Westman 2011.

Study characteristics
Patient sampling	Primary objectives: aims of this study were: to compare the ability of MTA visual assessment rating scales, a multivariate MRI classification method and manually measured hippocampal volumes to distinguish between participants with AD and healthy elderly controls to assess how well the 3 techniques perform when predicting future conversion from MCI to AD Study population: participants with MCI originated from AddNeuroMed project, recruited from local memory clinics of the 6 participating sites across Europe Selection criteria: inclusion criteria: MMSE score range 24‐30 GDS score ≤ 5 age ≥ 65 years medication stable good general health. Exclusion criteria: meet the DSM‐ IV criteria for dementia significant neurological or psychiatric illness other than AD significant unstable systematic illness or organ failure. scores 0.5 on CDR scale Study design: prospective longitudinal study
Patient characteristics and setting	Clinical presentations: participants with MCI; it was preferable that the participant and informant reported occurrence of memory problems Age mean (SD): 74.0 ± 6 Gender (% men): 49% Education years mean (SD): 8.7 ± 4.3 ApoE4 carriers (%): not reported Neuropsychological tests: employed; MMSE mean (SD): 27.2 ± 1.6 Clinical stroke excluded: not specified Co‐morbidities: not reported Number enrolled: 101 Number available for analysis: 101 Setting: AddNeuroMed cohort Country: Finland, Italy, Greece, UK, Poland, France (AddNeuroMed) Period: not reported Language: English
Index tests	Index test: MRI manual method for estimation of hippocampal volume and MRI visual method for estimation of medial temporal lobe volume. MRI automated method was also used to generate regional volume and cortical thickness measures (57 variables). Manufacturer: 6 different MR systems: 4 GE, 1 Siemens and 1 Picker (information retrieved from AddNeuroMed protocol (Simmons 2009) Tesla strength: 1.5 (Simmons 2009) Assessment methods: data acquisition for the AddNeuroMed study was designed to be compatible with the ADNI. detailed quality control carried out on all MIs according to the AddNeuroMed quality control procedure. Manual measurements were performed on a HERMES workstation. The visual rating assessment was performed according to Scheltens 1992. Regarding the automated method, it utilised a pipeline developed by Fischl and Dale that produces regional cortical thickness (31 areas) and volumetric (23 areas) measures. The 57 variables were used for a multivariate analysis. Description of positive cases definition by index test as reported: positive cases were defined only for the visual method (age‐dependent cut‐off) Examiners: for the manual and visual methods, a single rater blinded to diagnosis performed the corresponding assessment. Interobserver variability: for the manual method the ICC of the measurements were 0.93; for the visual method, the intra‐rater reliability was 0.81 on right side and on left side 0.78. Weighted kappa was 0.93 on both sides
Target condition and reference standard(s)	Target condition: AD Prevalence of AD in the sample: 19/101 (19% of enrolled participants) Stable MCI or converted to other dementia: 82 (81%) non‐AD converters Reference standards: NINCDS‐ADRDA criteria (McKhann 1984); not specified in the published article; this information is reported in Liu 2010, another AddNeuroMed study Mean clinical follow‐up: 1 year
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	Visual rating assessment of the medial temporal lobe gave similar prediction accuracy to multivariate classification and manual hippocampal volumes. This suggests a potential future role for computerised methods as a complement to clinical assessment of AD.
Conflict of interests	The study was supported by InnoMed (Innovative Medicines in Europe). No patents, products in development or marketed products to declare
Notes	Source of funding: InnoMed (FP6‐2004‐LIFESCIHEALTH‐5) 2 x 2 table: data from the published article; in order to avoid duplicate, only the results of the manual method were used for the review purpose. The automated method was excluded because provided a mixed index test (volume and thickness)
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?	Yes
		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?	No
Was the index test performed by a single operator or interpreted by consensus in a joint session?	Yes
		High	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