affect the use of amyloid PET results and were not controlled for in this study.

We have shown an effect of amyloid PET scans on diagnostic thinking and patient management when used in addition to routine diagnostic workup. Studies ongoing in the United States and Europe (Imaging Dementia鈥擡vidence for Amyloid Scanning¹¹ and Amyloid Imaging to Prevent Alzheimer鈥檚 Disease⁴³) are expanding these observations on a larger scale and launching health technology assessments that will quantify cost-effectiveness of amyloid PET in clinical routine. Future efforts will need to focus on direct comparisons of amyloid PET with other (most importantly, cerebrospinal fluid) biomarkers with the aim of defining diagnostic algorithms and guidelines.

Corresponding Author: Marina Boccardi, PhD, LANVIE鈥揕aboratory of Neuroimaging of Aging, University of Geneva, Chemin du Petit Bel-Air 2, B芒timent Voirons, CH 1225, Ch锚ne Bourg, Gen猫ve, Suisse (mboccardifbf@googlemail.com).

Accepted for Publication: August 2, 2016.

Published Online: October 31, 2016. doi:10.1001/jamaneurol.2016.3751

Author Contributions: Dr Boccardi had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Muscio, Padovani, Frisoni.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Boccardi, Altomare, Frisoni.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Boccardi, Altomare, Ferrari, Frisoni.

Obtained funding: Padovani, Frisoni.

Study supervision: Boccardi, Festari, Muscio, Frisoni.

Conflict of Interest Disclosures: Dr Boccardi has received research grants from Piramal and served as a paid member of advisory boards for Eli Lilly. Dr Guerra taught courses for fees to GE Healthcare and Eli Lilly personnel. Dr Paghera received honoraria for participating on a scientific advisory board for Eli Lilly and taught courses for fees for Avid and Eli Lilly. Dr Zanetti received honoraria for speaking at symposia for Angelini and Roche and for participating on a scientific advisory board for Angelini. Dr Borroni served as a paid member of an advisory board for Eli Lilly. Dr Ciccone received grants from the Italian Medicines Agency and personal fees from Boehringer Ingelheim and TEVA. Dr Padovani received honoraria for speaking at symposia from GE Healthcare, Lundbeck, and Novartis, and for participating on scientific advisory boards for GE Healthcare, Eli Lilly, and Novartis. Dr Frisoni has served as a paid member of advisory boards for Roche, Lilly, BMS, Bayer, Lundbeck, Elan, AstraZeneca, Pfizer, Taurx, Wyeth, GE Healthcare, and Baxter. He received research grants from Wyeth Int, Lilly Int, Lundbeck Italia, GE Healthcare, Avid/Lilly, Roche, Piramal, and the Alzheimer鈥檚 Association. In the last 2 years he received speaker honoraria from Lundbeck, Piramal, GE Healthcare, and Avid/Lilly. No other disclosures were reported.

Funding/Support: This study was sponsored by Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Centro San Giovanni di Dio Fatebenefratelli and Avid Radiopharmaceuticals, Inc. The study was conducted at IRCCS San Giovanni di Dio Fatebenefratelli; Avid Radiopharmaceuticals, Inc provided [¹⁸F]-florbetapir at no cost.

Role of the Funder/Sponsor: Avid Radiopharmaceuticals had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: The Incremental Diagnostic Value of Amyloid PET With [¹⁸F]-Florbetapir (INDIA-FBP) Working Group Members are Luigi Antelmi, MS, Samantha Galluzzi, MD, Michela Pievani, PhD, Alberto Redolfi, MS, and Anna Tarallo, MS (Laboratory of Alzheimer鈥檚 Neuroimaging and Epidemiology, Istituto di Ricovero e Cura a Carattere Scientifico [IRCCS] Centro San Giovanni di Dio Fatebenefratelli, Brescia); Anupa Arora, MD (Avid Radiopharmaceuticals, Philadelphia, Pennsylvania); Monica Bertocchi, MD, Eugenia Chit貌, MD, and Davide V. Moretti, MD (Alzheimer's Unit鈥揗emory Clinic, IRCCS Centro San Giovanni di Dio Fatebenefratelli); Raffaele Giubbini, MD, Carlo Rodella, PhD, and Luca Camoni, positron emission tomography (PET) technician (Department of Nuclear Medicine, University of Brescia, Brescia); Valentina Massetti, PET technician, and Michela Andreoli, PET technician (Department of Nuclear Medicine, Poliambulanza Foundation, Brescia); Giuseppe Bellelli, MD (School of Medicine and Surgery, University of Milano鈥揃icocca, Milan, Italy); Sara Fascendini, MD (European Foundation of Biomedical Research, Center of Excellence Alzheimer, Briolini Hospital of Gazzaniga, Bergamo, Italy); Flavia Mattioli, MD (Neuropsychology Unit, Department of Medical Sciences, Azienda Socio Sanitaria Territoriale Spedali Civili, Brescia); Renato Turco, MD (Department of Rehabilitation, Fondazione Teresa Camplani, Casa di cura Ancelle della Carit脿, Cremona, Italy); Giuliana Vezzadini, MD (Neuromotor Rehabilitation Medicine, Salvatore Maugeri Foundation Clinic of Work and Rehabilitation IRCCS, Castel Goffredo, Mantova, Italy); Vanessa Raimondi, MS (Neurology Unit, Ospedale Maggiore di Crema, Cremona, Italy); Sara Mondini, PhD (Department of General Psychology, University of Padova, Padova, Italy); Elisa Carolina Zanacchi, MS (Alzheimer Evaluation Unit, Istituto Ospedaliero di Sospiro Onlus Foundation, Sospiro, Cremona, Italy); Marta Grigolo, MS (Department of Medicine and Rehabilitation, Istituto Clinico Sant鈥橝nna, Brescia); Alessandra Pezzini, MS (Geriatric General Rehabilitation, Fondazione Richiedei, Palazzolo sull鈥橭glio, Brescia); Giacinta Bilotti, MD, Barbara Bigni, MD, Paola Zavarise, MD, and Gael Ngonga, MD (Neurology Unit, Istituto Clinico Citt脿 di Brescia, Brescia, Italy); Gian Paolo Anzola, MD (Service of Neurology, Piccole Figlie Hospital, Parma, Italy); Rosanna Turrone, MS (Centre for Aging Brain and Neurodegenerative Disorders, Neurology Unit, University of Brescia); Gianluca Guizzetti, MD, and Marina Zanetti, MS (Hospice, Istituto Polifunzionale Sociosanitario Foundation Cardinal Giorgio Gusmini, Vertova, Bergamo, Italy).