This proposal is requesting a one-time renewal of a Midcareer Investigator Award in Patient-Oriented Research (K24). The candidate, Dr. Angela Jefferson, is a neuropsychologist whose interdisciplinary research program focuses on understanding the impact of cardiovascular and cerebrovascular integrity on the pathogenesis and clinical manifestation of Alzheimer's disease and small vessel disease. Dr. Jefferson is a Professor of Neurology at Vanderbilt University Medical Center and founding Director of the Vanderbilt Memory & Alzheimer's Center. Since completing her training 13 years ago, Dr. Jefferson has established herself as a productive clinical researcher with strong NIH funding and a high-impact, prolific publication record. Over the last decade, including the original K24 funding period (2013-2018), she has demonstrated a strong commitment to professional education and mentorship. This K24 renewal will be instrumental in continuing to provide protected time for Dr. Jefferson to expand her clinical research capabilities. In particular, she will expand her expertise in cerebrospinal fluid biomarkers of Alzheimer's disease to include innovative molecular biomarkers reflecting concomitant pathways, such as extracellular matrix remodeling, microglial activation, and synaptic dysfunction. She will also expand the breadth of proteomic biomarkers at her disposal by leveraging state of the art discovery-based mass spectrometry methods. These tools will substantially enrich our understanding of the mechanisms by which compromised vascular health relates to abnormal brain aging and inform strategies to prevent or delay the pathological cascade associated with cognitive impairment and dementia. Furthermore, the proposed award will allow Dr. Jefferson to continue to use her research program as a platform to mentor early career investigators, including undergraduate, graduate, and medical students; postdoctoral fellows; and early career faculty in patient-oriented research in cognitive aging, Alzheimer's disease, and small vessel disease. This proposal integrates Dr. Jefferson's interdisciplinary research team and resources available through the Vanderbilt Memory & Alzheimer's Center and Vanderbilt Institute for Clinical and Translational Research to offer a rich training environment for mentees. The training and research facilitated by this K24 mechanism renewal will not only advance knowledge regarding cardiovascular and cerebrovascular pathways contributing to the pathogenesis and clinical manifestation of Alzheimer's disease and small vessel disease, but it will also develop a cadre of next-generation cognitive aging researchers well- positioned to make meaningful contributions to the field.

Public Health Relevance

Understanding risk factors and mechanisms for small vessel disease and Alzheimer's disease is essential in managing the growing public health crisis of Alzheimer's disease and related dementias, particularly as effective prevention strategies and therapeutic targets become available. This award will provide the candidate with ongoing protected time to mentor early career investigators in patient-oriented cognitive aging research while gaining new expertise and skills in the application of innovative biomarkers.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Midcareer Investigator Award in Patient-Oriented Research (K24)
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Neuroscience of Aging Review Committee (NIA)
Program Officer
Anderson, Dallas
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Vanderbilt University Medical Center
United States
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Jefferson, Angela L; Cambronero, Francis E; Liu, Dandan et al. (2018) Higher Aortic Stiffness Is Related to Lower Cerebral Blood Flow and Preserved Cerebrovascular Reactivity in Older Adults. Circulation 138:1951-1962
Gifford, Katherine A; Liu, Dandan; Neal, Jacquelyn E et al. (2018) Validity and Normative Data for the Biber Figure Learning Test: A Visual Supraspan Memory Measure. Assessment :1073191118773870
Emrani, Sheina; Libon, David J; Lamar, Melissa et al. (2018) Assessing Working Memory in Mild Cognitive Impairment with Serial Order Recall. J Alzheimers Dis 61:917-928
Deming, Yuetiva; Dumitrescu, Logan; Barnes, Lisa L et al. (2018) Sex-specific genetic predictors of Alzheimer's disease biomarkers. Acta Neuropathol 136:857-872
Cambronero, Francis E; Liu, Dandan; Neal, Jacquelyn E et al. (2018) APOE genotype modifies the association between central arterial stiffening and cognition in older adults. Neurobiol Aging 67:120-127
Moore, Elizabeth E; Hohman, Timothy J; Badami, Faizan S et al. (2018) Neurofilament relates to white matter microstructure in older adults. Neurobiol Aging 70:233-241
Osborn, Katie E; Liu, Dandan; Samuels, Lauren R et al. (2018) Cerebrospinal fluid ?-amyloid42 and neurofilament light relate to white matter hyperintensities. Neurobiol Aging 68:18-25
Hohman, Timothy J; Dumitrescu, Logan; Cox, Nancy J et al. (2017) Genetic resilience to amyloid related cognitive decline. Brain Imaging Behav 11:401-409
Lane, Elizabeth M; Hohman, Timothy J; Jefferson, Angela L et al. (2017) Insulin-like growth factor binding protein-2 interactions with Alzheimer's disease biomarkers. Brain Imaging Behav 11:1779-1786
Bell, S P; Liu, D; Samuels, L R et al. (2017) Late-Life Body Mass Index, Rapid Weight Loss, Apolipoprotein E ?4 and the Risk of Cognitive Decline and Incident Dementia. J Nutr Health Aging 21:1259-1267

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