Cerebral Microbleeds May Block Brain Blood Flow
Chronic hypoperfusion may put cognitively normal seniors at risk for neurodegeneration.
Even in cognitively normal older patients, cerebral microbleeds may portend a higher risk of neurodegeneration and cognitive impairment, researchers found.
In a single-center study of 55 patients, the presence of any cerebral microbleed showed a trend toward reduced cerebral blood flow, although the finding wasn't statistically significant, according to William Klunk, MD, PhD, of the University of Pittsburgh, and colleagues.But when they homed in on cortical cerebral microbleeds, there was a significant reduction in cerebral blood flow (P=0.0003), they reported online in JAMA Neurology.
"Chronic hypoperfusion may put these people at risk for neuronal injury and neuronal degeneration," they wrote.
Cerebral microbleeds, or remnants of the leakage of red blood cells from small cerebral vessels, are a common incidental finding on MRI in healthy older patients. They've also been found in patients with symptomatic intracerebral hemorrhage and Alzheimer's, and are associated with two types of small-vessel disease: cerebral amyloid angiopathy (CAA) and arteriosclerosis/lipohyalinosis.
Some studies have also shown them to be associated with greater cognitive impairment, but the mechanism behind how this type of small vessel disease could contribute to cognitive deficits isn't clear.
Klunk and colleagues conducted a cross-sectional study of 55 cognitively normal patients with mean age of about 87, all of whom were asymptomatic; 21 of them (38%) had cerebral microbleeds.
They found that patients who had any cerebral microbleeds had a trend toward reduced cerebral blood flow, but it wasn't significant.
However, when they focused specifically on cortical cerebral microbleeds, they found significant reductions in cerebral blood flow in multiple brain regions (percentage difference in global cerebral blood flow of -25.3%, P=0.0003).
The cortical regions with the most significant reductions in cerebral blood flow were the frontal, parietal (-37.6%, P<0.0001), and precuneus cortices (-31.8%,P=0.0006), with lesser but still significant reductions in the occipital cortex on the voxelwise analysis, they reported.
There was also a significant association between cortical cerebral microbleeds and greater prevalence of infarcts (24% versus 6%, P=0.047).
Finally, there was no difference in cortical amyloid between participants with and without cerebral microbleeds based on Pittsburgh compound B PET scans (P=0.06).
"Although not a standard subgroup to evaluate, cortical cerebral microbleeds are a subset of lobar cerebral microbleeds and suggest underlying cerebral amyloid angiopathy," they wrote.
They added that the data will help researchers better understand the temporal relationships between cerebral amyloid angiopathy, cerebral small vessel disease, cerebral blood flow, cerebral metabolism, neurodegeneration, fibrillary amyloid beta, and cognition.
Klunk and colleagues also found that patients with cortical cerebral microbleeds had a trend toward greater prevalence of non-zero global Clinical Dementia Rating (CDR) scale scores compared with those without, but the findings weren't significant (45% versus 19%, P=0.12).
There were no differences in cortical amyloid levels between patients with and without cerebral microbleeds, and no association between the presence of cerebral microbleeds and fibrillar amyloid beta burden or APOE*4 carrier status, they reported.
The study was limited by its small sample size, by the advanced age of the participants, and by its cross-sectional design. Still, the researchers concluded that the findings suggest resting-state cerebral blood flow could be a marker of small vessel disease related to cerebral microbleeds.
"Our findings suggest that asymptomatic elderly individuals with cortical cerebral microbleeds are exposed to chronic cerebral hypoperfusion, although no causal association can be inferred from the present data," they wrote. "However, this combination, which may reflect widespread cerebral amyloid angiopathy-related cerebrovascular dysfunction, could put these elderly individuals at risk for neuronal injury or cerebrovascular events."
"Early diagnosis of cerebral amyloid angiopathy and markers of disease severity -- potentially resting-state cerebral blood flow -- could be key elements for understanding the pathophysiology of cerebral amyloid angiopathy and developing treatments," they concluded.
They also pointed out that longitudinal evaluation of the participants in the study will yield additional information on the ties between small vessel disease, cerebral blood flow, neurodegeneration, fibrillar amyloid beta, and cognition.
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