Journal
NEUROLOGY
Volume 82, Issue 14, Pages 1266-1273Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0000000000000285
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Funding
- Australian Commonwealth Scientific Industrial and Research Organization
- Edith Cowan University
- Mental Health Research Institute
- Alzheimer's Australia
- National Ageing Research Institute
- Austin Health
- CogState Ltd.
- Hollywood Private Hospital
- Sir Charles Gardner Hospital
- National Health and Medical Research Council
- Dementia Collaborative Research Centres program
- Science and Industry Endowment Fund
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Objective:We sought to determine the incidence and associations of lobar microbleeds (LMBs) in a longitudinal cohort with C-11-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 C-11-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 epsilon 4+ 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 epsilon 4+, 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 -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.
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