Wiltfang 2003.

Study characteristics
Patient Sampling	The study included 19 patients with CJD, 19 patients with AD and 26 non‐demented controls. Sampling procedure not reported. Separate data were available for the performance of biomarkers in distinguishing between AD and CJD participants. We did not include data on performance of the index test to discriminate AD participants from controls. Exclusion criteria: not reported.
Patient characteristics and setting	The sample considered in the review in the review comprised of 19 AD and 19 CJD participants. Sex: 5 males and 14 females for AD; 9 males and 10 females for CJD Age (median) (y): 76 (range, 54–80) for AD; 66 (range, 37–88) for CJD Sources of recruitment: specialist care setting. Not reported whether inpatients or outpatients. The study was conducted in Germany.
Index tests	Patients gave CSF samples. CSF sampling methods not described. Abeta42 was measured using SDS‐PAGE immunoblot. Threshold: 1900 pg/ml; not prespecified; Cut‐offs were determined by ROC analysis. Were the index test results reported without knowledge of the reference standard? [Not reported]
Target condition and reference standard(s)	Target condition: Alzheimer's disease dementia (differential diagnosis of AD from CJD) Reference standards: NINCDS‐ADRDA and DSM‐IV for AD. Clinical diagnosis of CJD was based on the clinical criteria (Otto 2002). 11/19 patients were later neuropathologically verified as definite CJD cases. Clinical diagnoses were established prior the results of the index test.
Flow and timing	The interval between established clinical diagnosis and CSF sample collection was not reported.However, it appears that CSF samples were collected short after establishing the clinical differential diagnosis of AD and CJD. Sample included in the analysis: 19 AD; 19 CJD AD vs CJD (n=38) Sensitivity: 100%; Specificity: 58% (p264) TP=19; FP=8; FN=0; TN=11 (Calculated in Revman5)
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?	No
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
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
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk