Ong 2015.

Study characteristics
Patient sampling	Primary objectives: assess the clinical utility of β‐amyloid imaging with 18F‐florbetaben in MCI by evaluating its prognostic accuracy for progression to AD, comparing semiquantitative with visual scan assessment, and exploring the relationships among β‐amyloid imaging, hippocampal volume (HV) and memory over time Study population: participants with MCI referred from local memory clinics Selection criteria: entry criteria were MCI with presentation of progressive cognitive decline and at least 1 neuropsychological test score falling 1.5 SDs below published means. Exclusion criteria not reported Study design: prospective longitudinal study
Patient characteristics and setting	Clinical presentations: MCI according to Petersen 2004 criteria Age mean (SD): MCI with normal hippocampal volume: 71 ± 6; MCI with hippocampal atrophy: 75 ± 7 Gender (% men): not stated Education years mean (SD): MCI with normal hippocampal volume: 12.4 ± 3.2; MCI with hippocampal atrophy: 15.3 ± 3.5 ApoE4 carriers (%): not stated Neuropsychological tests: employed; MMSE mean (SD): MCI with normal hippocampal volume: 27.6 ± 1.8; MCI with hippocampal atrophy: 26.9 ± 1.7 Clinical stroke excluded: not specified Co‐morbidities: not reported Number enrolled: 45 Number available for analysis: 45 Setting: local memory clinics Country: Australia Period: May 2008‐December 2009 Language: English
Index tests	Index test: MRI automated method for estimation of hippocampal volume Manufacturer: not specified Tesla strength: not specified Assessment methods: hippocampal volume was derived from T1 MPRAGE MRI sequence using Neuroquant software Description of positive cases definition by index test as reported: cut‐off for hippocampal atrophy was determined by double ROC analysis on the hippocampal volumes measured by Neuroquant of 23 AD participants and 143 healthy controls from the "Australian Imaging, Biomarkers and Lifestyle (AIBL)" study Examiners: blindness was specified only for the amyloid PET rater Interobserver variability: not provided
Target condition and reference standard(s)	Target condition: AD Diagnostic classification at 2 years was performed by a neurologist blind to PET and quantitative MRI results Prevalence of AD in the sample: 20/45 (44% of enrolled participants) Stable MCI or converted to other dementia: 25 (56%) MCI not converted to AD (21 stable MCI and 4 MCI converted to other dementia: 1 to progressive sopranuclear palsy, 2 to frontotemporal lobar degeneration, 1 to LBD Reference standards: NINCDS‐ADRDA criteria (McKhann 1984) for AD Mean clinical follow‐up: 2 years
Flow and timing	Withdrawals explained and losses to follow‐up: none reported Uninterpretable MRI results have not been reported
Comparative
Key conclusions by the authors	Amyloid imaging facilitates accurate detection of prodromal AD. As neurodegeneration progresses, and in contrast with the early stages of the disease, hippocampal atrophy and not amyloid status, seems to drive memory decline
Conflict of interests	Study authors declare their competing interests
Notes	Source of funding: study was initiated by Professor CC Rowe, sponsored by Bayer Healthcare AG, Berlin, Germany, and funded in part by NHMRC grant 509166 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?	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?	Yes
Was the index test performed by a single operator or interpreted by consensus in a joint session?	Unclear
		Unclear	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