Spies 2010.

Study characteristics
Patient Sampling	Retrospective study using clinical and CSF information from a database at a university medical centre Alzheimer's centre. The database contains clinical data as well as biobanked CSF and serum of consecutive patients. All 138 patients with a clear cut diagnosis of dementia, whose CSF was available for Abeta42 and Abeta40 analysis, were included. In addition, 47 non‐demented controls without neurological problems were included. Separate data were available for the performance of biomarkers in distinguishing AD from various other types of dementia. We did not include data on performance of the index test to discriminate AD participants from controls. Inclusion criteria: participants with clear diagnosis of dementia.
Patient characteristics and setting	The sample considered in the review comprises of 138 participants: 69 AD, 26 VD, 27 FTD and 16 DLB. Demographic details are not presented for all patients. Sex: 34 males and 35 females for AD; 17 males and 9 females for VD; 19 males and 8 females for FTD; 12 males and 4 females for DLB Age (SD) (y): 69±8 for AD; 35±29 for VD (n=20); 34 ±21 for FTD (n=26); 76±8 for DLB Disease duration (mo): 29±23 for AD (n=60); 72±9 for VD; 65±7 for FTD; 34±27 for DLB (n=8) Sources of recruitment: specialist care setting; CSF database of the Radboud University Nijmegen Medical Centre, The Netherlands. Not reported whether inpatients or outpatients
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: Not reported; 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 VD, FTD and DLB)) Reference standards: NINCDS‐ADRDA for AD Clinical diagnosis of VD was based on NINDS‐AIREN, of FTD on Neary criteria, of DLB on McKeith criteria. Clinical diagnosis was established prior the results of the index test.
Flow and timing	Dates not provided for CSF sample collection. Sample included in the analysis: 69 AD; 69 non‐AD (26 VD, 27 FTD and 16 DLB) AD vs VD (n=95) Sensitivity=83%; Specificity=69% (Table 2, p475) TP=57; FP=8; FN=12; TN=18 (Calculated in RevMan5) AD vs FTD (n=96) Sensitivity=94%; Specificity=85% (Table 2, p475) TP=65; FP=4; FN=4; TN=23 (Calculated in RevMan5) AD vs DLB (n=85) Sensitivity=65%; Specificity=75% (Table 2, p475) TP=45; FP=4; FN=24; TN=12 (Calculated in RevMan5) AD vs non‐AD (n=138) Sensitivity=83%; Specificity=74% (Table 2, p475) TP=57; FP=18; FN=12; TN=51 (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?	No
Was a case‐control design avoided?	No
Did the study avoid inappropriate exclusions?	Yes
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?	Unclear
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Unclear risk