Utility of cerebrovascular imaging biomarkers to detect cerebral amyloidosis

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.

FIGURE 1

Differential prediction of Aβ‐PET positivity by CVD‐related MRI findings. Forest plots show the adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for each cohort: Cognitively unimpaired (CU, N = 611, red), mild cognitive impairment (MCI, N = 531, green), and dementia (DEM, N = 210, blue), compared to the overall effect (black). ORs were derived from logistic regression models adjusted for relevant covariates. Cerebral microbleeds (CMBs) and white matter hyperintensity volume (WMHv) are shown to be significant predictors in varying degrees across cohorts. Lacunar infarcts were significant predictors in the CU cohort, only. Statistical significance determined by the Wald test is denoted as follows: *p < 0.05, **p < 0.01, ***p < 0.001.