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@ARTICLE{Schirge:277548,
      author       = {Schirge, Philine Marie and Perneczky, Robert and Taoka,
                      Toshiaki and Ruiz-Rizzo, Adriana L and Ersoezlue, Ersin and
                      Forbrig, Robert and Guersel, Selim and Kurz, Carolin and
                      Brendel, Matthias and Hellmann-Regen, Julian and Priller,
                      Josef and Schneider, Anja and Jessen, Frank and Düzel,
                      Emrah and Buerger, Katharina and Teipel, Stefan and Laske,
                      Christoph and Peters, Oliver and Spruth, Eike and
                      Fliessbach, Klaus and Rostamzadeh, Ayda and Glanz, Wenzel
                      and Janowitz, Daniel and Kilimann, Ingo and Sodenkamp,
                      Sebastian and Ewers, Michael and Rauchmann, Boris-Stephan},
      title        = {{P}erivascular space and white matter hyperintensities in
                      {A}lzheimer's disease: associations with disease progression
                      and cognitive function.},
      journal      = {Alzheimer's research $\&$ therapy},
      volume       = {17},
      number       = {1},
      issn         = {1758-9193},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DZNE-2025-00437},
      pages        = {62},
      year         = {2025},
      abstract     = {Alzheimer's disease (AD) is the leading cause of dementia,
                      characterized by the accumulation of amyloid-beta (Aβ) and
                      neurofibrillary tangles. Recent studies emphasize the role
                      of vascular factors, including the glymphatic system, in AD
                      pathogenesis, particularly in Aβ clearance. The diffusion
                      tensor image analysis along the perivascular space
                      (DTI-ALPS; ALPS-Index) has emerged as a novel, non-invasive
                      method to evaluate the glymphatic system in vivo, showing
                      glymphatic insufficiency in AD. This study aimed to
                      investigate alterations in the function of the glymphatic
                      system in individuals with AD versus healthy controls (HC),
                      and to explore its association with Aβ, cerebrovascular
                      disease (CVD), white matter hyperintensities (WMH), and
                      cognitive function.DTI MRI data from three independent study
                      cohorts (ActiGliA: AD n = 16, Controls n = 18; DELCODE: AD n
                      = 54, Controls n = 67; ADNI: AD n = 43, Controls n = 49)
                      were used to evaluate the perivascular space (PVS)
                      integrity; a potential biomarker for glymphatic activity.
                      The DTI-Along the Perivascular Space technique was used to
                      measure water diffusion along PVS providing an index to
                      assess the efficiency of the glymphatic system's waste
                      clearance function. WMH load was quantified in FLAIR MRI
                      using the lesion segmentation tool. We quantified WMHs
                      volume within our defined region of interest (ROI) and
                      excluded participants with any WMHs to avoid confounding the
                      ALPS-Index. Associations with cerebrospinal fluid (CSF) AD
                      hallmark biomarkers, cognitive performance (MMSE) and
                      clinical severity (CDR) were assessed.AD patients had a
                      significantly lower ALPS-Index vs. healthy controls
                      (ActiGliA: AD: mean = 1.22, SD = 0.12; Controls: mean =
                      1.36, SD = 0.14, p = 0.004; DELCODE: AD: mean = 1.26, SD =
                      0.18; Controls: mean = 1.34, SD = 0.2, p = 0.035; ADNI: AD:
                      mean = 1.08, SD = 0.24; Controls: mean = 1.19, SD = 0.13, p
                      = 0.008). The ALPS-Index was associated with CSF Aβ
                      concentration, WMH number and MMSE and CDR. WMH, found in
                      the ROIs correlated negatively with the ALPS-Index.This
                      study highlights the potential of the DTI-ALPS-Index as a
                      biomarker for glymphatic dysfunction in AD. It underscores
                      the importance of considering vascular factors and the
                      glymphatic system in the pathogenesis and diagnosis of AD as
                      WMHs in the ROI could cause disturbances and inaccurate
                      indices.},
      keywords     = {Humans / Alzheimer Disease: diagnostic imaging / Alzheimer
                      Disease: pathology / Female / Male / White Matter:
                      diagnostic imaging / White Matter: pathology / Aged /
                      Disease Progression / Glymphatic System: diagnostic imaging
                      / Glymphatic System: pathology / Diffusion Tensor Imaging:
                      methods / Cognition: physiology / Aged, 80 and over /
                      Amyloid beta-Peptides: cerebrospinal fluid / Amyloid
                      beta-Peptides: metabolism / Magnetic Resonance Imaging:
                      methods / Brain: diagnostic imaging / Brain: pathology /
                      Alzheimer's disease (Other) / Amyloid-beta (Other) /
                      Cognitive decline (Other) / Dementia (Other) / Diffusion
                      tensor imaging (Other) / Perivascular space (Other) /
                      Amyloid beta-Peptides (NLM Chemicals)},
      cin          = {AG Simons / AG Dichgans / Clinical Research (Munich) / AG
                      Dirnagl / AG Endres / AG Priller / AG Schneider / AG Jessen
                      / Patient Studies (Bonn) / AG Düzel / AG Teipel / AG Gasser
                      / ICRU},
      ddc          = {610},
      cid          = {I:(DE-2719)1110008 / I:(DE-2719)5000022 /
                      I:(DE-2719)1111015 / I:(DE-2719)1810002 / I:(DE-2719)1811005
                      / I:(DE-2719)5000007 / I:(DE-2719)1011305 /
                      I:(DE-2719)1011102 / I:(DE-2719)1011101 / I:(DE-2719)5000006
                      / I:(DE-2719)1510100 / I:(DE-2719)1210000 /
                      I:(DE-2719)1240005},
      pnm          = {351 - Brain Function (POF4-351) / 353 - Clinical and Health
                      Care Research (POF4-353) / 899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-351 / G:(DE-HGF)POF4-353 /
                      G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40098158},
      doi          = {10.1186/s13195-025-01707-9},
      url          = {https://pub.dzne.de/record/277548},
}