Periventricular hyperintensities are associated with elevated cerebral amyloid

Abstract

Objective: To investigate the association between periventricular white mater hyperintensities (PVWMH) and biomarkers of elevated cerebral β-amyloid (Aβ) in the Alzheimer's Disease Neuroimaging Initiative, a large prospective multicenter observational study.

Methods: The burden of frontal, parietal, and occipital PVWMH on 3T fluid-attenuated inversion recovery MRI was evaluated in 698 cognitively normal participants and participants with mild cognitive impairment (MCI) using a novel semiquantitative visual rating scale. Results were correlated with CSF-Aβ, florbetapir-PET, and fluorodeoxyglucose (FDG)-PET.

Results: Increased burden of parietal, occipital, and frontal PVWMH was associated with elevated cerebral amyloid evidenced by high florbetapir-PET signal (p < 0.01) and low CSF-Aβ (p < 0.01). In logistic regression models, including PVWMH, age, sex, APOE status, vascular risk factors, pulse pressure, vascular secondary prevention medications, education, ethnicity, and race, parietal, occipital, and frontal PVWMH burden was independently associated with high florbetapir-PET uptake (p < 0.05). In a similar logistic regression model, parietal and occipital (p < 0.05) but not frontal (p = 0.05) PVWMH were independently associated with CSF-Aβ. Weaker associations were found between parieto-occipital PVWMH and elevated CSF-tau (p < 0.05) and occipital PVWMH and elevated CSF-phospho-tau (p < 0.05). PVWMH were associated with cerebral hypometabolism on FDG-PET independent of CSF-Aβ levels (p < 0.05). Absolute and consistency of agreement intraclass correlation coefficients were, respectively, 0.83 and 0.83 for frontal, 0.78 and 0.8 for parietal, and 0.45 and 0.75 for occipital PVWMH measurements.

Conclusions: Increased PVWMH were associated with elevated cerebral amyloid independent of potential confounders such as age, APOE genotype, and vascular risk factors. The mechanisms underlying the association between PVWMH and cerebral amyloid remain to be clarified.

Figure 1. Examples of periventricular white matter hyperintensities (PVWMH) grading and measurement

Grade 0 (A) = no PVWMH; grade 1 (B) = PVWMH present but not extending to deep sulcal cortex; grade 2 (C) = PVWMH extending to deep sulcal cortex but not into a gyrus; grade 3 (D) = PVWMH extending into a gyrus but not reaching superficial gyral cortex in 1 gyrus; grade 4 (E) = PVWMH extending to superficial gyral cortex in 1 gyrus; grade 5 (F) = PVWMH extending to superficial gyral cortex in 2 gyri; grade 6 (G, H) = PVWMH extending to superficial gyral cortex in 3 or more gyri. Frontal periventricular hyperintensities measurement (green line in I) and parietal periventricular hyperintensities measurement (green line in J) are displayed.