This study examines the issue of """"""""silent"""""""" strokes in the relationship between the structural stability of atherosclerotic carotid plaque and the development of nonmotor symptomatology, including brain atrophy and cognitive decline. It addresses the question of the role of carotid emboli in """"""""silent"""""""" stroke and their cognitive sequelae. The study uses human carotid endarterectomy patients to study three specific aims. The first uses ultrasound to relate plaque elasticity and its development of mechanical strain features with pulsation and the histopathophysiology of the plaque for ulcer, hemorrhage and thinning of stabilizing fibrous cap at the point of these mechanical strain features. The second examines ultrasound detected elasticity strain features in the plaques and the presence of transcranial Doppler TCD detectable microemboli. The third looks at ultrasound strain deficits, microemboli, cognitive decline and brain MRI evidence of focal and generalized atrophy. Understanding the structural plaque abnormalities, which render a carotid plaque mechanically unstable and at risk of embolization will demonstrate a pathophysiologic mechanism in individuals who are likely to suffer not only classic episodic major strokes, but also functional progressive decline from the contribution of microemboli to cerebral """"""""silent"""""""" stroke and cognitive decline.

Public Health Relevance

Cerebrovascular disease remains a major health problem with increasing impact on an aging population. Studies suggest that clinical and """"""""silent"""""""" stroke affects 11 million Americans per year. Vascular aging from atherosclerosis is a major contributor to this problem. For this reason, we propose a study of carotid atherosclerosis developing novel markers for carotid plaque instability which may result in the presence of multiple microemboli, which in turn may contribute to increased symptomatology, both classic strokes, as well as, cognitive decline. If successful, this study will greatly increase our understanding of the pathophysiology of symptoms from atherosclerosis, as well as, lead to the development of potential new measures to detect this disorder noninvasively.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Acute Neural Injury and Epilepsy Study Section (ANIE)
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Koenig, James I
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University of Wisconsin Madison
Schools of Medicine
United States
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Jackson, Daren C; Sandoval-Garcia, Carolina; Rocque, Brandon G et al. (2016) Cognitive Deficits in Symptomatic and Asymptomatic Carotid Endarterectomy Surgical Candidates. Arch Clin Neuropsychol 31:1-7
Wang, X; Mitchell, C C; Varghese, T et al. (2016) Improved Correlation of Strain Indices with Cognitive Dysfunction with Inclusion of Adventitial Layer with Carotid Plaque. Ultrason Imaging 38:194-208
Wang, Xiao; Jackson, Daren C; Mitchell, Carol C et al. (2016) Classification of Symptomatic and Asymptomatic Patients with and without Cognitive Decline Using Non-invasive Carotid Plaque Strain Indices as Biomarkers. Ultrasound Med Biol 42:909-18
Berman, Sara E; Wang, Xiao; Mitchell, Carol C et al. (2015) The relationship between carotid artery plaque stability and white matter ischemic injury. Neuroimage Clin 9:216-22
Jones, Jana E; Jackson, Daren C; Chambers, Karlee L et al. (2015) Children with epilepsy and anxiety: Subcortical and cortical differences. Epilepsia 56:283-90
Jackson, Daren C; Lin, Jack J; Chambers, Karlee L et al. (2014) Birth weight and cognition in children with epilepsy. Epilepsia 55:901-8
Wang, X; Jackson, D C; Mitchell, C C et al. (2014) Estimation of ultrasound strain indices in carotid plaque and correlation to cognitive dysfunction. Conf Proc IEEE Eng Med Biol Soc 2014:5627-30
Wang, Xiao; Jackson, Daren C; Varghese, Tomy et al. (2014) Correlation of cognitive function with ultrasound strain indices in carotid plaque. Ultrasound Med Biol 40:78-89
Walker, Natalie M; Jackson, Daren C; Dabbs, Kevin et al. (2013) Is lower IQ in children with epilepsy due to lower parental IQ? A controlled comparison study. Dev Med Child Neurol 55:278-82
Jackson, Daren C; Dabbs, Kevin; Walker, Natalie M et al. (2013) The neuropsychological and academic substrate of new/recent-onset epilepsies. J Pediatr 162:1047-53.e1

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