Prieto del Val 2016.

Study characteristics
Patient sampling	Primary objectives: investigate to what extent oscillatory EEG changes during memory encoding and/or retrieval enhance the accuracy of MTA in predicting conversion from amnestic MCI to AD Study population: participants were recruited from senior citizens' associations, normal community health screening and hospital outpatient services. Selection criteria: inclusion and exclusion criteria: aged 50‐80 years old MMSE scores between 24 and 30 subjective memory complaints corroborated by the informant objective memory loss confirmed by the Spanish version of the Logical Memory subtest extracted from the WMS‐3rd Edition (scorings 1.5 SD below the age‐appropriate mean) absence of impairment in cognitive areas other than memory as revealed by neuropsychological testing CDR global score of 0.5 (QD) normal independence function no criteria for dementia no presence of neurological or psychiatric illness Those participants with periventricular and/or deep white matter lesions in MRI as revealed by scores ≥ 2 on the Fazekas scale were excluded from the study. Individuals with a history of stroke and/or significant cerebrovascular conditions, clinically significant sensory impairment, past or current alcohol abuse, or those consuming medication known to affect memory, were not allowed to participate. None of the participants were taking cholinesterase inhibitors, and/or psychiatric medication at the time of recruiting or during the study. Participants were excluded from the analysis if any psychiatric or neurological illness other than AD was present, and if participants presented with a systemic illness or signs of organ failure. Included patients met core clinical criteria for MCI due to AD with an intermediate level of certainty (Albert 2011) Study design: prospective study
Patient characteristics and setting	Clinical presentation: amnestic MCI Age mean (SD): MCI who progressed to AD: 69.7 ± 6.5 years; MCI non‐converters to AD: 68.4 ± 7.1 years Gender (% men): MCI who progressed to AD: 44%; MCI non‐converters to AD: 28% Education years mean (SD): MCI who progressed to AD: 7.7 ± 6.3 years; MCI non‐converters to AD: 7.3 ± 5.1 years ApoE4 carriers (%): not reported Neuropsychological tests: employed; MMSE mean (SD): MCI who progressed to AD: 26.4 ± 2.7; MCI non‐converters to AD: 26.8 ± 2.1 Clinical stroke excluded: yes Co‐morbidities: not reported Number enrolled: 34 Number available for analysis: 34 Setting: Pablo de Olavide Univesity Country: Spain Period of study: not specified
Index tests	Index test: MRI automated method for estimation of hippocampal and amygdala volume Manufacturer: Philips Tesla strength: 1.5 T Assessment methods: MRI data were preprocessed using Freesurfer v5.3. Removal of non‐brain tissues was manually performed to increase the accuracy of segmentation. Volumetric measures were obtained for left and right sides of the hippocampus and amygdala Description of positive cases definition by index test as reported: not specified. The main outcome measure was the averaged AUC; additionally averaged overall accuracy, sensitivity and specificity based on the cut‐off value maximised with the Youden index was computed (Youden 1950) Examiners: no details about radiologist Interobserver variability: not reported
Target condition and reference standard(s)	Target condition: AD Prevalence of AD in the sample: 16/34 (47% of cases included in the analysis) Stable MCI or converted to other dementia: 18/34 (53%); 18 stable MCI Reference standard: NINCDS‐ADRDA criteria and DSM IV criteria. AD participants had to further present MMSE scores ranging from 12‐28 and a CDR global score of 1 (mild dementia). 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 results support the idea that synaptic integrity/function in the posterior cingulate cortex is affected during prodromal AD and has the potential of improving early detection when combined with MRI biomarkers.
Conflict of interests	The study authors declare no competing financial interests
Notes	Source of funding: the work was supported by research grants from the Spanish Ministry of Economy and Competitiveness (PSI2014‐55747‐R, SAF2011‐25463); the Regional Ministry of Innovation, Science and Enterprise, Junta de Andalucia (P12‐CTS‐2327); and CIBERNED (CB06/05/1111) 2 x 2 table: data from the published article. In order to avoid duplication, we only used the results of amygdala for this review.
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?	Yes
		Low