Mosconi 2004.

Study characteristics
Patient sampling	People with aMCI, recruited over a 2‐year period. Sampling procedure not described. Exclusion criteria: major psychiatric or medical disease; using medication that could affect brain structure or function (previous subarachnoid or intra‐cerebral haemorrhage, intra‐cranial tumour, hydrocephalus, psychosis, major depression, alcoholism, epilepsy, ischaemic stroke, vascular dementia and other dementing illnesses, anaemia, untreated thyroid dysfunction, renal insufficiency, non‐stabilised diabetes mellitus).
Patient characteristics and setting	37 MCI participants, diagnosed with the Petersen 2001 criteria at baseline. Gender: converters: 5 women; 3 men; non‐converters: 15 women; 14 men Age: converters: 69 ± 4 years; non‐converters: 63 ± 8 years APOEɛ4: total: APOE4(+)16; APOE4(‐) 21. APOE4(+) MCI‐non‐converters: 11/16; APOE4(+) MCI‐converters: 5/16; APOE4(‐) MCI‐non‐converters: 18/21; APOE4(‐) MCI‐converters: 3/21 MMSE: MCI‐non‐converters: 28.1 ± 1.6; MCI‐converters: 23.9 ± 1.7 Education: MCI‐non‐converters: 10.0 ± 5.0; MCI‐converters: 8.0 ± 3.0 Sources of referral: not reported Sources of recruitment: not reported. The recruitment was carried out according to the general protocol of the Network for Efficiency and Standardisation of Dementia Diagnosis research project (Herholz 2002).
Index tests	¹⁸F‐FDG PET scan PET scans were performed using GE Advance PET devices (Milwaukee, WI). Scans were acquired in 2D mode with an axial field of view of 153 mm, an in‐plane full width at half‐maximum (FWHM) of 4.6 mm, and slice thickness of 4.25 mm. Participants were injected with a dose of 110 to 370 MBq of [¹⁸F] FDG in a resting state with eyes closed and ears unplugged in a dimly‐lighted room with minimal background noise. A polycarbonate head holder was used to reduce head movement during the scan. The uptake interval between FDG injection and scan start was on average 42 ± 19 minutes. The average scan duration was 19 ± 3 minutes. Images were reconstructed using filtered back‐projection including correction for attenuation measured by transmission scan and scatter using standard software as supplied by scanner manufacturers. Basic image processing and voxel‐based data analyses were performed using SPM99 routines (Wellcome Department of Cognitive Neurology, London, UK) implemented in MATLAB (Mathworks, Sherborn, MA). An isotropic Gaussian filter was used to smooth the spatially normalised PET images with an FWHM of 12 mm. Individual counts were normalised to mean global activity using proportional scaling to obtain relative cerebral metabolic rate for glucose (rCMRglc) values from FDG radioactivity measurements. To minimise 'edge effects' without excluding hypometabolic tissue, only those voxels with values > 80% of the mean for the whole brain were retained for all statistical analyses. Global calculation was obtained with respect to the mean voxel value. The writers defined the precuneus (PreCu), anterior (ACC), and posterior (PCC) cingulate cortex, inferior parietal lobule (IPL), superior (STG) and middle (MiTG) temporal gyrus, and superior (SFG), middle (MiFG), and inferior frontal (IFG) gyrus, on both hemispheres, as candidate areas for possible rCMRglc alterations. Threshold: no specific rCMRglc value is referred as threshold. The writers characterise a PET scan as positive or negative for significant rCMRglc reductions in certain cerebral areas with emphasis on the inferior parietal lobule (IPL). No threshold or related quantitative data are provided. 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 Clinicians conducting follow‐up were blinded to APOE results. Unclear whether they were unaware of the ¹⁸F‐FDG results.
Flow and timing	Duration of follow‐up: mean 12.1 ± 0.6 months At baseline 37 MCI. At follow‐up: 37 participants: 8 MCI‐ADD; 29 MCI‐MCI (p 2335) Sensitivity: 38%; Specificity: 97% (p 2336) Number included in analysis: 37 TP = 3; FP = 1; FN = 5; TN = 28 (calculated in Review Manager 5) Loss to follow‐up: none All participants appear to have been included in the analyses (conversion/non‐conversion outcomes were reported for 37 participants).
Comparative
Notes	Additional information were requested from the trial investigators regarding the threshold but no further information was available at the time this review was prepared (email on 5th September 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?	Yes
		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?	Unclear
		Unclear	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?	No
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
		Low