Abu‐Rumeileh 2018.

Study characteristics
Patient Sampling	Retrospective analysis of CSF samples at the Institute of Neurological Sciences of Bologna obtained between 2005 and 2016. Samples were taken from patients with a clinical, genetic, or pathologically confirmed diagnosis of FTD or ADD, and cognitively healthy controls. A sub‐sample of 141 FTD patients were selected who did not have co‐existing DLB, ADD, prion diease, or vascular dementia. Sampling procedure: not reported. Separate data were available for the performance of biomarkers in distinguishing between ADD from FTD. We did not include data on performance of the index test to discriminate ADD participants from controls. Exclusion criteria: patients with CBS were excluded, as were those with significant cerebrovascular pathology on brain imaging. DLB was excluded clinically. No other exclusion criteria were detailed.
Patient characteristics and setting	The sample considered in the review comprised of 201 participants, 60 ADD and 141 FTD. All participants underwent clinical history, neurological examination, neuropsychological testing, and neuroimaging. In addition, some participants had post‐mortem diagnoses and results from molecular genetic testing. Education, gender, and age at the time of lumbar puncture were similar in ADD and FTD. MMSE score was lower in ADD (p < 0.05). Sex: 33 males, 27 females for ADD; 75 males and 66 females for FTD Age mean (SD) (y): 67.1±8.7 for ADD; 64.9 ±9.8 for FTD MMSE: 20.7±4.8 for ADD; 25.0±3.7 for FTD Disease duration (y): not reported Education (y): 10.8±4.8 for ADD; 8.9±4.0 for FTD Sources of recruitment: CSF samples submitted for analysis at the Institute of Neurological Sciences of Bologna
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: >482 ng/L; not prespecified; determined by ROC analysis. Were the index test results reported without knowledge of the reference standard? [No]
Target condition and reference standard(s)	Target condition: Alzheimer's disease (differential diagnosis of ADD from FTD) Reference standards: International Working Group 2 (IWG‐2) criteria for ADD and CSF biomarker profile. FTD were classified using criteria for the following subtypes: behavioural variant, non‐fluent variant of primary progressive aphasia, sematic variant of primary progressive aphasia, amyotrophic lateral sclerosis, corticobasal syndrome, progressive supranuclear palsy and FTD with parkinsonism. FTD was neuropathologically confirmed in four cases, and 22 cases had additional molecular genetic findings which supported the diagnosis. Ten participants with FTD were excluded where the CSF biomarker profile was in‐keeping with a diagnosis of ADD. The final clinical diagnosis was confirmed after at least two years of follow‐up. The reference standard results were reported using knowledge of the results of index test.
Flow and timing	The final clinical diagnosis was established after 24 months of follow‐up. AD vs FTD (n=201) AD=60; bvFTD=53; Sensitivity=89%; Specificity=80% (Table 2, p381) TP=53; FP=11; FN=7; TN=42 (calculated in RevMan5) Missing data: Data were requested from the author on the bvFTD subtype and ADD. 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?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		Unclear 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?	No
Could the reference standard, its conduct, or its interpretation have introduced bias?		High 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?	No
Could the patient flow have introduced bias?		High risk