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CSF tau and the CSF tau/ABeta ratio for the diagnosis of Alzheimer's disease dementia and other dementias in people with mild cognitive impairment (MCI)

Overview of attention for article published in Cochrane database of systematic reviews, March 2017
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  • In the top 5% of all research outputs scored by Altmetric
  • Among the highest-scoring outputs from this source (#35 of 10,636)
  • High Attention Score compared to outputs of the same age (99th percentile)
  • High Attention Score compared to outputs of the same age and source (99th percentile)

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59 news outlets
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12 tweeters

Citations

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69 Dimensions

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226 Mendeley
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Title
CSF tau and the CSF tau/ABeta ratio for the diagnosis of Alzheimer's disease dementia and other dementias in people with mild cognitive impairment (MCI)
Published in
Cochrane database of systematic reviews, March 2017
DOI 10.1002/14651858.cd010803.pub2
Pubmed ID
Authors

Craig Ritchie, Nadja Smailagic, Anna H Noel-Storr, Obioha Ukoumunne, Emma C Ladds, Steven Martin

Abstract

Research suggests that measurable change in cerebrospinal fluid (CSF) biomarkers occurs years in advance of the onset of clinical symptoms (Beckett 2010). In this review, we aimed to assess the ability of CSF tau biomarkers (t-tau and p-tau) and the CSF tau (t-tau or p-tau)/ABeta ratio to enable the detection of Alzheimer's disease pathology in patients with mild cognitive impairment (MCI). These biomarkers have been proposed as important in new criteria for Alzheimer's disease dementia that incorporate biomarker abnormalities. To determine the diagnostic accuracy of 1) CSF t-tau, 2) CSF p-tau, 3) the CSF t-tau/ABeta ratio and 4) the CSF p-tau/ABeta ratio index tests for detecting people with MCI at baseline who would clinically convert to Alzheimer's disease dementia or other forms of dementia at follow-up. The most recent search for this review was performed in January 2013. We searched MEDLINE (OvidSP), Embase (OvidSP), BIOSIS Previews (Thomson Reuters Web of Science), Web of Science Core Collection, including Conference Proceedings Citation Index (Thomson Reuters Web of Science), PsycINFO (OvidSP), and LILACS (BIREME). We searched specialized sources of diagnostic test accuracy studies and reviews. We checked reference lists of relevant studies and reviews for additional studies. We contacted researchers for possible relevant but unpublished data. We did not apply any language or data restriction to the electronic searches. We did not use any methodological filters as a method to restrict the search overall. We selected those studies that had prospectively well-defined cohorts with any accepted definition of MCI and with CSF t-tau or p-tau and CSF tau (t-tau or p-tau)/ABeta ratio values, documented at or around the time the MCI diagnosis was made. We also included studies which looked at data from those cohorts retrospectively, and which contained sufficient data to construct two by two tables expressing those biomarker results by disease status. Moreover, studies were only selected if they applied a reference standard for Alzheimer's disease dementia diagnosis, for example, the NINCDS-ADRDA or Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. We screened all titles generated by the electronic database searches. Two review authors independently assessed the abstracts of all potentially relevant studies, and the full papers for eligibility. Two independent assessors performed data extraction and quality assessment. Where data allowed, we derived estimates of sensitivity at fixed values of specificity from the model we fitted to produce the summary receiver operating characteristic (ROC) curve. In total, 1282 participants with MCI at baseline were identified in the 15 included studies of which 1172 had analysable data; 430 participants converted to Alzheimer's disease dementia and 130 participants to other forms of dementia. Follow-up ranged from less than one year to over four years for some participants, but in the majority of studies was in the range one to three years. Conversion to Alzheimer's disease dementia The accuracy of the CSF t-tau was evaluated in seven studies (291 cases and 418 non-cases).The sensitivity values ranged from 51% to 90% while the specificity values ranged from 48% to 88%. At the median specificity of 72%, the estimated sensitivity was 75% (95% CI 67 to 85), the positive likelihood ratio was 2.72 (95% CI 2.43 to 3.04), and the negative likelihood ratio was 0.32 (95% CI 0.22 to 0.47).Six studies (164 cases and 328 non-cases) evaluated the accuracy of the CSF p-tau. The sensitivities were between 40% and 100% while the specificities were between 22% and 86%. At the median specificity of 47.5%, the estimated sensitivity was 81% (95% CI: 64 to 91), the positive likelihood ratio was 1.55 (CI 1.31 to 1.84), and the negative likelihood ratio was 0.39 (CI: 0.19 to 0.82).Five studies (140 cases and 293 non-cases) evaluated the accuracy of the CSF p-tau/ABeta ratio. The sensitivities were between 80% and 96% while the specificities were between 33% and 95%. We did not conduct a meta-analysis because the studies were few and small. Only one study reported the accuracy of CSF t-tau/ABeta ratio.Our findings are based on studies with poor reporting. A significant number of studies had unclear risk of bias for the reference standard, participant selection and flow and timing domains. According to the assessment of index test domain, eight of 15 studies were of poor methodological quality.The accuracy of these CSF biomarkers for 'other dementias' had not been investigated in the included primary studies. Investigation of heterogeneity The main sources of heterogeneity were thought likely to be reference standards used for the target disorders, sources of recruitment, participant sampling, index test methodology and aspects of study quality (particularly, inadequate blinding).We were not able to formally assess the effect of each potential source of heterogeneity as planned, due to the small number of studies available to be included. The insufficiency and heterogeneity of research to date primarily leads to a state of uncertainty regarding the value of CSF testing of t-tau, p-tau or p-tau/ABeta ratio for the diagnosis of Alzheimer's disease in current clinical practice. Particular attention should be paid to the risk of misdiagnosis and overdiagnosis of dementia (and therefore over-treatment) in clinical practice. These tests, like other biomarker tests which have been subject to Cochrane DTA reviews, appear to have better sensitivity than specificity and therefore might have greater utility in ruling out Alzheimer's disease as the aetiology to the individual's evident cognitive impairment, as opposed to ruling it in. The heterogeneity observed in the few studies awaiting classification suggests our initial summary will remain valid. However, these tests may have limited clinical value until uncertainties have been addressed. Future studies with more uniformed approaches to thresholds, analysis and study conduct may provide a more homogenous estimate than the one that has been available from the included studies we have identified.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 226 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 <1%
Germany 1 <1%
Unknown 224 99%

Demographic breakdown

Readers by professional status Count As %
Student > Master 44 19%
Student > Ph. D. Student 33 15%
Student > Bachelor 32 14%
Researcher 30 13%
Student > Doctoral Student 20 9%
Other 37 16%
Unknown 30 13%
Readers by discipline Count As %
Medicine and Dentistry 63 28%
Psychology 24 11%
Neuroscience 22 10%
Nursing and Health Professions 15 7%
Agricultural and Biological Sciences 14 6%
Other 41 18%
Unknown 47 21%

Attention Score in Context

This research output has an Altmetric Attention Score of 481. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 September 2018.
All research outputs
#17,930
of 13,565,336 outputs
Outputs from Cochrane database of systematic reviews
#35
of 10,636 outputs
Outputs of similar age
#938
of 262,351 outputs
Outputs of similar age from Cochrane database of systematic reviews
#1
of 259 outputs
Altmetric has tracked 13,565,336 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 10,636 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 21.1. This one has done particularly well, scoring higher than 99% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 262,351 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 99% of its contemporaries.
We're also able to compare this research output to 259 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 99% of its contemporaries.