1. Perivascular space enlargement accelerates in ageing and Alzheimer’s disease pathology: evidence from a three-year longitudinal multicentre study
- Author
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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, and Gabriel Ziegler
- Subjects
Enlarged perivascular spaces ,Virchow–Robin spaces ,Alzheimer’s disease ,Alzheimer’s pathology ,Longitudinal analysis ,Multicentre study ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Neurology. Diseases of the nervous system ,RC346-429 - 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 .
- Published
- 2024
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