Please wait a minute...
 Home  About the Journal Editorial Board Aims & Scope Peer Review Policy Subscription Contact us
 
Early Edition  //  Current Issue  //  Open Special Issues  //  Archives  //  Most Read  //  Most Downloaded  //  Most Cited
Aging and disease    2015, Vol. 6 Issue (6) : 437-443     DOI: 10.14336/AD.2015.0429
Original Article |
Topography of Cortical Microbleeds in Alzheimer’s Disease with and without Cerebral Amyloid Angiopathy: A Post-Mortem 7.0-Tesla MRI Study
De Reuck J.*(), Auger F., Durieux N., Deramecourt V., Cordonnier C., Pasquier F., Maurage C.A., Leys D., Bordet R.
Université de Lille 2, INSERM U1171, F-59000 Lille, France
Download: PDF(1014 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks    
Abstract  

Cortical microbleeds (CMBs) detected on T2*-weighted gradient-echo (GRE) magnetic resonance imaging (MRI) are considered as a possible hallmark of cerebral amyloid angiopathy (CAA). The present post-mortem 7.0-tesla MRI study investigates whether topographic differences exist in Alzheimer’s brains without (AD) and with CAA (AD-CAA). The distribution of CMBs in thirty-two post-mortem brains, consisting of 12 AD, 8 AD-CAA and 12 controls, was mutually compared on T2*-GRE MRI of six coronal sections of a cerebral hemisphere. The mean numbers of CMBs were determined in twenty-two different gyri. As a whole there was a trend of more CMBs on GRE MRI in the prefrontal section of the AD, the AD-CAA as well as of the control brains. Compared to controls AD brains had significantly more CMBs in the superior frontal, the inferior temporal, the rectus and the cinguli gyrus, and in the insular cortex. In AD-CAA brains CMBs were increased in all gyri with exception of the medial parietal gyrus and the hippocampus. AD-CAA brains showed a highly significant increase of CMBs in the inferior parietal gyrus (p value: 0.001) and a significant increase in the precuneus and the cuneus (p value: 0.01) compared to the AD brains. The differences in topographic distribution of CMBs between AD and AD-CAA brains should be further investigated on MRI in clinically suspected patients.

Keywords 7.0-tesla magnetic resonance imaging      topography of post-mortem cortical microbleeds      Alzheimer’s disease      cerebral amyloid angiopathy (CAA)     
Corresponding Authors: De Reuck J.     E-mail: dereuck.j@gmail.com.
About author:

present address: Kunming Biomed International, Kunming, Yunnan, 650500, China

Issue Date: 01 December 2015
Service
E-mail this article
E-mail Alert
RSS
Articles by authors
De Reuck J.
Auger F.
Durieux N.
Deramecourt V.
Cordonnier C.
Pasquier F.
Maurage C.A.
Leys D.
Bordet R.
Cite this article:   
De Reuck J.,Auger F.,Durieux N., et al. Topography of Cortical Microbleeds in Alzheimer’s Disease with and without Cerebral Amyloid Angiopathy: A Post-Mortem 7.0-Tesla MRI Study[J]. Aging and disease, 2015, 6(6): 437-443.
URL:  
http://www.aginganddisease.org/EN/10.14336/AD.2015.0429     OR     http://www.aginganddisease.org/EN/Y2015/V6/I6/437
Frontal LobeTemporal LobeParietal lobeOccipital Lobe
Frontalis inferiorTemporalis inferiorPostcentralisLingualis
Frontalis mediusTemporalis mediusInsulaPrecuneus
Frontalis superiorTemporalis superiorParietalis inferiorCuneus
PrecentralisHippocampusParietalis mediusOccipitotemporalis
RectusDentatusParietalis superior
OrbitalisParahippocampalisCinguli
Table 1  Brain regions and gyri of interest on magnetic resonance imaging
ItemsControl (n= 12)AD (n= 12)AD-CAA (n= 8)
Age: years (interquartile range)64 (60-78)68 (63-76)70 (63-88)
Gender (% males)676750
Vascular risk factors (%)
Arterial hypertension174238
Diabetes171725
Hypercholesterolemia171725
Smoking0813
Antithrombotic drug use253350
Neuropathological lesions: mean values (SD)
White matter changes0.3 (0.8)0.8 (0.8)1.3 (1.3)
Lacunar infarcts0.0 (0.0)0.0 (0.0)0.3 (0.7)
Territorial infarcts0.0 (0.0)0.1 (0.3)0.0 (0.0)
Lobar haematomas0.0 (0.0)0.0 (0.0)0.0 (0.0)
Cortical microinfarcts0.1 (0.3)0.8 (1.1)1.4 (1.1)*
Cortical microbleeds0.1 (0.3)0.4 (0.7)1.1 (0.6)*
Table 2  Demographic and neuropathological features in controls and in Alzheimer patients without (AD) and with cerebral amyloid angiopathy (AD-CAA)
Figure 1.  Mean numbers of cortical microbleeds in the six coronal sections on T2*-weighted gradient-echo magnetic resonance imaging. An anterior-posterior decreasing gradient of the cortical microbleeds is observed in the Alzheimer brains with and without cerebral amyloid angiopathy as well as in the control brains.
Figure 2.  Parietal coronal section. Cortical microbleeds on T2*-weighted gradient-echo magnetic resonance imaging of a whole coronal parietal brain section and more in detail in the gyrus parietalis inferior (A) and in the precuneus (B). The arrows indicate the presence of some cortical microbleeds.
GyrusC (n= 12)AD (n= 12)AD-CAA (n= 8)P value AD/AD-CAA
Frontalis inferior0.8 (0.9)2.3 (2.7)4.8 (2.9)**0.03
Frontalis medius1.2 (1.4)1.9 (1.4)4.3 (2.5)*0.03
Frontalis superior1.2 (1.4)3.1 (1.8)*6.7 (3.4)**0.02
Precentralis1.1 (1.5)2.1 (1.3)2.8 (0.8)*0.27
Rectus0.4 (0.7)1.5 (1.2)*4.4 (3.8)**0.07
Orbitalis0.8 (1.1)2.1 (2.0)4.3 (1.6)**0.02
Temporalis inferior0.4 (1.0)2.6 (3.0)*3.4 (2.6)**0.30
Temporalis medius0.5 (0.8)1.9 (1.9)3.7 (2.9)**0.16
Temporalis superior0.6 (1.1)1.5 (1.2)3.9 (3.2)**0.06
Hippocampus0.4 (0.8)0.8 (0.8)1.1 (1.6)1.0
Dentatus0.7 (1.2)1.9 (2.1)2.4 (1.7)*0.38
Parahippocampalis0.5 (1.1)1.0 (1.6)2.0 (1.2)*0.05
Postcentralis0.7 (0.9)2.3 (2.6)2.9 (1.6)**0.18
Insula0.0 (0.0)1.8 (2.7)*2.4 (1.8)**0.18
Parietalis inferior0.3 (0.4)0.7 (0.6)2.9 (2.2)**0.001**
Parietalis medius1.2 (1.4)1.7 (1.0)2.9 (2.6)0.34
Parietalis superior0.6 (0.5)1.7 (1.6)2.7 (2.3)*0.31
Cinguli0.4 (0.6)1.5 (1.7)*3.0(2.0)**0.02
Lingualis Precuneus Cuneus Occipitotemporalis0.3(0.9) 0.6 (1.0) 0.5 (0.9) 0.6 (1.0)1.4(2.7) 0.9 (1.6) 0.8 (1.5) 2.4 (2.2)2.9(2.2)** 3.3 (2.8)* 3.2 (2.6)* 4.6 (3.0)**0.03 0.01* 0.01* 0.18
Table 3  Mean numbers of cortical microbleeds with standard deviations between bracquets in the different gyri of control and Alzheimer brains without (AD) and with cerebral amyloid angiopathy (AD-CAA)
Figure 3.  Occipital coronal section. Cortical microbleeds on T2*-weighted gradient-echo magnetic resonance imaging of a whole coronal occipital brain section (A) and more in detail in the cuneus (B). The arrows indicate the presence of some cortical microbleeds.
[1] Greenberg SM, Vernooij MW, Cordonnier C, Viswanathan A, Al-Shari Salman R, Warach S,et al (2009). Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol, 8: 165-174.
[2] Cordonnier C, Al-Shahi Salman R, Wardlaw J (2007). Spontaneous brain microbleeds, systematic review, subgroup analyses and standards for study design and reporting. Brain, 130: 1988-2003.
[3] Cordonnier C, van der Flier WM, Sluimer JD, Leys D, Barkhof F, Scheltens Ph (2006). Prevalence and severity of microbleeds in a memory clinic setting. Neurology, 66: 1356-1360.
[4] Goos JD, Kester MI, Barkhof F, Klein M, Scheltens P, van der Flier WM (2009). Patients with Alzheimer disease with multiple microbleeds: relation with cerebrospinal fluid biomarkers and cognition. Stroke, 40: 3455-3460.
[5] Nakata-Kudo Y, Mizuno T, Yamada K, Shiga K, Yoshikawa K, Mori S,et al (2006). Microbleeds in Alzheimer disease are more related to cerebral amyloid angiopathy than to cerebrovascular disease. Dement Geriatr Cogn Disord, 22: 8-14.
[6] Ellis RJ, Olichney JM, Thal LJ, Mirra SS, Morris JC, Beekly BS,et al (1996). Cerebral amyloid angiopathy in the brains of patients with Alzheimer’s disease: the CERAD experience, Part XV. Neurology, 46: 1592-1596.
[7] De Reuck J, Deramecourt V, Cordonnier C, Leys, Maurage CA, Pasquier F (2011). The impact of cerebral amyloid angiopathy on the occurrence of cerebrovascular lesions in demented patients with Alzheimer features: a neuropathological study. Eur J Neurol, 18: 913-918.
[8] Vismanathan A, Greenberg SM (2011). Cerebral amyloid angiopathy in the elderly. Ann Neurol, 70: 871-880.
[9] Knudsen KA, Rosand J, Karluk D, Greenberg SM (2001). Clinical diagnosis of cerebral amyloid angiopathy. Neurology, 56: 537-539.
[10] Rosand J, Muzikansky A, Kumar A, Wisco JJ, Smith EE, Betensky RA,et al (2005). Spatial clustering of hemorrhages in probable cerebral amyloid angiopathy. Ann Neurol, 58: 459-462.
[11] De Reuck J, Cordonnier C, Deramecourt V, Auger F, Durieux N, Bordet R,et al (2013). Microbleeds in postmortem brains of Alzheimer disease: a T2*-weighted gradient-echo 7.0 T magnetic resonance imaging study. Alzheimer Dis Assoc Disord, 27: 162-165.
[12] Lee SH, Kim SM, Kim N, Yoon BW, Roh JK (2007). Cortico-subcortical distribution of microbleeds is different between hypertension and cerebral amyloid angiopathy. J Neurol Sci. 258: 111-114.
[13] De Reuck J (2012). The significance of small cerebral bleeds in neurodegenerative dementia syndromes. Aging Dis, 4: 307-312.
[14] De Reuck J, Deramecourt V, Cordonnier C, Leys D, Pasquier F, Maurage C-A (2011). Prevalence of small cerebral bleeds in patients with a neurodegenerative dementia: a neuropathological study. J Neurol Sci, 30: 63-66.
[15] De Reuck J, Auger F, Cordonnier C, Deramecourt V, Durieux N, Pasquier F,et al (2011). Comparison of 7.0-T2*-magnetic resonance imaging of cerebral bleeds in post-mortem brain sections of Alzheimer patients with their neuropathological correlates. Cerebrovasc Dis 2011, 31: 511-517.
[16] Roberts M, Hanaway J.Atlas of the human brain in section. Philadelphia. Lea & Febiger, 1970.
[17] Sproull NL.“Hypothesis testing”. Handbook of Research Methods: A Guide for Practitioners and Students in the Social Science (2nd ed.). Lanham. Scarecrow Press, 2002: 49-64.
[18] Peca S, McCreary CR, Donaldson E, Kumarpillai G, Shobha N, Sanchez K,et al (2013). Neurovascular decoupling is associated with severity of cerebral amyloid angiopathy. Neurology, 81: 1659-1665.
[19] Radua J, Philips ML, Russell T, Lawrence N, Marshall N, Kalidindi S,et al (2010). Neural response to specific components of fearful faces in healthy and schizophrenic adults. Neuroimage, 49: 939-946.
[20] Cavanna AE, Trimble MR (2006). The precuneus: a review of its functional anatomy and behaviour correlates. Brain, 129: 564-583.
[21] Rodrigues G, Morbelli S, Brugnolo A, Calvini P, Girtler N, Piccardo A,et al (2005). Global cognitive impairment should be taken into account in SPECT-neuropsychology correlations: the example of verbal memory in very mild Alzheimer’s disease. Eur J Nucl Med Mol Imaging, 32: 1186-1192.
[22] Semendeferi K, Damasio H, Frank R (1997). The evolution of the frontal lobes: a volumetric analysis based on three-dimensional reconstructions of magnetic resonance scans of human and ape brains. J Hum Evol, 32: 375-388.
[1] Jong Bin Bae,Ji Won Han,Kyung Phil Kwak,Bong Jo Kim,Shin Gyeom Kim,Jeong Lan Kim,Tae Hui Kim,Seung-Ho Ryu,Seok Woo Moon,Joon Hyuk Park,Jong Chul Youn,Dong Young Lee,Dong Woo Lee,Seok Bum Lee,Jung Jae Lee,Jin Hyeong Jhoo,Ki Woong Kim. Is Dementia More Fatal Than Previously Estimated? A Population-based Prospective Cohort Study[J]. Aging and disease, 2019, 10(1): 1-11.
[2] Antonina Luca, Carmela Calandra, Maria Luca. Molecular Bases of Alzheimer’s Disease and Neurodegeneration: The Role of Neuroglia[J]. Aging and disease, 2018, 9(6): 1134-1152.
[3] Sone Daichi, Imabayashi Etsuko, Maikusa Norihide, Ogawa Masayo, Sato Noriko, Matsuda Hiroshi, Japanese-Alzheimer’s Disease Neuroimaging Initiative. Voxel-based Specific Regional Analysis System for Alzheimer’s Disease (VSRAD) on 3-tesla Normal Database: Diagnostic Accuracy in Two Independent Cohorts with Early Alzheimer’s Disease[J]. Aging and disease, 2018, 9(4): 755-760.
[4] Morroni Fabiana, Sita Giulia, Graziosi Agnese, Turrini Eleonora, Fimognari Carmela, Tarozzi Andrea, Hrelia Patrizia. Neuroprotective Effect of Caffeic Acid Phenethyl Ester in A Mouse Model of Alzheimer’s Disease Involves Nrf2/HO-1 Pathway[J]. Aging and disease, 2018, 9(4): 605-622.
[5] Xu Yangqi, Liu Xiaoli, Shen Junyi, Tian Wotu, Fang Rong, Li Binyin, Ma Jianfang, Cao Li, Chen Shengdi, Li Guanjun, Tang Huidong. The Whole Exome Sequencing Clarifies the Genotype- Phenotype Correlations in Patients with Early-Onset Dementia[J]. Aging and disease, 2018, 9(4): 696-705.
[6] Ding Qiong, Tanigawa Kitora, Kaneko Jun, Totsuka Mamoru, Katakura Yoshinori, Imabayashi Etsuko, Matsuda Hiroshi, Hisatsune Tatsuhiro. Anserine/Carnosine Supplementation Preserves Blood Flow in the Prefrontal Brain of Elderly People Carrying APOE e4[J]. Aging and disease, 2018, 9(3): 334-345.
[7] Shen Ting, You Yuyi, Joseph Chitra, Mirzaei Mehdi, Klistorner Alexander, Graham Stuart L., Gupta Vivek. BDNF Polymorphism: A Review of Its Diagnostic and Clinical Relevance in Neurodegenerative Disorders[J]. Aging and disease, 2018, 9(3): 523-536.
[8] Peng Fangyu, Xie Fang, Muzik Otto. Alteration of Copper Fluxes in Brain Aging: A Longitudinal Study in Rodent Using 64CuCl2-PET/CT[J]. Aging and disease, 2018, 9(1): 109-118.
[9] Castillo-Carranza Diana L, Nilson Ashley N, Van Skike Candice E, Jahrling Jordan B, Patel Kishan, Garach Prajesh, Gerson Julia E, Sengupta Urmi, Abisambra Jose, Nelson Peter, Troncoso Juan, Ungvari Zoltan, Galvan Veronica, Kayed Rakez. Cerebral Microvascular Accumulation of Tau Oligomers in Alzheimer’s Disease and Related Tauopathies[J]. Aging and disease, 2017, 8(3): 257-266.
[10] Sternberg Zohara, Hu Zihua, Sternberg Daniel, Waseh Shayan, Quinn Joseph F., Wild Katharine, Jeffrey Kaye, Zhao Lin, Garrick Michael. Serum Hepcidin Levels, Iron Dyshomeostasis and Cognitive Loss in Alzheimer’s Disease[J]. Aging and disease, 2017, 8(2): 215-227.
[11] Zaia Annamaria, Maponi Pierluigi, Di Stefano Giuseppina, Casoli Tiziana. Biocomplexity and Fractality in the Search of Biomarkers of Aging and Pathology: Focus on Mitochondrial DNA and Alzheimer’s Disease[J]. Aging and disease, 2017, 8(1): 44-56.
[12] Wang Jianhui, Cheng Xiaorui, Zeng Ju, Yuan Jiangbei, Wang Zhongfu, Zhou Wenxia, Zhang Yongxiang. LW-AFC Effects on N-glycan Profile in Senescence-Accelerated Mouse Prone 8 Strain, a Mouse Model of Alzheimer’s Disease[J]. Aging and disease, 2017, 8(1): 101-114.
[13] Gurses Murat Serdar, Ural Mustafa Numan, Gulec Mehmet Akif, Akyol Omer, Akyol Sumeyya. Pathophysiological Function of ADAMTS Enzymes on Molecular Mechanism of Alzheimer’s Disease[J]. Aging and disease, 2016, 7(4): 479-490.
[14] Day Ryan J., McCarty Katie L., Ockerse Kayla E., Head Elizabeth, Rohn Troy T.. Proteolytic Cleavage of Apolipoprotein E in the Down Syndrome Brain[J]. Aging and disease, 2016, 7(3): 267-277.
[15] Onyango Isaac G., Dennis Jameel, Khan Shaharyah M.. Mitochondrial Dysfunction in Alzheimer’s Disease and the Rationale for Bioenergetics Based Therapies[J]. Aging and disease, 2016, 7(2): 201-214.
Viewed
Full text


Abstract

Cited

  Shared   
Copyright © 2014 Aging and Disease, All Rights Reserved.
Address: Aging and Disease Editorial Office 3400 Camp Bowie Boulevard Fort Worth, TX76106 USA
Fax: (817) 735-0408 E-mail: editorial@aginganddisease.org
Powered by Beijing Magtech Co. Ltd