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Differential Impact of Neurofilament Light Subunit on Cognition and Functional Outcome in Memory Clinic Patients with and without Vascular Burden

Journal article
Authors Sindre Rolstad
Anne Ingeborg Berg
Carl Eckerström
Boo Johansson
Anders Wallin
Published in Journal of Alzheimers Disease
Volume 45
Issue 3
Pages 873-881
ISSN 1387-2877
Publication year 2015
Published at Institute of Neuroscience and Physiology
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Department of Psychology
Pages 873-881
Language en
Links dx.doi.org/10.3233/jad-142694
Keywords Amyloid-beta(1-42), cerebrospinal fluid, cognition, dementia, mild cognitive impairment, CEREBROSPINAL-FLUID BIOMARKERS, WHITE-MATTER CHANGES, ALZHEIMER-DISEASE, CSF BIOMARKERS, DIAGNOSTIC-CRITERIA, PROTEIN-LEVELS, DEMENTIA, IMPAIRMENT, DECLINE, PROFILES
Subject categories Neurology

Abstract

The neurofilament light (NF-L) subunit is mainly expressed in large-caliber myelinated axons, and elevated concentrations in the cerebrospinal fluid (CSF) are correlated with damage to white matter and subcortical regions. Because the correlation between NF-L and cognition and functional impairment is largely unknown, we investigated associations in patients (n = 622) with (n = 199) and without (n = 423) vascular burden in subjective cognitive impairment (SCI, n = 168), mild cognitive impairment (MCI, n = 261), and dementia (n = 193). Patients were staged according to disease severity and the presence/absence of cerebrovascular disease. CSF amyloid-beta(1-42) (A beta(1-42))was included in all models due to its concomitant influence on vascular and primary etiology. Linear regression was used to assess associations between NF-L and A beta(1-42) and five cognitive domains of a comprehensive neuropsychological battery as well as with functional impairment using the Clinical Dementia Rating. Changes in these outcomes at the 2-year follow-up were also evaluated. In SCI and MCI patients with vascular burden, higher NF-L concentrations were associated with baseline cognitive performance (beta = -0.38 to -0.58) and executive decline (beta = -0.44). Lower A beta(1-42) levels were associated with worse cognitive performance in dementia (beta = 0.46 to 0.51). In MCI and dementia patients without vascular burden, higher NF-L (beta = -0.30 to -0.34) and lower A beta(1-42) concentrations (beta = 0.30) were associated with reduced cognitive performance. Higher NF-L concentrations (beta = -0.26) were associated with functional decline in patients with vascular burden. CSF NF-L is associated with cognition in patients with and without vascular etiology. These associations were greater in pre-dementia phases in those with vascular etiology and vice versa in those without vascular burden.

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