Alzheimer’s Research & Therapy (Oct 2024)
Perivascular space enlargement accelerates in ageing and Alzheimer’s disease pathology: evidence from a three-year longitudinal multicentre study
- Inga Menze,
- Jose Bernal,
- Pinar Kaya,
- Çağla Aki,
- Malte Pfister,
- Jonas Geisendörfer,
- Renat Yakupov,
- Roberto Duarte Coello,
- Maria d. C. Valdés-Hernández,
- Michael T. Heneka,
- Frederic Brosseron,
- Matthias C. Schmid,
- Wenzel Glanz,
- Enise I. Incesoy,
- Michaela Butryn,
- Ayda Rostamzadeh,
- Dix Meiberth,
- Oliver Peters,
- Lukas Preis,
- Dominik Lammerding,
- Daria Gref,
- Josef Priller,
- Eike J. Spruth,
- Slawek Altenstein,
- Andrea Lohse,
- Stefan Hetzer,
- Anja Schneider,
- Klaus Fliessbach,
- Okka Kimmich,
- Ina R. Vogt,
- Jens Wiltfang,
- Claudia Bartels,
- Björn H. Schott,
- Niels Hansen,
- Peter Dechent,
- Katharina Buerger,
- Daniel Janowitz,
- Robert Perneczky,
- Boris-Stephan Rauchmann,
- Stefan Teipel,
- Ingo Kilimann,
- Doreen Goerss,
- Christoph Laske,
- Matthias H. Munk,
- Carolin Sanzenbacher,
- Petra Hinderer,
- Klaus Scheffler,
- Annika Spottke,
- Nina Roy-Kluth,
- Falk Lüsebrink,
- Katja Neumann,
- Joanna Wardlaw,
- Frank Jessen,
- Stefanie Schreiber,
- Emrah Düzel,
- Gabriel Ziegler
Affiliations
- Inga Menze
- German Centre for Neurodegenerative Diseases (DZNE)
- Jose Bernal
- German Centre for Neurodegenerative Diseases (DZNE)
- Pinar Kaya
- German Centre for Neurodegenerative Diseases (DZNE)
- Çağla Aki
- German Centre for Neurodegenerative Diseases (DZNE)
- Malte Pfister
- Department of Neurology, University Hospital Magdeburg
- Jonas Geisendörfer
- Department of Neurology, University Hospital Magdeburg
- Renat Yakupov
- German Centre for Neurodegenerative Diseases (DZNE)
- Roberto Duarte Coello
- Centre for Clinical Brain Sciences, The University of Edinburgh, 49 Little France Crescent
- Maria d. C. Valdés-Hernández
- Centre for Clinical Brain Sciences, The University of Edinburgh, 49 Little France Crescent
- Michael T. Heneka
- Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg
- Frederic Brosseron
- German Centre for Neurodegenerative Diseases (DZNE)
- Matthias C. Schmid
- German Centre for Neurodegenerative Diseases (DZNE)
- Wenzel Glanz
- German Centre for Neurodegenerative Diseases (DZNE)
- Enise I. Incesoy
- German Centre for Neurodegenerative Diseases (DZNE)
- Michaela Butryn
- German Centre for Neurodegenerative Diseases (DZNE)
- Ayda Rostamzadeh
- Department of Psychiatry, Medical Faculty, University of Cologne
- Dix Meiberth
- German Centre for Neurodegenerative Diseases (DZNE)
- Oliver Peters
- German Centre for Neurodegenerative Diseases (DZNE)
- Lukas Preis
- Institute of Psychiatry and Psychotherapy, Freie Universität Berlin and Humboldt-Universität zu Berlin
- Dominik Lammerding
- Institute of Psychiatry and Psychotherapy, Freie Universität Berlin and Humboldt-Universität zu Berlin
- Daria Gref
- Institute of Psychiatry and Psychotherapy, Freie Universität Berlin and Humboldt-Universität zu Berlin
- Josef Priller
- UK Dementia Research Institute Centre at the University of Edinburgh, Edinburgh Bioquarter, 49 Little France Crescent, Edinburgh Bioquarter
- Eike J. Spruth
- German Centre for Neurodegenerative Diseases (DZNE)
- Slawek Altenstein
- German Centre for Neurodegenerative Diseases (DZNE)
- Andrea Lohse
- Department of Psychiatry and Psychotherapy, Charité
- Stefan Hetzer
- Berlin Center for Advanced Neuroimaging, Charité
- Anja Schneider
- German Centre for Neurodegenerative Diseases (DZNE)
- Klaus Fliessbach
- German Centre for Neurodegenerative Diseases (DZNE)
- Okka Kimmich
- German Centre for Neurodegenerative Diseases (DZNE)
- Ina R. Vogt
- German Centre for Neurodegenerative Diseases (DZNE)
- Jens Wiltfang
- German Centre for Neurodegenerative Diseases (DZNE)
- Claudia Bartels
- Department of Psychiatry and Psychotherapy, University Medical Center Goettingen
- Björn H. Schott
- German Centre for Neurodegenerative Diseases (DZNE)
- Niels Hansen
- Department of Psychiatry and Psychotherapy, University Medical Center Goettingen
- Peter Dechent
- Department of Cognitive Neurology, MR-Research in Neurosciences, Georg-August-University Goettingen
- Katharina Buerger
- German Centre for Neurodegenerative Diseases (DZNE)
- Daniel Janowitz
- Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich
- Robert Perneczky
- German Centre for Neurodegenerative Diseases (DZNE)
- Boris-Stephan Rauchmann
- Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich
- Stefan Teipel
- German Centre for Neurodegenerative Diseases (DZNE)
- Ingo Kilimann
- German Centre for Neurodegenerative Diseases (DZNE)
- Doreen Goerss
- German Centre for Neurodegenerative Diseases (DZNE)
- Christoph Laske
- German Centre for Neurodegenerative Diseases (DZNE)
- Matthias H. Munk
- German Centre for Neurodegenerative Diseases (DZNE)
- Carolin Sanzenbacher
- German Centre for Neurodegenerative Diseases (DZNE)
- Petra Hinderer
- German Centre for Neurodegenerative Diseases (DZNE)
- Klaus Scheffler
- Department for Biomedical Magnetic Resonance, University of Tübingen
- Annika Spottke
- German Centre for Neurodegenerative Diseases (DZNE)
- Nina Roy-Kluth
- German Centre for Neurodegenerative Diseases (DZNE)
- Falk Lüsebrink
- German Centre for Neurodegenerative Diseases (DZNE)
- Katja Neumann
- Department of Neurology, University Hospital Magdeburg
- Joanna Wardlaw
- Centre for Clinical Brain Sciences, The University of Edinburgh, 49 Little France Crescent
- Frank Jessen
- German Centre for Neurodegenerative Diseases (DZNE)
- Stefanie Schreiber
- German Centre for Neurodegenerative Diseases (DZNE)
- Emrah Düzel
- German Centre for Neurodegenerative Diseases (DZNE)
- Gabriel Ziegler
- German Centre for Neurodegenerative Diseases (DZNE)
- DOI
- https://doi.org/10.1186/s13195-024-01603-8
- Journal volume & issue
-
Vol. 16,
no. 1
pp. 1 – 16
Abstract
Abstract Background Perivascular space (PVS) enlargement in ageing and Alzheimer’s disease (AD) and the drivers of such a structural change in humans require longitudinal investigation. Elucidating the effects of demographic factors, hypertension, cerebrovascular dysfunction, and AD pathology on PVS dynamics could inform the role of PVS in brain health function as well as the complex pathophysiology of AD. Methods We studied PVS in centrum semiovale (CSO) and basal ganglia (BG) computationally over three to four annual visits in 503 participants (255 females; meanage = 70.78 ± 5.78) of the ongoing observational multicentre “DZNE Longitudinal Cognitive Impairment and Dementia Study” (DELCODE) cohort. We analysed data from subjects who were cognitively unimpaired (n = 401), had amnestic mild cognitive impairment (n = 71), or had AD (n = 31). We used linear mixed-effects modelling to test for changes of PVS volumes in relation to cross-sectional and longitudinal age, as well as sex, years of education, hypertension, white matter hyperintensities, AD diagnosis, and cerebrospinal-fluid-derived amyloid (A) and tau (T) status (available for 46.71%; A-T-/A + T-/A + T + n = 143/48/39). Results PVS volumes increased significantly over follow-ups (CSO: B = 0.03 [0.02, 0.05], p A-T-, p FDR = 0.004) or who were amyloid positive but tau negative (A + T + > A + T-, p FDR = 0.07). CSO-PVS volumes increased at a faster rate with amyloid positivity as compared to amyloid negativity (A + T-/A + T + > A-T-, p FDR = 0.021). Conclusion Our longitudinal evidence supports the relevance of PVS enlargement in presumably healthy ageing as well as in AD pathology. We further discuss the region-specific involvement of white matter hyperintensities and neurotoxic waste accumulation in PVS enlargement and the possibility of additional factors contributing to PVS progression. A comprehensive understanding of PVS dynamics could facilitate the understanding of pathological cascades and might inform targeted treatment strategies. Trial registration German Clinical Trials Register DRKS00007966. Registered 04.05.2015 – retrospectively registered, https://drks.de/search/en/trial/DRKS00007966 .
Keywords
- Enlarged perivascular spaces
- Virchow–Robin spaces
- Alzheimer’s disease
- Alzheimer’s pathology
- Longitudinal analysis
- Multicentre study