Association of Cognitive Impairment With Free Water in the Nucleus Basalis of Meynert and Locus Coeruleus to Transentorhinal Cortex Tract

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000013206
Author(s):  
Winston Thomas Chu ◽  
Wei-en Wang ◽  
Laszlo Zaborszky ◽  
Todd Eliot Golde ◽  
Steven DeKosky ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Locus Coeruleus ◽  
Entorhinal Cortex ◽  
Light Chain ◽  
Free Water ◽  
Nucleus Basalis ◽  
Nucleus Basalis Of Meynert ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Transentorhinal Cortex

Objective:Determine the relationship between diffusion microstructure and early changes in Alzheimer’s disease (AD) severity as assessed by clinical diagnosis, cognitive performance, dementia severity, and plasma concentrations of neurofilament light chain.Methods:Diffusion MRI scans were collected on cognitively normal participants (CN), patients with early mild cognitive impairment (EMCI), late mild cognitive impairment (LMCI), and AD. Free water (FW) and FW-corrected fractional anisotropy were calculated in the locus coeruleus to transentorhinal cortex tract, four magnocellular regions of the basal forebrain (e.g. nucleus basalis of Meynert), entorhinal cortex, and hippocampus. All patients underwent a battery of cognitive assessments; neurofilament light chain levels were measured in plasma samples.Results:FW was significantly higher in EMCI compared to CN in the locus coeruleus to transentorhinal cortex tract, nucleus basalis of Meynert, and hippocampus (mean Cohen d = 0.54; pfdr<0.05). FW was significantly higher in AD compared to CN in all the examined regions (mean Cohen d = 1.41; pfdr<0.01). Additionally, FW in the hippocampus, entorhinal cortex, nucleus basalis of Meynert, and locus coeruleus to transentorhinal cortex tract positively correlated with all five cognitive impairment metrics, and neurofilament light chain levels (mean r2 = 0.10; pfdr<0.05).Conclusions:These results show that higher FW is associated with greater clinical diagnosis severity, cognitive impairment, and neurofilament light chain. They also suggest that FW elevation occurs in the locus coeruleus to transentorhinal cortex tract, nucleus basalis of Meynert, and hippocampus in the transition from CN to EMCI, while other basal forebrain regions and the entorhinal cortex are not affected until a later stage of AD. FW is a clinically relevant and non-invasive early marker of structural changes related to cognitive impairment.

scholarly journals Cerebrospinal fluid neurofilament light chain tracks cognitive impairment in multiple sclerosis

2019 ◽  
Vol 266 (9) ◽  
pp. 2157-2163 ◽  
Author(s):  
Lorenzo Gaetani ◽  
Nicola Salvadori ◽  
Viviana Lisetti ◽  
Paolo Eusebi ◽  
Andrea Mancini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Light Chain ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

scholarly journals Peran Neurofilament Light Chain sebagai Biomarker Prediktor Risiko Cognitive Impairment pada Penderita Chronic Kidney Disease

2019 ◽  
Vol 2 (3) ◽  
pp. 7-8
Author(s):  
Nella Rosyalina Damayanti ◽  
Divayari Gardiani
Keyword(s):  
Chronic Kidney Disease ◽  
Cognitive Impairment ◽  
Kidney Disease ◽  
Single Molecule ◽  
Light Chain ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

Latar Belakang: Chronic Kidney Disease (CKD) dapat menyebabkan cognitive impairment yang dapat menurunkan kualitas hidup dan kesejahteraan emosional pasien. Neurofilament Light Chain (NF-L) merupakan protein yang terletak di aksoplasma yang berperan menjaga struktur neuron. Diskusi: Defisit kognitif yang terjadi pada pasien dengan CKD diakibatkan toksin uremik yang menyebabkan cedera saraf. Prevalensi defisit kognitif berkisar 20-50% pada pasien CKD moderat dan 70% pada pasien CKD berat/ menjalani dialisis. Penurunan fungsi kognitif memiliki korelasi positif dengan penurunan eGFR pada pasien CKD. Kadar NF-L serum ditemukan mengalami peningkatan pada pasien setelah cedera akut pada otak seperti iskemia, perdarahan, dan pada pasien dengan penyakit neurodegeneratif seperti Alzheimer, dibandingkan pada individu sehat. Kadar NF-L serum dapat dideteksi dengan menggunakan pengujian single molecule array (Simoa). Simpulan: Pemeriksaan NF-L dapat dijadikan biomarker terjadinya defisit kognitif pada pasien CKD. Kata Kunci: Chronic Kidney Disease, Neurofilament Light Chain, Fungsi Kognitif, Biomarker

scholarly journals Elevated Levels of Serum Neurofilament Light Chain Associated with Cognitive Impairment in Vascular Dementia

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Weibin Ma ◽  
Jingjing Zhang ◽  
Jialei Xu ◽  
Depeng Feng ◽  
Xiaoling Wang ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Vascular Dementia ◽  
Single Molecule ◽  
Light Chain ◽  
Peripheral Blood ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Biochemical Characteristics ◽  
Significant Difference

Objective. Vascular dementia (VaD) is a progressive neurodegenerative disease with cognitive decline caused by cerebrovascular factors. Despite the great progress made in the past decade, VaD still lacks effective treatments and peripheral blood biomarkers. In this study, we tested the level of peripheral blood neurofilament light chain (NfL) in VaD patients and explored its relationship with cognitive impairment. Method. A total of 176 study subjects including 80 normal controls (NC) and 96 VaD patients were included in our study. Upon admission, we collected clinical and biochemical characteristics of all research subjects. We also evaluate the Montreal cognitive assessment scale (MoCA) scores of all subjects. The serum NfL level was measured by the single-molecule array (Simoa) method. Results. The years of education in the NC group and VaD group were ( 11.65 ± 3.04 ) years and ( 10.53 ± 3.87 ) years, respectively. Compared with VaD patients, the NC group has a higher level of education ( p = 0.037 ). Furthermore, the results of Simoa indicated that VaD subjects had higher serum NfL levels compared with the NC group [( 8.49 ± 2.37 ) pg/ml vs. ( 19.26 ± 4.71 ) pg/ml, p < 0.001 ]. In terms of other clinical and biochemical characteristics, there was no significant difference between VaD and NC. The Spearman correlation analysis indicated that educational years have a significant positive correlation with MoCA scores ( r = 0.238 , p = 0.041 ), while age and serum NfL levels have a significantly negative correlation with MoCA scores (age: r = − 0.213 , p = 0.040 ; NfL: r = − 0.395 , p = 0.027 ). However, further multiple regression analysis showed that only serum NfL level might serve as an independent risk factor for cognitive decline in VaD ( β = 0.317 , p = 0.021 ). Conclusion. The serum NfL levels in VaD subjects are significantly elevated, which may be used as a potential peripheral blood marker for predicting cognitive impairment in patients with VaD.

Combination of Plasma Neurofilament Light Chain and Mini-Mental State Examination Score Predicts Progression from Mild Cognitive Impairment to Alzheimer’s Disease within 5 Years

2021 ◽  
pp. 1-14
Author(s):  
Nicolas Darmanthé ◽  
Hossein Tabatabaei-Jafari ◽  
Nicolas Cherbuin ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Light Chain ◽  
Mental State ◽  
Mini Mental State Examination ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Risk Of Progression ◽  
State Examination

Background: Individuals with mild cognitive impairment (MCI) are at high risk of progression to Alzheimer’s disease (AD) dementia, but some remain stable. There is a need to identify those at higher risk of progression to improve patient management and outcomes. Objective: To evaluate the trajectory of plasma neurofilament light chain (pNFL) prior to progression from MCI to AD dementia, the performance of pNFL, in combination with the Mini-Mental State Examination (MMSE), as a predictor of progression from MCI to AD dementia and to inform clinicians on the use of pNFL as a predictive biomarker. Methods: Participants (n = 440) with MCI and longitudinal follow-up (mean = 4.2 years) from the AD Neuroimaging Initiative dataset were included. pNFL as a marker for neurodegeneration and the MMSE as a cognitive measure were investigated as simple/practical predictors of progression. The risk of progressing from MCI to AD dementia associated with pNFL and MMSE scores was assessed using Cox and logistic regression models. Results: The current risk of progression to AD dementia was 37%higher in individuals with high pNFL (>  56 ng/L) compared to those with average pNFL (≤40 ng/L). A combination of baseline pNFL and MMSE could differentiate those who progressed within 5 years (AUC = 0.75) from stable individuals. Including change in MMSE over 6-12 months further improved the model (AUC = 0.84). Conclusion: Our findings reveal that combining pNFL with a simple dementia screener (MMSE) can reliably predict whether a person with MCI is likely to progress to AD dementia within 5 years.

scholarly journals CSF Biomarkers Reflecting Protein Pathology and Axonal Degeneration Are Associated with Memory, Attentional, and Executive Functioning in Early-Stage Parkinson′s Disease

2020 ◽  
Vol 21 (22) ◽  
pp. 8519
Author(s):  
Linda P. Oosterveld ◽  
Tessa I. Kuiper ◽  
Nour K. Majbour ◽  
Inge M. W. Verberk ◽  
Karin D. van Dijk ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Executive Functioning ◽  
Light Chain ◽  
Early Stage ◽  
Csf Biomarkers ◽  
Phosphorylated Tau ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Cognitive Domains ◽  
Csf Biomarker

In early-stage Parkinson′s disease (PD), cognitive impairment is common, and a variety of cognitive domains including memory, attention, and executive functioning may be affected. Cerebrospinal fluid (CSF) biomarkers are potential markers of cognitive functioning. We aimed to explore whether CSF α-synuclein species, neurofilament light chain, amyloid-β42, and tau are associated with cognitive performance in early-stage PD patients. CSF levels of total-α-synuclein and phosphorylated-α-synuclein, neurofilament light chain, amyloid-β42, and total-tau and phosphorylated-tau were measured in 26 PD patients (disease duration ≤5 years and Hoehn and Yahr stage 1–2.5). Multivariable linear regression models, adjusted for age, gender, and educational level, were used to assess the relationship between CSF biomarker levels and memory, attention, executive and visuospatial function, and language performance scores. In 26 early-stage PD patients, attention and memory were the most commonly affected domains. A higher CSF phosphorylated-α-synuclein/total-α-synuclein ratio was associated with better executive functioning (sβ = 0.40). Higher CSF neurofilament light was associated with worse memory (sβ = −0.59), attentional (sβ = −0.32), and executive functioning (sβ = −0.35). Reduced CSF amyloid-β42 levels were associated with poorer attentional functioning (sβ = 0.35). Higher CSF phosphorylated-tau was associated with worse language functioning (sβ = −0.33). Thus, CSF biomarker levels, in particular neurofilament light, were related to the most commonly affected cognitive domains in early-stage PD. This indicates that CSF biomarker levels may identify early-stage PD patients who are at an increased risk of developing cognitive impairment.

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