Jang 2018.

Study characteristics
Patient sampling	Primary objectives: investigate the use of CVRS for predicting dementia and elucidate its association with cognitive change in patients with MCI over a 3‐year follow‐up Study population: participants from the ADNI study Selection criteria: MCI who had a baseline MRI scan as well as amyloid PET study and at least ≥ 1 follow‐up visits after initial assessment were included. All participants had a MMSE score of ≥ 24, a global CDR score of 0.5, a CDR memory score of ≥ 0.5, and a score indicating impairment on the delayed recall of Story A of the WMS‐R Exclusion criteria: according to ADNI protocol Study design: prospective longitudinal study (participants from ADNI study)
Patient characteristics and setting	Clinical presentation: MCI according to ADNI protocol. Diagnosis of MCI was made according to the presence of objective memory impairment Age mean (SD): MCI who progressed to AD: 72.1 ± 7.2 years; MCI non‐converters to AD: 71.1 ± 7.5 years Gender (% men): MCI who progressed to AD: 54%; MCI non‐converters to AD: 53% Education years median (range): 16 (14‐18) in both MCI groups ApoE4 carriers (%): MCI who progressed to AD: 68%; MCI non‐converters to AD: 40% Neuropsychological tests: employed; MMSE (range) MCI who progressed to AD: 28 (26‐29); MCI non‐converters to AD: 29 (28‐30) Clinical stroke excluded: not specified Co‐morbidities: not reported Number enrolled: 340 Number available for analysis: 340 Setting: ADNI database (multicentre study)‐ ADNI‐GO/ADNI2 cohort Country: USA and Canada Period of study: ADNI was launched in 2003, data used in this study downloaded from the ADNI database on December 2017 Language: English
Index tests	Index test: MRI visual method to estimate hippocampal atrophy, cortical atrophy, subcortical atrophy, small vessel disease Manufacturer: those used in ADNI study (GE Healthcare, Philips Medical System, Siemens Medical Solution (Jack 2008b) Tesla strength: 3 T Assessment methods: CVRS includes visual scales of hippocampal atrophy, cortical atrophy, subcortical atrophy (ventricular enlargement) and for staging small vessel disease; the rater used a template‐based scoring program on a tablet computer that calculated the total score automatically. Description of positive cases definition by index test as reported: not specified (score ranging from 0‐30, a higher score represents more deficits but a threshold was not reported; allocation scores by the CVRS was 8 points for hippocampal atrophy, 9 points for cortical atrophy, 6 points for ventricular atrophy, and 7 points for small vessel disease) Examiners: 3 raters blinded to demographic and clinical information Interobserver variability: inter‐rater and intra‐rater reliability with 34 randomly selected MRI scans were 0.941 and 0.936
Target condition and reference standard(s)	Target condition: AD Prevalence of AD in the sample: 69/340 (20% of cases included in the analysis) Stable MCI or converted to other dementia: 271/340 (80%); 271 stable MCI Reference standard: AD diagnosis according to NINCDS‐ADRDA (McKhann 1984) Median clinical follow‐up: 3 years
Flow and timing	Withdrawals and losses to follow‐up: none reported Uninterpretable MRI results have not been reported
Comparative
Key conclusions by the authors	Baseline CVRS predicted the progression to dementia in MCI and was independently associated with longitudinal cognitive decline
Conflict of interests	Funding for this work was derived in part from the following commercial sources: Araclon Biotech; BioClinica, Inc.; Biogen; Bristol‐Myers Squibb Company; CereSpir, Inc.; Eisai Inc.; Elan Pharmaceuticals, Inc; Eli Lilly and Company; EuroImmun; F. Hoffmann‐La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Lumosity; Lundbeck; Merck & Co, Inc; Meso Scale Diagnostics, LLC; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics
Notes	Source of funding: data collection and sharing for this project was funded by ADNI (NIH Grant U01 AG024904) and Department of Defense ADNI (award number W81XWH‐12‐2‐0012) 2 x 2 table: data from the published article; in order to avoid duplicate, we only used the results of lateral ventricles for the purposes of this review
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?	No
Was the index test performed by a single operator or interpreted by consensus in a joint session?	No
		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