Maddalena 2003.

Study characteristics
Patient Sampling	Prospective study recruiting 100 consecutive dementia patients through a memory disorders clinic. 31 controls were also recruited among cognitively intact patients and added to the sample. Separate data were available on the performance of biomarkers to distinguish between AD and non‐AD dementia. We did not include data on performance of the index test to discriminate AD participants from controls. Exclusion criteria not reported. Referral through health services such as GP, community health etc. 31 controls were included. No exclusion criteria were specified.
Patient characteristics and setting	The sample considered in the review comprised of 81 participants, 51 AD and 30 non‐AD dementia (8 VD; 2 cerebral amyloid angiopathy; 2 DLB; 3 FTLD; 4 Parkinson's dementia; 1 progressive supranuclear palsy; 2 corticobasal degeneration; 3 CJD; 2 Huntington disease; 2 cerebral autosomal dominant arteriopathy with subcortical infarctions and leukoencephalopathy; 1 neuroacanthocytosis). Ninteen participants with other neurological disorders and thirty one controls were not considered in this review. Patients underwent thorough clinical examination, including providing medical and family history; neurological, internal, and psychiatric examinations; routine laboratory testing; and CT or MRI of brain. Sex: 54 males and 46 females (total cohort) Age (SD) (y): 70.1±8.7 (range=51‐87) for AD; 66.3±11.2 (range=40‐90) for non‐AD dementia MMSE: 21.3±5.3 for AD; 21.1±5.7 for non‐AD dementia Sources of referral: GP, community health services, specialists in neurology, psychiatry or geriatrics. Sources of recruitment: memory disorders unit, outpatients, University of Zurich, Switzerland
Index tests	Patients gave CSF samples. Abeta42 was measured using enzyme‐linked immunosorbent assays, obtained from Innogenetics NV, Gent, Belgium. Threshold: 490 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 non‐AD dementia) Reference standards: NINCDS‐ADRDA for AD. Clinical diagnosis of DLB was based on McKeith criteria, of VD on NINDS‐AIREN criteria, of FTD on The Lund and Manchester Group criteria. Clinical diagnosis was established prior the results of the index test.
Flow and timing	Lumbar puncture was performed and CSF samples were obtained within one week of neuropsychological testing. Sample included in the analysis: 51 AD and 30 non‐AD dementia (8 VD; 3 FTD; 2 DLB; 2 PDD; 2 CJD; 2 cerebral amyloid angiopathy; 11 other) AD vs non‐AD (n=81) Sensitivity=78%; Specificity=70% (Table, p1205) TP=40; FP=9; FN=11; TN=21 (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?	Yes
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