Erten‐Lyons 2006.

Study characteristics
Patient sampling	Primary objectives: examine whether presymptomatic rates of regional and total brain volume loss distinguish MCI participants that subsequently decline to dementia Study population: participants with MCI Selection criteria: all Oregon Brain Aging Study participants who had at least 3 annual neuropsychological examinations and ≥ 2 analysed MRI scans for the time of interest. MCI defined clinically as CDR = 0.5 on 2 independent examinations separated by at least 6 months and not meeting diagnostic criteria for dementia. Exclusion criteria: not reported Study design: longitudinal population study
Patient characteristics and setting	Clinical presentations: MCI defined clinically as CDR = 0.5 on 2 independent examinations separated by at least 6 months and not meeting diagnostic criteria for dementia Age mean (SD): MCI who progressed to dementia: 88 ± 5; stable MCI: 86 ± 7 Gender (% men): MCI who progressed to dementia: 17%; stable MCI: 50% Education years mean (SD): MCI who progressed to dementia: 13 ± 3.3; stable MCI: 15 ± 3.4 ApoE4 carriers (%): MCI who progressed to dementia: 21%; stable MCI: 17% Neuropsychological tests: employed; MMSE mean (SD): MCI who progressed to dementia: 27.13 ± 2.05; stable MCI: 27.5 ± 1.87 Clinical stroke excluded: not specified Co‐morbidities: not specified Number enrolled: 37 Number available for analysis: 37 Setting: memory clinic (single‐centre) Country: USA Period: not reported Language: English
Index tests	Index test: MRI semi‐automated method for estimation of the hippocampal, ventricular and whole brain volumes Manufacturer: not reported Tesla strength: 1.5 T (Kaye 1997) Assessment methods: semi‐automated according to (Kaye 1997). Analysis of the MRI images was performed with computer‐assisted techniques utilising a program called REGION Description of positive cases definition by index test as reported: not specified Examiners: not reported Interobserver variability: among 3 operators who scored the same set of 5 MRI scans, the ICC was 0.98 for the intracranial volume and 0.97 for the temporal lobe atrophy (Kaye 1997)
Target condition and reference standard(s)	Target condition: probable AD Prevalence of AD in the sample: 22/37 (59.5% of enrolled participants), including 17 probable AD and 5 possible AD Stable MCI or converted to other dementia: 15 (40.5%), including 14 participants who remained stable and 1 with VD Reference standards: not reported Mean clinical follow‐up: 7.6 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	Results suggest that patients with MCI that decline to dementia have smaller hippocampal volumes at baseline and greater rates of generalised and regional brain atrophy several years before symptom onset compared with those who remain stable
Conflict of interests	Study authors declared no conflict of interest
Notes	Source of funding: supported by the Merit Review Grant, Office of Research and Development, Department of Veterans Affairs, National Institute on Aging, NIH AG08017, MO1 RR000334 2 x 2 table: data to complete 2 x 2 table provided by the study authors
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?	No
		High	Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Unclear
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
		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?	Unclear
Were all patients included in the analysis?	Yes
		Unclear