Microbleeds in Alzheimer Disease Are More Related to Cerebral Amyloid Angiopathy than Cerebrovascular Disease

Abstract

Cerebral amyloid angiopathy (CAA) is one of the cardinal pathological features in the vascular components of Alzheimer’s disease (AD). CAA itself results in disrupted microvasculature, mainly in the cerebral cortex, eventually leading to a brain cortical or subcortical hemorrhage in a population of elderly people, but clinically overt brain hemorrhages are not so frequent in AD patients. Here we assessed 50 AD patients and 26 controls to detect latent brain hemorrhages with gradient-echo T₂*-weighted images, a sensitive magnetic resonance imaging technique to detect hemosiderin components in the brain. Microbleeds, demarcated as low-intensity spots in T₂*-weighted images, were detected in 16.7% of AD patients without cerebrovascular disease (CVD) and in 12.5% of those with CVD, while no microbleeding was detected in the control subjects. No significant difference was observed between the microbleed-positive group and the microbleed-negative counterpart in their clinical background, such as hypertension, the use of antiplatelet drugs and smoking. In addition, white matter high intensities in the T₂-weighted image were significantly more confluent in the microbleed-positive AD group than its negative counterpart. In conclusion, our evaluation of AD brains revealed that latent microbleeds in AD patients are more frequent than in normal controls. Microbleeds not being related to common hemorrhagic risk factors, but being significantly related to white matter pathologies suggested that microbleeds in AD may be associated with CAA, but not with hypertension or CVD.

Prevalence and Topography of Small Hypointense Foci Suggesting Microbleeds on 3T Susceptibility-Weighted Imaging in Various Types of Dementia

“…In healthy subjects or patients with subjective complaints, the prevalence of SHF depicted on 2D T2*-weighted gradient recalled-echo images ranged from 0% to 21%. 14,23,24 It ranged from 18% to 32% in AD 22,25 and from 65% to 85% in VaD 22,26 ; in patients with MCI, it was reported to be 20%. 22 On a 1.5T SWI study by Goos et al, 28 the prevalence of SHF was 30% in subjective complaints, 39% in AD, and 44% in MCI.…”

“…42 Among the neurodegenerative dementia groups, the order of the prevalence of ␤-amyloid binding was similar to that of the relative prevalence of SHF in our study. On the basis of neuropathologic studies, 23,43 microbleeds are frequently observed in the brains of patients with AD and are mainly related to ␤-amyloid pathology (cerebral amyloid angiopathy). Moreover, a neuropathologic study showed a relatively high prevalence of ␤-amyloid pathology and cortical microhemorrhages in the brains of patients with DLB 27,44 and a low prevalence of ␤-amyloid pathology in patients with FTLD.…”

“…19,22,23,25 According to Pettersen et al,19 in patients with AD, SHF are primarily found at occipital sites. Among our patients with AD, there was no significant difference in the location of SHF in frontal, temporal, parietal, and occipital areas.…”

“…11,[19][20][21] Among patients with cognitive disorders, those with AD, MCI, and VaD tend to have SHF. 22 In healthy subjects, the prevalence of SHF detected by 2D T2*-weighted GRE imaging ranged from 0% to 21% 14,23,24 ; it increased to 32% in patients with AD, 25 to 20%…”

Cerebral Microbleeds: Different Prevalence, Topography, and Risk Factors Depending on Dementia Diagnosis—The Karolinska Imaging Dementia Study

“…Alzheimer disease, for instance, is reported to have a CMB prevalence of 18%-32% versus 3%-11% in healthy populations imaged with MR field strengths of 1T-1.5T. [6][7][8][9][10][11][12][13][14][15] Consequently, CMBs are hypothesized to play an important role in the disease mechanisms of dementia as well as being a marker of the synergistic effects between vascular and amyloid pathology. 16 Of further interest, CAA and hypertension are the most common causes of intracerebral hemorrhage, with CMBs being proposed as a possible predictor of intracerebral hemorrhage.…”