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

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      Disease Markers
      Hindawi

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          Abstract

          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.

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          Most cited references33

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          Neurofilaments as biomarkers in neurological disorders

          Neuroaxonal damage is the pathological substrate of permanent disability in various neurological disorders. Reliable quantification and longitudinal follow-up of such damage are important for assessing disease activity, monitoring treatment responses, facilitating treatment development and determining prognosis. The neurofilament proteins have promise in this context because their levels rise upon neuroaxonal damage not only in the cerebrospinal fluid (CSF) but also in blood, and they indicate neuroaxonal injury independent of causal pathways. First-generation (immunoblot) and second-generation (enzyme-linked immunosorbent assay) neurofilament assays had limited sensitivity. Third-generation (electrochemiluminescence) and particularly fourth-generation (single-molecule array) assays enable the reliable measurement of neurofilaments throughout the range of concentrations found in blood samples. This technological advancement has paved the way to investigate neurofilaments in a range of neurological disorders. Here, we review what is known about the structure and function of neurofilaments, discuss analytical aspects and knowledge of age-dependent normal ranges of neurofilaments and provide a comprehensive overview of studies on neurofilament light chain as a marker of axonal injury in different neurological disorders, including multiple sclerosis, neurodegenerative dementia, stroke, traumatic brain injury, amyotrophic lateral sclerosis and Parkinson disease. We also consider work needed to explore the value of this axonal damage marker in managing neurological diseases in daily practice.
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            Association of Plasma Neurofilament Light With Neurodegeneration in Patients With Alzheimer Disease

            Question What is the importance of plasma neurofilament light in Alzheimer disease? Findings In this case-control study of 193 cognitively healthy controls, 197 patients with mild cognitive impairment, and 180 patients with Alzheimer disease dementia, plasma neurofilament light was associated with Alzheimer disease and correlated with future progression of cognitive decline, brain atrophy, and brain hypometabolism. Meaning Plasma neurofilament light may be a promising noninvasive biomarker for Alzheimer disease. Importance Existing cerebrospinal fluid (CSF) or imaging (tau positron emission tomography) biomarkers for Alzheimer disease (AD) are invasive or expensive. Biomarkers based on standard blood test results would be useful in research, drug development, and clinical practice. Plasma neurofilament light (NFL) has recently been proposed as a blood-based biomarker for neurodegeneration in dementias. Objective To test whether plasma NFL concentrations are increased in AD and associated with cognitive decline, other AD biomarkers, and imaging evidence of neurodegeneration. Design, Setting, and Participants In this prospective case-control study, an ultrasensitive assay was used to measure plasma NFL concentration in 193 cognitively healthy controls, 197 patients with mild cognitive impairment (MCI), and 180 patients with AD dementia from the Alzheimer’s Disease Neuroimaging Initiative. The study dates were September 7, 2005, to February 13, 2012. The plasma NFL analysis was performed in September 2016. Main Outcomes and Measures Associations were tested between plasma NFL and diagnosis, Aβ pathologic features, CSF biomarkers of neuronal injury, cognition, brain structure, and metabolism. Results Among 193 cognitively healthy controls, 197 patients with mild cognitive impairment, and 180 patients with AD with dementia, plasma NFL correlated with CSF NFL (Spearman ρ = 0.59, P  < .001). Plasma NFL was increased in patients with MCI (mean, 42.8 ng/L) and patients with AD dementia (mean, 51.0 ng/L) compared with controls (mean, 34.7 ng/L) ( P  < .001) and had high diagnostic accuracy for patients with AD with dementia vs controls (area under the receiver operating characteristic curve, 0.87, which is comparable to established CSF biomarkers). Plasma NFL was particularly high in patients with MCI and patients with AD dementia with Aβ pathologic features. High plasma NFL correlated with poor cognition and AD-related atrophy (at baseline and longitudinally) and with brain hypometabolism (longitudinally). Conclusions and Relevance Plasma NFL is associated with AD diagnosis and with cognitive, biochemical, and imaging hallmarks of the disease. This finding implies a potential usefulness for plasma NFL as a noninvasive biomarker in AD. This case-control study compares patients with mild cognitive impairment, patients with AD dementia, and cognitively healthy patients to test whether plasma neurofilament light concentrations are increased in patients with AD and associated with cognitive decline, other AD biomarkers, and imaging evidence of neurodegeneration.
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              Vascular dementia.

              Vascular dementia is one of the most common causes of dementia after Alzheimer's disease, causing around 15% of cases. However, unlike Alzheimer's disease, there are no licensed treatments for vascular dementia. Progress in the specialty has been difficult because of uncertainties over disease classification and diagnostic criteria, controversy over the exact nature of the relation between cerebrovascular pathology and cognitive impairment, and the paucity of identifiable tractable treatment targets. Although there is an established relation between vascular and degenerative Alzheimer's pathology, the mechanistic link between the two has not yet been identified. This Series paper critiques some of the key areas and controversies, summarises treatment trials so far, and makes suggestions for what progress is needed to advance our understanding of pathogenesis and thus maximise opportunities for the search for new and effective management approaches.
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                Author and article information

                Contributors
                Journal
                Dis Markers
                Dis Markers
                DM
                Disease Markers
                Hindawi
                0278-0240
                1875-8630
                2020
                1 November 2020
                : 2020
                : 6612871
                Affiliations
                Department of Neurology, Liaocheng People's Hospital, Liaocheng, Shandong, China 252000
                Author notes

                Academic Editor: Wen-Jun Tu

                Author information
                https://orcid.org/0000-0001-6919-0883
                Article
                10.1155/2020/6612871
                7652600
                33204362
                d8dcc49e-c8d2-4cae-ba7a-495c2b5368e0
                Copyright © 2020 Weibin Ma et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 October 2020
                : 20 October 2020
                : 22 October 2020
                Funding
                Funded by: Department of Neurology, Liaocheng People's Hospital
                Categories
                Research Article

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