Microbleeds, Mortality, and Stroke in Alzheimer Disease: The MISTRAL Study
Marije R Benedictus1, Niels D Prins1, Jeroen D C Goos1
1Alzheimer Center, Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
Importance:
Microbleeds are more prevalent in patients with Alzheimer disease (AD) compared with the general elderly population. In addition, microbleeds have been found to predict mortality in AD.
Objective:
To investigate whether microbleeds in AD increase the risk for mortality, stroke (including intracerebral hemorrhage), and cardiovascular events.
Design, Setting And Participants:
The MISTRAL (do MIcrobleeds predict STRoke in ALzheimer's disease) Study is a longitudinal cohort study within the memory clinic-based Amsterdam Dementia Cohort. We selected all patients with AD with a baseline visit between January 2, 2002, and December 16, 2009, and microbleeds (n = 111) and matched those (1:2) for age, sex, and magnetic resonance imaging scanner to 222 patients with AD without microbleeds. After a minimal follow-up of 3 years, information on all-cause mortality, stroke-related mortality, and cardiovascular mortality was obtained between November 1, 2012, and May 1, 2014. In addition, we obtained information on the occurrence of incident stroke or transient ischemic attack, cardiovascular events, and nursing home admittance.
Main Outcomes And Measures:
Stroke-related mortality, incident stroke, and intracerebral hemorrhage.
Results:
Patients had a mean (SD) age of 71.2 (7.8) years and 127 (42%) were female. Compared with having no microbleeds, microbleeds in lobar locations were associated with an increased risk for stroke-related mortality (hazard ratio [HR], 33.9; 95% CI, 2.5-461.7), whereas nonlobar microbleeds were associated with an increased risk for cardiovascular mortality (HR, 12.0; 95% CI, 3.2-44.7). In addition, lobar microbleeds were associated with an increased risk for incident stroke (HR, 3.8; 95% CI, 1.5-10.1) and nonlobar microbleeds with an increased risk for cardiovascular events (HR, 6.2; 95% CI, 1.5-25.0). Even higher risks for incident stroke and cardiovascular events were found in patients using antithrombotic medication. All 5 patients with an intracerebral hemorrhage had lobar microbleeds at baseline; 4 of them used antithrombotics.
Conclusions And Relevance:
In patients with AD, the presence of nonlobar microbleeds was associated with an increased risk for cardiovascular events and cardiovascular mortality. Patients with lobar microbleeds had an increased risk for stroke and stroke-related mortality, indicating that these patients should be treated with the utmost care.
Insights
Microbleeds in Alzheimer disease (AD) patients increase risks. Lobar microbleeds are linked to stroke and mortality, while nonlobar microbleeds are associated with cardiovascular events and mortality.
Area of Science:
- Neurology
- Cardiology
- Geriatrics
Background:
- Microbleeds are common in Alzheimer disease (AD) patients and predict mortality.
- The specific impact of microbleed location on AD patient outcomes requires further investigation.
Purpose of the Study:
- To determine if microbleeds in AD patients elevate risks for mortality, stroke, and cardiovascular events.
- To differentiate the risks associated with lobar versus nonlobar microbleeds in AD.
Main Methods:
- Longitudinal cohort study (MISTRAL Study) of 111 AD patients with microbleeds and 222 matched controls without microbleeds.
- Follow-up of at least 3 years to record all-cause mortality, stroke-related mortality, cardiovascular mortality, incident stroke, transient ischemic attack, cardiovascular events, and nursing home admittance.
- Analysis of microbleed location (lobar vs. nonlobar) and its association with clinical outcomes.
Main Results:
- Lobar microbleeds significantly increased the risk of stroke-related mortality (HR, 33.9) and incident stroke (HR, 3.8).
- Nonlobar microbleeds were associated with increased cardiovascular mortality (HR, 12.0) and cardiovascular events (HR, 6.2).
- Patients using antithrombotic medication showed even higher risks for stroke and cardiovascular events; all intracerebral hemorrhages occurred in patients with lobar microbleeds, mostly on antithrombotics.
Conclusions:
- Nonlobar microbleeds in AD patients are linked to higher risks of cardiovascular events and mortality.
- Lobar microbleeds in AD patients are associated with increased risks of stroke and stroke-related mortality.
- These findings highlight the importance of careful management for AD patients with microbleeds, considering their location.
Related Concept Videos
01:29Alzheimer Disease l: Introduction
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