Contribution of cerebrovascular lesions to neurodegeneration and cognitive decline

@misc{chen2026contribution,
  title = {{Contribution of cerebrovascular lesions to neurodegeneration and cognitive decline}},
  author = {Z. Chen and S. Raeesi and A. Metz and R. Moqadam and K. M. Chadwick and Y. Zeighami and M. Dadar},
  howpublished = {medRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.04.26364698},
  url = {https://www.medrxiv.org/content/10.64898/2026.10.04.26364698v1},
  note = {CC BY-NC-ND},
}

TY  - UNPB
TI  - Contribution of cerebrovascular lesions to neurodegeneration and cognitive decline
AU  - Z. Chen
AU  - S. Raeesi
AU  - A. Metz
AU  - R. Moqadam
AU  - K. M. Chadwick
AU  - Y. Zeighami
AU  - M. Dadar
PY  - 2026
DA  - 2026/10/04
PB  - medRxiv
DO  - 10.64898/2026.10.04.26364698
UR  - https://www.medrxiv.org/content/10.64898/2026.10.04.26364698v1
AB  - IntroductionCerebral small vessel disease (CSVD) lesions, including white matter hyperintensities (WMHs), lacunar infarcts, cerebral microbleeds (CMBs), and enlarged perivascular spaces (PVSs) are associated with increased risk of dementia. In this study, we aimed to examine their associations with risk factors, neurodegeneration, and cognition over a follow-up period of ten years.  Methods289 participants (183 females, mean age: 73.7 {+/-} 5.7) with multi-modal magnetic resonance imaging (MRI) and clinical assessments from the Consortium for the Early Identification of Alzheimers Disease (CIMA-Q) were included. CSVD lesions and neurodegeneration were quantified using automated tools. Linear regression and mixed effects models examined the cross-sectional and longitudinal associations between lesions, risk factors, neurodegeneration, and cognitive decline.  ResultsRisk factors showed the strongest cross-sectional associations with PVS number and CMB presence, and the strongest longitudinal associations with WMH and PVS volume progression (p < 0.05). WMH and PVS volumes significantly increased over time (p < 0.01), with faster WMH progression among participants who experienced cognitive decline during study follow-ups. Higher WMH volume was associated with poorer global cognition and executive function, and presence of lacunae was associated with faster decline in executive function. Finally, both WMH and PVS were associated with longitudinal atrophy across several cortical regions.  ConclusionsVascular risk factors were associated with CSVD burden and progression, and WMH and PVS progression were further associated with cortical atrophy and cognitive decline, underscoring the interconnected contributions of vascular risk, CSVD, and neurodegeneration to cognitive aging and dementia risk.  HIGHLIGHTO_LIWhite matter hyperintensities (WMHs) and perivascular spaces (PVS) showed significant longitudinal increases over up to 10 years of study follow-ups. C_LIO_LIVascular risk factors were associated with CSVD burden (PVSs, cerebral microbleeds, and WMHs) and progression (PVSs and WMHs). C_LIO_LIGreater WMH burden was associated with poorer global cognition and executive function, while lacunar infarcts were associated with faster longitudinal decline in executive function. C_LIO_LIWMH and PVS progression were associated with longitudinal cortical atrophy, linking CSVD progression with neurodegenerative changes. C_LI
ER  -