Stefani 2005.

Study characteristics
Patient Sampling	Patients (n=140) were consecutively evaluated at a university hospital Alzheimer's centre, 86 patients were subsequently enrolled. A control group of 24 non‐demented participants were also recruited. We did not include data on performance of the index test to discriminate ADD participants from controls. Exclusion criteria: isolated deficits or mostly subjective memory loss and/or stable MMSE (+/>25/30) on revisit; neuropsychological profile and behavioural symptoms suggest a diagnosis of FTD; suspected diagnosis of DLB; clinically manifest stroke in the last six months
Patient characteristics and setting	110 participants were enrolled in the study: 35 ADD, 31 ADD with WMC, 20 VD and 24 controls. The sample considered in the review comprises of 55 participants: 35 ADD and 20 VD. All patients provided medical history and underwent neurological examination, MMSE, complete blood screening (including thyroid function and B12), neuropsychological examination and neuroimaging. Neuropsychological follow‐up included more comprehensive neuropsychological testing, including a standardised neuropsychological battery (Mental Deterioration Battery) and a complete psychiatric evaluation Sex: 16 males and 19 females for AD; 16 males and 16 females for AD & WMC; 11 males and 9 females for VD Age (years at LP): 72.2±8.1 for AD; 71.2±7.7 for AD & WMC; 73.6±6.8 for VD MMSE: 18.2±1.7 for AD; 19.1±1.5 for AD & WMC; 20.1±2.0 for VD Disease duration (mo at time of LP): 44.2±9.5 for AD; 143.5±8.9 for AD & WMC; 60.5±15.5 for VD Sources of recruitment: Alzheimer Center of the Department of Neuroscience,Tor Vergata University Hospital, Rome, Italy. 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: 493 pg/ml; not prespecified; 750 pg/ml for AD & AD with WMC vs VD; 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 1. AD and 2. AD & AD with WMC from VD) Reference standards: NINCDS‐ADRDA and DSM IV criteria for AD; NINCDS‐ADRDA criteria and MRI showing brain imaging findings suggesting subcortical vascular lesions for AD with WMC. Clinical diagnosis of VD was based on NINDS‐AIREN criteria. Clinical diagnosis was established prior the results of the index test.
Flow and timing	The interval between established clinical diagnosis and CSF sample collection was not reported. However, it appears that CSF samples were collected short after establishing the clinical diagnosis and following informed consent. Sample included in the analysis: 35 ADD; 20 VD AD vs VD (n=55) (cut‐off 493 pg/ml) Sensitivity=77%; Specificity=80% (p86) TP=27; FP=4; FN=8; TN=16 (Calculated in RevMan5) All ADD and VD patients enrolled in the primary study were included in analysis. We did not considered ADD participants with WMC 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?	Yes
Was a case‐control design avoided?	No
Did the study avoid inappropriate exclusions?	Yes
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