What is the clinical impact of cerebrospinal fluid biomarkers on final diagnosis and management in patients with mild cognitive impairment in clinical practice? Results from a nation-wide prospective survey in France

Abstract

ObjectivesNew diagnostic criteria for Alzheimer’s disease (AD) include cerebrospinal fluid (CSF) biomarkers that allow diagnosis at the stage of mild cognitive impairment (MCI). However, the impact of CSF biomarkers in MCI populations in clinical practice has been poorly evaluated. The objective of this study is to assess the use and impact in clinical practice of AD CSF biomarkers in French memory clinics.DesignWe performed a nation-wide, prospective survey between March 2012 and September 2014. Data over the same period was extracted from the French National Database (Banque Nationale Alzheimer, BNA) and compared with the results of the survey.Setting29 secondary and tertiary memory clinics in France.ParticipantsClinicians prescribing lumbar puncture (LP) in order to measure AD CSF biomarkers. Clinicians completed a two-part questionnaire for each of their patients undergoing LP.Primary and secondary outcome measuresAssessment of diagnosis, level of confidence before and after CSF biomarkers and impact on management in patients who underwent LP for CSF AD biomarkers in clinical routine.Results977 questionnaires were completed, of which 61 were excluded because of unknown initial/final diagnosis or non-contributory CSF results. Of 916 patients reported, 153 (16.7%) had MCI as the initial diagnosis, of which 51 (33.3%) displayed an AD profile. CSF biomarkers resulted in a change in diagnosis in 44 patients (28.8%). Confidence level significantly increased after LP (8.3±1.4vs 6.73±1.18, p<0.0001), and CSF results modified management in 71/156 patients (46.4%), including 36 (23.5%) enrolled in clinical trials. Comparison of change in diagnosis with the BNA population revealed no difference (32.24%, p=0.4).ConclusionThis nation-wide survey, reflecting clinical practice in French memory clinics, describes the impact of CSF AD biomarkers in patients with MCI in clinical practice.

2020 update on the clinical validity of cerebrospinal fluid amyloid, tau, and phospho-tau as biomarkers for Alzheimer’s disease in the context of a structured 5-phase development framework

“…In a study that examined all patients visiting a tertiary center for cognitive screening during a 1-year period [ 172 ], the use of CSF AD biomarkers led to a change in diagnosis in 7% of patients and a 5% increase in diagnostic confidence; CSF findings were also shown to affect clinical management (e.g., additional investigations, greater follow-up, and clinical trial selection) in 23% of patients. Similar findings were also recently described by Cognat et al [ 173 ]. Other findings from a study that focused on the clinical utility of [ 18 F]flutemetamol in a tertiary memory clinic setting [ 174 ], however, showed that the primary reason (57% of patients) for referral for Amyloid PET in MCI patients was a clinical suspicion of AD in the context of unclear or negative CSF findings.…”

Head‐to‐head comparison of clinical performance of CSF phospho‐tau T181 and T217 biomarkers for Alzheimer's disease diagnosis

“…Brain imaging and neuropsychological assessment remain essential for diagnosis; however, both have limited value to distinguish amyloid‐positivity 48 . Even with CSF testing, Mid‐p‐tau181 is only changed in late prodromal AD and Aβ positivity does not always signal MCI‐AD, 19,20,49 reinforcing potential clinical utility of the early and AD‐specific N‐p‐tau217 and N‐p‐tau181 biomarkers.…”

Body Fluid Biomarkers for Alzheimer’s Disease—An Up-To-Date Overview

“…Evidence for these findings relies on autopsy studies, antemortem lumbar CSF analyses, and functional imaging studies based on positron emission tomography using Aβ ligands, e.g., 11c-labelled Pittsburgh Compound [ 42 ]. Nonetheless, the use of these biomarkers in routine clinical practice is still in its infancy [ 40 ], as there are still some limitations that must be overcome, such as the interindividual differences in the production of Aβ or the overlapping between CSF and Aβ 1-42 between neurodegenerative disorders, as in Creutzfeldt–Jakob disease, dementia with Lewy bodies, frontotemporal lobar degeneration, and prodromal and manifest (subcortical) vascular dementia [ 47 , 48 ]. As such, most studies analyze Aβ levels in comparison with T-tau and P-tau values in order to increase accuracy [ 35 ].…”