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@ARTICLE{Liu:275864,
      author       = {Liu, Kathy Y and Betts, Matthew J and Hämmerer, Dorothea
                      and Düzel, Emrah and Mather, Mara and Roiser, Jonathan P
                      and Schneider, Anja and Spottke, Annika and Rostamzadeh,
                      Ayda and Schott, Björn H and Rauchmann, Boris Stephan and
                      Laske, Christoph and Janowitz, Daniel and Spruth, Eike Jakob
                      and Ersözlü, Ersin and Lüsebrink, Falk and Jessen, Frank
                      and Frommann, Ingo and Kilimann, Ingo and Wiltfang, Jens and
                      Brustkern, Johanna and Priller, Josef and Hellmann-Regen,
                      Julian David Nicolai and Buerger, Katharina and Fliessbach,
                      Klaus and Scheffler, Klaus and Kleineidam, Luca and Stark,
                      Melina and Ewers, Michael and Wagner, Michael and Peters,
                      Oliver and Dechent, Peter and Perneczky, Robert and
                      Sodenkamp, Sebastian and Hetzer, Stefan and Teipel, Stefan
                      and Glanz, Wenzel and Howard, Robert},
      title        = {{L}ocus coeruleus signal intensity and emotion regulation
                      in agitation in {A}lzheimer's disease.},
      journal      = {Brain communications},
      volume       = {7},
      number       = {1},
      issn         = {2632-1297},
      address      = {[Oxford]},
      publisher    = {Oxford University Press},
      reportid     = {DZNE-2025-00099},
      pages        = {fcae457},
      year         = {2025},
      abstract     = {Hyperphosphorylated tau accumulation is seen in the
                      noradrenergic locus coeruleus from the earliest stages of
                      Alzheimer's disease onwards and has been associated with
                      symptoms of agitation. It is hypothesized that compensatory
                      locus coeruleus-noradrenaline system overactivity and
                      impaired emotion regulation could underlie agitation
                      propensity, but to our knowledge this has not previously
                      been investigated. A better understanding of the
                      neurobiological underpinnings of agitation would help the
                      development of targeted prevention and treatment strategies.
                      Using a sample of individuals with amnestic mild cognitive
                      impairment and probable mild Alzheimer's disease dementia
                      from the German Center for Neurodegenerative Diseases
                      (DZNE)-Longitudinal Cognitive Impairment and Dementia
                      (DELCODE) study cohort (N = 309, aged 67-96 years, $51\%$
                      female), we assessed cross-sectional relationships between a
                      latent factor representing the functional integrity of an
                      affect-related executive regulation network and agitation
                      point prevalence and severity scores. In a subsample of
                      individuals with locus coeruleus MRI imaging data (N = 37,
                      aged 68-93 years, $49\%$ female), we also investigated
                      preliminary associations between locus coeruleus MRI
                      contrast ratios (a measure of structural integrity, whole or
                      divided into rostral, middle, and caudal thirds) and
                      individual affect-related regulation network factor scores
                      and agitation measures. Regression models controlled for
                      effects of age and clinical disease severity and, for models
                      including resting-state functional MRI connectivity
                      variables, grey matter volume and education years. Agitation
                      point prevalence showed a positive relationship with a
                      latent factor representing the functional integrity (and a
                      negative relationship with a corresponding structural
                      measure) of the affect-related executive regulation network.
                      Locus coeruleus MRI contrast ratios were positively
                      associated with agitation severity (but only for the rostral
                      third, in N = 13) and negatively associated with the
                      functional affect-related executive regulation latent factor
                      scores. Resting-state functional connectivity between a
                      medial prefrontal cortex region and the left amygdala was
                      related to locus coeruleus MRI contrast ratios. These
                      findings implicate the involvement of locus coeruleus
                      integrity and emotion dysregulation in agitation in
                      Alzheimer's disease and support the presence of potential
                      compensatory processes. At the neural level, there may be a
                      dissociation between mechanisms underlying agitation risk
                      per se and symptom severity. Further studies are needed to
                      replicate and extend these findings, incorporating
                      longitudinal designs, measures of autonomic function and
                      non-linear modelling approaches to explore potential causal
                      and context-dependent relationships across Alzheimer's
                      disease stages.},
      keywords     = {Alzheimer (Other) / agitation (Other) / autonomic (Other) /
                      emotion regulation (Other) / locus coeruleus (Other)},
      cin          = {AG Düzel / AG Schneider / AG Spottke / Clinical Research
                      Platform (CRP) / AG Fischer / AG Gasser / AG Dirnagl / AG
                      Jessen / AG Wagner / AG Teipel / AG Wiltfang / AG Endres /
                      AG Peters / AG Priller / Patient Studies (Bonn) / AG
                      Dichgans / ICRU},
      ddc          = {610},
      cid          = {I:(DE-2719)5000006 / I:(DE-2719)1011305 /
                      I:(DE-2719)1011103 / I:(DE-2719)1011401 / I:(DE-2719)1410002
                      / I:(DE-2719)1210000 / I:(DE-2719)1810002 /
                      I:(DE-2719)1011102 / I:(DE-2719)1011201 / I:(DE-2719)1510100
                      / I:(DE-2719)1410006 / I:(DE-2719)1811005 /
                      I:(DE-2719)5000000 / I:(DE-2719)5000007 / I:(DE-2719)1011101
                      / I:(DE-2719)5000022 / I:(DE-2719)1240005},
      pnm          = {353 - Clinical and Health Care Research (POF4-353) / 352 -
                      Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39801712},
      pmc          = {pmc:PMC11724426},
      doi          = {10.1093/braincomms/fcae457},
      url          = {https://pub.dzne.de/record/275864},
}