Anchisi 2005.

Study characteristics
Patient sampling	Consecutive sample of 67 right‐handed participants with mild cognitive impairment (Dr Perani email on 22nd October 2013) and 41 healthy controls. We only included data on performance of the index test to discriminate between people with MCI who converted to dementia and those who remained stable. Exclusion criteria: depression and behavioural disorders. No further information.
Patient characteristics and setting	67 participants with MCI, diagnosed with the Mayo Clinical criteria (Petersen 2001) at baseline, were recruited from 4 centres enrolled in the Network for Efficiency and Standardisation of Dementia Diagnosis Fifth European Framework Research Project. 48 participants were assessed at follow‐up Gender: total sample 34 men; 33 women. MCI‐non‐converters: 20M, 14F; MCI‐converters: 5M; 9F; Drop‐outs: 9M, 10F Age: total sample mean 67.7 ± 8.3; MCI‐non‐converters: 65.0 ± 9.0; MCI‐converters: 71.1 ± 3.9; Drop‐outs: 70.1 ± 8.3 APOEɛ4: not reported MMSE: mean: total sample 27.7 ±1.7; MCI‐non‐converters: 28.4 ± 1.1; MCI‐converters: 26.6 ± 1.7; Drop‐outs: 27.2 ± 2.3 22.7 ± 11.0; Drop‐outs: 29.7 ± 19.2 Education: total sample mean 11.0 ± 4; MCI‐non‐converters: 11.2 ± 4.5; MCI‐converters: 9.1 ± 5.0; Drop‐outs: 12.2 ± 4.8 Sources of referral: primary care physicians (Dr Perani email on 22nd October 2013) Sources of recruitment: outpatients from 4 University Departments (Milan, Brescia, Cologne and Dresden) (Dr Perani email on 22nd October 2013)
Index tests	¹⁸F‐FDG PET scan Studies were performed according to previously described methods (Herholz 2002). The software packages SPM99 (Wellcome Department of Cognitive Neurology, University College, London, England) and MATLAB 6.1 (MathWorks Inc, Sherborn, Mass) were used for image pre‐processing. Images were spatially normalised to a reference stereotactic template (Montreal Neurological Institute, McGill University, Montreal, Quebec) by a 12‐parameter transformation and smoothed by a Gaussian kernel of 12x12x12‐mm voxels full width at half maximum. The hypometabolic regions in participants with mild cognitive impairment who developed Alzheimer's disease compared with controls, obtained by SPM99 analysis, were used to define volume of interest (VOI). Using only clusters > 700 voxels, 3 VOIs in the temporo‐parietal regions and posterior cingulate cortex were selected. The regional sensorimotor ¹⁸F‐FDG uptake ratio (regional cerebral glucose metabolism) was used as the index test. Sensitivity and specificity data were reported for a threshold of 1.138, which was derived from ROC analysis. Threshold: rCGM‐r = 1.138; not prespecified At baseline 67 MCI. A number of test+ and test‐ participants reported only for 48 MCI participants who had follow‐up data: 19 with positive ¹⁸F‐FDG test (≤ 1.138); 29 with negative ¹⁸F‐FDG test (> 1.138) 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 Unclear whether clinicians conducting follow‐up were aware of the ¹⁸F‐FDG PET results.
Flow and timing	Duration of follow‐up: median follow‐up 12 months; range: 12 ‐ 27 months At baseline 67 MCI. At follow‐up: 48 participants: 14 MCI‐ADD; 34 MCI‐MCI (p 1730) Sensitivity: 92.9%; Specificity: 82.4%; NPV: 96.55%; PPV: 68.4% (at the threshold of rCGM‐r = 1.138; p1731) Number included in analysis: 48 TP = 13; FP = 6; FN = 1; TN = 28 (calculated in Review Manager 5) Loss to follow‐up: 19; no further information.
Comparative
Notes	We contacted the trial investigators who provided some additional data for the 'Patient selection' and 'Patient characteristics and setting' items (email on 22nd October 2013).
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
		Low	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?	No
		High