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

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.

[1]  P Kapeller,et al.  Histopathologic analysis of foci of signal loss on gradient-echo T2*-weighted MR images in patients with spontaneous intracerebral hemorrhage: evidence of microangiopathy-related microbleeds. , 1999, AJNR. American journal of neuroradiology.

[2]  J. Hatazawa,et al.  Assessment of lacunar hemorrhage associated with hypertensive stroke by echo-planar gradient-echo T2*-weighted MRI. , 2000, Stroke.

[3]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[4]  Eric E. Smith,et al.  Hemorrhage Burden Predicts Recurrent Intracerebral Hemorrhage After Lobar Hemorrhage , 2004, Stroke.

[5]  V. Mok,et al.  Cerebral microbleeds and white matter changes in patients hospitalized with lacunar infarcts , 2004, Journal of Neurology.

[6]  A Hofman,et al.  Hypertension and cerebral white matter lesions in a prospective cohort study. , 2002, Brain : a journal of neurology.

[7]  Rhoda Au,et al.  Cerebral Microbleeds: Prevalence and Associations With Cardiovascular Risk Factors in the Framingham Study , 2004, Stroke.

[8]  H Lechner,et al.  White matter signal abnormalities in normal individuals: correlation with carotid ultrasonography, cerebral blood flow measurements, and cerebrovascular risk factors. , 1988, Stroke.

[9]  Soichiro Shimizu,et al.  Cerebral microbleeds in Alzheimer’s disease , 2003, Journal of Neurology.

[10]  Eric E. Smith,et al.  Amyloid Angiopathy–Related Vascular Cognitive Impairment , 2004, Stroke.

[11]  L. Thal,et al.  Cerebral infarction in Alzheimer's disease is associated with severe amyloid angiopathy and hypertension. , 1995, Archives of neurology.

[12]  S. Atlas,et al.  Intracranial hemorrhage: gradient-echo MR imaging at 1.5 T. Comparison with spin-echo imaging and clinical applications. , 1988, Radiology.

[13]  S. Greenberg,et al.  White matter lesions, cognition, and recurrent hemorrhage in lobar intracerebral hemorrhage , 2004, Neurology.

[14]  R. Kalaria Cerebrovascular Degeneration Is Related to Amyloid‐β Protein Deposition in Alzheimer's Disease a , 1997 .

[15]  K. Yoshikawa,et al.  Subclinical Brain Hemorrhages in Alzheimer's Disease: Evaluation by Magnetic Resonance T2*‐Weighted Images , 2002, Annals of the New York Academy of Sciences.

[16]  R. Kalaria Cerebrovascular degeneration is related to amyloid-beta protein deposition in Alzheimer's disease. , 1997, Annals of the New York Academy of Sciences.

[17]  L. Thal,et al.  Cerebral amyloid angiopathy in the brains of patients with Alzheimer's disease , 1996, Neurology.

[18]  M. van Buchem,et al.  Microbleeds in hereditary cerebral hemorrhage with amyloidosis- Dutch type , 2005, Neurology.