Increased number of microinfarcts in Alzheimer disease at 7-T MR imaging.

PURPOSE To assess the prevalence and number of cortical microinfarcts in patients with Alzheimer disease (AD) by using a 7-T magnetic resonance (MR) imaging system, to assess the independent association of cortical microinfarcts with cognitive dysfunction, and to investigate potential confounding effects of the coexisting presence of cerebral amyloid angiopathy (CAA). MATERIALS AND METHODS The local institutional review board approved this study. In all cases, informed consent was obtained. High-spatial-resolution fluid-attenuated inversion recovery and T2*-weighted images were acquired in 14 AD patients and 18 control subjects to assess the presence of microinfarcts and microbleeds. Presence of CAA was assessed according to the Boston criteria. Image analysis was performed independently by two reviewers. Mann-Whitney U test was performed to assess differences in number of microinfarcts between groups. Negative binomial regression models were used to assess the association between diagnosis of AD and diagnosis of CAA and number of microinfarcts, between diagnosis of AD and number of microbleeds and number of microinfarcts, and between cognitive function and number of microinfarcts, all corrected for age and sex. RESULTS Interobserver agreement was excellent for detecting microinfarcts (κ = 0.91) (P < .001). Patients with AD demonstrated higher number (P = .005) of microinfarcts (mean, 7.2) compared with control subjects (mean, 1.8). Negative binomial regression models showed an independent association between AD and number of microinfarcts (P = .006) and a trend for CAA and microinfarcts (P = .052). A negative correlation was found between cognitive function and the number of microinfarcts (P = .009). CONCLUSION Patients with AD show more microinfarcts than do control subjects, the number of microinfarcts correlates with global cognitive performance, and the presence of microinfarcts was mainly AD rather than CAA related.

[1]  Geert Jan Biessels,et al.  Cerebral Microinfarcts: A Systematic Review of Neuropathological Studies , 2012, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[2]  Olga Pletnikova,et al.  Effect of infarcts on dementia in the Baltimore longitudinal study of aging , 2008, Annals of neurology.

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

[4]  M. Brundel,et al.  Cerebral microinfarcts: A systematic review of neuropathological studies , 2011, Alzheimer's & Dementia.

[5]  Peter R Luijten,et al.  Visualization of cerebral microbleeds with dual‐echo T2*‐weighted magnetic resonance imaging at 7.0 T , 2010, Journal of magnetic resonance imaging : JMRI.

[6]  S. Greenberg,et al.  The Pathophysiology and Clinical Presentation of Cerebral Amyloid Angiopathy , 2012, Current Atherosclerosis Reports.

[7]  S. Greenberg,et al.  Silent ischemic infarcts are associated with hemorrhage burden in cerebral amyloid angiopathy , 2009, Neurology.

[8]  Peter R Luijten,et al.  High‐resolution magnetization‐prepared 3D‐FLAIR imaging at 7.0 Tesla , 2010, Magnetic resonance in medicine.

[9]  P. Hof,et al.  The relationship between cerebral amyloid angiopathy and cortical microinfarcts in brain ageing and Alzheimer's disease , 2013, Neuropathology and applied neurobiology.

[10]  H. Braak,et al.  Neuropathology and Cognitive Impairment in Alzheimer Disease: A Complex but Coherent Relationship , 2009, Journal of neuropathology and experimental neurology.

[11]  L. White Brain lesions at autopsy in older Japanese-American men as related to cognitive impairment and dementia in the final years of life: a summary report from the Honolulu-Asia aging study. , 2009, Journal of Alzheimer's disease : JAD.

[12]  H. Vinters,et al.  Cerebral Microinfarcts Associated with Severe Cerebral β‐Amyloid Angiopathy , 2010, Brain pathology.

[13]  M. Maeda,et al.  In vivo Detection of Cortical Microinfarcts on Ultrahigh‐Field MRI , 2013, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[14]  R. Kalaria,et al.  Cerebral hypoperfusion accelerates cerebral amyloid angiopathy and promotes cortical microinfarcts , 2011, Acta Neuropathologica.

[15]  S. Greenberg,et al.  Cerebral amyloid angiopathy , 1998, Neurology.

[16]  Steven Warach,et al.  Cerebral Microbleeds : A Field Guide to their Detection and Interpretation , 2012 .

[17]  S. Haneuse,et al.  Pathological correlates of dementia in a longitudinal, population‐based sample of aging , 2007, Annals of neurology.

[18]  Bradley T. Hyman,et al.  Apolipoprotein E ε4 Is Associated With the Presence and Earlier Onset of Hemorrhage in Cerebral Amyloid Angiopathy , 1996 .

[19]  Eric E. Smith,et al.  Cerebral microinfarcts: the invisible lesions , 2012, The Lancet Neurology.

[20]  J. Baron,et al.  Acute ischaemic brain lesions in intracerebral haemorrhage: multicentre cross-sectional magnetic resonance imaging study. , 2011, Brain : a journal of neurology.

[21]  C. Jack,et al.  Ecology of the aging human brain. , 2011, Archives of neurology.

[22]  Peter R Luijten,et al.  Generalized multiple-layer appearance of the cerebral cortex with 3D FLAIR 7.0-T MR imaging. , 2012, Radiology.

[23]  P. Hof,et al.  Cortical microinfarcts and demyelination affect cognition in cases at high risk for dementia , 2007, Neurology.

[24]  Hidekazu Tomimoto,et al.  Cortical microinfarcts in Alzheimer's disease and subcortical vascular dementia , 2009, Neuroreport.

[25]  Peter R Luijten,et al.  In Vivo Detection of Cerebral Cortical Microinfarcts with High-Resolution 7T MRI , 2013, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[26]  B. Ouyang,et al.  Acute Brain Infarcts After Spontaneous Intracerebral Hemorrhage: A Diffusion-Weighted Imaging Study , 2010, Stroke.

[27]  J. R. Landis,et al.  The measurement of observer agreement for categorical data. , 1977, Biometrics.

[28]  S. Greenberg,et al.  Characteristic distributions of intracerebral hemorrhage–associated diffusion-weighted lesions , 2012, Neurology.

[29]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease: Report of the NINCDS—ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease , 2011, Neurology.

[30]  D. Werring,et al.  Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum , 2011, Journal of Neurology, Neurosurgery & Psychiatry.

[31]  P. Hof,et al.  Sorting out the clinical consequences of ischemic lesions in brain aging: A clinicopathological approach , 2007, Journal of the Neurological Sciences.

[32]  D. Le Bihan,et al.  Intracortical Infarcts in Small Vessel Disease: A Combined 7-T Postmortem MRI and Neuropathological Case Study in Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy , 2011, Stroke.

[33]  R. Kraftsik,et al.  Cerebral Hypoperfusion Generates Cortical Watershed Microinfarcts in Alzheimer Disease , 2002, Stroke.

[34]  P. Hof,et al.  Cortical Microinfarcts and Demyelination Significantly Affect Cognition in Brain Aging , 2004, Stroke.

[35]  B T Hyman,et al.  Apolipoprotein E epsilon 4 is associated with the presence and earlier onset of hemorrhage in cerebral amyloid angiopathy. , 1996, Stroke.