Kapaki 2003.

Study characteristics
Patient Sampling	Participants from an outpatient clinic diagnosed with AD and non‐AD dementia were followed‐up for at least three years in an effort to ensure the correct diagnosis, and doubtful cases were rejected. 70 patients with dementia (49 AD; 15 non‐AD; 6 VD) were recruited. 49 controls were also included. Sample procedure not reported. Separate data were available for the performance of the biomarkers in distinguishing AD from non‐AD dementia, and AD from VD. We did not include data on performance of the index test to discriminate AD participants from controls. Exclusion criteria: patients with dementia due to metabolic causes and patients with a history of alcohol abuse, MRI infarctions (except VD patients), or B12 deficiency were excluded.
Patient characteristics and setting	The sample considered in the review comprised of 70 participants: 49 AD, 15 non‐AD (6 DLB; 4 FTD; 1 with Parkinson's disease; 2 with progressive supranuclear pulsy; 2 with corticobasal‐ganglionic degeneration) and 6 with VD. All participants had detailed evaluation (medical history, physical and neurological examination, blood tests to exclude metabolic causes of dementia) and MRI. Sex: 31 males and 18 females for AD; 11 males and 4 females for non‐AD dementia; 4 males and 2 females for VD Age (SD) (y): 67.6 ± 9.3 for AD; 61.3 ± 5.1 for non‐AD dementia; 69 ± 4 for VD Sources of recruitment: an outpatient clinic, Athens National University, Greece.
Index tests	Patients gave CSF samples. The samples were collected in polypropylene tubes, centrifuged, aliquoted, and stored at ‐70°C and analysed. Abeta42 was measured using enzyme‐linked immunosorbent assays, obtained from Innogenetics NV, Gent, Belgium. Threshold: 435 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 (1. differential diagnosis of AD from non‐AD dementia; 2. differential diagnosis of AD from VD) Reference standards: NINCDS‐ADRDA for AD. Clinical diagnosis of VD was based on NINDS‐AIREN criteria, of DLB and Parkinson's dementia on McKeith criteria, of FTD on Neary 1999 criteria, of progressive supranuclear palsy according on NINDS‐SPSP criteria. Criteria of corticobasal‐ganglionic degeneration were not not specified. Clinical diagnosis was 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 shortly after the clinical diagnosis was established. Sample included in the analysis: 49 AD; 6 VD; 15 non‐AD (6 DLB; 4 FTD; 1 with PD dementia; 2 with progressive supranuclear pulsy; 2 with corticobasal‐ganglionic degeneration) 1. AD vs non‐AD dementia (n=64) Sensitivity=71%; Specificity=80% (Abstract) TP=35; FP=3; FN=14; TN=12 (calculated in Revman5) 2. AD vs VD (n=55) Sensitivity=82%; Specificity=67% (Abstract) TP=40; FP=2; FN=9; TN=4 (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?	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?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk