2009 — 2012 |
Sumowski, James Francis |
K99Activity Code Description: To support the initial phase of a Career/Research Transition award program that provides 1-2 years of mentored support for highly motivated, advanced postdoctoral research scientists. R00Activity Code Description: To support the second phase of a Career/Research Transition award program that provides 1 -3 years of independent research support (R00) contingent on securing an independent research position. Award recipients will be expected to compete successfully for independent R01 support from the NIH during the R00 research transition award period. |
Impact of Cognitive Reserve On Memory Functioning in Multiple Sclerosis @ Kessler Foundation, Inc.
DESCRIPTION (provided by applicant): As indicated by NCMRR, the primary goal of patient-oriented research is to develop the "scientific knowledge necessary to enhance the health, productivity, independence, and quality-of-life of people with disabilities." Multiple sclerosis is a prevalent and chronic neurologic disease associated with memory dysfunction and cerebral inefficiency, which encumber productivity, limit independence, and frequently diminish the quality of life among many young and middle aged persons with MS. Despite this, the etiology of memory dysfunction in MS is very poorly explained by brain pathology alone, perhaps due to yet undiscovered protective factors. This CDA project will investigate the role of cognitive reserve in protecting persons with MS from disease- related memory dysfunction and cerebral inefficiency. Cognitive reserve theory proposes that enriching life experiences (such as educational attainment) increase the capacity and efficiency of neural networks. When cerebral functioning is challenged by neurologic disease, individuals with more cognitive reserve are better able to cope with the increased cognitive demands. This has been demonstrated in Alzheimer's Disease and other neurologic conditions, but the current proposal is the first to directly investigate cognitive reserve in MS. During the mentored phase of this grant, I will investigate whether cognitive reserve protects persons with MS from the deleterious effects of brain pathology on learning and memory. My primary training aim is to develop competence in fMRI. Combined with the rich research training at KMRREC, fMRI training will enable me to investigate the protective role of cognitive reserve on cerebral efficiency in MS, and prepare me for a career as an independent patient-oriented researcher utilizing this innovative technology. These projects represent the first steps in my plan to pursue a more comprehensive research program directed toward (1) identifying sources of protective cognitive reserve and (2) using these sources as a means to reduce the negative impact of neurologic disease on quality of life for persons with MS in particular, and neurologic patients in general. This Career Development Award is a necessary and essential step in my plans to become an independent patient-oriented researcher. PUBLIC HEALTH RELEVANCE: Demonstration of the protective role of cognitive reserve in MS will fill wide gaps in the MS and cognitive reserve literatures. Identification of low cognitive reserve as a risk factor will improve prognoses of cognitive dysfunction, thereby promoting early intervention cognitive rehabilitation. I will pursue a program of research to identify other modifiable sources of reserve, which can then be utilized for preventative neurorehabilitation.
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0.985 |
2016 |
Sumowski, James Francis |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Project-001 @ Icahn School of Medicine At Mount Sinai
Thousands of young adults are diagnosed with relapsing-remitting multiple sclerosis (RRMS) in the United States each year, a life-long neurologic disease leading to cognitive decline in fifty percent of patients within the first few years of diagnosis. RRMS is typically diagnosed between ages 20 and 40, a time when young adults are finishing their education, establishing careers, and raising families. As such, cognitive decline limits functional independence and reduces quality of life currently and for the rest of their lives. We are unable to predict which RRMS patients will suffer cognitive decline, and, once patients decline, we have no effective treatments for cognitive impairment. As such, the best ?treatment? of cognitive impairment in RRMS patients may be ?prevention,? and prediction is an essential step toward building a science and clinical practice of prevention. Prediction is difficult because patients with similar disease burden often have discrepant outcomes. With the support of my K99/R00 from NICHD/NCMRR, I have shown in several cross-sectional studies that many RRMS patients possess ?reserve? against cognitive decline, afforded either genetically (larger maximal lifetime brain growth [MLBG]) or environmentally (intellectually-enriching experiences). That is, larger MLBG and/or greater intellectual enrichment moderate/attenuate the deleterious effect of MS disease burden (e.g., lesion volume) on cognitive outcomes. Aim 1 is the first longitudinal study to examine whether larger MLBG and greater intellectual enrichment protect against cognitive decline in RRMS patients. Our results will identify MLBG and intellectual enrichment as cost-effective, safe, and easily-acquired markers of future cognitive decline in RRMS, which will improve prediction of cognitive decline clinically (guiding early intervention), and facilitate the identification of at-risk patients for prevention research. [MLBG and lifetime enrichment (estimated with vocabulary) will help predict future cognitive decline, but both are outside one?s current control. Aim 2 will (a) investigate whether a current cognitively-stimulating lifestyle (e.g., reading, hobbies) independently lowers risk for cognitive decline, (b) identify which types of leisure are most protective against decline in cognitive efficiency and memory, respectively, and (c) examine neuroanatomical substrates for reserve against cognitive decline. Aim 2 will inform the development and evaluation of early interventions to build reserve.] Aim 3 will use functional MRI to identify specific patterns of current (baseline) brain function linked to cognitive preservation over time. Such markers can be used as benchmarks of success in early intervention / prevention research. Rather than waiting years to learn if an intervention successfully prevented decline, one can evaluate whether an intervention altered brain activity to more closely match a pattern linked to cognitive preservation. Results of this R01 will improve prediction of cognitive decline in RRMS patients, and [lay the groundwork for the development of evidence-based early interventions to build reserve in RRMS. Our team of investigators has the experience, expertise, and resources to successfully complete this large-scale and important R01 project.]
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0.909 |
2016 — 2020 |
Sumowski, James Francis |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Protection Against Cognitive Decline in Ms: Longitudinal Investigation of Reserve @ Icahn School of Medicine At Mount Sinai
? DESCRIPTION (provided by applicant): Thousands of young adults are diagnosed with relapsing-remitting multiple sclerosis (RRMS) in the United States each year, a life-long neurologic disease leading to cognitive decline in fifty percent of patients within the first few years of diagnosis. RRMS is typically diagnosed between ages 20 and 40, a time when young adults are finishing their education, establishing careers, and raising families. As such, cognitiv decline limits functional independence and reduces quality of life currently and for the rest of their lives. We are unable to predict which RRMS patients will suffer cognitive decline, and, once patients decline, we have no effective treatments for cognitive impairment. As such, the best treatment of cognitive impairment in RRMS patients may be prevention, and prediction is an essential step toward building a science and clinical practice of prevention. Prediction is difficult because patients with similar disease burden often have discrepant outcomes. With the support of my K99/R00 from NICHD/NCMRR, I have shown in several cross-sectional studies that many RRMS patients possess reserve against cognitive decline, afforded either genetically (larger maximal lifetime brain growth [MLBG]) or environmentally (intellectually-enriching experiences). That is, larger MLBG and/or greater intellectual enrichment moderate/attenuate the deleterious effect of MS disease burden (e.g., lesion volume) on cognitive outcomes. Aim 1 is the first longitudinal study to examine whether larger MLBG and greater intellectual enrichment protect against cognitive decline in RRMS patients. Our results will identify MLBG and intellectual enrichment as cost-effective, safe, and easily-acquired markers of future cognitive decline in RRMS, which will improve prediction of cognitive decline clinically (guiding early intervention), and facilitate the identification of at-risk patients for prevention research. [MLBG and lifetime enrichment (estimated with vocabulary) will help predict future cognitive decline, but both are outside one's current control. Aim 2 will (a) investigate whether a current cognitively-stimulating lifestyle (e.g., reading, hobbies) independently lowers risk for cognitive decline, (b) identify which types of leisure are most protective against decline in cognitive efficiency and memory, respectively, and (c) examine neuroanatomical substrates for reserve against cognitive decline. Aim 2 will inform the development and evaluation of early interventions to build reserve.] Aim 3 will use functional MRI to identify specific patterns of current (baseline) brain function linked to cognitive preservation over time. Such markers can be used as benchmarks of success in early intervention / prevention research. Rather than waiting years to learn if an intervention successfully prevented decline, one can evaluate whether an intervention altered brain activity to more closely match a pattern linked to cognitive preservation. Results of this R01 will improve prediction of cognitive decline in RRMS patients, and [lay the groundwork for the development of evidence-based early interventions to build reserve in RRMS. Our team of investigators has the experience, expertise, and resources to successfully complete this large-scale and important R01 project.]
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0.909 |
2021 |
Sumowski, James Francis |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Reserve Against Disability in Early Multiple Sclerosis (Radiems) Longitudinal Cohort Study @ Icahn School of Medicine At Mount Sinai
Multiple sclerosis (MS) is a prevalent chronic neurologic disease diagnosed during early adulthood that often leads to cognitive and sensorimotor decline. Inflammatory demyelinating lesions are key neuropathological features of MS, but neurodegeneration leading to gray matter loss is prominent, begins early, and is the main driver of functional decline. Lack of neuroregenerative therapies or functionally restorative treatments highlights a need to identify modifiable risk and protective factors that preserve gray matter and function. This R01 renewal of the Reserve against Disability in Early MS (RADIEMS) cohort extends our prior work on ?reserve? against disability to establish a much-needed framework for investigating functional decline in MS. We propose a dynamic model of reserve in which candidate modifiable risk and protective factors contribute to functional outcomes through (a) maintenance of gray matter (Aim 1), or (b) by modulating one?s ability to maintain function despite loss of gray matter (compensation; Aim 2). RADIEMS enrolled 185 MS patients diagnosed ?5.0 years (median=2.0) receiving high resolution MRIs and comprehensive cognitive and sensorimotor evaluations at baseline (Y0) and Y3; this renewal adds Y6 and Y8 follow-ups. Retention is excellent (95.0%). Aim 1a investigates whether MIND diet consumption (e.g., leafy greens, fish, nuts, berries) and body mass index (BMI) independently predict maintenance of (a) cerebral gray matter and (b) cognitive and sensorimotor functional outcomes over Y0-Y3-Y6-Y8. We will also evaluate percent body fat measured via bioelectrical impedance as a key culprit in obesity-related morbidity. Aim 1b assesses whether links between MIND diet and BMI with functional outcomes are mediated through gray matter change. Aim 1c analyzes blood and stool samples banked at Y3 for metabolomics & microbiome sequencing to identify nutrient and gut microbiotic mediators of dietary effects on outcomes. Aim 2a: preliminary data link depressed mood to poor cognitive and gait speed / endurance, which fluctuate with mood changes over time. We will assess whether cognitive and sensorimotor functions fluctuate with mood across Y0-Y3-Y6-Y8, and if mood moderates links between gray matter loss and outcomes. We will also investigate independent contributions of positively-valanced aspects of psychological function. Aim 2b assessed whether memory fluctuates with subjective (Y0-Y3-Y6-Y8) and objective (Y6-Y8) sleep disturbance. Little is known about sleep quality and functional outcomes in MS. A large subsample of patients will undergo actigraphy and ambulatory polysomnography at Y6 & Y8; we expect sleep efficiency (especially sleep fragmentation) to explain memory. RADIEMS is a large deeply-phenotyped cohort study of functional outcomes in early MS: a unique and valuable resource for the field. This R01 renewal extends our work on reserve to establish a critical framework for investigating functional decline. This dynamic model will be tested and updated over time to understand mechanistic mediators of risk and protective factors to inform the development of interventions to preserve gray matter and improve functional outcomes.
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0.909 |