Herholz 2011.

Study characteristics
Patient sampling	A subset of 94 MCI participants' baseline data, available for all measures of interest, was used from the ADNI, a multicentre project with approximately 50 medical centre and university sites across the United States and Canada. Exclusion criteria: not reported.
Patient characteristics and setting	94 participants with MCI, diagnosed with the Petersen 2010 and CDR = 0.5 at baseline, were recruited from ADNI data. Gender: 28 women, 66 men Age: Total: 75.0 ± 7.6 years APOEɛ4: not reported MMSE: 27.1 ± 1.59 Education; not reported Sources of referral: not reported Sources of recruitment: multicentre
Index tests	¹⁸F‐FDG PET scan PET scans represented the brain activity 30 – 60 mins after injection of ¹⁸F‐FDG; had been reconstructed using 3D backprojection, 3D ordered‐subset expectation maximisation, or Fourier rebinning/2D ordered‐subset expectation maximisation; were scaled to a common global average value; and were re‐oriented into a standard 160 x 160 x 96 voxel image grid (voxel size, 1.5 x 1.5 x 1.5 mm) along the anterior commissure‐posterior commissure. The AD t‐sum was calculated. It indicates the severity of the metabolic decrease in those brain areas that are typically affected by AD (multimodal association cortices mostly located in the temporal and parietal lobes), including an adjustment for age effects. The AD t‐sum was converted into a PET score by reference to its upper limit (Herholz 2002) ROI: temporal and parietal lobes PET score = log2 {(ADtsum/11,089) + 1)} Threshold: rCGMglc of t sum > 11.090 (Herholz 2002); prespecified. 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: clinical dementia rating (not specified) and ADAS‐cog Unclear whether clinicians conducting follow‐up were aware of the ¹⁸F‐FDG results.
Flow and timing	Duration of follow‐up: 24 months Participants were required to have had 4 ¹⁸F‐FDG PET scans at baseline, 6m, 12m, and 24m. At 24‐month follow‐up: 30 MCI‐ADD, 64 MCI‐non‐convertors (57 MCI‐MCI; 7 MCI‐normal cognition); sensitivity = 57%; specificity = 67% (p 1220) 45% abnormal ¹⁸F‐FDG tests (Table 2, p 1220): 38 test positive; 56 test negative Number included in analysis: 94 TP = 17; FP = 21; FN = 13; TN = 43 (Calculated in Review Manager 5) Loss to follow‐up: none
Comparative
Notes
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?	Yes
		Low	Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Unclear
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
		High	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
		Low