Title

Incidence of cerebral microbleeds in preclinical Alzheimer disease

Document Type

Journal Article

Publisher

Lippincott Williams and Wilkins

Faculty

Faculty of Health, Engineering and Science

School

School of Medical Sciences

RAS ID

18799

Comments

This article was originally published as: Yates P.A., Desmond P.M., Phal P.M., Steward C., Szoeke C., Salvado O., Ellis K.A., Martins R.N., Masters C.L., Ames D., Villemagne V.L., Rowe C.C. (2014). Incidence of cerebral microbleeds in preclinical Alzheimer disease. Neurology, 82(14), 1266-1273. Original article available here

Abstract

Objective: We sought to determine the incidence and associations of lobar microbleeds (LMBs) in a longitudinal cohort with 11C-Pittsburgh compound B (PiB) PET imaging. Methods: One hundred seventy-four participants from the observational Australian Imaging, Biomarkers and Lifestyle Study of Ageing (97 with normal cognition [NC], 37 with mild cognitive impairment [MCI], and 40 with Alzheimer disease [AD] dementia) were assessed at 3 time points over 3 years with 3-tesla susceptibility-weighted MRI and 11C-PiB PET. MRIs were inspected for microbleeds, siderosis, infarction, and white matter hyperintensity severity, blind to clinical and PiB findings. Neocortical PiB standardized uptake value ratio, normalized to cerebellar cortex, was dichotomized as positive or negative (PiB+/-, standardized uptake value ratio >1.5). Annualized LMB incidence was calculated, and logistic regression was used to determine the association of incident LMBs with PiB, APOE ε4+ status, and cerebrovascular disease. Results: LMBs were present in 18.6% of NC, 24.3% of MCI, and 40% of AD participants (p < 0.05 vs NC). LMB incidence was 0.2 ± 0.6 per year in NC participants, 0.2 ± 0.5 in MCI, and 0.7 ± 1.4 in AD (p < 0.03 vs NC) and was 6-fold higher in PiB+ than PiB-NC. Incident LMBs were associated with age, APOE ε4+, PiB+, and baseline LMBs. Incidence of multiple LMBs was also associated with lacunar infarction and white matter hyperintensity severity. Conclusions: Older age, baseline LMBs, higher β-amyloid burden, and concomitant cerebrovascular disease may all confer higher risk of incident LMBs. This should be considered when designing protocols for amyloid-modifying clinical trials.

DOI

10.1212/WNL.0000000000000285

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