Eckerstrom 2013.

Study characteristics
Patient sampling	Primary objectives: to study prediction of dementia in MCI using neuropsychological tests, commonly used CSF biomarkers, and hippocampal volume Study population: participants with MCI Selection criteria: exclusion criteria: age > 79 or < 49, MMSE score < 19, acute/instable somatic disease, severe psychiatric disorder, substance abuse, pseudodementia, or confusion caused by drugs Study design: prospective longitudinal (the Gothenburg MCI study)
Patient characteristics and setting	Clinical presentations: MCI defined according to the criteria of the International Working Group on Mild Cognitive Impairment (Winblad 2004), GDS:3 Age mean (SD): MCI who progressed to AD: 70 ± 6.5; MCI who progressed to all dementia subtypes: 69.3 ± 6.3; stable MCI: 66.4 ± 6.8 Gender (% men): 43% Education years mean (SD): MCI who progressed to AD: 10.0 ± 2.9; MCI who progressed to all dementia subtypes:10.4 ± 3.4; Stable MCI: 12.3 ± 3.6 ApoE4 carriers (%): not reported Neuropsychological tests: employed; MMSE mean (SD): MCI who progressed to AD: 28.0 ± 1.1; MCI who progressed to all dementia subtypes: 27.2 ± 2; stable MCI: 28.3 ± 1.8 Clinical stroke excluded: yes (Gothenburg study protocol) Co‐morbidities: not reported Number enrolled: 42 Number available for analysis: 42 for dementia (AD and other type); 34 for AD Setting: memory clinic (single‐centre study) Country: Sweden Period: Gothenburg study started in 1999 Language: English
Index tests	Index test: MRI manual method for estimation of left and right hippocampus volumes Manufacturer: Philips NT5 Tesla strength: 0.5 T Assessment methods: manual segmentation protocol as in Eckerstrom 2008 Description of positive cases definition by index test as reported: not specified Examiners: as in Eckerstrom 2008 Interobserver variability: as in Eckerstrom 2008
Target condition and reference standard(s)	Target condition: AD was the primary target condition; other dementias were the secondary target conditions Prevalence of AD in the sample: 13/42 (31% of 42 enrolled participants) Stable MCI or converted to other dementia: 29 (69%). In this group, 8 cases converted to non‐AD dementia Reference standards: NINCDS‐ADRDA (McKhann 1984) for AD diagnosis, Erkinjuntti criteria (Erkinjuntti 2000) for VD diagnosis, Lund and Manchester criteria (The Lund and Manchester Groups 1994) for FTD diagnosis. According to the MCI Gothenburg study protocol, the specialist physician was blinded to psychometric, CSF, and imaging results, except for assessment of white matter change Mean clinical follow‐up: 2 years
Flow and timing	Withdrawals and losses to follow‐up: not specified if the 8 cases that converted to other dementias were included in the analysis (in the non‐AD dementia group) Uninterpretable MRI results have not been reported
Comparative
Key conclusions by the authors	The main findings of the study were that in the diagnosis of dementia, combinations of markers performed better than individual markers, and that neuropsychological tests had overall better diagnostic accuracy than CSF biomarkers and, particularly, hippocampal volume
Conflict of interests	Not reported
Notes	Source of funding: grants from Swedish research council; Demensfonden, Pfannenstills stifltelse, Alzheimerfonden, Swedish Brain Power, Sahlgrenska University Hospital 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?	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?	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?	Unclear
		Unclear