Brettschneider 2006.

Study characteristics
Patient Sampling	248 patients (109 AD, 41 VD,15 FTD, 25 MCI and 58 controls) were recruited from the Memory Clinic of the Department of Neurology, University Hospital of Ulm over 3 years. Sample procedure not reported. Separate data were available for the performance of biomarkers in distinguishing between AD and other types of dementia. 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	248 participants were included in the study: 109 AD, 41 VD,15 FTD, 25 MCI and 58 controls. Medical history, neurological, neuropsychiatric, neuroradiological and neuropsychological examinations were obtained. Control group: 34 patients presented with tension‐type headache and showed no evidence of a structural, hemorrhagic or inflammatory lesion; 24 patients fulfilled the criteria of a major depressive disorder. CSF samples were collected over 3 years. Separate data were extractable for the accuracy of biomarkers in distinguishing AD dementia from i) FTD & VD and ii) non‐AD dementia. The sample considered in the review comprised of 165 participants (109 AD, 41 VD,15 FTD). Sex: 39 males and 70 females for AD; 24 males and 17 females for VD; 8 males and 7 females for FTD Age: 71 (43‐88) for AD; 75 (47‐88) for VD; 68 (43‐77) for FTD Disease duration (y): 2 (0.5‐10) for AD; 1.75 (0.5‐9) for VD; 2 (0.5‐4) for FTD Sources of referral: secondary care. Not reported Sources of recruitment: Memory Clinic of the Department of Neurology, University Hospital of Ulm, Germany
Index tests	Patients gave CSF samples. The samples were collected in polypropylene tubes, centrifuged, aliquoted, and stored at ‐80°C and analysed. Abeta42 was measured using enzyme‐linked immunosorbent assays, obtained from Innogenetics NV, Gent, Belgium. Threshold: 612ng/L, not pre‐specified, cut‐offs were derived from 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 (1. differential diagnosis of AD from VD & FTD; 2. differential diagnosis of AD from non‐AD dementia) Reference standards: NINCDS‐ADRDA criteria Alzheimer's disease dementia Clinical diagnosis of VD was based on NINDS‐AIREN criteria, of FTD on Neary 1998 criteria, of MCI on Pettersen 1999, prior the results of the index test.
Flow and timing	The interval between established clinical diagnosis and blood sample collection was not reported.However, it appears that CSF samples were collected short after establishing the clinical diagnosis of the participants included in the study. Sample included in the analysis: 109 AD; 56 non‐AD (41 VD; 15 FTD) AD vs non‐AD (n=165) Sensitivity=82%; Specificity=46% (Table 3, p294) TP=89; FP=30; FN=20; TN=26 (calculated in RevMan5) All recruited participants with diagnosed dementia were included in the analysis.
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