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Updated: Jul 17, 2025
Visualization of Amyloid β Deposits in the Human Brain with Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry
Published on: March 7, 2019
Cerebral Microbleed Patterns and Cortical Amyloid-β: The ARIC-PET Study
Derrick N Okine1, David S Knopman2, Thomas H Mosley3
1National Institute of Neurological Disorders and Stroke Intramural Research Program, NIH, Bethesda, MD (D.N.O., R.F.G.).
Background:
Cerebral microbleeds (CMBs) are associated with cognitive decline, but their importance outside of cerebral amyloid angiopathy and the mechanisms of their impact on cognition are poorly understood. We evaluated the cross-sectional association between CMB patterns and cerebral Aβ (amyloid-β) deposition, by florbetapir positron emission tomography.
Methods:
The longitudinal ARIC study (Atherosclerosis Risk in Communities) recruited individuals from 4 US communities from 1987 to 1989. From 2012 to 2014, the ARIC-PET (Atherosclerosis Risk in Communities - Positron Emission Tomography) ancillary recruited 322 nondemented ARIC participants who completed 3T brain magnetic resonance imaging with T2*GRE as part of ARIC visit 5 to undergo florbetapir positron emission tomography imaging. Magnetic resonance imaging images were read for CMBs and superficial siderosis; on positron emission tomography, global cortical standardized uptake value ratio >1.2 was considered a positive Aβ scan. Multivariable logistic regression models evaluated CMB characteristics in association with Aβ positivity. Effect modification by sex, race, APOE status, and cognition was evaluated.
Results:
CMBs were present in 24% of ARIC-PET participants. No significant associations were found between CMBs and Aβ positivity, but a pattern of isolated lobar CMBs or superficial siderosis was associated with over 4-fold higher odds of elevated Aβ when compared with those with no CMBs (odds ratio, 4.72 [95% CI, 1.16-19.16]). A similar elevated risk was not observed in those with isolated subcortical or mixed subcortical and either lobar CMBs or superficial siderosis. Although no significant interactions were found, effect estimates for elevated Aβ were nonsignificantly lower (P>0.10, odds ratio, 0.4-0.6) for a mixed CMB pattern, and odds ratios were nonsignificantly higher for lobar-only CMBs for 4 subgroups: women (versus men); Black participants (versus White participants), APOE ε4 noncarriers (versus carriers), and cognitively normal (versus mild cognitive impairment).
Conclusions:
In this community-based cohort of nondemented adults, lobar-only pattern of CMBs or superficial siderosis is most strongly associated with brain Aβ, with no elevated risk for a mixed CMB pattern. Further studies are needed to understand differences in CMB patterns and their meaning across subgroups.
Insights
Isolated lobar cerebral microbleeds (CMBs) or superficial siderosis strongly correlate with elevated brain amyloid-beta (Aβ) in nondemented adults. Other CMB patterns showed no increased Aβ risk, suggesting specific CMB types are key indicators.
Area of Science:
- Neurology
- Neuroimaging
- Gerontology
Background:
- Cerebral microbleeds (CMBs) are linked to cognitive decline, but their role beyond cerebral amyloid angiopathy and their precise impact on cognition remain unclear.
- Understanding the relationship between specific CMB patterns and underlying neuropathology, such as amyloid-beta (Aβ) deposition, is crucial for elucidating cognitive decline mechanisms.
Purpose of the Study:
- To investigate the cross-sectional association between distinct cerebral microbleed (CMB) patterns and cerebral amyloid-beta (Aβ) deposition.
- To evaluate whether specific CMB patterns are associated with increased odds of elevated Aβ levels in a community-based cohort.
Main Methods:
- Utilized data from the Atherosclerosis Risk in Communities (ARIC) study, specifically the ARIC-PET ancillary study.
- Included 322 non-demented participants who underwent 3T brain MRI for CMB and superficial siderosis detection and florbetapir positron emission tomography (PET) for Aβ imaging.
- Employed multivariable logistic regression to analyze CMB characteristics in relation to Aβ positivity, assessing effect modification by sex, race, APOE status, and cognition.
Main Results:
- Cerebral microbleeds (CMBs) were identified in 24% of participants.
- No overall significant association was found between CMBs and Aβ positivity.
- A pattern of isolated lobar CMBs or superficial siderosis was significantly associated with over four-fold higher odds of elevated Aβ (OR, 4.72 [95% CI, 1.16-19.16]) compared to no CMBs. Isolated subcortical or mixed CMB patterns did not show this elevated risk.
Conclusions:
- In non-demented adults, an isolated lobar pattern of CMBs or superficial siderosis is strongly associated with brain Aβ deposition.
- A mixed CMB pattern did not confer an elevated risk for Aβ positivity.
- Further research is warranted to explore the differential meaning of various CMB patterns across diverse demographic subgroups.
