Schreiber 2015.

Study characteristics
Patient sampling	401 amnestic MCI participants were selected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The study was performed from September 2010, to August 2014; data analysis was performed from September 2014, to May 2015. The participants were between 55 to 90 (inclusive) years old with memory complaints or cognitive impairment corroborated by an informant, CDR 0.5, and MMSE > 24, Hachinski less than or equal to 4, Geriatric Depression Scale less than 6, without any significant neurologic disease other than suspected incipient Alzheimer’s disease, had completed at least 6 years of education, were fluent in Spanish or English. No sampling criteria was specified
Patient characteristics and setting	401 amnestic MCI participants diagnosed by CDR = 0.5 at time of performing the test, were recruited from ADNI data. The mean age was 71.6 (+ 7.5) years for all participants. Gender: 182 female in MCI group. APOE ϵ4 carrier: 198 participants were positive in the MCI group. MMSE: the mean MMSE in the MCI group was 28.1 (+ 1.7). Years of education: the mean for those in the MCI group was 16.2 (+ 2.7) years. Sources of referral mixed: memory clinics, newspaper ads, radio, and other public media campaigns. Setting: multicentre, no other specific data regarding setting was reported.
Index tests	Florbetapir image data were acquired from a variety of PET scanners (Siemens PET systems, GE, Phillips). 18F‐florbetapir administration mCi (MBq) dose: approximately 10 mCi (370 MBq). Time between the 18F‐florbetapir injection and PET acquisition: between 50 to 70 minutes after injection of approximately 10 mCi, a 20‐min emission scan (acquired in 4 × 5 min frames) was obtained. The four frames were coregistered to one another, averaged, interpolated to a uniform image and voxel size (160 × 106 × 96, 1.5mm3), and smoothed to a uniform resolution (8 mm full width half maximum) to account for differences between scanners. Visual analysis was performed on axial, sagittal, and coronal slices, in an inverse gray scale, using software that permitted adjustment of image brightness and contrast to each reader’s specifications. Florbetapir positivity was defined as increased tracer uptake in the cerebral cortex that was visually perceived as reduced or absent white matter/gray matter contrast in at least one cortical (frontal, parietal, temporal, occipital) region detectable on more than two adjacent scan slices. The reader was trained using an online electronic training tool produced by the company who produced the tracer, and the reader was blinded to all clinical data and any other imaging test of each participant. Quantitative analysis: To quantify cortical Aβ, preprocessed florbetapir image data and coregistered structural magnetic resonance images (MRI) were analysed using Freesurfer v4.5.0 MPRAGE scans of one structural 1.5T or 3T MRI scan within 2 months of florbetapir scans were segmented and parcellated into individual cortical regions, used to extract the mean florbetapir uptake from the gray matter of the ROI (lateral and medial frontal, anterior, and posterior cingulate, lateral parietal, and lateral temporal regions) relative to uptake in the whole cerebellum (white and gray matter). The threshold used was a SUVR > 1.11 determined at baseline.(Landau 2012, Landau 2013).
Target condition and reference standard(s)	Target condition: Alzheimer’s disease (progression from MCI to ADD) Reference standard: NINCDS‐ADRDA criteria Unclear whether clinicians conducting follow‐up were aware of the ¹⁸F‐florbetapir PET scan results.
Flow and timing	Participants belonged to the ADNI database, the study was performed from September 2010 to August 2014. .All participants received the same reference standard. Duration of follow‐up: a median progression‐free follow‐up time of 1.6 years Number included in analysis: MCI Visual assessment: 401 MCI: 196 MCI with 18F‐florbetapir positive test: 54 converted to ADD and 142 remained stable; 205 MCI with 18F‐florbetapir negative test: 7 converted to ADD and 198 remained stable. TP = 54; FP = 142; FN = 7; TN = 198 SUVR > 1.11: 401 MCI: 221 MCI with 18F‐florbetapir positive test; 53 converted to ADD and 168 remained stable; 180 MCI with 18F‐florbetapir negative test: 8 converted to ADD and 172 remained stable. TP = 53; FP = 168; FN = 8; TN = 172 Loss to follow‐up: data appeared to have been reported for all 401 participants.
Comparative
Notes	Dr Schreiber kindly sent the ADNI identification code for each MCI participant (mail received 04/07/2017).
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
		Unclear	Low
DOMAIN 2: Index Test All tests
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
Was the PET scan interpretation done by a trained reader physician?	Yes
Was there a clear definition of a positive result?	Yes
		Low	Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
		Unclear	Unclear
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Was the study free of commercial funding?	Yes
		Low

^{Aβ: Amyloid Beta
 ADD: Alzheimer's disease dementia
 ADNI: Alzheimer's Disease Neuroimaging Initiative
 APOE ϵ4: Apolipoprotein E4
 CDR: Clinical dementia rating
 CIND: Cognitive impairment not dementia
 CT: Computed tomography
 DSM‐IV: Diagnostic and Statistical Manual of Mental Disorders (4th ed.)
 FN: False negative
 FP: False positive
 MBq: Megabecquerel
 MCI: Mild cognitive impairment
 mCi: Millicurie
 MMSE: Mini‐mental state examination
 MPRAGE: Magnetization‐Prepared Rapid Gradient‐Echo
 NINCDS‐ADRDA: National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association
 PET: Positron emission tomography
 ROI: Region of interest
 SUVR: Standardised uptake value ratio}

^{T: Tesla
 TN: True negative
 TP: True positive}