Empirical assessment of biases in cerebrospinal fluid biomarkers of Alzheimer's disease: an umbrella review and re-analysis of data from meta-analyses

Jeong, Dong Yeon and Lee, Jinhee and Kim, Jong Yeob and Lee, Keum Hwa and Li, Han and Lee, Jun Young and Jeong, Gwang Hun and Yoon, Sojung and Park, Eun Lyeong and Hong, Sung Hwi and Kang, Joon Won and Song, Tae-Jin and Leyhe, Thomas and Eisenhut, Michael and Kronbichler, Andreas and Smith, Lee and Solmi, Marco and Stubbs, Brendon and Koyanagi, Ai and Jacob, Louis and Stickley, Andrew and Thompson, Trevor and Dragioti, Elena and Oh, Hans and Brunoni, Andre R. and Carvalho, Andre F. and Kim, Min Seo and Yon, Dong Keon and Lee, Seung Won and Yang, Jee Myung and Ghayda, Ramy A. and Shin, Jae Il and Fusar-Poli, Paolo (2021) Empirical assessment of biases in cerebrospinal fluid biomarkers of Alzheimer's disease: an umbrella review and re-analysis of data from meta-analyses. European Review for Medical and Pharmacological Sciences, 25 (3). pp. 1536-1547. ISSN 2284-0729

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Abstract

OBJECTIVE: Alzheimer’s 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 (I2≥75%) was observed in 73% and small-study effects under Egger’s 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.

Item Type:	Journal Article
Keywords:	Alzheimer’s disease, CSF biomarkers, Umbrella Review, Meta-analysis, Excess significance
Faculty:	Faculty of Science & Engineering
SWORD Depositor:	Symplectic User
Depositing User:	Symplectic User
Date Deposited:	17 Nov 2020 10:23
Last Modified:	09 Sep 2021 18:51
URI:	https://arro.anglia.ac.uk/id/eprint/706056

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