Perivascular space enlargement accelerates in ageing and Alzheimer's disease pathology: evidence from a three-year longitudinal multicentre study.

Humans Female Male Aged Alzheimer Disease / pathology Longitudinal Studies Aging / pathology Glymphatic System / pathology Magnetic Resonance Imaging Cognitive Dysfunction / pathology Brain / pathology Aged, 80 and over Cross-Sectional Studies White Matter / pathology Middle Aged

Alzheimer’s disease Alzheimer’s pathology Enlarged perivascular spaces Longitudinal analysis Multicentre study Virchow–Robin spaces

Journal

Alzheimer's research & therapy

ISSN: 1758-9193

Titre abrégé: Alzheimers Res Ther

Pays: England

ID NLM: 101511643

Informations de publication

Date de publication:
31 Oct 2024

Historique:

received: 20 06 2024

accepted: 15 10 2024

medline: 1 11 2024

pubmed: 1 11 2024

entrez: 1 11 2024

Statut: epublish

Résumé

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. We studied PVS in centrum semiovale (CSO) and basal ganglia (BG) computationally over three to four annual visits in 503 participants (255 females; mean PVS volumes increased significantly over follow-ups (CSO: B = 0.03 [0.02, 0.05], p < 0.001; BG: B = 0.05 [0.03, 0.07], p < 0.001). PVS enlargement rates varied substantially across subjects and depended on the participant's age, white matter hyperintensities volumes, and amyloid and tau status. PVS volumes were higher across elderly participants, regardless of region of interest (CSO: B = 0.12 [0.02, 0.21], p = 0.017; BG: B = 0.19 [0.09, 0.28], p < 0.001). Faster BG-PVS enlargement related to lower baseline white matter hyperintensities volumes (ρ 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. German Clinical Trials Register DRKS00007966. Registered 04.05.2015 - retrospectively registered, https://drks.de/search/en/trial/DRKS00007966 .

Sections du résumé

BACKGROUND BACKGROUND

METHODS METHODS

We studied PVS in centrum semiovale (CSO) and basal ganglia (BG) computationally over three to four annual visits in 503 participants (255 females; mean

RESULTS RESULTS

PVS volumes increased significantly over follow-ups (CSO: B = 0.03 [0.02, 0.05], p < 0.001; BG: B = 0.05 [0.03, 0.07], p < 0.001). PVS enlargement rates varied substantially across subjects and depended on the participant's age, white matter hyperintensities volumes, and amyloid and tau status. PVS volumes were higher across elderly participants, regardless of region of interest (CSO: B = 0.12 [0.02, 0.21], p = 0.017; BG: B = 0.19 [0.09, 0.28], p < 0.001). Faster BG-PVS enlargement related to lower baseline white matter hyperintensities volumes (ρ

CONCLUSION CONCLUSIONS

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 BACKGROUND

German Clinical Trials Register DRKS00007966. Registered 04.05.2015 - retrospectively registered, https://drks.de/search/en/trial/DRKS00007966 .

Identifiants

DOI: 10.1186/s13195-024-01603-8 PMID: 39482759

pubmed: 39482759

doi: 10.1186/s13195-024-01603-8

pii: 10.1186/s13195-024-01603-8

doi:

Types de publication

Journal Article Multicenter Study Observational Study

Langues

eng

Sous-ensembles de citation

Pagination

242

Informations de copyright

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