Monge Argilés 2014.

Study characteristics
Patient sampling	Primary objectives: compare the early diagnostic utility of AD biomarkers in the CSF with those in brain MRI in conditions found in our clinical practice, and to ascertain the diagnostic accuracy of both techniques used together Study population: pure amnestic MCI or multidomain MCI Selection criteria: patients with amnestic MCI, > 55 years, MMSE score of 20‐27 and score of < 78 on the informant questionnaire. Participants signed an informed consent form to be included in the study and to undergo lumbar puncture. Exclusion criteria: dementia or any other neurological, psychiatric or systemic condition that could lead to cognitive impairment; anticoagulant treatment; absence of informed consent; GDS score > 5 Study design: prospective longitudinal study
Patient characteristics and setting	Clinical presentations: pure amnestic MCI or multidomain MCI according to Petersen criteria of 2006 (Yaffe 2006) Age mean (SD): MCI who progressed to AD: 73 ± 7; stable MCI: 73 ± 7 Gender (% men): MCI who progressed to AD: 33%; stable MCI: 47% Education years mean: MCI who progressed to AD: 6; stable MCI: 4.3 ApoEϵ4 carriers (%): not stated Neuropsychological tests: employed; MMSE mean (SD): MCI who progressed to AD: 23 ± 1.2; stable MCI: 24 ± 2.4 Clinical stroke excluded: not specified Co‐morbidities: not reported Number enrolled: 30 Number available for analysis: 30 Setting: Alicante Hospital Universitario Country: Spain Period: 2008‐2009 Language: English
Index tests	Index test: MRI visual method for estimation of MTA Manufacturer: GE Tesla strength: 1.5 Tesla Assessment methods: 2 radiologists visually quantified MTA according to the method described by Korf 2004. According to Scheltens 1997, the MTA scale ranges from 0 (no atrophy)‐4 (severe atrophy) and takes into account the width of the choroid fissure, the height of the hippocampus, and the width of the temporal horn. The MTA scale was applied to the right and left medial temporal lobe Description of positive cases definition by index test as reported: the summed score of left and right temporal lobes was used as well as the dichotomised summed score: no atrophy (score 0‐2) and atrophy (score ≥ 3) Examiners: the radiologists were skilled and blinded to clinical data Interobserver variability: ICCs between the 2 radiologists were 0.80 and 0.85
Target condition and reference standard(s)	Target condition: AD Prevalence of AD in the sample: 15/30 (50% of enrolled participants) Stable MCI or converted to other dementia: 15 (50%) stable MCI Reference standards: NINCDS‐ADRDA criteria (McKhann 1984). Mean clinical follow‐up: 2 years
Flow and timing	Withdrawals explained and losses to follow‐up: none reported Uninterpretable MRI results have not been reported
Comparative
Key conclusions by the authors	Diagnostic accuracy of biomarkers in cerebrospinal fluid is higher than that of biomarkers in MRI. Combined use of both techniques is highly accurate for either early diagnosis or exclusion of AD in patients with MCI
Conflict of interests	Sutdy authors declare having no conflict of interest
Notes	Source of funding: the study was partially funded by Novartis Espana and Grunenthal Espana 2 x 2 table: data from the published article
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?	Yes
Did the study avoid inappropriate exclusions?	No
		High	Low
DOMAIN 2: Index Test All tests
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
Did the study provide a clear pre‐specified definition of what was considered to be a "positive" result of the index test?	Yes
Was the index test performed by a single operator or interpreted by consensus in a joint session?	Unclear
		Low	Low
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
		Low	Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
		Low