Perivascular space and white matter hyperintensities in Alzheimer's disease: associations with disease progression and cognitive function.
Philine Marie Schirge, Robert Perneczky, Toshiaki Taoka, Adriana L Ruiz-Rizzo, Ersin Ersoezlue, Robert Forbrig, Selim Guersel, Carolin Kurz, Matthias Brendel, Julian Hellmann-Regen, Josef Priller, Anja Schneider, Frank Jessen, Emrah D��zel, Katharina Buerger, Stefan Teipel, Christoph Laske, Oliver Peters, Eike Spruth, Klaus Fliessbach, Ayda Rostamzadeh, Wenzel Glanz, Daniel Janowitz, Ingo Kilimann, Sebastian Sodenkamp, Michael Ewers, Boris-Stephan Rauchmann
Author Information
Philine Marie Schirge: Department of Psychiatry and Psychotherapy, LMU Hospital, LMU Munich, Munich, Germany.
Robert Perneczky: Department of Psychiatry and Psychotherapy, LMU Hospital, LMU Munich, Munich, Germany.
Toshiaki Taoka: Department of Innovative Biomedical Visualization (iBMV), Graduate School of Medicine, Nagoya University, Nagoya, Japan.
Adriana L Ruiz-Rizzo: Department of Neurology, Jena University Hospital, Jena, Germany.
Ersin Ersoezlue: German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
Robert Forbrig: Institute of Neuroradiology, LMU Hospital, LMU Munich, Munich, Germany.
Selim Guersel: Department of Psychiatry and Psychotherapy, LMU Hospital, LMU Munich, Munich, Germany.
Carolin Kurz: Department of Psychiatry and Psychotherapy, LMU Hospital, LMU Munich, Munich, Germany.
Matthias Brendel: Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
Julian Hellmann-Regen: German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
Josef Priller: German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
Anja Schneider: German Center for Neurodegenerative Diseases (DZNE)Venusberg-Campus, Bonn, Germany.
Frank Jessen: German Center for Neurodegenerative Diseases (DZNE)Venusberg-Campus, Bonn, Germany.
Emrah D��zel: German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
Katharina Buerger: German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany.
Stefan Teipel: German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.
Christoph Laske: German Center for Neurodegenerative Diseases (DZNE), T��bingen, Germany.
Oliver Peters: German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
Eike Spruth: German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
Klaus Fliessbach: German Center for Neurodegenerative Diseases (DZNE)Venusberg-Campus, Bonn, Germany.
Ayda Rostamzadeh: Department of Psychiatry, University of Cologne, Medical Faculty, Kerpener Strasse 62, 50924, Cologne, Germany.
Wenzel Glanz: German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
Daniel Janowitz: Institute for Stroke and Dementia Research (ISD), Ludwig Maximilian University Hospital, Ludwig Maximilian University, Munich, Germany.
Ingo Kilimann: German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.
Sebastian Sodenkamp: German Center for Neurodegenerative Diseases (DZNE), T��bingen, Germany.
Michael Ewers: German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany.
Boris-Stephan Rauchmann: Institute of Neuroradiology, LMU Hospital, LMU Munich, Munich, Germany. boris.rauchmann@med.uni-muenchen.de.
BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia, characterized by the accumulation of amyloid-beta (A��) and neurofibrillary tangles. Recent studies emphasize the role of vascular factors, including the glymphatic system, in AD pathogenesis, particularly in A�� 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 A��, cerebrovascular disease (CVD), white matter hyperintensities (WMH), and cognitive function. METHODS: 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. RESULTS: 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 A�� concentration, WMH number and MMSE and CDR. WMH, found in the ROIs correlated negatively with the ALPS-Index. CONCLUSIONS: 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.
