Kapaki 2008.

Study characteristics
Patient Sampling	A total of 203 participants (76 AD; 34 FTLD; 93 healthy controls) were prospectively enrolled in the study. No further information on sampling procedure. Separate data were available for the performance of biomarkers in distinguishing between AD from FTD and AD from FTLD. We did not include data on performance of the index test to discriminate AD participants from controls. Exclusion criteria: secondary causes of dementia.
Patient characteristics and setting	110 participants were considered in the review: 76 AD and 34 FTLD (24 FTD; 5 PPA; 5 FTD with motor neuron signs). All patients underwent detailed clinical, neuropsychologic, biochemical, and neuroimaging examination (magnetic resonance imaging in all patients and, additionally, single photon emission computed tomography in all FTLD patients), to exclude secondary causes of dementia and establish the diagnosis. In addition, at least 2‐years follow‐up was available to ensure the correct diagnosis. None of the patients were under cholinesterase inhibitors at the time of lumbar puncture. Sex: 28 males and 48 females for AD; 20 males and 14 females for FTLD Age mean (SD) (y): 66.0 ± 10.0 for AD; 3.1 ± 2.7 for FTLD Disease duration (y): 3.4 ± 2.8 for AD; 61.0 ± 9.0 for FTLD Sources of referral: not reported Sources of recruitment: specialist care setting, Athens National University, Greece. 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: 451 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 dementia from FTD, and AD from FTLD) Reference standard: NINCDS‐ADRDA criteria for AD The clinical diagnosis of FTLD was established on Neary 1998 criteria. At least 2‐years follow‐up was available to ensure the correct diagnosis, prior the results of the index test. Disease duration was defined as the time between the onset of the symptom(s) and CSF sampling.
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 establishing the clinical diagnoses. Sample included in the analysis: 76 AD and 34 FTD (FTLD: 24 FTD; 5 PPA; 5 FTD with motor neuron signs) AD vs FTD (FTLD) (N=107) TP=57; FP=9; FN=19; TN=22 (Fig 1b, p49) Sensitivity=75%; Specificity=71% (Calculated in RevMan) Missing data: 3 FTLD were not 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?	No
Could the patient flow have introduced bias?		Unclear risk