MedicalResearch.com Interview with:
Christopher Chen, FRCP
Department of Pharmacology
Yong Loo Lin School of Medicine
Memory Aging and Cognition Center
National University Health System
Saima Hilal, PhD
Department of Pharmacology, National University of Singapore
Department of Radiology, Epidemiology and Nuclear Medicine
Erasmus Medical Center, Rotterdam, the Netherlands
MedicalResearch.com: What is the background for this study?
Response: Cerebral microinfarcts (CMIs) are defined as small (usually <1 mm) regions of ischemic change found in the brain which are not readily visible on gross examination or on standard 1.5-T magnetic resonance imaging (MRI). On microscopy they appear as foci of neuronal loss, gliosis, pallor, or cysts.
Previous post mortem studies have shown that the presence of CMIs is relatively common in elderly individuals without dementia (24%) but more common in patients diagnosed with Alzheimer disease (43%) or vascular dementia (62%).
Whilst a single CMI is likely to be “silent” as the region of brain affected is probably too small to produce symptoms or neurologic deficits, however, as a large number of CMIs exist in many individuals, especially in the cerebral cortex and watershed areas, the overall effect has clinical importance – as shown by neuropathologic studies which demonstrate an important role of CMIs in cognitive dysfunction and dementia. However in vivo studies have been hampered by the inability to detect CMIs reliably on neuroimaging, leading to CMIs being termed “invisible” during life.
The advent of high spatial-definition 7-T MRI enabled the identification of cortical Cerebral microinfarcts in-vivo and importantly a study that directly compared 7-T and 3-T MRIs in the same patients reported that 3-T MRI detected about 1/3 of the lesions found on 7-T MRIs, suggesting that 3-T MRIs, which are more accessible than 7-T, may be able to detect larger cortical CMIs with a lower limit of approximately 1 mm in diameter.
Our group has made major contributions recently on the clinical associations of 3T MRI detected cortical CMIs in patients from memory clinics as well as in community based subjects. Associations were found with age, vascular risk factors, other MRI markers of cerebrovascular disease as well as cognition. However, the causes of CMIs remain unclear and may be heterogeneous with microembolism, microthrombosis, and foci of inflammation as possible causative factors.
MedicalResearch.com: What are the main findings?
Response: In order to further elucidate mechanisms and hence treatment, the current paper, reported in JAMA Neurology, investigated the association of cortical Cerebral microinfarcts with clinically overt cardiac disease and with 2 biomarkers of subclinical cardiac disease (N-terminal pro–brain natriuretic peptide and high-sensitivity cardiac troponin T).
In a multivariate analyses, the presence of cortical CMIs was strongly associated not only with clinically overt cardiac disease but also with cardiac biomarkers. Repeat analysis after exclusion of individuals with clinically overt cardiac disease showed a correlation of the
number of cortical CMIs with blood biomarkers of subclinical cardiac disease.
MedicalResearch.com: What should readers take away from your report?
Response: Cortical CMIs are detectable in vivo on widely available 3T MRI.
Cortical CMIs have an important role in studies of cerebrovascular disease, particularly with regard to cognitive dysfunction, and better understanding of the underlying pathophysiology may lead to improved treatment strategies.
The novel association with cardiac biomarkers could be attributed to underlying shared risk factors (although known cardiovascular risk factors were included in the multivariate model) or could represent subclinical cardiac disease as a cause of cortical CMIs. Together with the association with overt cardiac disease, the results suggest that cardiac dysfunction should be targeted as a potentially modifiable factor to prevent cortical CMI-related brain injury and hence cognitive impairment.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Additional studies in other populations may be needed to confirm and define the sensitivity, specificity, and reproducibility of 3-T MRI for Cerebral microinfarcts. Further prospective studies are needed to understand the additional value of markers of cardiac dysfunction in the development of cortical CMIs and whether cortical CMIs may serve as surrogate outcomes in evaluating the effectiveness of treatments for cerebrovascular disease–related cognitive impairment.
MedicalResearch.com: Is there anything else you would like to add?
Response: This study was funded by grants NMRC/CG/NUHS/2010 and NMRC/CG/013/2013 from the Singapore National Medical Research Council
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Hilal S, Chai YL, van Veluw S, Shaik MA, Ikram MK, Venketasubramanian N, Richards AM, Biessels GJ, Chen C. Association Between Subclinical Cardiac Biomarkers and Clinically Manifest Cardiac Diseases With Cortical Cerebral Microinfarcts. JAMA Neurol. Published online February 06, 2017. doi:10.1001/jamaneurol.2016.5335
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