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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.
GLOSSARY
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- AIBL=
- Australian Imaging, Biomarkers and Lifestyle Study of Ageing;
- CAA=
- cerebral amyloid angiopathy;
- CI=
- confidence interval;
- FLAIR=
- fluid-attenuated inversion recovery;
- GRE=
- gradient-recall echo;
- LMB=
- lobar microbleed;
- MCI=
- mild cognitive impairment;
- MP-RAGE=
- magnetization-prepared rapid-acquisition gradient echo;
- NC=
- normal cognition;
- OR=
- odds ratio;
- PiB=
- Pittsburgh compound B;
- SS=
- superficial siderosis;
- SUVR=
- standardized uptake value ratio;
- SWI=
- susceptibility-weighted imaging;
- TE=
- echo time;
- TR=
- repetition time;
- VRF=
- vascular risk factor;
- WMH=
- white matter hyperintensity
Footnotes
AIBL Research Group coinvestigators are listed on the Neurology® Web site at Neurology.org.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
- Received August 6, 2013.
- Accepted in final form December 29, 2013.
- © 2014 American Academy of Neurology
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