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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},
}