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

Abstract

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.

Acceptability and feasibility of plasma phosphorylated‐tau181 in two memory services

“…For example, in a study where clinicians were given simulated clinical vignettes, an AD clinical presentation along with AD CSF results led to a significantly increased odds of an AD diagnosis, however if clinicians received borderline CSF values, they used other clinical information to reach a diagnosis. 16,17 In a systematic review and meta-analysis of the clinical utility of CSF biomarkers in the diagnostic evaluation of cognitively impaired patients, clinicians' use of CSF biomarkers resulted in a pooled percentage change in diagnosis of 25%, an increase in diagnostic confidence of 14% and a pooled proportion of patients whose management changed of 31%. 16 This highlights that despite limitations in the data, the biomarker results still had the power to push diagnostic certainty and change management.…”

“…16,17 In a systematic review and meta-analysis of the clinical utility of CSF biomarkers in the diagnostic evaluation of cognitively impaired patients, clinicians' use of CSF biomarkers resulted in a pooled percentage change in diagnosis of 25%, an increase in diagnostic confidence of 14% and a pooled proportion of patients whose management changed of 31%. 16 This highlights that despite limitations in the data, the biomarker results still had the power to push diagnostic certainty and change management.…”

“…When interpreting a CSF biomarker profile, a clinician may find that a typical AD profile increases their diagnostic confidence by a small percentage in favour of an AD diagnosis. For example, in a study where clinicians were given simulated clinical vignettes, an AD clinical presentation along with AD CSF results led to a significantly increased odds of an AD diagnosis, however if clinicians received borderline CSF values, they used other clinical information to reach a diagnosis 16,17 …”

Neural Surface Antibodies and Neurodegeneration: Clinical Commonalities and Pathophysiological Relationships

“…In this setting, the differential diagnosis of AE from even rapidly progressive dementia should be relatively easy. Moreover, patients with neurodegenerative dementia should have additional supporting findings such as specific changes in CSF neurodegeneration markers (i.e., altered Aβ42, total tau and phosphorylated tau values and ratios) [ 72 ] or molecular imaging specific alterations that should be absent in patients with AE [ 73 ]. However, in clinical practice this distinction is not always straightforward.…”

Blood Analytes as Biomarkers of Mechanisms Involved in Alzheimer’s Disease Progression

“…However, the concurrent observation of gliosis and neuroinflammatory driving cells has highlighted the importance of the mutual relationship between those aberrant proteins and inflammatory molecules often secreted for triggering AD pathological changes [ 2 , 3 , 4 , 5 , 6 ]. In this context, understanding how global perturbations in metabolism and body functions are related to AD neuropathology would be crucial, albeit challenging, for a prompt diagnosis, a correct prognosis and effective treatments [ 1 , 7 ]. A potential tool for AD diagnosis and prognosis is represented by blood biomarkers [ 8 , 9 , 10 ].…”