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@ARTICLE{Billette:165172,
      author       = {Billette, Ornella V and Ziegler, Gabriel and Aruci, Merita
                      and Schütze, Hartmut and Kizilirmak, Jasmin M and Richter,
                      Anni and Altenstein, Slawek and Bartels, Claudia and
                      Brosseron, Frederic and Cardenas-Blanco, Arturo and Dahmen,
                      Philip and Dechent, Peter and Dobisch, Laura and Fliessbach,
                      Klaus and Freiesleben, Silka Dawn and Glanz, Wenzel and
                      Göerß, Doreen and Haynes, John Dylan and Heneka, Michael T
                      and Kilimann, Ingo and Kimmich, Okka and Kleineidam, Luca
                      and Laske, Christoph and Lohse, Andrea and Rostamzadeh, Ayda
                      and Metzger, Coraline and Munk, Matthias H and Peters,
                      Oliver and Preis, Lukas and Priller, Josef and Scheffler,
                      Klaus and Schneider, Anja and Spottke, Annika and Spruth,
                      Eike Jakob and Ramirez, Alfredo and Röske, Sandra and Roy,
                      Nina and Teipel, Stefan and Wagner, Michael and Wiltfang,
                      Jens and Wolfsgruber, Steffen and Yakupov, Renat and
                      Zeidman, Peter and Jessen, Frank and Schott, Björn and
                      Düzel, Emrah and Maass, Anne},
      collaboration = {Group, DELCODE Study},
      title        = {{N}ovelty-{R}elated f{MRI} {R}esponses of {P}recuneus and
                      {M}edial {T}emporal {R}egions in {I}ndividuals at {R}isk for
                      {A}lzheimer {D}isease.},
      journal      = {Neurology},
      volume       = {99},
      number       = {8},
      issn         = {0028-3878},
      address      = {[S.l.]},
      publisher    = {Ovid},
      reportid     = {DZNE-2022-01474},
      pages        = {e775 - e788},
      year         = {2022},
      abstract     = {We assessed whether novelty-related fMRI activity in medial
                      temporal lobe regions and the precuneus follows an inverted
                      U-shaped pattern across the clinical spectrum of increased
                      Alzheimer disease (AD) risk as previously suggested.
                      Specifically, we tested for potentially increased activity
                      in individuals with a higher AD risk due to subjective
                      cognitive decline (SCD) or mild cognitive impairment (MCI).
                      We further tested whether activity differences related to
                      diagnostic groups were accounted for by CSF markers of AD or
                      brain atrophy.We studied 499 participants aged 60-88 years
                      from the German Center for Neurodegenerative Diseases
                      Longitudinal Cognitive Impairment and Dementia Study
                      (DELCODE) who underwent task-fMRI. Participants included 163
                      cognitively normal (healthy control, HC) individuals, 222
                      SCD, 82 MCI, and 32 patients with clinical diagnosis of mild
                      AD. CSF levels of β-amyloid 42/40 ratio and
                      phosphorylated-tau181 were available from 232 participants.
                      We used region-based analyses to assess novelty-related
                      activity (novel > highly familiar scenes) in entorhinal
                      cortex, hippocampus, and precuneus as well as whole-brain
                      voxel-wise analyses. First, general linear models tested
                      differences in fMRI activity between participant groups.
                      Complementary regression models tested quadratic
                      relationships between memory impairment and activity.
                      Second, relationships of activity with AD CSF biomarkers and
                      brain volume were analyzed. Analyses were controlled for
                      age, sex, study site, and education.In the precuneus, we
                      observed an inverted U-shaped pattern of novelty-related
                      activity across groups, with higher activity in SCD and MCI
                      compared with HC, but not in patients with AD who showed
                      relatively lower activity than MCI. This nonlinear pattern
                      was confirmed by a quadratic relationship between memory
                      impairment and precuneus activity. Precuneus activity was
                      not related to AD biomarkers or brain volume. In contrast to
                      the precuneus, hippocampal activity was reduced in AD
                      dementia compared with all other groups and related to AD
                      biomarkers.Novelty-related activity in the precuneus follows
                      a nonlinear pattern across the clinical spectrum of
                      increased AD risk. Although the underlying mechanism remains
                      unclear, increased precuneus activity might represent an
                      early signature of memory impairment. Our results highlight
                      the nonlinearity of activity alterations that should be
                      considered in clinical trials using functional outcome
                      measures or targeting hyperactivity.},
      keywords     = {Alzheimer Disease: diagnosis / Amyloid beta-Peptides /
                      Biomarkers / Cognitive Dysfunction: diagnostic imaging /
                      Humans / Magnetic Resonance Imaging: methods / Parietal
                      Lobe: diagnostic imaging / Temporal Lobe: diagnostic imaging
                      / Amyloid beta-Peptides (NLM Chemicals) / Biomarkers (NLM
                      Chemicals)},
      cin          = {AG Maaß / AG Düzel / AG Wiltfang / AG Endres / Biomarker
                      / AG Speck / AG Peters / Patient Studies Bonn / KAP / AG
                      Teipel / AG Gasser / AG Priller / AG Wagner / Clinical
                      Research Platform (CRP) / AG Klockgether / AG Schneider / AG
                      Jessen / AG Fischer / Delcode},
      ddc          = {610},
      cid          = {I:(DE-2719)1311001 / I:(DE-2719)5000006 /
                      I:(DE-2719)1410006 / I:(DE-2719)1811005 / I:(DE-2719)1011301
                      / I:(DE-2719)1340009 / I:(DE-2719)5000000 /
                      I:(DE-2719)1011101 / I:(DE-2719)1340013 / I:(DE-2719)1510100
                      / I:(DE-2719)1210000 / I:(DE-2719)5000007 /
                      I:(DE-2719)1011201 / I:(DE-2719)1011401 / I:(DE-2719)1011001
                      / I:(DE-2719)1011305 / I:(DE-2719)1011102 /
                      I:(DE-2719)1410002 / I:(DE-2719)5000034},
      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},
      experiment   = {EXP:(DE-2719)DELCODE-20140101},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35995589},
      pmc          = {pmc:PMC9484732},
      doi          = {10.1212/WNL.0000000000200667},
      url          = {https://pub.dzne.de/record/165172},
}