Do Cerebral Microbleeds Lead to Cognitive Deficit?

Cognitively normal elderly individuals with cerebral microbleeds experience chronic cortical hypoperfusion and may be at risk of cognitive decline, a recent cross-sectional study reports.¹

Cerebral microbleeds are a common finding on magnetic resonance imaging in older individuals. Microbleeds have been detected in both healthy individuals and those with brain disease, such as symptomatic cerebral amyloid angiopathy and Alzheimer’s disease. Limited data demonstrate the role of microbleeds in predicting progression to dementia and severity of cognitive impairment.² If microbleeds and cognitive impairment are indeed associated, what is the nature of this association?

To answer the question, Nicholas Gregg and colleagues² measured the number and location of microbleeds, cerebral blood flow, and cortical β-amyloid, among other characteristics, in 55 cognitively normal individuals (average age 86.8 years) and analyzed these data to reveal any possible associations.

Study participants with cortical microbleeds had 25% reduction in resting-state cerebral blood flow, compared to participants with other microbleeds (subcortical, cerebellar, and brainstem), P=0.0003. Cerebral blood flow in participants with all microbleeds and without microbleeds did not differ (P=0.022; P<0.00625 was considered statistically significant).

Clearly, cortical microbleeds are different than microbleeds located in other brain regions. This observation aligns with past reports that link location of microbleeds to the form of vasculopathy and even to deficit in specific cognitive domains with which affected brain region is affiliated.

Although all study participants were identified as cognitively normal, participants with cortical microbleeds had a trend towards cognitive impairment (45% vs 19% of participants with and without cortical microbleeds, respectively, had nonzero global Clinical Dementia Rating scale score, P=0.12). These findings complement reports of decreased cerebral blood flow in patients with microbleeds diagnosed with cerebral amyloid angiopathy or Alzheimer disease.³ Individuals with cortical microbleeds regardless of cognitive deficit experience chronic cerebral hypoperfusion, which may promote cortical neurodegeneration. Cognitive deficit may be a consequence of neurodegeneration in these individuals.

Burden of β-amyloid and presence or number of microbleeds were not associated in the present study (P=0.6). Possible reasons for the lack of the association are old age and high prevalence of β-amyloid positivity in this cohort, authors speculate. Study participants with cortical microbleeds had met the Boston Criteria for possible or probable cerebral amyloid angiopathy, and authors noted “the potential of resting-state [cerebral blood flow] measured by arterial spin-labeled MRI to be a marker of [cerebral amyloid angiopathy].”

It is possible that these individuals with microbleeds, hypoperfusion of cerebral cortex, and a trend toward cognitive deficit have asymptomatic pathology of small cortical vessels. Presymptomatic diagnosis of progressive diseases like cerebral amyloid angiopathy using resting-state blood flow and other markers is important. For example, it can help understand progression of disease, develop early therapies, and select patients for clinical trials of therapies and vaccines. Hence, larger studies of markers of vascular disease are much needed. These studies should aim to clarify the association of microbleeds with cerebral blood flow and cognitive impairment.

References:

1. Gregg NM, et al. Incidental cerebral microbleeds and cerebral blood flow in elderly individuals. JAMA Neurol. 2015 Jul 13. [Epub ahead of print]

2. Martinez-Ramirez S, et al. Cerebral microbleeds: overview and implications in cognitive impairment. Alzheimers Res Ther. 2014;6:33.

3. Doi H, et al. Analysis of cerebral lobar microbleeds and a decreased cerebral blood flow in a memory clinic setting. Intern Med. 2015;54(9):1027-1033.