Amyloid Burden on PET and Other Risk Factors for Cerebral Microbleeds

Increased age, male gender, and the presence of baseline cerebral microbleeds (CMBs) is associated with increased risk for developing CMB in any location, while amyloid load in the occipital lobe is associated with developing lobar CMBs, according to study results published in Neurology.

Previous studies have shown that the incidence of CMBs increases with age and CMB burden is associated with the risk for hemorrhagic and ischemic stroke. However, limited data are available on the association between amyloid burden on positron emission tomography (PET) and the risk for CMBs. In light of the known association between lobar CMBs and cerebral amyloid angiopathy, the researchers hypothesized that amyloid burden may predict development of lobar CMBs but not deep CMBs.

The study included 651 adults aged ≥50 years (55% men, mean age 69.8±10 years) who took part in the population-based Mayo Clinic Study of Aging and underwent 3T magnetic resonance imaging between October 2011 and August 2017. CMBs were defined as homogeneous hypointense lesions in gray or white matter, which are distinct from iron or calcium deposits and vessel-flow voids on T2* gradient-recalled echo images. Most patients also underwent ¹¹C Pittsburgh compound B (PiB) PET scans.

The overall incidence rate for developing a new CMB in patients aged 50 to 89 years was 3.6 per 100 persons per year. The incidence increased from 1.5 new CMBs per 100 persons per year at age 50 years to 5.6 new CMBs per 100 persons per year at age 70 years and 11.6 new CMBs per 100 persons per year at age 90 years.

Using the piecewise exponential model, the incidence rates of CMBs in any location increased with age (hazard ratio [HR] for every 10 years, 1.40; 95% CI, 1.10-1.78; P =.007), male gender (HR, 1.79; 95% CI, 1.07 to 3.01; P =.027) and the presence of CMBs (HR, 4.02; 95% CI, 2.46 to 6.56; P <.001). As for the risk for lobar-only CMBs, only male gender (HR, 2.64; 95% CI, 1.31-5.32; P =.006) and the presence of any prior CMB (HR, 3.79; 95% CI, 2.09 to 6.87; P <.001) were significant factors.

While amyloid in various regions of interest on PET did not significantly predict deep CMB or lobar CMB, by substituting occipital amyloid PET load it became a direct predictor of incident lobar CMBs. However, the effect of baseline CMBs on the risk for future new CMBs was stronger than the effect of greater amyloid load at baseline.

The study had several limitations according to the researchers, including different length of follow-up, limited sample size, observational design, as well as possible limitation associated with the imaging modalities used.

“The incidence of CMBs increases steeply with age. While APOE4 and age act through amyloid to increase the risk of incident lobar CMBs, the presence of baseline CMBs was the most important predictor of future CMBs,” concluded the researchers.

Reference

Graff-Radford J, Lesnick T, Rabinstein AA, et al. Cerebral microbleed incidence, relationship to amyloid burden: The Mayo Clinic Study of Aging. Neurology. 2020;94(2):e190–e199. doi:10.1212/WNL.0000000000008735