CSF biomarkers for dementia

Keshavan, Ashvini; O’Shea, Frankie; Chapman, Miles D.; Hart, Melanie; Lunn, Michael P.; Paterson, Ross W.; Rohrer, Jonathan D.; Mummery, Catherine J.; Fox, Nick C.; Zetterberg, Henrik; Schott, Jonathan M.

doi:10.1136/practneurol-2021-003310

Cited by 8 publications

(4 citation statements)

References 35 publications

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“…Cerebrospinal fluid (CSF) biomarkers are currently used in the diagnostic investigation of AD at specialist tertiary Neurology Centres in the UK 5 . However, they are not routinely used in UK Memory Services 6,7 .…”

Section: Introductionmentioning

confidence: 99%

Clinical utility of cerebrospinal fluid biomarkers in the evaluation of cognitive impairment: a systematic review and meta-analysis

Hazan

Wing

Liu

et al. 2022

J Neurol Neurosurg Psychiatry

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BackgroundThe 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 settingObjectivesTo 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).MethodsSystematic 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.ResultsSearches 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.ConclusionsCSF 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.

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Section: Introductionmentioning

confidence: 99%

Clinical utility of cerebrospinal fluid biomarkers in the evaluation of cognitive impairment: a systematic review and meta-analysis

Hazan

Wing

Liu

et al. 2022

J Neurol Neurosurg Psychiatry

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“…Expansion of amyloid-PET requires increased tracer availability, access to PET imaging centres, nuclear medicine physicians, and reimbursement/approvals. While significant challenges, they are not insurmountable: protocols are in place to train clinical nurse specialists to perform LPs (13), and wide access to FDG-PET for cancer diagnosis and monitoring demonstrates that PET scanning using 18F tracers is feasible at scale.…”

Section: What Changes Are Needed?mentioning

confidence: 99%

Preparing for disease-modifying therapies in Alzheimer's disease

Belder,

Schott,

Fox

2023

The Lancet Neurology

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“…5 The final Aβ42 CRMs have also been used for re-calibrating commercial immunoassays for CSF Aβ42, including those that are FDA approved. 6 However, this approach is very laborious and time-consuming.…”

Section: Introductionmentioning

confidence: 99%

The CentiMarker Project: Standardizing Quantitative Alzheimer’s disease Fluid Biomarkers for Biologic Interpretation

Wang,

Li,

Xiong

et al. 2024

Preprint

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Introduction: Biomarkers have been essential to understanding Alzheimer's disease (AD) pathogenesis, pathophysiology, progression, and treatment effects. However, each biomarker measure is a representation of the biological target, the assay used to measure it, and the variance of the assay. Thus, biomarker measures are difficult to compare without standardization, and the units and magnitude of effect relative to the disease are difficult to appreciate, even for experts. To facilitate quantitative comparisons of AD biomarkers in the context of biologic and treatment effects, we propose a biomarker standardization approach between normal ranges and maximum abnormal AD ranges, which we refer to as CentiMarker, similar to the Centiloid approach used in PET. Methods: We developed a standardization scale that creates percentile values ranging from 0 for a normal population to 100 for the most abnormal measures across disease stages. We applied this scale to CSF and plasma biomarkers in autosomal dominant AD, assessing the distribution by estimated years from symptom onset, between biomarkers, and across cohorts. We then validated this approach in a large national sporadic AD cohort. Results: We found the CentiMarker scale provided an easily interpretable metric of disease abnormality. The biologic changes, range, and distribution of several AD fluid biomarkers including amyloid-β, phospho-tau and other biomarkers, were comparable across disease stages in both early onset autosomal dominant and sporadic late onset AD. Discussion: The CentiMarker scale offers a robust and versatile framework for the standardized biological comparison of AD biomarkers. Its broader adoption could facilitate biomarker reporting, allowing for more informed cross-study comparisons and contributing to accelerated therapeutic development.

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CSF biomarkers for dementia

Cited by 8 publications

References 35 publications

Clinical utility of cerebrospinal fluid biomarkers in the evaluation of cognitive impairment: a systematic review and meta-analysis

Clinical utility of cerebrospinal fluid biomarkers in the evaluation of cognitive impairment: a systematic review and meta-analysis

Preparing for disease-modifying therapies in Alzheimer's disease

The CentiMarker Project: Standardizing Quantitative Alzheimer’s disease Fluid Biomarkers for Biologic Interpretation

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