Role of Enlarged Perivascular Space in the Temporal Lobe in Cerebral Amyloidosis

Han Kyu Na, Han Kyeol Kim, Hye Sun Lee, Mina Park, Jae Hoon Lee, Young Hoon Ryu, Hanna Cho, Chul Hyoung Lyoo

Research output: Contribution to journalArticlepeer-review


Objective: Although growing evidence suggests that perivascular space (PVS) serves as a clearance route for amyloid and tau, the association between enlarged PVS (EPVS) and Alzheimer disease is highly inconsistent across studies. As the conventional visual rating systems for EPVS were insufficient to predict amyloid/tau/neurodegeneration (A/T/N) status, we developed a new rating scale for EPVS located in the temporal lobe (T-EPVS). Methods: EPVS located in the basal ganglia (BG-EPVS), centrum semiovale (CS-EPVS), and T-EPVS was visually rated in 272 individuals (healthy controls, n = 96; mild cognitive impairment, n = 106; dementia, n = 70) who underwent structural magnetic resonance imaging (MRI) and dual positron emission tomography scans (18F-flortaucipir and 18F-florbetaben). T-EPVS and BG-EPVS were defined as high degree when the counts in any hemisphere were >10, and the CS-EPVS cutoff was >20. Logistic regression models were constructed to investigate whether the regional EPVS burden was predictive of A/T/N status. The derived models were externally validated in a temporal validation cohort (n = 195) that underwent MRI studies using a different scanner. Results: Compared with those with low-degree T-EPVS (23/136, 16.9%), individuals with high-degree T-EPVS/CS-EPVS but low-degree BG-EPVS were more likely to exhibit amyloid positivity (46/56, 82.1%). High-degree T-EPVS burden (odds ratio [OR] = 7.251, 95% confidence interval [CI] = 3.296–15.952) and low-degree BG-EPVS (OR = 0.241, 95% CI = 0.109–0.530) were predictive of amyloid positivity. Although high-degree T-EPVS was associated with tau positivity, the association was no longer significant after adjusting for amyloid and neurodegeneration status. Interpretation: Investigating the burden and topographic distribution of EPVS including T-EPVS may be useful for predicting amyloid status, indicating that impaired perivascular drainage may contribute to cerebral amyloidosis. ANN NEUROL 2023.

Original languageEnglish
JournalAnnals of Neurology
Publication statusAccepted/In press - 2023

Bibliographical note

Funding Information:
This research was supported by a faculty research grant from Yonsei University College of Medicine (grant number: 6‐2021‐0094), the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (grant numbers: NRF2020R1F1A1076154 and NRF2018R1D1A1B07049386), and a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare, Republic of Korea (grant numbers: HI18C1159 and HU20C0164).

Publisher Copyright:
© 2023 American Neurological Association.

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology


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