Sjogren 2000.
| Study characteristics | |||
| Patient Sampling | Patients were consecutively recruited from either a prospective longitudinal study of patients with dementia (the Mölndal prospective dementia study; demented patients and controls), or similar studies at the Clinic of Neuropsychiatry, University Hospital, Malmö (all the dysthymia and 5 FTD patients) or similar studies at the Department of Geriatrics, Linköping (all the PD patients). Control group (32) without history, symptoms, or signs of psychiatric or neurological disease, malignant disease or systemic disorders and with MMSE score or at least 28 was also recruited. We did not include data on performance of the index test to discriminate AD participants from controls. Separate data were available for the performance of the biomarkers in distinguishing ADD from VD, and ADD from FTD. Exclsion criteria: participants with un‐specified dementia, mixed dementia, history of severe psychiatric disease, chronic alcoholism, non‐degenerative neurological disease, severe head injury, severe CNS infections, systemic diseases (e.g. maliganant tumour, liver disease), or secondary causes for dementia according to DSM‐III‐R were excluded |
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| Patient characteristics and setting | The sample considered in the review comprises of 102 participants: 37 early AD defined as onset at or before 65 years; 23 late AD defined as onset after 65 years; 17 FTD; 25 VD (subcortical white‐matter dementia, SWD, 'a putative subtype of VD'). We did not consider 23 Parkinson's disease (PD), 19 dysthymia and 32 controls in the analyses. All patients underwent a thorough clinical investigation including medical history, physical, neurologic and psychiatric examinations, laboratory blood tests, routine CSF analysis, ECG, chest X‐ray, EEG, CT or MRI of the brain and investigation of regional cerebral blood flow using SPECT or 133xenon inhalation technique. At all the localities, clinical evaluation and diagnosis were made according to a Swedish consensus (Wallin 1994) that complies with international standards. Sex: 27 males and 33 females for AD total sample; 62.4 ±10.2 for FTD; 18 males and 7 females for SWD; 17 males and 6 females for PD; 10 males and 9 females for dysthymia Age (SD) (y): 66.0 ±7.8 for AD total sample; 6 males and 11 females for FTD; 62.4 ±10.2 for SWD; 47.2±15.0 PD; 47.2±15.0 for dysthymia Disease duration (y): 3.5±2.3 for AD total sample; 4.9±3.1 for FTD; 2.8±1.9 for SWD Sources of recruitment: specialist care setting; multicentre; Institute of Clinical Neuroscience, Gobteborg University and Neuropsychiatric Clinic, Malmo University Hospital, Sweden. Not reported whether inpatients or outpatients |
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| Index tests | Patients gave CSF samples. The samples were collected in polypropylene tubes, stored on ice and sent to local laboratory and analysed. Abeta42 was measured using enzyme‐linked immunosorbent assays, obtained from Innogenetics NV, Gent, Belgium. Threshold: 537pg/mL, not pre‐specified, Cut‐off value, sensitivity and specificity were determined according to suggestions by Altman 1997. A specificity level of approximately 85% for controls (the proportion of true negative cases) was chosen when determining the cut‐off values. From the cut‐off levels, sensitivity values for each diagnostic group and CSF‐marker were obtained. This specificity level has been recommended in a consensus report on biochemical markers for AD (The Ronald and Nancy Reagan Research Institute, 1998). Were the index test results reported without knowledge of the reference standard? Not reported |
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| Target condition and reference standard(s) |
Target condition: Alzheimer's disease dementia (1. differential diagnosis of AD from VD; 2. differential diagnosis of AD from FTD) Reference standards: NINCDS‐ADRDA for AD. Clinical diagnosis of VD was based on NINDS‐AIREN criteria, of FTD on The Lund/Manchester criteria. Clinical diagnosis was established prior the results of the index test. |
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| Flow and timing | The interval between established clinical diagnosis and CSF sample collection was not reported.However, it appears that CSF samples were collected shortly after establishing the clinical diagnosis. Sample included in the analysis: 132 participants: 60 AD (37 early onset AD; 23 late onset AD); 17 FTD; 25 VD (SWD) AD vs VD (n=84) TP=56; FP=16; FN=4; TN=8 Sensitivity=93%; Specificity=33% (Calculated in RevMan5) AD vs FTD (n=77) TP=55; FP=7; FN=5; TN=10 Sensitivity=92%; Specificity=59% (Calculate in RevMan5) Missing data: CSF Abeta42 sample was unavailable from 1 VD participants |
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| Comparative | |||
| Notes | |||
| 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? | No | ||
| Did the study avoid inappropriate exclusions? | Unclear | ||
| Could the selection of patients have introduced bias? | High risk | ||
| Are there concerns that the included patients and setting do not match the review question? | Low concern | ||
| 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 | ||
| Could the reference standard, its conduct, or its interpretation have introduced bias? | Low risk | ||
| Are there concerns that the target condition as defined by the reference standard does not match the question? | Low concern | ||
| DOMAIN 4: Flow and Timing | |||
| Was there an appropriate interval between index test and reference standard? | Yes | ||
| Were all patients included in the analysis? | Yes | ||
| Could the patient flow have introduced bias? | Low risk | ||