Summary of findings 1. Summary of findings table.
| Patient population | People with a clinical diagnosis of dementia. | |||||||
| Review question | How accurate is CSF ABeta42 test for distinguishing Alzheimer's disease dementia (ADD) from other types of dementia? | |||||||
| Index test | Cerebrospinal fluid (CSF) ABeta42 test. | |||||||
| Reference standard | Clinical diagnostic criteria for dementia pathological subtypes (Appendix 1). | |||||||
| Target condition | ADD vs other dementia subtypes | |||||||
| Included studies | 39 studies (5000 participants). | |||||||
| Quality concerns | The majority of studies were classified at high or unclear risk of bias, particularly for patient selection (n = 28), and the index test (n = 25). The majority of studies were at low risk for applicability concerns (n = 33 to 36 for each domain). Studies were mainly at unclear risk of bias due to inadequate reporting. Few studies pre‐specified the test threshold and used optimal cut‐offs calculated using the study data. | |||||||
| Heterogeneity | The majority of studies in this review were conducted in specialist secondary care settings. The majority of studies conducted the index test in a similar manner. Sources of heterogeneity were: patient population and dementia subtype enrolled, test threshold used, and the diagnostic criteria and definition of ADD and dementia subtypes. | |||||||
| Differential Diagnosis |
Number of participants |
Number of studies | Number of participants with ADD | Pooled sensitivity (95% confidence interval) |
Pooled specificity (95% confidence interval) |
Pooled false positive rate (95% confidence interval) |
Pooled positive likelihood ratio (95% confidence interval) | Pooled negative likelihood ratio (95% confidence interval) |
| ADD vs non‐ADD | 1704 | 13 | 880 | 0.79 (0.73, 0.85) | 0.60 (0.52, 0.67) | 0.40 (0.33, 0.48) | 1.98 (1.58, 2.47) | 0.34 (0.24, 0.49) |
| ADD vs VaD | 1151 | 11 | 941 | 0.79 (0.75, 0.83) | 0.69 (0.55, 0.81) | 0.31 (0.20, 0.45) | 2.58 (1.75, 3.81) | 0.30 (0.25, 0.36) |
| ADD vs FTD | 1948 | 17 | 1371 | 0.85 (0.79, 0.89) | 0.72 (0.55, 0.84) | 0.28 (0.16, 0.45) | 3.00 (1.81, 5.00) | 0.21 (0.16, 0.28) |
| ADD vs DLB | 1929 | 9 | 1521 | 0.77 (0.70, 0.83) | 0.66 (0.51, 0.78) | 0.34 (0.22, 0.49) | 2.27 (1.57, 3.28) | 0.35 (0.28, 0.45) |
| ADD vs NPH | 336 | 4 | 258 | 0.84 (0.79, 0.88) | 0.42 (0.26, 0.60) | 0.58 (0.40, 0.74) | 1.45 (1.07, 1.97) | 0.38 (0.23, 0.63) |
| ADD vs CJD | 382 | 3 | 321 | 0.82 (0.77, 0.86) | 0.46 (0.34, 0.58) | 0.54 (0.42, 0.66) | 1.51 (1.15, 1.87) | 0.40 (0.26, 0.54) |
| ADD vs ARCDa | 53 | 1 | 33 | 0.80 | 0.85 | ‐ | ‐ | ‐ |
| Conclusions | Our results suggest that ABeta42 could be useful in improving differential diagnosis of the dementia syndrome, but the test is imperfect. It is unlikely that the ABeta42 biomarker would be used in isolation in clinical practice and ideally it should be used to support the diagnosis alongside full clinical, radiological, and neuropsychological assessment. Our review does not help answer questions around the added value of the test over routine diagnostics. | |||||||
| Implications | The test accuracy demonstrated does lend some support to the concept of using biomarkers to differentiate dementia type for tailored therapy. Clinical trials of anti‐amyloid interventions could consider using quantification of ABeta42 for patient selection. The biomarker does not guarantee an exclusively ADD population but it may help select those people most likely to benefit from the intervention. | |||||||
ADD: Alzheimer's disease dementia; ARCD: Alcohol‐related cognitive disorder; CJD: Creutzfeldt‐Jakob disease; DLB: Dementia with Lewy bodies; FTD: Frontotemporal dementia; LR: Likelihood ratio; NPH: Normal pressure hydrocephalus; Sens: sensitivity; Spec: specificity; VaD: Vascular dementia
aNote that there was only one study for the ADD vs ARCD comparison; therefore, data presented are from a single study