Pardo 2010.

Study characteristics
Patient sampling	19 MCI participants and 27 healthy controls underwent extensive medical and laboratory examination. The controls were recruited from the community. Sampling procedure not described. We only include data on performance of the index test to discriminate between participants with MCI who converted to dementia and those who remained stable. Exclusion criteria: not reported.
Patient characteristics and setting	19 MCI participants with MCI, diagnosed by the Petersen 1999 criteria at baseline. Gender: not reported Age: mean 80 years; range: 54 ‐ 83 years APOEɛ4: not reported MMSE: not reported Education: not reported Sources of referral: not reported Sources of recruitment: Memory loss clinic, Geriatric, Research, Education, and Clinical Center, the Minneapolis Veterans Affairs Medical Center MVAMC) in Minneapolis, USA
Index tests	¹⁸F‐FDG PET scan Participants received an intravenous injection of ¹⁸F‐FDG at a dose of 5 mCi/70 kg, as they reclined with eyes closed and ears open in a quiet dark room. After a 30‐min uptake period, they were transferred to an ECAT 953B or ECAT Exact scanner (Siemens, Knoxville, TN). Attenuation was measured. No arterial catheters were used for absolute quantitation. Baseline PET scan analysis was performed visually independently by two blinded, experienced physicians. The readers characterised the scans as normal or abnormal (if abnormal, ADD or FTD pattern). The patterns on which the PET readers characterised the scans as ADD or FTD are described in detail in the paper (p 328, paragraph 2.3). Also in 13 MCI cases and 15 controls, a computerised classifier (SVM) was applied. Using this method, 2 features were defined: lobe and cluster. Threshold: visual interpretation; threshold not prespecified. The only thresholds applied were those used for SVM analysis: Based on the lobar features, a brain lobe was labelled as MCI or normal if ≥ 50% of the cubes had the label MCI or normal respectively. The cluster feature used a template based on the average image of the MCI participants. Each cluster or connected region was identified by using a t threshold of 2. Index test was conducted before follow‐up. The readers of the PET scan were blinded to each other's opinions.
Target condition and reference standard(s)	Target condition: conversion from MCI to Alzheimer's disease dementia or other forms of dementia (FTD and LBD). Reference standard: not reported. Unclear whether clinicians conducting follow‐up were aware of the ¹⁸F‐FDG results.
Flow and timing	Duration of follow‐up: 3 years At follow‐up: JVP characterised the baseline PET scans of the 19 MCI participants as: 6 ADD, 1 FTD, 11 HC (healthy control), 1 artefact (non‐diagnostic). In summary: 7 PET (+) participants, 11 PET (‐) participants, 1 non‐diagnostic (for all forms of dementia); MAK characterised the baseline PET scans of the 19 MCI participants as: 10 ADD, 1 ADD/FTD, 3 FTD, 5 HC. In summary: 14 PET (+) participants, 5 PET (‐) participants (for all forms of dementia). Number included in analysis: 18 participants for JVP Note: The participant with ‘artefact’ PET scan not included; 19 participants for MAK. 1) Conversion from MCI to ADD (Table 2, p 331). Reader1 (JVP) At follow‐up: TP = 2; FP = 4; FN = 6; TN = 6 Reader2 (MAK): At follow‐up: TP = 3; FP = 7; FN = 6; TN = 3 Note: The PET scan read as ADD/FTD by MAK was accounted as index test (‐) 2) Conversion from MCI to any form of dementia (Table 2, p 331) Reader1 (JVP) TP = 6; FP = 1; FN = 7; TN = 4 Reader2 (MAK) At follow‐up: TP = 9; FP = 5; FN = 5; TN = 0 Note: The PET scan read as ADD/FTD by MAK was accounted as index test (+) 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?	Unclear
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?	Unclear
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
		High	High
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?	Unclear
Were all patients included in the analysis?	Yes
		Unclear