Bibl 2007.

Study characteristics
Patient Sampling	A total of 90 patients (30 ADD; 30 FTLD; 30 non‐demented disease controls) were selected on wards and the dementia outpatient clinic of the Universitiy of Goettingen and the dementia outpatient clinic of the Universitiy of Erlangen between 2000 and 2004. Sampling procedure: not reported. Separate data were available for the performance of biomarkers in distinguishing between ADD from FTLD. 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	The sample considered in the review comprised of 60 participants, 30 ADD and 30 FTLD. 30 non‐demented disease controls were not included. Diagnosis was established by a psychiatrist and a neurologist (blinded to biomarker results), all highly experienced in clinical differential diagnosis of dementias, on the basis of thorough anamnesis, clinical examination, results of neuropsychological assessment, clinical records of the patients and the best clinical judgement Sex: 13 males and 17 females for ADD; 21 males and 9 females for FTLD Age mean (SD) (y): 65.4 ± 7.3 for ADD; 61.6 ± 11.5 for FTLD. The mean age did not significantly differ between those two groups. MMSE: 19.3 ± 5.4 for ADD; 20.7 ± 8.9 for FTLD (for 26 participants). The mean age did not significantly differ between those two groups. Disease duration (y): not reported Sources of recruitment: mixed setting: the wards and the dementia outpatient clinic of the Univerity of Goettingen; 5 AD patients were recruited from the dementia outpatient clinic of the Universitiy of Erlangen; Germany
Index tests	Patients gave CSF samples. The samples were collected in polypropylene tubes, centrifuged, aliquoted, and stored at ‐80°C and analysed (within 2 days). Abeta42 was measured using enzyme‐linked immunosorbent assays, obtained from Innogenetics NV, Gent, Belgium. Threshold: not reported; determined by ROC analysis. Were the index test results reported without knowledge of the reference standard? [Yes]
Target condition and reference standard(s)	Target condition: Alzheimer's disease dementia (differential diagnosis of AD from FTLD) Reference standards: NINCDS‐ADRDA and DSM‐IV criteria for ADD. Diagnosis for FTLD was established on the McKhann 2001 and Neary 1988 criteria. Clinicians were blinded to biomarker results.
Flow and timing	The interval between established clinical diagnosis and CSF sample collection was not reported.
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?	No
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?		High risk