Increased Neurofilament Light Chain Blood Levels in Neurodegenerative Neurological Diseases

Neuronal damage is the morphological substrate of persisting neurological disability. Neurofilaments (Nf) are cytoskeletal proteins of neurons and their release into cerebrospinal fluid has shown encouraging results as a biomarker for neurodegeneration. This study aimed to validate the quantification of the Nf light chain (NfL) in blood samples, as a biofluid source easily accessible for longitudinal studies. Methods We developed and applied a highly sensitive electrochemiluminescence (ECL) based immunoassay for quantification of NfL in blood and CSF. Results Patients with Alzheimer’s disease (AD) (30.8 pg/ml, n=20), Guillain-Barré-syndrome (GBS) (79.4 pg/ml, n=19) or amyotrophic lateral sclerosis (ALS) (95.4 pg/ml, n=46) had higher serum NfL values than a control group of neurological patients without evidence of structural CNS damage (control patients, CP) (4.4 pg/ml, n=68, p<0.0001 for each comparison, p=0.002 for AD patients) and healthy controls (HC) (3.3 pg/ml, n=67, p<0.0001). Similar differences were seen in corresponding CSF samples. CSF and serum levels correlated in AD (r=0.48, p=0.033), GBS (r=0.79, p<0.0001) and ALS (r=0.70, p<0.0001), but not in CP (r=0.11, p=0.3739). The sensitivity and specificity of serum NfL for separating ALS from healthy controls was 91.3% and 91.0%. Conclusions We developed and validated a novel ECL based sandwich immunoassay for the NfL protein in serum (NfLUmea47:3); levels in ALS were more than 20-fold higher than in controls. Our data supports further longitudinal studies of serum NfL in neurodegenerative diseases as a potential biomarker of on-going disease progression, and as a potential surrogate to quantify effects of neuroprotective drugs in clinical trials

Lessons Learned Developing a Diagnostic Tool for HIV-Associated Dementia Feasible to Implement in Resource-Limited Settings: Pilot Testing in Kenya

Objective: To conduct a preliminary evaluation of the utility and reliability of a diagnostic tool for HIV-associated dementia (HAD) for use by primary health care workers (HCW) which would be feasible to implement in resource-limited settings. Background: In resource-limited settings, HAD is an indication for anti-retroviral therapy regardless of CD4 T-cell count. Anti-retroviral therapy, the treatment for HAD, is now increasingly available in resource-limited settings. Nonetheless, HAD remains under-diagnosed likely because of limited clinical expertise and availability of diagnostic tests. Thus, a simple diagnostic tool which is practical to implement in resource-limited settings is an urgent need. Methods: A convenience sample of 30 HIV-infected outpatients was enrolled in Western Kenya. We assessed the sensitivity and specificity of a diagnostic tool for HAD as administered by a primary HCW. This was compared to an expert clinical assessment which included examination by a physician, neuropsychological testing, and in selected cases, brain imaging. Agreement between HCW and an expert examiner on certain tool components was measured using Kappa statistic. Results: The sample was 57 % male, mean age was 38.6 years, mean CD4 T-cell count was 323 cells/mL, and 54 % had less than a secondary school education. Six (20%) of the subjects were diagnosed with HAD by expert clinical assessment. The diagnostic tool was 63 % sensitive and 67 % specific for HAD. Agreement between HCW and expert examiners was poor for many individual items of the diagnostic tool (K =.03–.65). This diagnostic tool had moderate sensitivity and specificity fo

"Now i see it, now i don't": Determining Threshold Levels of Facial Emotion Recognition for Use in Patient Populations

The importance of including measures of emotion processing, such as tests of facial emotion recognition (FER), as part of a comprehensive neuropsychological assessment is being increasingly recognized. In clinical settings, FER tests need to be sensitive, short, and easy to administer, given the limited time available and patient limitations. Current tests, however, commonly use stimuli that either display prototypical emotions, bearing the risk of ceiling effects and unequal task difficulty, or are cognitively too demanding and time-consuming. To overcome these limitations in FER testing in patient populations, we aimed to define FER threshold levels for the six basic emotions in healthy individuals. Forty-nine healthy individuals between 52 and 79 years of age were asked to identify the six basic emotions at different intensity levels (25%, 50%, 75%, 100%, and 125% of the prototypical emotion). Analyses uncovered differing threshold levels across emotions and sex of facial stimuli, ranging from 50% up to 100% intensities. Using these findings as "healthy population benchmarks", we propose to apply these threshold levels to clinical populations either as facial emotion recognition or intensity rating tasks. As part of any comprehensive social cognition test battery, this approach should allow for a rapid and sensitive assessment of potential FER deficits. (JINS, 2015, 21, 568-572)

[Consensus 2012 - diagnosis and treatment of patients with dementia in Swizerland]

Le consensus 2012 sur le diagnostic et le traitement des patients atteints de démence en Suisse a été élaboré par une conférence d’experts qui s’est déroulée du 23 au 25 mars 2012 à Lucerne. Après revue des données scientifiques récentes, les auteurs ont rédigé un projet qui a été soumis à de nombreux experts de la démence en Suisse dans le cadre d’une procédure de consultation. Après adaptation et révisions du document initial en fonction des remarques exprimées, l’ensemble des spécialistes consultés et les membres du groupe d’experts adhèrent expressément aux prises de position énoncées dans ce document. La conférence d’experts a été financée par le Forum Alzheimer Suisse.The 2012 Swiss consensus paper on diagnosis and management of patients suffering from dementia resulted from the work of an expert panel who met on March 23d to 25th in Luzern. Based on a literature review, panel members wrote a first draft that was subsequently circulated among multiple dementia experts in Switzerland. After adaptation and revisions according to comments, all consulted dementia specialists and panel members fully endorse the consensus content. The conference was financed by the Swiss Alzheimer Forum

Brain microstructure reveals early abnormalities more than two years prior to clinical progression from mild cognitive impairment to Alzheimer's disease.

Diffusion imaging is a promising marker of microstructural damage in neurodegenerative disorders, but interpretation of its relationship with underlying neuropathology can be complex. Here, we examined both volumetric and brain microstructure abnormalities in 13 amnestic patients with mild cognitive impairment (MCI), who progressed to probable Alzheimer's disease (AD) no earlier than 2 years after baseline scanning, in order to focus on early, and hence more sensitive, imaging markers. We compared them to 22 stable amnestic MCI patients with similar cognitive performance and episodic memory impairment but who did not show progression of symptoms for at least 3 years. Significant group differences were mainly found in the volume and microstructure of the left hippocampus, while white matter group differences were also found in the body of the fornix, left fimbria, and superior longitudinal fasciculus (SLF). Diffusion index abnormalities in the SLF were the sign of a subtle microstructural injury not detected by standard atrophy measures in the corresponding gray matter regions. The microstructural measure obtained in the left hippocampus using diffusion imaging showed the most substantial differences between the two groups and was the best single predictor of future progression to AD. An optimal prediction model (91% accuracy, 85% sensitivity, 96% specificity) was obtained by combining MRI measures and CSF protein biomarkers. These results highlight the benefit of using the information of brain microstructural damage, in addition to traditional gray matter volume, to detect early, subtle abnormalities in MCI prior to clinical progression to probable AD and, in combination with CSF markers, to accurately predict such progression