Fellgiebel 2007.

Study characteristics
Patient sampling	Prospective recruitment of 16 people with aMCI, presenting at a memory clinic for diagnostic evaluation. Sampling procedure not described. Exclusion criteria: people with metabolic disease that could affect cognitive function; people with other brain diseases; people with a diagnosis of depression according to DSM‐IV criteria
Patient characteristics and setting	16 participants, diagnosed with the Petersen 1999 criteria at baseline. 1 person in the initial study group refused further participation and has been replaced by a consecutively‐recruited comparable patient from the memory clinic to preserve the statistical power for prospectively planned follow‐up analyses. Gender: 9 men; 7 women. Age: total sample: mean age 68.6 ± 7.9 years; MCI‐MCI: 68.8 ± 10.0 years; MCI‐progressive: 68.5 ± 5.9 years (4/8 MCI‐ADD: 69.5 ± 7.9 years) APOEɛ4: not reported MMSE: mean 25.7 ± 2.7; MCI‐MCI: 27.3 ± 1.8; MCI‐progressive: 25.0 ± 2.1 (4/8 MCI‐ADD: 24.3 ± 1.5) Education: not reported Sources of referral: not reported Sources of recruitment: University Memory Clinic, Germany
Index tests	¹⁸F‐FDG PET scan Method of the index test administration described previously (Fellgiebel 2004): Acquisition was in 3D mode . 30 minutes after injection of 180 MBq ¹⁸F‐FDG, a sequence of 3 5‐minute frames was started and later combined to a single frame. Thereafter, the images were corrected for attenuation, scatter, and dead time. Standardised 3D stereotactic surface projections for each participant, compared with a normal database to provide Z scores. Threshold(s): AD‐typical findings were defined as significant decrease ( Z‐score > 2 in more than 50 adjacent pixels) of cerebral glucose metabolism in at least 1 of the brain regions that have been shown to be typically involved in early AD (parietal mesial or posterior cingulate and temporal regions); 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: Progression to Alzheimer's disease dementia was assumed if CDR reached 1. Follow‐up evaluation at variable time points (not specified), comprising neurological and psychiatric examination, CDR and MMSE. Progressive cognitive decline was defined as MMSE score reduction ≥ 2 and a clinical judgement of cognitive deterioration. Clinicians conducting follow‐up were blinded to the¹⁸F‐FDG PET results.
Flow and timing	Duration of follow‐up: Total sample: 19.6 ± 9.0 months; MCI‐MCI: 19.5 ± 9.3 months; MCI‐progressive: 17.6 ± 8.8 months (4/8 MCI‐ADD: 23.7 ± 2.0 months) At baseline: 16 MCI: 7 with ¹⁸F‐FDG positive; 9 with ¹⁸F‐FDG negative At follow‐up: 16 MCI: 7 FDG positive: 4 MCI‐ADD, 1 MCI‐MCI, 2 MCI‐progressive (non‐converters); 9 FDG‐: 7 MCI‐MCI ; 2 MCI‐progressive (non‐converters) (p 170). Number included in analysis: 16 TP = 4; FP = 3; FN = 0; TN = 9 Sensitivity: 100%; Specificity: 75%; PPV: 57%; NPV: 100% (calculated in Review Manager 5). Loss to follow‐up: 1/16; however, that participant was replaced by an additional, consecutively‐recruited patient from the memory clinic.
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?	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?	Unclear
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
		Unclear	Unclear
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
		Unclear