Galton 2005.

Study characteristics
Patient sampling	Primary objectives: examine the contribution of the Addenbrooke's Cognitive Examination (ACE), neuropsychological assessment, and a MRI–based temporal lobe rating scale to the prediction of which patients with questionable dementia will progress to AD Study population: a subgroup of patients with QD was recruited from the memory clinic in Addenbrooke's Hospital, Cambridge, for a longitudinal project. Included participants had undergone suitable MRI imaging at entry. Selection criteria: participants unable to undergo MRI for a variety of reasons including claustrophobia or pacemakers were excluded. Consecutive referrals were approached and screened to exclude extrapyramidal signs or hallucinations, VD, current cancer treatment, uncontrolled diabetes, and serious head injury. Patients with cerebrovascular events, epilepsy, and major depression were excluded. All participants were aged between 50 and 80 years at the time of recruitment. Study design: prospective longitudinal study
Patient characteristics and setting	Clinical presentations: QD met the following criteria: subjective complaint of memory impairment; normal ADL; and nondemented as evident from a MMSE score of ≥ 23 Such definition corresponded to MCI as defined by some groups of workers using the CDR scale but not by other groups who based the diagnosis of MCI on neuropsychological test performance. All included participants had a CDR score of 0.5. Age mean (SD): people with QD who progressed to AD: 71 ± 9; stable QD: 59 ± 8 Gender (% men): QD who progressed to AD: 54.5%; stable QD: 44.4% Education years mean (SD): not reported ApoE4 carriers (%): not reported Neuropsychological tests: employed; MMSE mean (SD) QD who progressed to AD: 24.8 ± 1.5; stable QD: 29 ± 0.9 Clinical stroke excluded: yes Co‐morbidities: not reported Number enrolled: 31 Number available for analysis: 29 Setting: memory clinic in Addenbrooke's Hospital, Cambridge Country: UK Period: 1997‐1999 Language: English
Index tests	Index test: MRI visual method for estimation of the left and right hippocampus, left and right parahippocampus, right lateral temporal lobe volumes Manufacturer: GE Tesla strength: not specified for all images (66% were performed at 1.5 T, 34% were scanned before with different not specified protocol) Assessment methods: visual method according to the Temporal Lobe Rating scale (Galton 2001) on coronal T1 images. The method built on the work of Scheltens 1992 but incorporates also temporal pole, parahippocampal region and the inferolateral temporal region Description of positive cases definition by index test as reported: ratings of each region were scored dichotomising as normal or questionable (0‐1) versus abnormal (2‐3) Examiners: the 50 coronal films were blinded and randomised to the examiner/examiners (not specified if > 1). Imagings were assessed in 2 sessions (to maintain concentration) Interobserver variability: not provided
Target condition and reference standard(s)	Target condition: AD Prevalence of AD in the sample: 11/29 (38% of cases included in the analysis) Stable MCI or converted to other dementia: 20 (69%). In this group 2 participants converted to LBD and were excluded from the analysis Reference standards: NINCDS‐ADRDA criteria (McKhann 1984). Onset of dementia was determined on functional grounds after interview and examination of the participant and family members and was independent of the neuropsychological and imaging findings Mean clinical follow‐up: 1.6 years
Flow and timing	Withdrawals and losses to follow‐up: 2/31 participants (6.5% of enrolled participants) converted to LBD and were excluded from the analysis. Uninterpretable MRI results have not been reported.
Comparative
Key conclusions by the authors	The medial temporal lobe is more atrophied in those participants at risk for dementia who subsequently convert to presumed AD. The Addenbrooke's Cognitive Examination was the best single predictor of progression to AD
Conflict of interests	Not reported
Notes	Source of funding: supported by an MRC‐LINK grant 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?	Yes
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?	Yes
Was the index test performed by a single operator or interpreted by consensus in a joint session?	Unclear
		Low	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