Plasma neurofilament light chain in memory clinic practice: Evidence from a real-life study.

OBJECTIVE: To explore the accuracy of plasma neurofilament light chain (NfL) as a biomarker for diagnosis and staging of cognitive impairment, in a large cohort with of previously diagnosed patients in clinical practice. METHODS: Retrospective, cross-sectional, monocentric study, from a tertiary memory clinic. Patients underwent cerebrospinal fluid core Alzheimer's disease (AD) biomarker evaluation using ELISA or Elecsys methods, and plasma NfL analysis using the single molecule array technology. The patients' biomarker data were examined for associations with: i/cognitive status ii/presence of neurodegenerative disease and iii/diagnostic groups. Associations between core CSF biomarkers and plasma NfL were determined. RESULTS: Participants (N = 558, mean age = 69.2 ± 8.8, 56.5% women) were diagnosed with AD (n = 274, considering dementia and MCI stages), frontotemporal dementia (FTD, n = 55), Lewy body disease (LBD, n = 40, considering MCI and dementia stages), other neurodegenerative diseases, n = 57 (e.g Supranuclear Palsy, Corticobasal syndrome), non-neurodegenerative cognitive impairment (NND, n = 79, e.g. vascular lesions, epilepsy or psychiatric disorders) or subjective cognitive impairment (SCI, n = 53). Mean plasma NfL (log, pg/mL) levels were higher in neurodegenerative than non-neurodegenerative disorders (1.35 ± 0.2 vs 1.16 ± 0.23, p < 0.001), higher in all diagnostic groups than in SCI (1.06 ± 0.23) p < 0.001), and associated with the stage of cognitive impairment (p < 0.001). The addition of plasma NfL to a clinical model (age, MMSE and APOE ε4 carriership) marginally improved the discrimination of degenerative from non-degenerative disorders in ROC analysis (AUC clinical model: 0.81, 95% CI = [0.77;0.85] AUC clinical model + plasma NfL: AUC = 0.83 95% CI = [0.78;0.87], delta Akaike information criterion = -11.7). DISCUSSION: Plasma NfL could help discrimination between degenerative and non-degenerative cognitive disorders, albeit not better than comprehensive clinical evaluation.

Comparison of CSF and plasma NfL and pNfH for Alzheimer's disease diagnosis: a memory clinic study.

Plasma neurofilament light chain (NfL) is a promising biomarker of axonal damage for the diagnosis of neurodegenerative diseases. Phosphorylated neurofilament heavy chain (pNfH) has demonstrated its value in motor neuron diseases diagnosis, but has less been explored for dementia diagnosis. In a cross-sectional study, we compared cerebrospinal fluid (CSF) and plasma NfL and pNfH levels in n = 188 patients from Lariboisière Hospital, Paris, France, including AD patients at mild cognitive impairment stage (AD-MCI, n = 36) and dementia stage (n = 64), non-AD MCI (n = 38), non-AD dementia (n = 28) patients and control subjects (n = 22). Plasma NfL, plasma and CSF pNfH levels were measured using Simoa and CSF NfL using ELISA. The correlation between CSF and plasma levels was stronger for NfL than pNfH (rho = 0.77 and rho = 0.52, respectively). All neurofilament markers were increased in AD-MCI, AD dementia and non-AD dementia groups compared with controls. CSF NfL, CSF pNfH and plasma NfL showed high performance to discriminate AD at both MCI and dementia stages from control subjects [AUC (area under the curve) = 0.82-0.91]. Plasma pNfH displayed overall lower AUCs for discrimination between groups compared with CSF pNfH. Neurofilament markers showed similar moderate association with cognition. NfL levels displayed significant association with mediotemporal lobe atrophy and white matter lesions in the AD group. Our results suggest that CSF NfL and pNfH as well as plasma NfL levels display equivalent performance in both positive and differential AD diagnosis in memory clinic settings. In contrast to motoneuron disorders, plasma pNfH did not demonstrate added value as compared with plasma NfL.

Plasma biomarkers of amyloid, tau, axonal, and neuroinflammation pathologies in dementia with Lewy bodies.

BACKGROUND: Increasing evidence supports the use of plasma biomarkers of amyloid, tau, neurodegeneration, and neuroinflammation for diagnosis of dementia. However, their performance for positive and differential diagnosis of dementia with Lewy bodies (DLB) in clinical settings is still uncertain. METHODS: We conducted a retrospective biomarker study in two tertiary memory centers, Paris Lariboisière and CM2RR Strasbourg, France, enrolling patients with DLB (n = 104), Alzheimer's disease (AD, n = 76), and neurological controls (NC, n = 27). Measured biomarkers included plasma Aß40/Aß42 ratio, p-tau181, NfL, and GFAP using SIMOA and plasma YKL-40 and sTREM2 using ELISA. DLB patients with available CSF analysis (n = 90) were stratified according to their CSF Aß profile. RESULTS: DLB patients displayed modified plasma Aß ratio, p-tau181, and GFAP levels compared with NC and modified plasma Aß ratio, p-tau181, GFAP, NfL, and sTREM2 levels compared with AD patients. Plasma p-tau181 best differentiated DLB from AD patients (ROC analysis, area under the curve [AUC] = 0.80) and NC (AUC = 0.78), and combining biomarkers did not improve diagnosis performance. Plasma p-tau181 was the best standalone biomarker to differentiate amyloid-positive from amyloid-negative DLB cases (AUC = 0.75) and was associated with cognitive status in the DLB group. Combining plasma Aß ratio, p-tau181 and NfL increased performance to identify amyloid copathology (AUC = 0.79). Principal component analysis identified different segregation patterns of biomarkers in the DLB and AD groups. CONCLUSIONS: Amyloid, tau, neurodegeneration and neuroinflammation plasma biomarkers are modified in DLB, albeit with moderate diagnosis performance. Plasma p-tau181 can contribute to identify Aß copathology in DLB.

Lumbar puncture training with healthcare simulation improves self-confidence and practical skills of French medical residents in geriatrics.

PURPOSE: To assess the skill level and self-confidence of medical residents in geriatrics with regard to conducting the lumbar puncture (LP) procedure and to study the potential benefits of training with simulation and virtual reality. METHODS: First, a questionnaire survey was conducted among all French residents in geriatrics in the Paris area to assess their knowledge and self-confidence regarding the practice of LP in older adults. Second, we set up a simulation LP training session combined with virtual reality (3D video) training for selected respondents of the first survey. Third, we performed post-simulation survey for the attendees of the simulation training. Finally, a follow-up survey was conducted to examine the change in self-confidence and the success rate in clinical practice. RESULTS: Fifty-five residents responded to the survey (response rate = 36.4%). The importance of mastering LP was fully recognized by the residents in geriatrics (95.3%), so most of them (94.5%) advocated for the need for additional practical training. Fourteen residents took part in the training (average rating = 4.7 on a 5-point scale). Simulation was regarded by 83% of the respondents as the most useful tool for their practice. We observed a significant pre/post-training mean improvement in self-estimated success of 20.6% (Wilcoxon matched-pairs signed-rank W = - 36, p = 0.008). The post-training success rate of the residents in real-life clinical practice was good (85.8%). CONCLUSION: Residents were aware of the importance of mastering LP and requested additional training. Simulation may represent a major driver to improve their self-confidence and practical skills.