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Incidence of cerebral microbleeds in preclinical Alzheimer disease
Open accessAbstract
OBJECTIVE: We sought to determine the incidence and associations of lobar microbleeds (LMBs) in a longitudinal cohort with (11)C-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 (11)C-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.
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“This broad range of detection could likely be attributed to the magnet field strength, with clinical strength 1.5 and 3T magnets likely underestimating the incidence of microbleeds compared with the research-grade 7T magnet (83, 246, 452, 530, 604, 669).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [669]
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“Thus, the risk of brain microhemorrhages related to Aβ immunotherapy may be a transient complication and possibly reduced in individuals with modest VAβ burden, who also have lower prevalence of spontaneous microbleeds [58, 59].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [58]
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“CNS microbleeds reflect loss of cerebrovascular integrity and are found in 25% of individuals with MCI (669) and 45-78% of individuals with early AD without dementia (83, 208, 246, 452, 476, 529, 604, 702).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [669]
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“Both VAβ and hypertensive or atherosclerotic microangiopathy are recognized clinical risk factors for cerebral microbleeds, with the former correlating stronger with bleeding in cortical/subcortical distribution [58, 59] while the later with bleeding to deep brain structures including basal ganglia and thalamic nuclei [60, 61].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [58]
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Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders
Sweeney, M. D., Sagare, A. P., & Zlokovic, B. V. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.188 · Cited by 3,076
Blood-Brain Barrier: From Physiology to Disease and Back
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Metadata
- Authors
- 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., & For the AIBL Research Group
- Affiliations
- Edith Cowan University (AU)
- ORCID
- Venue
- Neurology
- Published
- 2014-04-08
- Volume
- 82
- Issue
- 14
- Pages
- 1266-1273
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC4001205
- OpenAlex
- W1992608632
- Cited by
- 150
- References
- 41
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 9 · 2023: 7 · 2022: 16 · 2021: 16 · 2020: 11 · 2019: 13 · 2018: 10 · 2017: 12 · 2016: 13 · 2015: 20 · 2014: 7
- FWCI
- 13.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Bank (Australian Catholic University) (submittedVersion)
- Research Online (Edith Cowan University) (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Funders
- Eli Lilly and Company
- Pfizer
- Commonwealth Scientific and Industrial Research Organisation
- Dementia Collaborative Research Centres, Australia
- H. Lundbeck A/S
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Clinical Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- cerebral microbleeds, lobar microbleeds, preclinical Alzheimer's disease, mild cognitive impairment, amyloid PET, APOE ε4, cerebrovascular disease, lacunar infarction, white matter hyperintensities
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid, Aniline Compounds, Australia, Brain, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Thiazoles, Incidence, Intracranial Hemorrhages, Positron-Emission Tomography, Cerebral Small Vessel Diseases
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