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@ARTICLE{Ray:139720,
      author       = {Ray, Nicola J and Bradburn, Steven and Murgatroyd,
                      Christopher and Toseeb, Umar and Mir, Pablo and
                      Kountouriotis, George K and Teipel, Stefan J and Grothe,
                      Michel J},
      title        = {{I}n vivo cholinergic basal forebrain atrophy predicts
                      cognitive decline in de novo {P}arkinson's disease.},
      journal      = {Brain},
      volume       = {141},
      number       = {1},
      issn         = {0006-8950},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DZNE-2020-06042},
      pages        = {165-176},
      year         = {2018},
      abstract     = {See Gratwicke and Foltynie (doi:10.1093/brain/awx333) for a
                      scientific commentary on this article.Cognitive impairments
                      are a prevalent and disabling non-motor complication of
                      Parkinson's disease, but with variable expression and
                      progression. The onset of serious cognitive decline occurs
                      alongside substantial cholinergic denervation, but
                      imprecision of previously available techniques for in vivo
                      measurement of cholinergic degeneration limit their use as
                      predictive cognitive biomarkers. However, recent
                      developments in stereotactic mapping of the cholinergic
                      basal forebrain have been found useful for predicting
                      cognitive decline in prodromal stages of Alzheimer's
                      disease. These methods have not yet been applied to
                      longitudinal Parkinson's disease data. In a large sample of
                      people with de novo Parkinson's disease (n = 168), retrieved
                      from the Parkinson's Progressive Markers Initiative
                      database, we measured cholinergic basal forebrain volumes,
                      using morphometric analysis of T1-weighted images in
                      combination with a detailed stereotactic atlas of the
                      cholinergic basal forebrain nuclei. Using a binary
                      classification procedure, we defined patients with reduced
                      basal forebrain volumes (relative to age) at baseline, based
                      on volumes measured in a normative sample (n = 76).
                      Additionally, relationships between the basal forebrain
                      volumes at baseline, risk of later cognitive decline, and
                      scores on up to 5 years of annual cognitive assessments were
                      assessed with regression, survival analysis and linear mixed
                      modelling. In patients, smaller volumes in a region
                      corresponding to the nucleus basalis of Meynert were
                      associated with greater change in global cognitive, but not
                      motor scores after 2 years. Using the binary classification
                      procedure, patients classified as having smaller than
                      expected volumes of the nucleus basalis of Meynert had
                      ∼3.5-fold greater risk of being categorized as mildly
                      cognitively impaired over a period of up to 5 years of
                      follow-up (hazard ratio = 3.51). Finally, linear mixed
                      modelling analysis of domain-specific cognitive scores
                      revealed that patients classified as having smaller than
                      expected nucleus basalis volumes showed more severe and
                      rapid decline over up to 5 years on tests of memory and
                      semantic fluency, but not on tests of executive function.
                      Thus, we provide the first evidence that volumetric
                      measurement of the nucleus basalis of Meynert can predict
                      early cognitive decline. Our methods therefore provide the
                      opportunity for multiple-modality biomarker models to
                      include a cholinergic biomarker, which is currently lacking
                      for the prediction of cognitive deterioration in Parkinson's
                      disease. Additionally, finding dissociated relationships
                      between nucleus basalis status and domain-specific cognitive
                      decline has implications for understanding the neural basis
                      of heterogeneity of Parkinson's disease-related cognitive
                      decline.},
      keywords     = {Aged / Atrophy / Basal Forebrain: diagnostic imaging /
                      Basal Forebrain: metabolism / Brain Mapping / Cholinergic
                      Agents: metabolism / Cognition Disorders: diagnosis /
                      Cognition Disorders: etiology / Cognition Disorders:
                      pathology / Disease Progression / Female / Humans / Image
                      Processing, Computer-Assisted / Longitudinal Studies /
                      Magnetic Resonance Imaging / Male / Middle Aged / Motor
                      Activity / Neuropsychological Tests / Parkinson Disease:
                      complications / ROC Curve / Cholinergic Agents (NLM
                      Chemicals)},
      cin          = {Clinical Dementia Research Rostock /Greifswald ; AG Teipel},
      ddc          = {610},
      cid          = {I:(DE-2719)1510100},
      pnm          = {344 - Clinical and Health Care Research (POF3-344)},
      pid          = {G:(DE-HGF)POF3-344},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29228203},
      pmc          = {pmc:PMC5837422},
      doi          = {10.1093/brain/awx310},
      url          = {https://pub.dzne.de/record/139720},
}