Empirical assessment of biases in cerebrospinal fluid biomarkers of Alzheimers disease: an umbrella review and re-analysis of data from meta-analysesShow others and affiliations
2021 (English)In: European Review for Medical and Pharmacological Sciences, ISSN 1128-3602, Vol. 25, no 3, p. 1536-1547Article, review/survey (Refereed) Published
Abstract [en]
OBJECTIVE: Alzheimers disease (AD) is a leading cause of years lived with disability in older age, and several cerebrospinal fluid (CSF) markers have been proposed in individual meta-analyses to be associated with AD but field-wide evaluation and scrutiny of the literature is not available. MATERIALS AND METHODS: We performed an umbrella review for the reported associations between CSF biomarkers and AD. Data from available meta-analyses were reanalyzed using both random and fixed effects models. We also estimated between-study heterogeneity, small-study effects, excess significance, and prediction interval. RESULTS: A total of 38 meta-analyses on CSF markers from 11 eligible articles were identified and reanalyzed. In 14 (36%) of the meta-analyses, the summary estimate and the results of the largest study showed non-concordant results in terms of statistical significance. Large heterogeneity (I-2=75%) was observed in 73% and smallstudy effects under Eggers test were shown in 28% of CSF biomarkers. CONCLUSIONS: Our results suggest that there is an excess of statistically significant results and significant biases in the literature of CSF biomarkers for AD. Therefore, the results of CSF biomarkers should be interpreted with caution.
Place, publisher, year, edition, pages
VERDUCI PUBLISHER , 2021. Vol. 25, no 3, p. 1536-1547
Keywords [en]
Alzheimers disease; CSF biomarkers; Meta-analysis; Umbrella review; Excess significance
National Category
Neurology
Identifiers
URN: urn:nbn:se:liu:diva-174414DOI: 10.26355/eurrev_202102_24862ISI: 000619780200043PubMedID: 33629323OAI: oai:DiVA.org:liu-174414DiVA, id: diva2:1538725
Note
Funding Agencies|Health Education England (HEE) [ICA-CL-2017-03-001]; National Institute for Health Research (NIHR)National Institute for Health Research (NIHR) [ICA-CL-2017-03-001]; NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust; NIHRNational Institute for Health Research (NIHR)
2021-03-212021-03-212021-03-21