Lombardi 2018.

Study characteristics
Patient Sampling	A single‐centre retrospective observational study. 45 consecutive patients with an atypical presentation were recruited between 2014 and 2015. Patients were included where the diagnosis was uncertain after clinical evaluation, and who had CSF biomarkers available. Final diagnoses were: 32 ADD, 10 FTD, and 3 unclassified cognitive decline (UCD). Sampling procedure: not reported. Exclusion criteria: high vascular burden, prevailing extrapyramidal signs, or pathogenic mutations.
Patient characteristics and setting	Cases were selected by an expert neurologist who administered the diagnosis after at least one year of follow‐up. Two further neurologists who were blinded to the final diagnosis, determined the diagnosis in three different scenarios: clinical information only (neuropsychological assessment and neuroimaging), pathological information (amyloid‐PET imaging and/or CSF biomarkers), and FDG‐PET (brain metabolism). All participants underwent neuropsychological testing and brain imaging. Sex: 19 male, 13 female for ADD; 5 male, 5 female for FTD; 0 male, 3 female for UCD. Age mean (SD): 66.5 ± 9.9 for ADD; 67.4 ± 8.5 for FTD; 59.3 ± 11.9 for UCD. MMSE: 21.7 ± 4.3 for ADD; 22.6 ± 2.4 for FTD; 23 ± 3.5 for UCD. MMSE score was not significantly different in ADD compared to FTD. Disease duration (y): not reported. Sources of recruitment: retrospective, observational study.
Index tests	Patients gave CSF samples. The samples were collected at 8am, immediately centrifuged, and stored at ‐80°C and analysed (within 1 day). Abeta42 was measured using enzyme‐linked immunosorbent assays, (kit not specified). Threshold: pre‐specified at >650 pg/ml. Were the index test results reported without knowledge of the reference standard? [Unclear]
Target condition and reference standard(s)	Target condition: Alzheimer's disease (differential diagnosis of ADD from FTD or ADD from UCD). Reference standard: NIA‐AA criteria for ADD. FTD was diagnosed according to Gorno‐Tempini Rascovsky criteria. The final diagnosis was not blinded to the results of the index test.
Flow and timing	Data were provided by the author upon request. AD vs FTD (n=42) AD=32; FTD=10; Sensitivity=87%; Specificity=70% (Table 2, p381) TP=28; FP=3; FN=4; TN=7 (calculated in RevMan5) AD vs UCD (n=35) AD=32; UCD=3; Sensitivity=87%; Specificity=64% (Table 2, p381) TP=28; FP=1; FN=4; TN=2 (calculated in RevMan5) Missing data: No. 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?	Yes
Was a case‐control design avoided?	Yes
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?			High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Unclear
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?			High
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Unclear
Were all patients included in the analysis?	Unclear
Could the patient flow have introduced bias?		Unclear risk