Platero 2019.

Study characteristics
Patient sampling	Primary objectives: discriminate AD progression using a new hippocampal marker from T1‐wighted MRI: the local surface roughness Study population: participants were recruited from the Hospital Universitario San Carlos (Madrid), the Centre for Prevention of Cognitive Impairment (Madrid) and the Senior Center of the district of Chamartin (Madrid) Selection criteria: clinical diagnosis of MCI included the following features: self‐ or informant‐reported cognitive complaints objective evidence of impairment in ≥ 1 cognitive domains preserved independence in functional abilities not demented. Exclusion criteria not reported. All cases of MCI categorised as "MCI due to AD" with an intermediate level of likelihood (Albert 2011) Study design: prospective study (no details)
Patient characteristics and setting	Clinical presentation: amnestic MCI. In addition to meeting the clinical criteria, MCI participants showed signs of loss of the hippocampal volume compared with controls; they w ere definable as “MCI due to AD” with an intermediate likelihood according to Albert 2011. Hippocampal volumes were not used to establish any of the different diagnoses that were explored, since clinical and cognitive performance were used for this purpose Age mean (SD): MCI who progressed to AD: 75.6 ± 4.9 years; MCI non‐converters to AD: 73.2 ± 5.2 years Gender (% men): MCI who progressed to AD: 39%; MCI non‐converters to AD: 36% Education years mean (SD): MCI who progressed to AD: 7.94 ± 4.07 years; MCI non‐converters to AD: 8.77 ± 4.36 years ApoE4 carriers (%): not reported Neuropsychological tests: employed; MMSE mean (SD): MCI who progressed to AD: 25.8 ± 3.1; MCI non‐converters to AD: 27.0 ± 2.3 Clinical stroke excluded: not reported Co‐morbidities: not reported Number enrolled: 137 Number available for analysis: 97 Setting: Hospital Universitario San Carlos (Madrid), the Centre for Prevention of Cognitive Impairment (Madrid) and the Senior Center of the district of Chamartin (Madrid) Country: Spain Period of study: not specified Language: English
Index tests	Index test: automated method for estimation of hippocampal volume; hippocampal surface roughness and local surface roughness were also evaluated. Manufacturer: GE Tesla strength: 1.5 T Assessment methods: the markers were extracted from the automated hippocampal segmentation. For more robustness in terms of hippocampal segmentation errors, both left and right volumes were averaged and normalised with ICV. Description of positive cases definition by index test as reported: not specified Examiners: no details about radiologist Interobserver variability: not reported
Target condition and reference standard(s)	Target condition: AD Prevalence of AD in the sample: 36/97 (37% of cases included in the analysis) Stable MCI or converted to other dementia: 61/97 (63%); 61 stable MCI Reference standard: NINCDS‐ADRDA criteria Mean clinical follow‐up: 3 years
Flow and timing	Withdrawals and losses to follow‐up: 40 lost (missing follow‐up) Uninterpretable MRI results have not been reported
Comparative
Key conclusions by the authors	The LSR [local surface roughness] marker show better prediction of conversion to AD than normalised hippocampal volume. The results suggest the relevance of considering the LSR as a new hippocampal marker for the AD continuum.
Conflict of interests	No details
Notes	Source of funding: Spanish Ministry of Economy and Competitiveness, Grant/Award Numbers: IJCI‐2016‐30662, PSI2012‐38375‐C03‐01, PSI2009‐14415‐C03‐01 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?	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?	Unclear
		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