Pathogenesis of cerebral microbleeds: In vivo imaging of amyloid and subcortical ischemic small vessel disease in 226 individuals with cognitive impairment

Park, Jae Hyun; Seo, Sang Won; Kim, Chang-Soo; Kim, Geon Ha; Noh, Han-Jin; Kim, Sung Tae; Kwak, Ki Chang; Yoon, Uicheul; Lee, Jong Min; Lee, Jong Weon; Shin, Jae Sung; Kim, Chi Hun; Noh, Young; Cho, Hanna; Kim, Hee Jin; Yoon, Cindy W.; Oh, Seung Jun; Kim, Jae Seung; Choe, Yearn Seong; Lee, Kyung Han; Lee, Jae Hong; Ewers, Michael; Weiner, Michael W.; Werring, David J.; Na, Duk L.

doi:10.1002/ana.23845

Cited by 146 publications

(115 citation statements)

References 32 publications

(38 reference statements)

Supporting

Mentioning

105

Contrasting

Order By: Relevance

“…20 Deep MBs have been suggested to be relevant to subcortical small vessel disease (SVD), such as lacunar infarction or white matter lesions, but not to amyloid burden. 21 Thus, deep or infratentorial MBs strongly suggest the existence of hypertensive microangiopathy rather than CAA.…”

Section: Brain Images and Photomicrographs Of Evacuated Hematoma Anmentioning

confidence: 99%

Clinico-Radiological Characteristics and Pathological Diagnosis of Cerebral Amyloid Angiopathy-Related Intracerebral Hemorrhage

Doden

Sato

Sasahara

et al. 2016

Journal of Stroke and Cerebrovascular Diseases

View full text Add to dashboard Cite

Objective: We aim to clarify the clinico-radiological characteristics of cerebral amyloid angiopathy-related intracerebral hemorrhage and to investigate the efficacy of pathological diagnosis using biopsy specimens. Method: We retrospectively reviewed 253 consecutive patients with cortico-subcortical hemorrhage who had been admitted to Aizawa Hospital between January 2006 and July 2013. We had performed craniotomy and hematoma evacuation in 48 patients, as well as biopsy of the evacuated hematoma, cerebral parenchyma adjacent to the hematoma, or both, and they were classified according to the histological results (positive or negative for vascular amyloid deposition) and to the Boston criteria. We compared the clinicoradiological characteristics of cerebral amyloid angiopathy-related intracerebral hemorrhage. We also investigated the detection rate of cerebral amyloid angiopathy with respect to the origins of the specimens. Results: Pathological examination revealed that 22 subjects were positive for vascular amyloid. The number of the cerebral microbleeds located in the deep or infratentorial region was significantly larger in the negative group than in the positive group (P < .05). There was no significant difference in the distribution of lobar cerebral microbleeds and in the prevalence of hypertension. In the probable cerebral amyloid angiopathyrelated intracerebral hemorrhage patients, the probability of having vascular amyloid detected by biopsy of both hematoma and parenchyma was 100%. Rebleeding in the postoperative periods was observed in 2 cases (9.1%) of the positive group.Conclusions: Our results demonstrate the importance and safety of biopsy simultaneously performed with hematoma evacuation. Deep or infratentorial microbleeds are less correlated with cerebral amyloid angiopathy-related intracerebral hemorrhage than with noncerebral amyloid angiopathy-related intracerebral hemorrhage.

show abstract

Section: Brain Images and Photomicrographs Of Evacuated Hematoma Anmentioning

confidence: 99%

Clinico-Radiological Characteristics and Pathological Diagnosis of Cerebral Amyloid Angiopathy-Related Intracerebral Hemorrhage

Doden

Sato

Sasahara

et al. 2016

Journal of Stroke and Cerebrovascular Diseases

View full text Add to dashboard Cite

show abstract

“…The relevance of microbleeds in dementias became evident with the availability of improved functional imaging technologies. [4][5][6] Although CAA is recapitulated in various mouse models of AD, 3,[7][8][9] there is a paucity of functional imaging studies in AD models. 10 Brain endothelial cells (EC) signal to vascular smooth muscle cells to regulate cerebral blood flow (CBF).…”

Section: Introductionmentioning

confidence: 99%

Chronic Rapamycin Restores Brain Vascular Integrity and Function Through NO Synthase Activation and Improves Memory in Symptomatic Mice Modeling Alzheimer’s Disease

Lin¹,

Zheng

Halloran

et al. 2013

J Cereb Blood Flow Metab

181

204

View full text Add to dashboard Cite

Vascular pathology is a major feature of Alzheimer's disease (AD) and other dementias. We recently showed that chronic administration of the target-of-rapamycin (TOR) inhibitor rapamycin, which extends lifespan and delays aging, halts the progression of AD-like disease in transgenic human (h)APP mice modeling AD when administered before disease onset. Here we demonstrate that chronic reduction of TOR activity by rapamycin treatment started after disease onset restored cerebral blood flow (CBF) and brain vascular density, reduced cerebral amyloid angiopathy and microhemorrhages, decreased amyloid burden, and improved cognitive function in symptomatic hAPP (AD) mice. Like acetylcholine (ACh), a potent vasodilator, acute rapamycin treatment induced the phosphorylation of endothelial nitric oxide (NO) synthase (eNOS) and NO release in brain endothelium. Administration of the NOS inhibitor L-NG-Nitroarginine methyl ester reversed vasodilation as well as the protective effects of rapamycin on CBF and vasculature integrity, indicating that rapamycin preserves vascular density and CBF in AD mouse brains through NOS activation. Taken together, our data suggest that chronic reduction of TOR activity by rapamycin blocked the progression of AD-like cognitive and histopathological deficits by preserving brain vascular integrity and function. Drugs that inhibit the TOR pathway may have promise as a therapy for AD and possibly for vascular dementias.

show abstract

“…Therefore, occipital CMBs in the M‐CMBs group could have been caused by HV only, or alternatively, by HV with adjunct CAA. Synergistic effects of HV and CAA on the development of lobar CMB has indeed been reported in patients with M‐CMBs in radiological (Cordonnier & van der Flier, 2011; Fazekas et al., 1999; Park et al., 2013) and neuropathological studies (Ellis et al., 1996; Olichney et al., 1995; Thal, Ghebremedhin, Orantges, & Wiestler, 2003). In addition, the presence of multiple lobar CMBs in itself may reflect CAA, even if these are not SL‐CMBs (Benedictus et al., 2013; Mesker et al., 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Mixed (deep/infratentorial with lobar) CMBs (M‐CMBs) are also thought to reflect HV (Greenberg et al., 2009; Vernooij et al., 2008). HV and CAA may synergistically contribute to the development of lobar CMBs (Cordonnier & van der Flier, 2011; Fazekas et al., 1999; Kim et al., 2016; Lee, Kim, Kim, Yoon, & Roh, 2007; Park et al., 2013; Smith et al., 2010). …”

Section: Introductionmentioning

confidence: 99%

Background and distribution of lobar microbleeds in cognitive dysfunction

et al. 2017

View full text Add to dashboard Cite

ObjectivesCerebral microbleeds (CMBs) are often observed in memory clinic patients. It has been generally accepted that deep CMBs (D‐CMBs) result from hypertensive vasculopathy (HV), whereas strictly lobar CMBs (SL‐CMBs) result from cerebral amyloid angiopathy (CAA) which frequently coexists with Alzheimer's disease (AD). Mixed CMBs (M‐CMBs) have been partially attributed to HV and also partially attributed to CAA. The aim of this study was to elucidate the differences between SL‐CMBs and M‐CMBs in terms of clinical features and regional distribution.MaterialsWe examined 176 sequential patients in our memory clinic for clinical features and CMB location using susceptibility‐weighted images obtained on a 3T‐MRI. The number of lobar CMBs in SL‐CMBs and M‐CMBs was counted in each cerebral lobe and their regional density was adjusted according to the volume of each lobe.ResultsOf the total 176 patients, 111 patients (63.1%) had CMBs. Within the patients who had CMBs, M‐CMBs were found in 54 patients (48.6%), followed by SL‐CMBs in 35 (31.5%) and D‐CMBs in 19 (17.1%). The SL‐CMB group showed a significantly higher prevalence of family history of dementia, whereas the M‐CMB group showed an increasing trend toward hypertension and smoking. The prevalence of AD was significantly higher in the SL‐CMBs group, whereas the prevalence of AD with cerebrovascular disease was higher in the M‐CMBs group. The regional density of lobar CMBs was significantly higher in the occipital lobe in the M‐CMB group, whereas the SL‐CMB group showed higher regional density between regions an increasing tendency in the parietal and occipital lobe.ConclusionThe between‐group differences in clinical features and regional distribution indicate there to be an etiological relationship of SL‐CMBs to AD and CAA, and M‐CMBs to both HV and CAA.

show abstract

Pathogenesis of cerebral microbleeds: In vivo imaging of amyloid and subcortical ischemic small vessel disease in 226 individuals with cognitive impairment

Cited by 146 publications

References 32 publications

Clinico-Radiological Characteristics and Pathological Diagnosis of Cerebral Amyloid Angiopathy-Related Intracerebral Hemorrhage

Clinico-Radiological Characteristics and Pathological Diagnosis of Cerebral Amyloid Angiopathy-Related Intracerebral Hemorrhage

Chronic Rapamycin Restores Brain Vascular Integrity and Function Through NO Synthase Activation and Improves Memory in Symptomatic Mice Modeling Alzheimer’s Disease

Background and distribution of lobar microbleeds in cognitive dysfunction

Contact Info

Product

Resources

About