Landau 2010.

Study characteristics
Patient sampling	Retrospective analysis of 85 people with MCI taken from a larger study. Participants had MCI and baseline data were available for all measures of interest to the current study. No exclusion criteria were specified.
Patient characteristics and setting	85 participants with MCI (Petersen 2010 and CDR = 0.5 criteria), whose data were analysed, were recruited from the ADNI, a multicentre project with approximately 50 medical centre and university sites across the United States and Canada. Approximately 200 cognitively normal older participants, 400 participants with MCI, and 200 with early AD are enrolled in ADNI, all of whom have had MRI scanning; approximately 50% have had PET scanning, and approximately 50% also agreed to lumbar puncture. MCI participants were classified as single‐domain or multi‐domain amnestic MCI (Petersen 2003). Gender: 56 men; 29 women. MCI‐non‐converters: 37M, 20F; MCI‐converters: 19M, 9F Age: MCI‐non‐converters: mean 78 ± 7.4 years; MCI‐converters: mean 78.3 ± 7.5 years APOEɛ4: MCI‐non‐converters: 14 (25%); MCI‐converters: 11 (41%) MMSE: MCI‐non‐converters: mean 27.3 ± 1.6; MCI‐converters: mean 26.4 ± 1.7 Education: MCI‐non‐converters: mean 16.3 ± 2.8; MCI‐converters: mean 16.4 ± 2.6 Sources of referral: not reported Sources of recruitment: multicentre
Index tests	¹⁸F‐FDG PET scan PET images were acquired 30 – 60 minutes post‐injection. Images were averaged, spatially aligned, interpolated to a standard voxel size, intensity normalised, and smoothed to a common resolution of 8 mm full width at half maximum. Spatial normalisation of each individual’s PET volume to the standard ¹⁵O‐H₂O PET template was conducted using SPM5 (template voxel dimensions: 91 x 109 x 91; voxel size: 2 mm x 2 mm x 2 mm). The regions of interest selected were study‐independent, frequently associated with decline in AD and MCI (no further details). Optimal diagnostic thresholds were derived from a ROC analysis. Threshold: 1.21 (Table 2 – most likely this value refers to rCMRglc); not prespecified. The mean ± SD values on ¹⁸F‐FDG scan are referred on Table 1: MCI‐non‐converters: 1.22 ± 0.14; MCI‐converters: 1.13 ± 0.10 Index test was conducted before follow‐up.
Target condition and reference standard(s)	Target condition: conversion from MCI to Alzheimer's disease dementia Reference standard: NINCDS‐ADRDA criteria. Cognitive decline was measured by ADAS–Cognitive Subscale (Rosen 1984) and standard diagnostic criteria. Unclear whether clinicians conducting follow‐up were aware of the ¹⁸F‐FDG results.
Flow and timing	Duration of follow‐up: 1.9 ± 0.4 years; maximum 3 years Follow‐up occurred at multiple time points (6, 12, 18, 24 and 36 months) At baseline 85 participants with MCI. At follow‐up: 85 participants: 28 MCI‐ADD; 57 MCI‐MCI (p 232) Information from the author: At follow‐up: 51 MCI with positive ¹⁸F‐FDG biomarker: 21 MCI‐ADD, 30 MCI‐MCI; 34 MCI with negative ¹⁸F‐FDG biomarker: 7 MCI‐ADD, 27 MCI‐MCI Number included in analysis: 85 TP = 21; FP = 30; FN = 7; TN = 27 Loss to follow‐up: none; all 85 participants appear to have been included in the analysis.
Comparative
Notes	We contacted the trial investigators who provided relevant data tor the 2 x 2 table to be completed (email on 24th January 2013).
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
		High	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?	No
		High	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	Low
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
		Low