VanderFlier 2005.

Study characteristics
Patient sampling	Primary objectives: to investigate whether MRI‐based volumes of whole brain, medial temporal lobe and white matter hyperintensities predict progression of cognitive decline in a sample of elderly people without dementia Study population: elderly people without dementia who were consecutively referred to the memory clinic for cognitive complaints (MCI and subjective memory complaints) Selection criteria: MCI memory complaint normal ADL normal general cognitive function abnormal memory for age not demented. MCI was diagnosed when both the interview and neuropsychological tests results gave evidence of memory impairment in the absence of general cognitive decline. Exclusion criteria: age < 60 years, baseline diagnosis of dementia, other neurologic or psychiatric comorbidity and abnormalities on MRI except white matter hyperintensities or an incidental small lacunar lesion (5 mm diameter) Study design: prospective longitudinal study (VUMC cohort)
Patient characteristics and setting	Clinical presentations: amnestic MCI according to Petersen 1995 and 1999 (Petersen 1999) Age mean (SD): 75 ± 7 years Gender (% men): 29% Education years mean (SD): 10 ± 3 ApoE4 carriers (%): not stated Neuropsychological tests: employed; MMSE mean (SD): 26.0 ± 2 Clinical stroke excluded: not specified Co‐morbidities: not reported Number enrolled: 17 Number available for analysis: 15 Setting: VUMC cohort Country: Netherlands Period: not reported Language: English
Index tests	Index test: MRI manual method for estimation of hippocampus, medial temporal lobe volume; MRI semiautomated method for estimation of whole brain Manufacturer: Philips Medical Systems, Best, the Netherlands Tesla strength: 1.5 Assessment methods: manual segmentation of the medial temporal lobe volume (including hippocampus and parahippocampal gyrus) was performed using the software DISPLAY (Pruessner 2002). The whole brain volume was segmented using in‐house‐developed semiautomated software (Division of Image Processing (LKEB), Department of Radiology, Leiden University Medical Center) Description of positive cases definition by index test as reported: not specified Examiners: all measurements were performed by a single rater who was blind to participant identity and diagnosis Interobserver variability: ICC for medial temporal lobe volume was 0.91. Interrater reliability of whole brain volume was 1.0
Target condition and reference standard(s)	Target condition: AD Prevalence of AD in the sample: 9/15 (60% of participants included in the analysis) Stable MCI or converted to other dementia: 6 (40%) non converter to AD dementia Reference standards: NINCDS‐ADRDA criteria (McKhann 1984). Diagnosis was made in a multidisciplinary consensus meeting Mean clinical follow‐up: 1.8 years
Flow and timing	Withdrawals explained and losses to follow‐up: 2/17 participants (12%) were lost to follow‐up, reasons unclear (reasons for losses in MCI group were reported together with those of the subjective memory complaint group: 1 participant died, 1 could not be traced, 3 refused to participate, 1 refused to participate in the follow‐up study) Uninterpretable MRI results have not been reported
Comparative
Key conclusions by the authors	Results suggest that regional damage to the medial temporal lobes underlies initial mild cognitive impairment, whereas more global brain changes, such as whole brain atrophy and WMH [white matter hyperintensities], contribute to further progression of cognitive decline
Conflict of interests	Information not available
Notes	Source of funding: contract/grant sponsor: Internationale Stichting Alzheimer Onderzoek (ISAO). 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?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
		Low	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?	No
		High