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@ARTICLE{Coors:276820,
author = {Coors, Annabell and Bönniger, Meta-Miriam and Santos,
Marina and Lohner, Valerie and Koch, Alexandra and Ettinger,
Ulrich and Aziz, N Ahmad and Breteler, Monique M B},
title = {{A}ssociations of {P}lasma {N}eurofilament {L}ight {L}evels
{W}ith {B}rain {M}icrostructure and {M}acrostructure and
{C}ognition in the {C}ommunity-{B}ased {R}hineland {S}tudy.},
journal = {Neurology},
volume = {104},
number = {6},
issn = {0028-3878},
address = {Philadelphia, Pa.},
publisher = {Wolters Kluwer},
reportid = {DZNE-2025-00333},
pages = {e210278},
year = {2025},
abstract = {Plasma neurofilament light chain (NfL) level is a sensitive
yet aspecific marker of neurodegeneration. Its
neuroanatomical and functional correlates in the general
population are not fully elucidated. We thus assessed how
brain's macrostructures and microstructures and cognitive
function are related to plasma NfL levels in cognitively
unimpaired adults over a wide age range.Our analyses were
based on cross-sectional data from the Rhineland Study, a
community-based prospective cohort study. This study
includes people from the age of 30 onwards who live in 2
geographically defined areas in Bonn, Germany, and have
sufficient command of the German language. Plasma NfL levels
were measured using the Simoa platform and then
log-transformed and adjusted for plate position, batch
number, and Analyzer (HD-1 or HD-X). Brain imaging data were
collected on a 3 Tesla scanner and included volumetric
measures, metrics of the diffusion tensor and the neurite
orientation dispersion and density imaging model, and white
matter hyperintensity load. Memory performance, processing
speed, and executive function were assessed using
traditional cognitive tasks and an eye movement battery. We
used multivariable regression models to assess the relations
between brain structure and plasma NfL levels and between
plasma NfL levels and cognitive performance.The study sample
consisted of 5,589 participants aged 30-95 years (mean age
55 ± 13.7 years, $56.1\%$ women) without neurodegenerative
diseases. Higher plasma NfL levels were associated with
lower isotropic volume fraction (-0.030; $95\%$ CI -0.051 to
-0.010; pFDR = 0.011), lower neurite density index (ß =
-0.031; $95\%$ CI -0.053 to -0.008; pFDR = 0.014), and
higher axial diffusivity (ß = 0.037; $95\%$ CI 0.013-0.062;
p = 0.005; pFDR = 0.011). The strongest association was with
the orientation dispersion index (ß = -0.063; $95\%$ CI
-0.085 to -0.041; pFDR < 0.001). Furthermore, higher plasma
NfL levels tended to be associated with a lower processing
speed domain score (ß = -0.046; $95\%$ CI -0.084 to -0.009;
p = 0.014; pFDR = 0.056) and longer prosaccade latency (ß =
0.039; $95\%$ CI 0.000-0.078; p = 0.049; pFDR =
0.480).Higher plasma NfL levels mainly reflect worse white
matter microstructural integrity, especially lower axonal
density, in a relatively healthy, community-based sample.
This suggests that plasma NfL levels allow for early
detection of subtle differences in brain microstructure.},
keywords = {Humans / Male / Female / Middle Aged / Neurofilament
Proteins: blood / Aged / Cognition: physiology /
Cross-Sectional Studies / Brain: diagnostic imaging / Adult
/ Aged, 80 and over / Germany / Prospective Studies /
Neuropsychological Tests / White Matter: diagnostic imaging
/ White Matter: pathology / Cohort Studies / Biomarkers:
blood / Neurofilament Proteins (NLM Chemicals) /
neurofilament protein L (NLM Chemicals) / Biomarkers (NLM
Chemicals)},
cin = {AG Breteler / AG Aziz},
ddc = {610},
cid = {I:(DE-2719)1012001 / I:(DE-2719)5000071},
pnm = {354 - Disease Prevention and Healthy Aging (POF4-354)},
pid = {G:(DE-HGF)POF4-354},
experiment = {EXP:(DE-2719)Rhineland Study-20190321},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39977717},
doi = {10.1212/WNL.0000000000210278},
url = {https://pub.dzne.de/record/276820},
}