Visser 2002.

Study characteristics
Patient sampling	Primary objectives: to investigate whether MTA predicted outcome in patients with MCI and whether assessment of the medial temporal lobe could increase the diagnostic accuracy of age and delayed recall for outcome Study population: patients with MCI were selected from the Maastricht Memory Clinic, a university affiliated outpatient clinic for patients with cognitive impairments. Patients were referred to the clinic by a general practitioner, a neurologist, or a psychiatrist Selection criteria: inclusion criteria were a score on the Global Deterioration Scale of 2 or 3. Exclusion criteria were age < 50 years, a baseline diagnosis of dementia according to the DSM‐IV criteria, sensory impairment, psychosis, panic disorder, bipolar disorder, a score on the Hamilton depression rating scale‐17 items (HDRS) > 22, or cognitive problems in relation to cerebrovascular events, neurodegenerative diseases (for example, Parkinson's disease or Huntington's disease), brain neoplasm, head trauma, drug intoxication, alcohol misuse, hypothyroid or hyperthyroid function, or vitamin deficiency Study design: prospective longitudinal study
Patient characteristics and setting	Clinical presentations: MCI definition based on Global Deterioration Score according to Reisberg 1982 Age mean (SD): 65 ± 9.5 years Gender (% men): 58 % Education years mean (SD): 10.7 ± 3.2 ApoE4 carriers (%): not stated Neuropsychological tests: employed; MMSE mean (SD): 27.7 ± 1.8 Clinical stroke excluded: yes (conversely vascular disorders were permitted if not related to the onset of cognitive impairment) Co‐morbidities: MCI had vascular risk factors or vascular disorders such as hypertension (diastolic blood pressure > 95, systolic blood pressure > 170 on a single measurement, or treatment for hypertension) (N = 8), total cholesterol serum concentrations > 6.0 mmoL/L (N = 5), smoking (N = 6), angina pectoris (N = 1), transient ischaemic attack (N = 2), and lacunar infarction on MRI (N = 2) Number enrolled: 31 Number available for analysis: 30 for the MTA estimation, 29 for the hippocampal volume estimation Setting: : Maastricht Memory Clinic Country: Netherlands Period: not reported Language: English
Index tests	Index test: MRI manual method for estimation of hippocampal and parahippocampal gyrus volumes, MRI visual method for estimation of MTA Manufacturer: Gyroscan ACS‐II, Philips Tesla strength: 1.5 Assessment methods: data were transferred to a SUN workstation and the ROI were measured with ShowImage (developed at the Department of Clinical Physics and Informatics, Vrije Universiteit, Amsterdam, The Netherlands). The brain structures were manually traced with a mouse‐driven cursor. Measurements were done with reference to an anatomical atlas (Duvernoy 1988). Visual method according to Scheltens 1992. Description of positive cases definition by index test as reported: volumes and MTA rating were classified on the basis of the zeta score in tertiles; tertiles are based on a reference population of healthy participants. A low tertile score was indicative of a small volume. A cut‐off was not specified. Examiners: the manual method for estimation of the hippocampal and parahippocampal gyrus volumes was performed by 1 rater. The MTA was scored by a neurologist. All raters were blinded to all clinical information. Interobserver variability: regarding the manual method the ICC between the first and second measurement was 0.95 for the hippocampus, 0.92 for the parahippocampal gyrus; regarding the visual method, the intrarater reliability was substantial (kappa = 0.70)
Target condition and reference standard(s)	Target condition: AD Prevalence of AD in the sample: 7/30 (23% of participants included in the analysis) Stable MCI or converted to other dementia: 23 (77%) non‐AD dementia (20 stable MCI and 3 participants converted to non‐AD dementia) Reference standards: NINCDS‐ADRDA criteria (McKhann 1984) The diagnosis at follow‐up was made by an experienced neuropsychiatrist who was unaware of the results of the baseline assessment including the MRI data. Mean clinical follow‐up: 1.9 years
Flow and timing	Withdrawals explained and losses to follow‐up: 1/31 cases (3%) for missing Information on the presence or absence of AD. 1 lost for the manual method Uninterpretable MRI results have not been reported
Comparative
Key conclusions by the authors	The ability to detect patients at high risk for AD among those with MCI increases when data on age and memory function are combined with measures of MTA. Volumetry of the hippocampus is preferred, but qualitative rating of MTA is a good alternative.
Conflict of interests	Information not available
Notes	Source of funding: not reported The MRI scan of 1 participant was not available for volumetry and only the qualitative rating was performed for this scan. 2 x 2 table: data available from 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?	No
		High