Cerebral microbleeds: a review of clinical, genetic, and neuroimaging associations

Abstract

Cerebral microbleeds (microbleeds) are small, punctuate hypointense lesions seen in T2* Gradient-Recall Echo (GRE) and Susceptibility-Weighted (SWI) Magnetic Resonance Imaging (MRI) sequences, corresponding to areas of hemosiderin breakdown products from prior microscopic hemorrhages. They occur in the setting of impaired small vessel integrity, commonly due to either hypertensive vasculopathy or cerebral amyloid angiopathy. Microbleeds are more prevalent in individuals with Alzheimer's disease (AD) dementia and in those with both ischemic and hemorrhagic stroke. However they are also found in asymptomatic individuals, with increasing prevalence with age, particularly in carriers of the Apolipoprotein (APOE) ε4 allele. Other neuroimaging findings that have been linked with microbleeds include lacunar infarcts and white matter hyperintensities on MRI, and increased cerebral β-amyloid burden using (11)C-PiB Positron Emission Tomography. The presence of microbleeds has been suggested to confer increased risk of incident intracerebral hemorrhage - particularly in the setting of anticoagulation - and of complications of immunotherapy for AD. Prospective data regarding the natural history and sequelae of microbleeds are currently limited, however there is a growing evidence base that will serve to inform clinical decision-making in the future.

Keywords: Alzheimer’s disease; MRI imaging; amyloid imaging; cerebral amyloid angiopathy; intracerebral hemorrhage; microbleeds; positron-emission tomography; stroke.

Figure 1

Diffuse (predominantly non-lobar) Microbleeds in an 81-year-old lady referred with AD-type dementia (MMSE 22/30, CDR 1, CDR-SOB 5.5). SWI image (A), with coregistered FLAIR (B), T2 (C) and 11C-PiB PET (D) images demonstrating severe deep white matter hyperintensities but no significant beta-amyloid burden (neocortical SUVR = 1.2), suggesting that the presentation is due to severe cerebral small vessel disease, rather than Alzheimer’s disease.

Figure 2

Lobar Microbleed (red arrow) and Superficial Hemosiderosis (white arrows) in a 66-year-old lady referred initially with amnestic MCI (MMSE 22/30, CDR 0.5, CDR-SOB 4.5), subsequently diagnosed with AD-type dementia. SWI image (A), with coregistered FLAIR (B), T2 (C) and 11C-PiB PET (D) images demonstrating severe deep white matter hyperintensities with elevated beta-amyloid burden (neocortical SUVR = 1.7).