Clerici 2009.

Study characteristics
Patient sampling	30 right‐handed participants with MCI. Sampling procedure not described. Information from the author: 16 aMCI came from the Del Sole 2008 study; 14 snaMCI were added to the current study. Exclusion criteria: i) presence of a DSM‐IV psychiatric disorder, including dementia or of organic brain pathology or of organic illness affecting the brain; ii) significant history of head injury; iii) major systematic illness; iv) history of drug and alcohol dependence; v) history of stroke.
Patient characteristics and setting	30 MCI (16 aMCI and 14 snaMCI) participants were recruited from the Department of Neurology. The participants had experienced cognitive problems and contacted the clinic for examination. Most of the participants (approximately 85%) were referred by their GPs or by a specialist, while approximately 15% came of their own initiative. The diagnostic criteria for MCI were: 1. Subjective and objective anamnestic evidence of progressive cognitive impairment for more than 6 months; 2. Normal activities of daily living; 3. MMSE score of 24 or greater; 4. a CDR score of 0.5; and 5. a score > 1.5 SD below the mean on at least 1 cognitive dimension, as evaluated by neuropsychological assessment. Gender: aMCI: 10 women (62.5%) and 6 men (37.5%); snaMCI: 10 women (71.4%) and 4 men (28.6%) Age: aMCI: 74.92 ± 7.6 years; snaMCI: 73.62 ± 6.3 years APOEɛ4: not reported MMSE: aMCI: 25.82 ± 1.5; snaMCI: 26.72 ± 1.9 Education: aMCI: 9.1 ± 4.5 years; snaMCI: 8.7 ± 4.0 years Sources of referral: GP surgeries or specialists (85%) or self referral (15%) Sources of recruitment: Center for Research and Treatment of Cognitive Dysfunctions of the Department of Neurology, University of Milan, Italy
Index tests	¹⁸F‐FDG PET scan An activity of 185‐370 MBq of ¹⁸F‐FGD, depending on person’s weight, was injected intravenously in resting condition with eyes closed and ears unplugged; the participants were asked to rest quietly for the next 45 minutes. The studies were performed using an ECAT ACCELL scanner (Siemens Medical Systems, Erlangen, Germany). PET data of MCI participants were compared to a control group of 7 cognitively normal elderly participants described in previous study of the group (Del Sole 2008). The aMCI and snaMCI groups were first compared to controls (as described in the Del Sole 2008 study) and then to each other on a voxel‐by‐voxel basis using a 2‐sample t test. Each PET study was analysed separately (according to the method described in the Del Sole 2008 study) to assess regional cerebral metabolic abnormalities in individual participants. Briefly, the SPM(t) maps of each person were converted to binary masks, where single pixels of the images were either a 0 in areas of normal ¹⁸F‐FDG uptake or 1 in areas of decreased uptake. The mask images were summed together to generate a map of overlapping regions of metabolic impairment. Threshold: Each scan was considered positive when a cluster of at least 100 consecutive voxel (size 2 x 2 x 2 mm³) had a metabolism lower that the control group (with P set at < 0.01 level); prespecified (Dr Clerici email on 23rd August 2013) Index test was conducted before follow‐up.
Target condition and reference standard(s)	Target condition: conversion from MCI to Alzheimer's disease dementia or other forms of dementia Reference standard: NINCDS‐ADRDA and DSM‐IV for AD dementia; McKeith criteria for LBD; Lund and Manchester criteria for FTD Not clear whether clinicians conducting follow‐up were aware of the ¹⁸F‐FDG PET results.
Flow and timing	Duration of follow‐up: aMCI group: last follow‐up 18 months; snaMCI group: follow‐up at 12, 24, and 37 months Information from the author: At baseline: 26 ¹⁸F‐FDG+ tests; 4 ¹⁸F‐FDG‐ tests at baseline At follow‐up (37 months): 12 aMCI with ¹⁸F‐FDG+: 11 aMCI converters (10 aMCI‐ADD; 1aMCI‐LBD), 1 lost to follow‐up 4 aMCI with ¹⁸F‐FDG‐: 1aMCI‐ADD; 2aMCI‐MCI; 1 lost to follow‐up 14 snaMCI with ¹⁸F‐FDG+: 7 converters (2 snaMCI‐ADD; 2 snaMCI–FTD; 3 snaMCI‐LBD) and 5 non‐converters (5 snaMCI‐ snaMCI) and 2 lost to follow‐up Number included in analysis: 26 TP = 12; FP = 11; FN = 1; TN = 2 for Alzheimer's disease dementia TP = 18; FP = 5; FN = 1; TN = 2 for all forms of dementia Loss to follow‐up: In total 4 MCI participants: 2 aMCI and 2 snaMCI. No further details.
Comparative
Notes	We contacted the trial investigators who provided relevant data tor the 2 x 2 table to be completed (email on 23rd August 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?	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	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
		Unclear