Article Text

Download PDFPDF
Clinical utility of cerebrospinal fluid biomarkers in the evaluation of cognitive impairment: a systematic review and meta-analysis
  1. Jemma Hazan,
  2. Michelle Wing,
  3. Kathy Y Liu,
  4. Suzanne Reeves,
  5. Robert Howard
  1. Division of Psychiatry, University College London, London, UK
  1. Correspondence to Dr Jemma Hazan, University College London, London, UK; j.hazan{at}


Background The analytical and clinical validity of cerebrospinal (CSF) biomarkers has been extensively researched in dementia. Further work is needed to assess the ability of these biomarkers to improve diagnosis, management and health outcomes in the clinical setting

Objectives To assess the added value and clinical utility of CSF biomarkers in the diagnostic assessment of cognitively impaired patients under evaluation for Alzheimer’s disease (AD).

Methods Systematic literature searches of Medline, EMBASE, PsycINFO and Web of Science research databases were conducted on 17 December 2022. Data from relevant studies were extracted and independently screened for quality using a tool for bias. Clinical utility was measured by clinicians’ changes in diagnosis, diagnostic confidence and patient management (when available), after their examination of patients’ CSF biomarkers. Cost-effectiveness was assessed by consideration of additional cost per patient and quality-adjusted life years.

Results Searches identified 17 studies comprising 2090 patient participants and 593 clinicians. The meta-analysis revealed that clinicians’ use of CSF biomarkers resulted in a pooled percentage change in diagnosis of 25% (95% CI 14 to 37), an increase in diagnostic confidence of 14% (95% CI 9 to 18) and a pooled proportion of patients whose management changed of 31% (95% CI 12 to 50). CSF biomarkers were deemed cost-effective, particularly in memory services, where pre-test AD prevalence is higher compared with a primary care setting.

Conclusions CSF biomarkers can be a helpful additional diagnostic tool for clinicians assessing patients with cognitive impairment. In particular, CSF biomarkers consistently improved clinicians’ confidence in diagnosing AD and influenced on diagnostic change and patient management. Further research is needed to study the clinical utility of blood-based biomarkers in the clinical setting.

  • CSF

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Contributors All authors contributed to the conception and design of the review. MW and JH completed the data collection. JH and KYL performed the data analysis and interpretation. All authors contributed to drafting of the article, revision of the article and final approval of the version to be published.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.