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@ARTICLE{Lu:162239,
      author       = {Lu, Ran and Aziz, N Ahmad and Reuter, Martin and Stöcker,
                      Tony and Breteler, Monique M B},
      title        = {{E}valuation of the {N}euroanatomical {B}asis of
                      {O}lfactory {D}ysfunction in the {G}eneral {P}opulation},
      journal      = {JAMA otolaryngology - head $\&$ neck surgery},
      volume       = {147},
      number       = {10},
      issn         = {2168-6181},
      address      = {Chicago, Ill.},
      publisher    = {American Medical Association},
      reportid     = {DZNE-2021-01293},
      pages        = {855 - 863},
      year         = {2021},
      abstract     = {Olfactory dysfunction is a prodromal manifestation of many
                      neurodegenerative disorders, including Alzheimer and
                      Parkinson disease. However, its neuroanatomical basis is
                      largely unknown.To assess the association between olfactory
                      brain structures and olfactory function in adults 30 years
                      or older and to examine the extent to which olfactory bulb
                      volume (OBV) mediates the association between central
                      olfactory structures and olfactory function.This
                      cross-sectional study analyzed baseline data from the first
                      639 participants with brain magnetic resonance imaging (MRI)
                      in the Rhineland Study, an ongoing population-based cohort
                      study in Bonn, Germany. Participants were enrolled between
                      March 7, 2016, and October 31, 2017, and underwent brain MRI
                      and olfactory assessment. Data were analyzed from March 1,
                      2018, to June 30, 2021.Volumetric measures were derived from
                      3-T MRI T1-weighted brain scans, and OBV was manually
                      segmented on T2-weighted images. The mean volumetric brain
                      measures from the right and left sides were calculated,
                      adjusted by head size, and normalized to all
                      participants.Performance on the 12-item smell identification
                      test (SIT-12) was used as a proxy for olfactory function.A
                      total of 541 participants with complete data on MRI-derived
                      measures and SIT-12 scores were included. This population
                      had a mean (SD) age of 53.6 (13.1) years and comprised 306
                      women $(56.6\%).$ Increasing age (difference in SIT-12
                      score, -0.04; $95\%$ CI, -0.05 to -0.03), male sex (-0.26;
                      $95\%$ CI, -0.54 to 0.02), and nasal congestion (-0.28;
                      $95\%$ CI, -0.66 to 0.09) were associated with worse
                      olfactory function (SIT-12 scores). Conversely, larger OBV
                      was associated with better olfactory function (difference in
                      SIT-12 score, 0.46; $95\%$ CI, 0.29-0.64). Larger volumes of
                      amygdala (difference in OBV, 0.12; $95\%$ CI, 0.01-0.24),
                      hippocampus (0.16; $95\%$ CI, 0.04-0.28), insular cortex
                      (0.12; $95\%$ CI, 0.01-0.24), and medial orbitofrontal
                      cortex (0.10; $95\%$ CI, 0.00-0.20) were associated with
                      larger OBV. Larger volumes of amygdala (volume × age
                      interaction effect, 0.17; $95\%$ CI, 0.03-0.30),
                      parahippocampal cortex (0.17; $95\%$ CI, 0.03-0.31), and
                      hippocampus (0.21; $95\%$ CI, 0.08-0.35) were associated
                      with better olfactory function only in older age groups. The
                      age-modified association between volumes of central
                      olfactory structures and olfactory function was largely
                      mediated through OBV.This cross-sectional study found that
                      olfactory bulb volume was independently associated with odor
                      identification function and was a robust mediator of the
                      age-dependent association between volumes of central
                      olfactory structures and olfactory function. Thus,
                      neurodegeneration-associated olfactory dysfunction may
                      primarily originate from the pathology of peripheral
                      olfactory structures, suggesting that OBV may serve as a
                      preclinical marker for the identification of individuals who
                      are at an increased risk of neurodegenerative diseases.},
      keywords     = {Adult / Aged / Amygdala: diagnostic imaging / Cerebral
                      Cortex: diagnostic imaging / Cross-Sectional Studies /
                      Female / Germany / Hippocampus: diagnostic imaging / Humans
                      / Magnetic Resonance Imaging / Male / Middle Aged /
                      Olfaction Disorders: diagnostic imaging / Olfaction
                      Disorders: physiopathology / Olfactory Bulb: diagnostic
                      imaging / Organ Size / Prefrontal Cortex: diagnostic
                      imaging},
      cin          = {AG Aziz / AG Reuter / AG Stöcker / AG Breteler},
      ddc          = {610},
      cid          = {I:(DE-2719)5000071 / I:(DE-2719)1040310 /
                      I:(DE-2719)1013026 / I:(DE-2719)1012001},
      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:34436517},
      pmc          = {pmc:PMC8391780},
      doi          = {10.1001/jamaoto.2021.2026},
      url          = {https://pub.dzne.de/record/162239},
}