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Published on: April 23, 2021
Determinants of cerebral microbleed presence and burden in CADASIL
Jessica Lebenberg1,2, Louis Lambert1,2, Laura Tintoré-Carbonell1,2
1Inserm 1127, Institut du Cerveau, ICM, F-75013, Paris, France.
Insights
Cerebral microbleeds (CMBs) in CADASIL patients are linked to age and hypertension, influencing lesion presence and count. These findings highlight hypertension’s role in microbleed development and overall cerebrovascular disease severity.
Area of Science:
- Neurology
- Medical Imaging
- Genetics
Background:
- Cerebral microbleeds (CMBs) affect one-third of CADASIL patients, increasing with age.
- Previous studies on CMB factors are limited by statistical methods and measurement variability.
Purpose of the Study:
- To assess factors associated with cerebral microbleeds (CMBs) in CADASIL patients.
- To address limitations in handling zero-inflated, long-tailed distributions and measurement variability.
Main Methods:
- A large CADASIL cohort was analyzed using demographic, vascular, genetic, imaging, and clinical data.
- Hurdle modeling was employed to differentiate factors for CMB presence versus lesion counts, accounting for measurement variability.
- Three models focused on demographic/biological factors, MRI markers, and clinical variables.
Main Results:
- CMB presence correlated with age, male sex, and hypertension.
- MRI markers like white matter hyperintensity volume and lacune count were associated with CMBs.
- Clinical factors including stroke history and gait disturbances were linked to CMB presence.
Conclusions:
- Hurdle modeling effectively separates determinants of CMB occurrence from accumulation.
- Hypertension may reduce the threshold for CMB emergence, particularly with aging.
- CMB burden reflects overall cerebrovascular disease severity and microangiopathic processes.
Background & Aims:
Cerebral microbleeds (CMBs) are observed in one-third of CADASIL patients and increase with age. Factors associated with CMBs vary across studies, likely due to inadequate handling of their zero-inflated, long-tailed distribution and lack of accounting for measurement variability. We aimed to assess these factors while addressing these limitations.
Methods:
CMBs were assessed in a large CADASIL cohort, with demographic, vascular, genetic, imaging, and clinical data. White matter hyperintensity volume (WMH), lacune count, and brain parenchymal fraction (BPF) were measured. A Hurdle model was used to distinguish factors associated with CMB presence from those related to lesion counts, while accounting for measurement variability. Three models were built with: (1) demographic/biological factors; (2) MRI markers; and (3) clinical variables.
Results:
Beyond the consistent effect of the MRI sequence, in Model 1, CMB presence was associated with age, male sex and hypertension, while counts were associated only with age. In Model 2, CMB presence was associated with age, hypertension, and lacune count; counts were higher with WMH and antiplatelet use, and lower with EGFr 1-6 mutations and BPF. In Model 3, CMB presence was associated with age, hypertension, stroke history and gait disturbances; counts were associated with education, lacune count, MMSE ≤24, and hypercholesterolemia measured at the study visit.
Conclusions:
Hurdle modeling distinguishes determinants of CMB occurrence from accumulation. Hypertension appears to lower the threshold for lesion emergence along aging. CMB burden is associated with the burden of cerebrovascular lesions, brain atrophy and clinical severity, supporting worsening of the microangiopathic process, with specific impact related to mutation type.
