Utility of cerebrovascular imaging biomarkers to detect cerebral amyloidosis

Alzheimers Dement. 2024 Oct;20(10):7220-7231. doi: 10.1002/alz.14207. Epub 2024 Sep 1.

Abstract

Introduction: The relationship between cerebrovascular disease (CVD) and amyloid beta (Aβ) in Alzheimer's disease (AD) is understudied. We hypothesized that magnetic resonance imaging (MRI)-based CVD biomarkers-including cerebral microbleeds (CMBs), lacunar infarction, and white matter hyperintensities (WMHs)-would correlate with Aβ positivity on positron emission tomography (Aβ-PET).

Methods: We cross-sectionally analyzed data from the Alzheimer's Disease Neuroimaging Initiative (ADNI, N = 1352). Logistic regression was used to calculate odds ratios (ORs), with Aβ-PET positivity as the standard-of-truth.

Results: Following adjustment, WMHs (OR = 1.25) and superficial CMBs (OR = 1.45) remained positively associated with Aβ-PET positivity (p < 0.001). Deep CMBs and lacunes exhibited a varied relationship with Aβ-PET in cognitive subgroups. The combined diagnostic model, which included CVD biomarkers and other accessible measures, significantly predicted Aβ-PET (pseudo-R2 = 0.41).

Discussion: The study highlights the translational value of CVD biomarkers in diagnosing AD, and underscores the need for more research on their inclusion in diagnostic criteria.

Clinicaltrials: gov: ADNI-2 (NCT01231971), ADNI-3 (NCT02854033).

Highlights: Cerebrovascular biomarkers linked to amyloid beta (Aβ) in Alzheimer's disease (AD). White matter hyperintensities and cerebral microbleeds reliably predict Aβ-PET positivity. Relationships with Aβ-PET vary by cognitive stage. Novel accessible model predicts Aβ-PET status. Study supports multimodal diagnostic approaches.

Keywords: ADNI; Alzheimer's disease; amyloid beta; cerebrovascular disease; magnetic resonance imaging; positron emission tomography; small vessel disease.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / diagnostic imaging
  • Amyloid beta-Peptides* / metabolism
  • Amyloidosis / diagnostic imaging
  • Biomarkers*
  • Brain / diagnostic imaging
  • Brain / pathology
  • Cerebral Amyloid Angiopathy / diagnostic imaging
  • Cerebral Amyloid Angiopathy / pathology
  • Cerebrovascular Disorders / diagnostic imaging
  • Cross-Sectional Studies
  • Female
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Neuroimaging
  • Positron-Emission Tomography*
  • White Matter / diagnostic imaging
  • White Matter / pathology

Substances

  • Biomarkers
  • Amyloid beta-Peptides

Associated data

  • ClinicalTrials.gov/NCT01231971
  • ClinicalTrials.gov/NCT02854033