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@ARTICLE{Steinacker:140376,
author = {Steinacker, Petra and Anderl-Straub, Sarah and
Diehl-Schmid, Janine and Semler, Elisa and Uttner, Ingo and
von Arnim, Christine A F and Barthel, Henryk and Danek,
Adrian and Fassbender, Klaus and Fliessbach, Klaus and
Foerstl, Hans and Grimmer, Timo and Huppertz, Hans-Jürgen
and Jahn, Holger and Kassubek, Jan and Kornhuber, Johannes
and Landwehrmeyer, Bernhard and Lauer, Martin and Maler,
Juan Manuel and Mayer, Benjamin and Oeckl, Patrick and
Prudlo, Johannes and Schneider, Anja and Volk, Alexander E
and Wiltfang, Jens and Schroeter, Matthias L and Ludolph,
Albert C and Otto, Markus and group, FTLDc study and
Albrecht, Franziska and Bisenius, Sandrine and Feneberg,
Emily and Haefner, Sibylle and Kasper, Elisabeth and
Kurzwelly, Delia and Lampe, Leonie and Levin, Johannes and
Lornsen, Finn and Luley, Maxine and Oberstein, Timo and
Pellkofer, Hannah and Prix, Catharina and
Richter-Schmidinger, Tanja and Roth, Nina and Sabri, Osama
and Schachner, Lisa and Schomburg, Robert and Schönecker,
Sonja and Schuemberg, Katharina and Spottke, Annika and
Teipel, Stefan and Wilken, Petra and Zech, Heike},
title = {{S}erum neurofilament light chain in behavioral variant
frontotemporal dementia.},
journal = {Neurology},
volume = {91},
number = {15},
issn = {0028-3878},
address = {[S.l.]},
publisher = {Ovid},
reportid = {DZNE-2020-06698},
pages = {e1390-e1401},
year = {2018},
abstract = {Objective: To determine the association of serum
neurofilament light chain (NfL) with functional
deterioration and brain atrophy during follow-up of patients
with behavioral variant frontotemporal dementia
(bvFTD).Methods: Blood NfL levels from 74 patients with
bvFTD, 26 with Alzheimer disease (AD), 17 with mild
cognitive impairment (MCI), and 15 healthy controls (Con) at
baseline and follow-up were determined and analyzed for the
diagnostic potential in relation to functional assessment
(Clinical Dementia Rating Scale Sum of Boxes [CDR-SOB],
frontotemporal lobar degeneration–related CDR-SOB,
Mini-Mental State Examination [MMSE]) and brain
volumetry.Results: At baseline, serum NfL level correlated
with CSF NfL (bvFTD r = 0.706, p < 0.0001; AD/MCI r = 0.666,
p = 0.0003). Highest serum levels were observed in bvFTD (p
<0 0.0001 vs Con and MCI, p = 0.0078 vs AD, respectively).
Discrimination of bvFTD from Con/MCI/AD was possible with
$91\%/74\%/74\%$ sensitivity and $79\%/74\%/58\%$
specificity. At follow-up, serum NfL increased in bvFTD and
AD (p = 0.0039 and p = 0.0006, respectively). At baseline
and follow-up, NfL correlated with functional scores of
patients with bvFTD (e.g., CDR-SOB [baseline] r = 0.4157, p
= 0.0006; [follow-up] r = 0.5629, p < 0.0001) and with
atrophy in the gray and white matter of many brain regions
including frontal and subcortical areas (e.g., frontal lobe:
r = −0.5857, p < 0.0001; $95\%$ confidence interval
−0.7415 to −0.3701). For patients with AD/MCI, NfL
correlated with the functional performance as well (e.g.,
CDR-SOB [baseline] r = 0.6624, p < 0.0001; [follow-up] r =
0.5659, p = 0.0003) but not with regional brain
volumes.Conclusions: As serum NfL correlates with functional
impairment and brain atrophy in bvFTD at different disease
stages, we propose it as marker of disease severity, paving
the way for its future use as outcome measure for clinical
trials.Classification of evidence: This study provides Class
III evidence that for patients with cognitive problems,
serum NfL concentration discriminates bvFTD from other forms
of dementia.},
keywords = {Aged / Alzheimer Disease: blood / Alzheimer Disease:
cerebrospinal fluid / Alzheimer Disease: diagnostic imaging
/ Alzheimer Disease: genetics / Atrophy / Biomarkers: blood
/ Biomarkers: cerebrospinal fluid / Brain: pathology /
Cognitive Dysfunction: blood / Cognitive Dysfunction:
cerebrospinal fluid / Cognitive Dysfunction: diagnostic
imaging / Cognitive Dysfunction: genetics / Diagnosis,
Differential / Disease Progression / Female / Follow-Up
Studies / Frontotemporal Dementia: blood / Frontotemporal
Dementia: diagnostic imaging / Frontotemporal Dementia:
genetics / Frontotemporal Dementia: pathology / Humans /
Male / Middle Aged / Mutation / Neurofilament Proteins:
blood / Organ Size / Prospective Studies / Biomarkers (NLM
Chemicals) / Neurofilament Proteins (NLM Chemicals) /
neurofilament protein L (NLM Chemicals)},
cin = {AG Teipel / AG Wiltfang},
ddc = {610},
cid = {I:(DE-2719)1510100 / I:(DE-2719)1410006},
pnm = {344 - Clinical and Health Care Research (POF3-344) / 342 -
Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-344 / G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30209235},
doi = {10.1212/WNL.0000000000006318},
url = {https://pub.dzne.de/record/140376},
}