To address the National Institute on Aging?s strategic aim of understanding mechanisms underlying the pathogenesis of AD, related dementias, and neurodegenerative disorders of aging (Goal D-2), we propose an extension to Project 1 of the currently funded Center for the Study of Aphasia Recovery (C-STAR; P50 DC014664, referred to here as POLAR) to investigate further neurological and health-related factors that predict cognitive-linguistic decline in stroke survivors. Aphasia, a language impairment caused by damage to the brain's language regions, persists chronically in approximately 30% of stroke survivors. POLAR is a treatment study that aims to identify neuroanatomical, behavioral, genetic, and demographic predictors of treated aphasia recovery in individuals with chronic left hemisphere stroke. Preliminary analyses have shown that not all individuals improve, and recent evidence suggests that approximately one-quarter of individuals with post-stroke aphasia experience cognitive-linguistic decline over time. The purpose of this project is to extend the follow-up window for the POLAR study, to one-year post aphasia treatment. There is evidence to suggest that declining performance in stroke-induced aphasia is attributed to pathologic changes in the brain's white matter, referred to as leukoaraiosis. Leukoaraiosis is common in stroke survivors, and is often attributed to age, as well as cardiovascular health and other health concerns. In the general population, it has been associated with cognitive decline and loss of functional ability. By extending follow-up interval for the POLAR study, this study will address a new aim of evaluating the progression of leukoaraiosis and how it affects overall cognitive-linguistic ability in stroke survivors. To this end, participants will undergo the same speech/language and cognitive testing administered at study baseline. Participants will also undergo the same magnetic resonance imaging (MRI) protocol as at baseline (see the attached POLAR Research Strategy). The extent of behavioral change will be evaluated and related to neuroanatomical changes. The role of cognitive reserve and other personal factors in mediating the effects of leukoaraiosis will also be explored. The world?s population is aging, and with this trend, the global burden of stroke and dementia is also increasing. The study of leukoaraiosis in post-stroke aphasia is critical for identifying factors that may indicate cognitive-linguistic decline in stroke survivors, as doing so will also inform efforts to improve the evaluation of individuals at risk for developing cognitive impairment, AD, and other dementias (NIA Strategic Goal D-3). The world?s population is aging, and by 2050, it is expected that 17% of the world?s population (i.e., 1.6 billion people) will be over the age of 65 (1). Along with this increase in older individuals, the global burden of stroke (2) and dementia (3) is also increasing. The coming decades are expected to see a significant growth in the number of individuals living longer with post-stroke sequelae, attributed to the decline in stroke mortality rates (2, 4) and an increase in stroke rates in younger individuals (e.g., 20-44 years old (5); 45-64 years old (6)). In parallel, as individuals age, the prevalence of Alzheimer?s disease (AD) and other dementias continues to increase (3). This epidemiological trend means that aging research must consider the effects of stroke on the aging brain ? and likewise ? stroke research must consider how processes associated with aging affect long term outcomes. In essence, stroke survivors are aging, and aging research must consider this population, especially considering that by 2030, the number of stroke survivors could reach 70 million people worldwide (2). Accordingly, to address the National Institute on Aging?s strategic aim of understanding mechanisms underlying the pathogenesis of AD, related dementias, and neurodegenerative disorders of aging (Goal D-2), we propose an extension to Project 1 of the currently funded Center for the Study of Aphasia Recovery (CSTAR; P50 DC014664, referred to here as POLAR) to investigate further neurological and health-related factors that predict cognitive-linguistic decline in stroke survivors.
Stroke is the leading cause of adult disability in the United States; aphasia, an impairment of the ability to process language, is one of the most devastating results of left hemisphere stroke. The purpose of the work proposed here is to improve recovery from aphasia by better understanding how neurophysiology and anatomy as well as theory driven aphasia treatment relate to long-term outcome. Subproject-1 Modeling treated recovery from aphasia Lead Investigator: Julius Fridriksson, Ph.D. DESCRIPTION (Description as provided by applicant): Stroke is the leading cause of serious adult disability in the United States. One of the most devastating impairments resulting from stroke is aphasia, a language impairment caused by left hemisphere damage involving cortical language areas. It is generally accepted that behavioral aphasia treatment is effective. Nevertheless, different patients experience very different degrees of benefit from aphasia treatment. Despite considerable differences in the response to aphasia treatment, the relationship between patient factors and treatment response is poorly understood and very few reliable prognostic indicators have been identified. This is a major problem, as both time and resources are wasted when clinicians do not know what patients are likely to respond to treatment, or which treatment best fits individual patients. The purpose of the current project is to develop a model that includes biographical and cognitive/linguistic factors to predict patients' response to aphasia treatment. Aphasia severity is one of the few factors that have been identified as a reliable predictor of performance in treatment; it is generally accepted that more severe aphasia is associated with poorer treatment outcomes. However, aphasia severity is a multidimensional construct and patients with similar overall severity scores might demonstrate very different language impairment profiles. To better understand how language impairment relates to treatment outcomes, the dual stream model (DS model;1) will be consulted. Specifically, we will test whether measures of proportional damage to the cortical areas that comprise the DS model improve prediction of aphasia treatment response, beyond biographical and cognitive/linguistic factors. Although the DS model is a functional model grounded in neuroanatomy, we expect measures of speech and language that assesses processes supported by the two major components of the DS model - the dorsal and ventral streams - might be redundant with measures of cortical damage. To understand whether our predictive model can be generalized across different kinds of treatment foci, each patient will undergo treatment devoted to phonological stimulation and a separate treatment phase focusing on semantic stimulation. Ultimately, the goal here is to construct a predictive model that will be made available on- line so that clinicians can enter test scores from individual patients to predic how likely a given patient is to respond to treatment, as well as the focus of that treatment. There is a great need for prognostic indicators of aphasia treatment response. At the completion of our research, we will understand why some patients respond better to aphasia treatment than others. We have selected treatment approaches that are routinely used in clinical practice, allowing for immediate translation of the findings directly into patient management. The current project will yield a vast dataset that will be made publicly available allowing others to study further aphasia treatment response in relation to cognitive/linguistic and lesion factors.
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