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Cerebral Amyloid Angiopathy Burden and Cerebral Microbleeds: Pathological Evidence for Distinct Phenotypes
Jonathan Graff-Radford1, Timothy G Lesnick2, Michelle M Mielke1,2
1Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Background:
The relationship between cerebral microbleeds (CMBs) on hemosiderin-sensitive MRI sequences and cerebral amyloid angiopathy (CAA) remains unclear in population-based participants or in individuals with dementia.
Objective:
To determine whether CMBs on antemortem MRI correlate with CAA.
Methods:
We reviewed 54 consecutive participants with antemortem T2*GRE-MRI sequences and subsequent autopsy. CMBs were quantified on MRIs closest to death. Autopsy CAA burden was quantified in each region including leptomeningeal/cortical and capillary CAA. By a clustering approach, we examined the relationship among CAA variables and performed principal component analysis (PCA) for dimension reduction to produce two scores from these 15 interrelated predictors. Hurdle models assessed relationships between principal components and lobar CMBs.
Results:
MRI-based CMBs appeared in 20/54 (37%). 10 participants had ≥2 lobar-only CMBs. The first two components of the PCA analysis of the CAA variables explained 74% variability. The first rotated component (RPC1) consisted of leptomeningeal and cortical CAA and the second rotated component of capillary CAA (RPC2). Both the leptomeningeal and cortical component and the capillary component correlated with lobar-only CMBs. The capillary CAA component outperformed the leptomeningeal and cortical CAA component in predicting lobar CMBs. Both capillary and the leptomeningeal/cortical components correlated with number of lobar CMBs.
Conclusion:
Capillary and leptomeningeal/cortical scores correlated with lobar CMBs on MRI but lobar CMBs were more closely associated with the capillary component. The capillary component correlated with APOEɛ4, highlighting lobar CMBs as one aspect of CAA phenotypic diversity. More CMBs also increase the probability of underlying CAA.
Insights
Cerebral microbleeds (CMBs) on MRI scans are linked to cerebral amyloid angiopathy (CAA). Capillary CAA showed a stronger association with lobar CMBs than leptomeningeal/cortical CAA, suggesting CMBs reflect CAA diversity.
Area of Science:
- Neurology
- Radiology
- Pathology
Background:
- The link between cerebral microbleeds (CMBs) detected by MRI and cerebral amyloid angiopathy (CAA) is not well understood in general populations or dementia patients.
- Further research is needed to clarify the relationship between CMBs and CAA.
Purpose of the Study:
- To investigate the correlation between antemortem MRI-identified CMBs and autopsy-confirmed CAA.
- To explore the specific components of CAA that relate to CMB presence and distribution.
Main Methods:
- Retrospective analysis of 54 participants with antemortem T2*GRE-MRI and autopsy data.
- Quantification of CMBs on MRI and CAA burden (leptomeningeal/cortical and capillary) at autopsy.
- Principal component analysis (PCA) to reduce dimensionality of CAA variables, followed by hurdle models to assess associations with lobar CMBs.
Main Results:
- CMBs were present in 37% of participants; 10 had lobar-only CMBs.
- PCA identified two main components of CAA: leptomeningeal/cortical and capillary.
- Both CAA components correlated with lobar-only CMBs, with capillary CAA showing a stronger association.
Conclusions:
- Capillary and leptomeningeal/cortical CAA components correlate with lobar CMBs, with capillary CAA being more predictive.
- Capillary CAA component association with APOEε4 suggests CMBs represent CAA phenotypic diversity.
- Increased CMBs indicate a higher likelihood of underlying CAA.
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