Topography and Determinants of Magnetic Resonance Imaging (MRI)-Visible Perivascular Spaces in a Large Memory Clinic Cohort

J Am Heart Assoc. 2017 Sep 22;6(9):e006279. doi: 10.1161/JAHA.117.006279.

Abstract

Background: Magnetic resonance imaging-visible perivascular spaces (PVS) are related to interstitial fluid clearance pathways (including amyloid-β) in the brain and are suggested to be a marker of cerebral small vessel disease. We investigated the role, topography, and possible implications of PVS in cognitive impairment.

Methods and results: A total of 1504 patients undergoing memory clinic investigation and an associated brain magnetic resonance imaging scan were included in this cross-sectional study. Magnetic resonance images were assessed for markers of small vessel disease. Additionally, 1039 patients had cerebrospinal fluid analysis of amyloid-β 42, total tau (T-tau), and phosphorylated tau (P-tau); 520 patients had apoE genotyping done. Results were analyzed with generalized linear models. A total of 289 (19%; 95% confidence interval, 17-21) had a high-grade PVS in the centrum semiovale (CSO) and 65 (4%; 95% confidence interval: 3%-5%) in the basal ganglia (BG). Centrum semiovale- and BG-PVS were both associated with high age (P<0.001), hypertension (P<0.001), probable cerebral amyloid angiopathy (P<0.05), moderate-to-severe white matter hyperintensities (P<0.001), cortical superficial siderosis (P<0.001), cerebral microbleeds (P<0.001), and PVS. centrum semiovale-PVS was separately associated with strictly lobar cerebral microbleeds (P=0.057). BG-PVS was associated with strictly deep cerebral microbleeds (P<0.001), lacunes (P<0.001), and vascular dementia (P=0.04). BG-PVS showed a tendency to be associated with high cerebrospinal fluid tau (B=0.002, P=0.04) in the whole cohort and in Alzheimer's disease (B=0.005; P=0.02). No other associations with cerebrospinal fluid or the apoE e4 allele was observed.

Conclusions: Centrum semiovale-PVS and BG-PVS have different underlying etiology, being associated with cerebral amyloid angiopathy and hypertensive vasculopathy, respectively, although a significant overlap between these pathologies is likely to exist.

Keywords: cerebral microbleed; cerebral small vessel disease; cognitive impairment; magnetic resonance imaging.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Apolipoproteins E / genetics
  • Biomarkers / cerebrospinal fluid
  • Brain Mapping / methods*
  • Cerebral Small Vessel Diseases / cerebrospinal fluid
  • Cerebral Small Vessel Diseases / diagnostic imaging*
  • Cerebral Small Vessel Diseases / genetics
  • Cerebral Small Vessel Diseases / psychology
  • Cognition*
  • Cognitive Dysfunction / cerebrospinal fluid
  • Cognitive Dysfunction / diagnostic imaging*
  • Cognitive Dysfunction / genetics
  • Cognitive Dysfunction / psychology
  • Cross-Sectional Studies
  • Female
  • Genotype
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Memory*
  • Middle Aged
  • Outpatient Clinics, Hospital*
  • Peptide Fragments / cerebrospinal fluid
  • Phosphorylation
  • Predictive Value of Tests
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • ApoE protein, human
  • Apolipoproteins E
  • Biomarkers
  • MAPT protein, human
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins