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@ARTICLE{Sabri:902739,
      author       = {Sabri, Osama and Meyer, Philipp M and Gräf, Susanne and
                      Hesse, Swen and Wilke, Stephan and Becker, Georg-Alexander
                      and Rullmann, Michael and Patt, Marianne and Luthardt, Julia
                      and Wagenknecht, Gudrun and Hoepping, Alexander and Smits,
                      Rene and Franke, Annegret and Sattler, Bernhard and Tiepolt,
                      Solveig and Fischer, Steffen and Deuther-Conrad, Winnie and
                      Hegerl, Ulrich and Barthel, Henryk and Schönknecht, Peter
                      and Brust, Peter},
      title        = {{C}ognitive correlates of α4β2 nicotinic acetylcholine
                      receptors in mild {A}lzheimer’s dementia},
      journal      = {Brain},
      volume       = {141},
      number       = {6},
      issn         = {0006-8950},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {FZJ-2021-04521},
      pages        = {1840 - 1854},
      year         = {2018},
      abstract     = {In early Alzheimer’s dementia, there is a need for PET
                      biomarkers of disease progression with close associations to
                      cognitive dysfunction that may aid to predict further
                      cognitive decline and neurodegeneration. Amyloid biomarkers
                      are not suitable for that purpose. The α4β2 nicotinic
                      acetylcholine receptors (α4β2-nAChRs) are widely abundant
                      in the human brain. As neuromodulators they play an
                      important role in cognitive functions such as attention,
                      learning and memory. Post-mortem studies reported lower
                      expression of α4β2-nAChRs in more advanced Alzheimer’s
                      dementia. However, there is ongoing controversy whether
                      α4β2-nAChRs are reduced in early Alzheimer’s dementia.
                      Therefore, using the recently developed
                      α4β2-nAChR-specific radioligand (−)-18F-flubatine and
                      PET, we aimed to quantify the α4β2-nAChR availability and
                      its relationship to specific cognitive dysfunction in mild
                      Alzheimer’s dementia. Fourteen non-smoking patients with
                      mild Alzheimer’s dementia, drug-naïve for cholinesterase
                      therapy, were compared with 15 non-smoking healthy controls
                      matched for age, sex and education by applying
                      (−)-18F-flubatine PET together with a neuropsychological
                      test battery. The one-tissue compartment model and Logan
                      plot method with arterial input function were used for
                      kinetic analysis to obtain the total distribution volume
                      (VT) as the primary, and the specific binding part of the
                      distribution volume (VS) as the secondary quantitative
                      outcome measure of α4β2-nAChR availability. VS was
                      determined by using a pseudo-reference region. Correlations
                      between VT within relevant brain regions and Z-scores of
                      five cognitive functions (episodic memory, executive
                      function/working memory, attention, language, visuospatial
                      function) were calculated. VT (and VS) were applied for
                      between-group comparisons. Volume of interest and
                      statistical parametric mapping analyses were carried out.
                      Analyses revealed that in patients with mild Alzheimer’s
                      dementia compared to healthy controls, there was
                      significantly lower VT, especially within the hippocampus,
                      fronto-temporal cortices, and basal forebrain, which was
                      similar to comparisons of VS. VT decline in Alzheimer’s
                      dementia was associated with distinct domains of impaired
                      cognitive functioning, especially episodic memory and
                      executive function/working memory. Using (−)-18F-flubatine
                      PET in patients with mild Alzheimer’s dementia, we show
                      for the first time a cholinergic α4β2-nAChR deficiency
                      mainly present within the basal forebrain-cortical and
                      septohippocampal cholinergic projections and a relationship
                      between lower α4β2-nAChR availability and impairment of
                      distinct cognitive domains, notably episodic memory and
                      executive function/working memory. This shows the potential
                      of (−)-18F-flubatine as PET biomarker of cholinergic
                      α4β2-nAChR dysfunction and specific cognitive decline.
                      Thus, if validated by longitudinal PET studies,
                      (−)-18F-flubatine might become a PET biomarker of
                      progression of neurodegeneration in Alzheimer’s dementia.},
      cin          = {ZEA-2},
      ddc          = {610},
      cid          = {I:(DE-Juel1)ZEA-2-20090406},
      pnm          = {5253 - Neuroimaging (POF4-525) / BMBF-01EZ0822 -
                      NorChloro-Fluoro HomoEpiBatidin (NCFHEB) ein potentieller
                      Positronen-Emission Tomographie-(PET) Marker der frühen
                      Alzheimer-Demenz (BMBF-01EZ0822)},
      pid          = {G:(DE-HGF)POF4-5253 / G:(DE-Juel1)BMBF-01EZ0822},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29672680},
      UT           = {WOS:000434113500030},
      doi          = {10.1093/brain/awy099},
      url          = {https://juser.fz-juelich.de/record/902739},
}