. 2020 Mar 2;2020(3):CD009628. doi: 10.1002/14651858.CD009628.pub2

Eckerstrom 2008.

Study characteristics
Patient sampling	Primary objectives: to validate the hypothesis that hippocampal atrophy predicts conversion from MCI to dementia, to relate baseline hippocampal volume to different forms of dementia, and to investigate the role of hippocampal side differences and rate of volume loss over time Study population: participants with mild cognitive impairment (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; MCI who progressed into non‐AD: 68.1; stable MCI: 66.6 Gender (% men): 43% Education years mean: MCI who progressed to AD: 10.0; MCI who progressed into non‐AD 10.9; stable MCI: 12.5 ApoE4 carriers (%): not reported Neuropsychological tests: employed; MMSE mean (SD): MCI who progressed to AD: 28.0; MCI who progressed into non‐AD 26.0; stable MCI: 28.3. Clinical stroke excluded: yes (Gothemburg study protocol) Co‐morbidities: not reported Number enrolled: 42 Number available for analysis: 42 Setting: memory clinic (single‐centre study) Country: Sweden Period: Gothemburg study started in 1999 Language: English
Index tests	Index test: MRI manual method for estimation of hippocampal volume Manufacturer: Philips Tesla strength: 0.5 (in Gothenburg MCI study T1‐weighted images from the 0.5 T scanner were used for manual volumetry of the hippocampus) Assessment methods: manual segmentation process consisted of two steps: pointwise landmark setting was done in the sagittal view of the reformatted coronal image where the demarcation in the original coronal image is indiscernible or difficult to interpret (Pantel 2000); segmentation of the hippocampus in the coronal images was done by continuous pen drawing. The Hipposegm program samples pointwise from the pen drawing Description of positive cases definition by index test as reported: 2 cut‐off criteria were chosen post hoc for left hippocampal volume (2200 and 1800 mm³) Examiners: 1st rater initially segmented all the scans in 1 session that extended over several weeks. The data from this session were used in the main analysis of the study. The raters were always blinded for group belonging, participant/control ID and other header data Interobserver variability: performed between 2 raters on 30 MRI scans. Single measure ICC was 0.663, average measure ICC was 0.797
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 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: none reported  Uninterpretable MRI results have not been reported
Comparative
Key conclusions by the authors	The main findings in this the published article are that hippocampal volume predicts conversion to dementia in MCI patients, and that left hippocampal volume seems to be the best marker for conversion
Conflict of interests	Not reported
Notes	Source of funding: this work was supported by grants from the Swedish Research Council (grants 2002‐5462, K2002‐21P‐14359‐01A and 09946) 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?	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?	Yes
		Low