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. 2018 Sep 1;75(9):1062-1070.
doi: 10.1001/jamaneurol.2018.1346.

Association of Amyloid Positron Emission Tomography With Changes in Diagnosis and Patient Treatment in an Unselected Memory Clinic Cohort: The ABIDE Project

Arno de Wilde  1 , Wiesje M van der Flier  1   2 , Wiesje Pelkmans  1 , Femke Bouwman  1 , Jurre Verwer  3 , Colin Groot  4 , Marieke M van Buchem  1 , Marissa Zwan  1 , Rik Ossenkoppele  1   4 , Maqsood Yaqub  4 , Marleen Kunneman  5 , Ellen M A Smets  5 , Frederik Barkhof  4   6 , Adriaan A Lammertsma  4 , Andrew Stephens  7 , Erik van Lier  8 , Geert Jan Biessels  3 , Bart N van Berckel  1   4 , Philip Scheltens  1
Affiliations

Association of Amyloid Positron Emission Tomography With Changes in Diagnosis and Patient Treatment in an Unselected Memory Clinic Cohort: The ABIDE Project

Arno de Wilde et al. JAMA Neurol. .

Abstract

Importance: Previous studies have evaluated the diagnostic effect of amyloid positron emission tomography (PET) in selected research cohorts. However, these research populations do not reflect daily practice, thus hampering clinical implementation of amyloid imaging.

Objective: To evaluate the association of amyloid PET with changes in diagnosis, diagnostic confidence, treatment, and patients' experiences in an unselected memory clinic cohort.

Design, setting, and participants: Amyloid PET using fluoride-18 florbetaben was offered to 866 patients who visited the tertiary memory clinic at the VU University Medical Center between January 2015 and December 2016 as part of their routine diagnostic dementia workup. Of these patients, 476 (55%) were included, 32 (4%) were excluded, and 358 (41%) did not participate. To enrich this sample, 31 patients with mild cognitive impairment from the University Medical Center Utrecht memory clinic were included. For each patient, neurologists determined a preamyloid and postamyloid PET diagnosis that existed of both a clinical syndrome (dementia, mild cognitive impairment, or subjective cognitive decline) and a suspected etiology (Alzheimer disease [AD] or non-AD), with a confidence level ranging from 0% to 100%. In addition, the neurologist determined patient treatment in terms of ancillary investigations, medication, and care. Each patient received a clinical follow-up 1 year after being scanned.

Main outcomes and measures: Primary outcome measures were post-PET changes in diagnosis, diagnostic confidence, and patient treatment.

Results: Of the 507 patients (mean [SD] age, 65 (8) years; 201 women [39%]; mean [SD] Mini-Mental State Examination score, 25 [4]), 164 (32%) had AD dementia, 70 (14%) non-AD dementia, 114 (23%) mild cognitive impairment, and 159 (31%) subjective cognitive decline. Amyloid PET results were positive for 242 patients (48%). The suspected etiology changed for 125 patients (25%) after undergoing amyloid PET, more often due to a negative (82 of 265 [31%]) than a positive (43 of 242 [18%]) PET result (P < .01). Post-PET changes in suspected etiology occurred more frequently in patients older (>65 years) than younger (<65 years) than the typical age at onset of 65 years (74 of 257 [29%] vs 51 of 250 [20%]; P < .05). Mean diagnostic confidence (SD) increased from 80 (13) to 89 (13%) (P < .001). In 123 patients (24%), there was a change in patient treatment post-PET, mostly related to additional investigations and therapy.

Conclusions and relevance: This prospective diagnostic study provides a bridge between validating amyloid PET in a research setting and implementing this diagnostic tool in daily clinical practice. Both amyloid-positive and amyloid-negative results had substantial associations with changes in diagnosis and treatment, both in patients with and without dementia.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Lammertsma is currently the principal investigator of a study sponsored by Avid. Research programs of Dr van der Flier have been funded by ZonMW, the Netherlands Organization of Scientific Research, Seventh European Framework Programme, Alzheimer Nederland, Cardiovascular Onderzoek Nederland, Stichting Dioraphte, Gieskes-Strijbis fonds, Boehringer Ingelheim, Piramal Imaging, Roche BV, Janssen Stellar, and Combinostics. All funding is paid to her institution. Dr Barkhof is a consultant for Biogen-Idec, Janssen Alzheimer Immunotherapy, Bayer-Schering, Merck-Serono, Roche, Novartis, Genzume, and Sanofi-Aventis; has received sponsoring from European Commission–Horizon 2020, National Institute for Health Research–University College London Hospitals Biomedical Research Centre, Scottish Multiple Sclerosis Register, TEVA, Novartis, and Toshiba; is supported by the University College London Hospitals NHS Foundation Trust Biomedical Research Center; and serves on the editorial boards of Radiology, Brain, Neuroradiology, Multiple Sclerosis Journal, and Neurology. Dr Stephens is a full-time employee of Piramal Imaging GmbH and owns stock. Dr van Lier is a full-time employee of BV Cyclotron VU. Dr Scheltens has acquired grant support (for the institution) from GE Healthcare, Danone Research, Piramal, and Merck. In the past 2 years, he has received consultancy/speaker fees (paid to the institution) from Lilly, GE Healthcare, Novartis, Sanofi, Nutricia, Probiodrug, Biogen, Roche, Avraham, and EIP Pharma. No other disclosures are reported.

Figures

Figure 1.
Figure 1.. Flowchart of Patient Inclusion
MCI indicates mild cognitive impairment; PET, positron emission tomography; VUMC, VU University Medical Center; UMCU, University Medical Center Utrecht.
Figure 2.
Figure 2.. Pre- and Post-Positron Emission Tomography (PET) Levels of Anxiety and Uncertainty
Pre- and post-PET changes in anxiety and uncertainty scores (mean [SD]). A, Pre- and post-PET anxiety in patients for whom the PET result was disclosed (n = 41). B, Pre- and post-PET anxiety in patients for whom the PET result was not disclosed (n = 21). C, Pre- and post-PET uncertainty in patients for whom the PET result was disclosed (n = 35; P < .05). D, Pre- and post-PET uncertainty in patients for whom the PET result was not disclosed (n = 19). MUIS indicates Mishel Uncertainty in Illness Scale; STAI, State-Trait Anxiety Inventory.
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