Drzezga 2005.

Study characteristics
Patient sampling	Prospective, consecutive recruitment of 30 participants with MCI who were referred for diagnostic evaluation by GPs, neurologists, psychiatrists, or other institutions. Exclusion criteria: people who met the diagnotic criteria for dementia or any other functional psychiatric disorder, including major depression; symptoms of diseases or abnormalities sufficient to cause memory impairment (e.g. Parkinson's disease, normal pressure hydrocephalus); major structural abnormalities on MRI (e.g. infarction, intra‐cerebral aneurysm, arteriovenous malformation); extra‐cerebral causes which could influence neuropsychological function (e.g. use of neuroleptics, substance abuse). The study excluded people with depression, but specified major depression sufficient to cause memory impairment.
Patient characteristics and setting	30 MCI participants, diagnosed with the Petersen 1999 and CDR 5 criteria, were recruited from a research unit. Baseline evaluation included medical, psychiatric and neurological examinations performed by an experienced psychiatrist. Paricipants had to meet the established diagnostic criteria for mild cognitive impairment: subjective complaint; performance of 1.5 SD below the age norm on the Consortium to establish a registry for Alzheimer's Disease (CERAD) delayed verbal recall test; CDR score of 0.5; preserved basic activities of daily living. Gender: 14 men; 16 women; MCI‐non‐converters: 8M, 10F; MCI‐converters: 6M, 6F Age: mean: total sample 70 ± 8 years; MCI‐non‐converters: 67.6 ± 8.2 years; MCI‐converters: 74.7 ± 4.7 years APOEɛ4: MCI‐non‐converters: 8/18; MCI‐converters: 9/12 MMSE: MCI‐non‐converters: 27.6 ± 1.5; MCI‐converters: 25.9 ± 2.1 Duration of symptoms: mean 2.6 ± 2.0 years Education: mean 11.6 ± 3.4 years Sources of referral: GP surgeries or neurologists or psychiatrists or other institutions Sources of recruitment: Research Unit for Cognitive Disorders, Technical University, Munich, Germany.
Index tests	¹⁸F‐FDG PET scan The index test was performed at the time of initial clinical evaluation. All participants received 370 MBq ¹⁸F‐FDG at rest with the eyes closed. Participants were positioned with the head parallel to the canthomeatal line within the gantry. 30 minutes after injection, PET was performed under standard resting condition (eyes closed in dimmed ambient light) using a Siemens 951 R/31 PET scanner (CTI). A sequence of 3 frames of 10 min was started and later combined into a single frame. Image data were acquired in 2‐dimensional mode with a total axial field of view of 10.5 cm and no interplane gap space. Attenuation correction was performed by a standard ellipse‐fitting method. For analysis of the PET data, a well‐established observer‐independent programme (NEUROSTAT; University of Michigan) was used to minimise observer bias. This method has been evaluated for clinical and scientific use in people with dementia and other cerebral disorders (Bartenstein 1997; Drzezga 1999; Ishii 2001; Minoshima 1995). The ROIs were defined to reflect functional divisions of the cerebral lobes, and each hemisphere was divided into the following regions: orbitofrontal, prefrontal, premotor, central, parietal superior and inferior, occipital, temporal anterior, temporal posterior and posterior cingulate. The results from the ROI analysis were not averaged together; each ROI was assessed individually. The detection of significant hypometabolism (as compared with a control population) in surface ROIs covering the posterior cingulate cortex accompanied by cortical hypometabolism in at least unilateral temporo‐parietal areas was determined as suggestive of early AD, based on findings of earlier studies (Drzezga 2003). According to this strategy, PET baseline results were classified as suggestive or not suggestive for AD. Threshold: A z‐score threshold of > 1.64 (1‐tail) corresponding to a P value of 0.05 (1‐tail) was applied for demarcation of significant abnormalities. This statistical threshold previously proved to be suitable for the diagnosis of DAT using the applied statistical tool (Bartenstein 1997; Minoshima 1995); 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: NINCDS‐ADRDA criteria ¹⁸F‐FDG PET results were blinded for the later outcome of the participants, and blinded for other clinical baseline information.
Flow and timing	Duration of follow‐up: 15 months (expanded to a mean 16 ± 2 months) At baseline: 30 participants: 13 with ¹⁸F‐FDG positive; 17 with ¹⁸F‐FDG negative (Abstract) At follow‐up: 12 MCI‐ADD; 18 MCI‐MCI (p 1628); sensitivity: 92%; specificity: 89% (Table 2, p 1629) Number included in analysis: 30 TP = 11; TN = 16; FP = 2; FN = 1 (Calculated in Review Manager 5) 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?	Yes
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?	Yes
		Low	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?	Yes
		Low