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Serum NfL in Alzheimer Dementia: Results of the Prospective Dementia Registry Austria

Background and Objectives: The neurofilament light chain (NfL) is a biomarker for neuro-axonal injury in various acute and chronic neurological disorders, including Alzheimer’s disease (AD). We here investigated the cross-sectional and longitudinal associations between baseline serum NfL (sNfL) leve...

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Autores principales: Kern, Daniela, Khalil, Michael, Pirpamer, Lukas, Buchmann, Arabella, Hofer, Edith, Dal-Bianco, Peter, Stögmann, Elisabeth, Scherfler, Christoph, Benke, Thomas, Ransmayr, Gerhard, Schmidt, Reinhold
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955532/
https://www.ncbi.nlm.nih.gov/pubmed/35334608
http://dx.doi.org/10.3390/medicina58030433
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author Kern, Daniela
Khalil, Michael
Pirpamer, Lukas
Buchmann, Arabella
Hofer, Edith
Dal-Bianco, Peter
Stögmann, Elisabeth
Scherfler, Christoph
Benke, Thomas
Ransmayr, Gerhard
Schmidt, Reinhold
author_facet Kern, Daniela
Khalil, Michael
Pirpamer, Lukas
Buchmann, Arabella
Hofer, Edith
Dal-Bianco, Peter
Stögmann, Elisabeth
Scherfler, Christoph
Benke, Thomas
Ransmayr, Gerhard
Schmidt, Reinhold
author_sort Kern, Daniela
collection PubMed
description Background and Objectives: The neurofilament light chain (NfL) is a biomarker for neuro-axonal injury in various acute and chronic neurological disorders, including Alzheimer’s disease (AD). We here investigated the cross-sectional and longitudinal associations between baseline serum NfL (sNfL) levels and cognitive, behavioural as well as MR volumetric findings in the Prospective Dementia Registry Austria (PRODEM-Austria). Materials and Methods: All participants were clinically diagnosed with AD according to NINCDS-ADRDA criteria and underwent a detailed clinical assessment, cognitive testing (including the Mini Mental State Examination (MMSE) and the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD)), the neuropsychiatric inventory (NPI) and laboratory evaluation. A total of 237 patients were included in the study. Follow-up examinations were done at 6 months, 1 year and 2 years with 93.3% of patients undergoing at least one follow-up. We quantified sNfL by a single molecule array (Simoa). In a subgroup of 125 subjects, brain imaging data (1.5 or 3T MRI, with 1 mm isotropic resolution) were available. Brain volumetry was assessed using the FreeSurfer image analysis suite (v6.0). Results: Higher sNfL concentrations were associated with worse performance in cognitive tests at baseline, including CERAD (B = −10.084, SE = 2.999, p < 0.001) and MMSE (B = −3.014, SE = 1.293, p = 0.021). The sNfL levels also correlated with the presence of neuropsychiatric symptoms (NPI total score: r = 0.138, p = 0.041) and with smaller volumes of the temporal lobe (B = −0.012, SE = 0.003, p = 0.001), the hippocampus (B = −0.001, SE = 0.000201, p = 0.013), the entorhinal (B = −0.000308, SE = 0.000124, p = 0.014), and the parahippocampal cortex (B = −0.000316, SE = 0.000113, p = 0.006). The sNfL values predicted more pronounced cognitive decline over the mean follow-up period of 22 months, but there were no significant associations with respect to change in neuropsychiatric symptoms and brain volumetric measures. Conclusions: the sNfL levels relate to cognitive, behavioural, and imaging hallmarks of AD and predicts short term cognitive decline.
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spelling pubmed-89555322022-03-26 Serum NfL in Alzheimer Dementia: Results of the Prospective Dementia Registry Austria Kern, Daniela Khalil, Michael Pirpamer, Lukas Buchmann, Arabella Hofer, Edith Dal-Bianco, Peter Stögmann, Elisabeth Scherfler, Christoph Benke, Thomas Ransmayr, Gerhard Schmidt, Reinhold Medicina (Kaunas) Article Background and Objectives: The neurofilament light chain (NfL) is a biomarker for neuro-axonal injury in various acute and chronic neurological disorders, including Alzheimer’s disease (AD). We here investigated the cross-sectional and longitudinal associations between baseline serum NfL (sNfL) levels and cognitive, behavioural as well as MR volumetric findings in the Prospective Dementia Registry Austria (PRODEM-Austria). Materials and Methods: All participants were clinically diagnosed with AD according to NINCDS-ADRDA criteria and underwent a detailed clinical assessment, cognitive testing (including the Mini Mental State Examination (MMSE) and the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD)), the neuropsychiatric inventory (NPI) and laboratory evaluation. A total of 237 patients were included in the study. Follow-up examinations were done at 6 months, 1 year and 2 years with 93.3% of patients undergoing at least one follow-up. We quantified sNfL by a single molecule array (Simoa). In a subgroup of 125 subjects, brain imaging data (1.5 or 3T MRI, with 1 mm isotropic resolution) were available. Brain volumetry was assessed using the FreeSurfer image analysis suite (v6.0). Results: Higher sNfL concentrations were associated with worse performance in cognitive tests at baseline, including CERAD (B = −10.084, SE = 2.999, p < 0.001) and MMSE (B = −3.014, SE = 1.293, p = 0.021). The sNfL levels also correlated with the presence of neuropsychiatric symptoms (NPI total score: r = 0.138, p = 0.041) and with smaller volumes of the temporal lobe (B = −0.012, SE = 0.003, p = 0.001), the hippocampus (B = −0.001, SE = 0.000201, p = 0.013), the entorhinal (B = −0.000308, SE = 0.000124, p = 0.014), and the parahippocampal cortex (B = −0.000316, SE = 0.000113, p = 0.006). The sNfL values predicted more pronounced cognitive decline over the mean follow-up period of 22 months, but there were no significant associations with respect to change in neuropsychiatric symptoms and brain volumetric measures. Conclusions: the sNfL levels relate to cognitive, behavioural, and imaging hallmarks of AD and predicts short term cognitive decline. MDPI 2022-03-16 /pmc/articles/PMC8955532/ /pubmed/35334608 http://dx.doi.org/10.3390/medicina58030433 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kern, Daniela
Khalil, Michael
Pirpamer, Lukas
Buchmann, Arabella
Hofer, Edith
Dal-Bianco, Peter
Stögmann, Elisabeth
Scherfler, Christoph
Benke, Thomas
Ransmayr, Gerhard
Schmidt, Reinhold
Serum NfL in Alzheimer Dementia: Results of the Prospective Dementia Registry Austria
title Serum NfL in Alzheimer Dementia: Results of the Prospective Dementia Registry Austria
title_full Serum NfL in Alzheimer Dementia: Results of the Prospective Dementia Registry Austria
title_fullStr Serum NfL in Alzheimer Dementia: Results of the Prospective Dementia Registry Austria
title_full_unstemmed Serum NfL in Alzheimer Dementia: Results of the Prospective Dementia Registry Austria
title_short Serum NfL in Alzheimer Dementia: Results of the Prospective Dementia Registry Austria
title_sort serum nfl in alzheimer dementia: results of the prospective dementia registry austria
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955532/
https://www.ncbi.nlm.nih.gov/pubmed/35334608
http://dx.doi.org/10.3390/medicina58030433
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