Nesteruk 2016.

Study characteristics
Patient sampling	Primary objectives: evaluate the usefulness of several biomarkers in predicting the conversion of MCI to AD: β‐amyloid and tau proteins in CSF and the volumetric evaluation of brain structures including the hippocampus in MRI Study population: MCI diagnosed in the Alzheimer's Department Selection criteria: MCI according to Winblad 2004: not normal, not demented; self‐ and/or informant‐report and impairment on objective cognitive tasks; evidence of decline over time on objective cognitive tasks and/or preserved basic ADL/minimal impairment in complex instrumental functions. The concept of MCI is comprehensive of heterogeneity of clinical presentation (amnestic/nonamnestic/single domain/multiple domains) and different aetiologies. Exclusion criteria not specified Study design: prospective longitudinal study
Patient characteristics and setting	Clinical presentations: definition of MCI according to Petersen 2004; all participants received a CDR score of 0.5 Age mean (SD): MCI who progressed to AD 70 ± 10; stable MCI: 61 ± 9 Gender (% men): 45% Education years mean: MCI who progressed to AD: 13.33 ± 3.43; stable MCI: 14.13 ± 2.74 ApoE4 carriers (%): not reported Neuropsychological tests: employed; MMSE mean (SD): MCI who progressed to AD: 27.22 ± 1.56; stable MCI: 27.58 ± 1.79 Clinical stroke excluded: not specified Co‐morbidities: not reported; multiple aetiologies were considered in the definition of MCI Number enrolled: 40 Number available for analysis: 40 Setting: Warsaw memory clinic Country: Poland Period: not reported Language: English
Index tests	Index test: MRI automated method for estimation of volumetric measures of the hippocampus and entorhinal cortex, posterior cingulate gyrus, parahippocampal gyrus, superior, medial, inferior temporal gyri Manufacturer: Toshiba Tesla strength: 1.5 Assessment methods: volume estimation was performed using Freesurfer software (version not specified). Discriminant analysis was conducted in MCI separately for all volumetric measurements, for CSF biomarkers, and for volumetric and CSF biomarkers together. Classification rate was available for single volumetric regions. No references to a validation of the classification method Description of positive cases definition by index test as reported: positive cases were defined presumably after the discriminant analysis Examiners: no details. It is not clear if Freesurfer operator conducted also the discriminant analysis. Interobserver variability: not provided
Target condition and reference standard(s)	Target condition: AD Prevalence of AD in the sample: 9/40 (22.5% of enrolled participants) Stable MCI or converted to other dementia: 31 (77.5%) stable MCI Reference standards: NIA‐AA criteria (McKhaan 2011). It was not specified if only the core clinical criteria were used for the diagnosis of AD or if MRI results were also used to support the diagnosis Mean clinical follow‐up: 0.8 ± 0.5 (conversion was evaluated within 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	Biomarkers seem to be important parameters in predicting the conversion of MCI to AD, in particular when biochemical biomarkers are used together with volumetric ones
Conflict of interests	Study authors reported no conflicts of interest
Notes	Source of funding: not reported 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?	Unclear
		High	Low
DOMAIN 2: Index Test All tests
Were the index test results interpreted without knowledge of the results of the reference standard?	Unclear
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?	Unclear
		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?	Unclear
		Unclear	Unclear
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