Perivascular Space Predicts Brain Hypometabolism of Individuals with Underlying Amyloid Pathology

J Alzheimers Dis. 2022;90(3):1329-1337. doi: 10.3233/JAD-220426.

Abstract

Background: Reduced signal on fluorodeoxyglucose-positron emission tomography (FDG-PET) is a valid proxy for neurodegeneration in Alzheimer's disease (AD). Perivascular space (PVS) is believed to be associated with AD pathology and cognitive decline.

Objective: This study aimed to investigate the associations of PVS with FDG-PET and cognitive performance based on the burden of amyloid pathology.

Methods: We used magnetic resonance imaging (MRI) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). MRI-visible PVS in basal ganglia (BG) and centrum semi-oval (CSO) were visually classified as: none/mild, moderate or frequent/severe. The association of PVS with brain FDG-PET was explored based on the burden of amyloid pathology, where a cerebrospinal fluid (CSF) t-tau/Aβ42 with the ratio≥0.27 was defined as high amyloid pathology. Moreover, the relationships between PVS and cognitive performance variables (ADNI-MEM and ADNI-EF) were studied.

Results: For participants with higher tau/Aβ42 ratio, CSO-PVS severity was independently associated with lower FDG-PET. There were significant interaction effects between moderate or frequent/severe CSO-PVS and time on FDG decline in people with high amyloid pathology. The interaction between CSO-PVS and time (follow-up) was consistently associated with ADNI-MEM and ADNI-EF decline in individuals with high amyloid pathology.

Conclusion: The study established the differential utility of PVS in BG and CSO for predicting brain metabolism. These findings suggest that CSO-PVS serves as a contributing factor to brain metabolism and cognitive decline associated with amyloid pathology.

Keywords: Amyloid; basal ganglia; centrum semi-oval; metabolism; perivascular space.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides / metabolism
  • Amyloidogenic Proteins / metabolism
  • Amyloidosis* / metabolism
  • Biomarkers / cerebrospinal fluid
  • Brain / pathology
  • Cognitive Dysfunction* / metabolism
  • Fluorodeoxyglucose F18 / metabolism
  • Humans
  • Magnetic Resonance Imaging
  • Neuroimaging / methods
  • Positron-Emission Tomography

Substances

  • Fluorodeoxyglucose F18
  • Amyloidogenic Proteins
  • Amyloid beta-Peptides
  • Biomarkers