Vascular risk factors and vascular disease are increasingly recognized as major contributors to cognitive impairment and dementia, including Alzheimer's disease (AD), but tend to be understudied despite their potential role as a target for prevention. As a stroke neurologist, with doctoral training in Clinical Investigation, the PI proposes to evaluate a particular form of vascular disease-congestive heart failure (CHF)-in association with cognitive performance and ?-amyloid deposition, which by leading hypotheses is the cause of AD. In one already-collected community-based cohort (The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS), funded through NHLBI and NINDS with Dr. Gottesman as a coinvestigator) and its ancillary R01 sub-cohort (The ARIC-PET study, funded through an NIA R01 with Dr. Gottesman as PI), Dr. Gottesman will evaluate associations between subclinical cardiac dysfunction and cognitive decline and ?- amyloid deposition, each. In addition, in an ongoing prospective clinical heart failure cohort (Diuresis Clinic Cognitive Cohort), Dr. Gottesman will evaluate the features of CHF that are associated with cognitive impairment, will evaluate if cognitive deficits are reversible in the setting of treatment of decompensated CHF, and will explore mechanism for any transient cognitive deficits in this setting (particularly, changes in cerebral blood flow and in inflammation). These studies will provide the structure for the PI's proposed mentoring plan, as will her other ongoing research in the area of the vascular contribution to cognitive impairment and AD, with an emphasis on neuroepidemiologic approaches. As part of this mid-career mentoring award, the PI will focus on training future investigators interested in the vascular contribution to AD. Because this is an area in which interventions or preventive therapies might be undertaken that could either directly reduce AD burden, or could identify persons at high risk who might benefit from future AD-specific treatments, it is clear that trainees are needed who understand the importance of how to measure and define vascular risk factors and disease, and how to address potential biases in analyses related to persons with cognitive impairment and dementia. The mentoring plan will focus on direct exposure to primary data collection within clinical cohorts and within epidemiologic cohorts, secondary data analysis of epidemiologic data, and an interdisciplinary approach to research. The proposed research in this K-24 application uses a particular vascular disease model (CHF) that is a likely important contributor to cognitive impairment and dementia, and in which impairments might be reversible or preventable. The specific goals of this K-24 application are: (1) to characterize and explore mechanisms for cognitive dysfunction associated with congestive heart failure; and (2) to recruit and mentor new investigators in a range of disciplines from the Schools of Medicine and Public Health at Johns Hopkins, to include, but not limited to, neurology, psychiatry, neuropsychology, geriatrics, epidemiology, and biostatistics.

Public Health Relevance

The goal of this project is to provide mentoring support for research in the neuroepidemiology of the vascular contribution to cognitive impairment and Alzheimer's disease (AD). Vascular disease is a preventable contributor to AD, and this K24 award will focus on training future investigators in research in this area. As a stroke neurologist with doctoral training in Clinical Investigation, Dr. Gottesman has a strong track record of mentoring trainees and junior clinician-investigators, and through this award will study congestive heart failure as a subtype of vascular disease in which to explore the vascular contribution to cognitive impairment and AD.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24AG052573-03
Application #
9476187
Study Section
Neuroscience of Aging Review Committee (NIA)
Program Officer
Anderson, Dallas
Project Start
2016-08-01
Project End
2021-04-30
Budget Start
2018-05-01
Budget End
2019-04-30
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Neurology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Walker, Keenan A; Walston, Jeremy; Gottesman, Rebecca F et al. (2018) Midlife Systemic Inflammation is Associated with Frailty in Later Life: The ARIC Study. J Gerontol A Biol Sci Med Sci :
Faigle, Roland; Cooper, Lisa A; Gottesman, Rebecca F (2018) Race Differences in Gastrostomy Tube Placement After Stroke in Majority-White, Minority-Serving, and Racially Integrated US Hospitals. Dysphagia 33:636-644
Bongiorno, Diana M; Daumit, Gail L; Gottesman, Rebecca F et al. (2018) Comorbid Psychiatric Disease Is Associated With Lower Rates of Thrombolysis in Ischemic Stroke. Stroke 49:738-740
Walker, Keenan A; Gottesman, Rebecca F; Wu, Aozhou et al. (2018) Association of Hospitalization, Critical Illness, and Infection with Brain Structure in Older Adults. J Am Geriatr Soc 66:1919-1926
Schneider, Andrea L C; Wang, Dan; Ling, Geoffrey et al. (2018) Prevalence of Self-Reported Head Injury in the United States. N Engl J Med 379:1176-1178
Walker, Keenan A; Windham, B Gwen; Brown, Charles H et al. (2018) The Association of Mid- and Late-Life Systemic Inflammation with Brain Amyloid Deposition: The ARIC-PET Study. J Alzheimers Dis 66:1041-1052
Witt, Lucy S; Rotter, Jason; Stearns, Sally C et al. (2018) Heart Failure and Cognitive Impairment in the Atherosclerosis Risk in Communities (ARIC) Study. J Gen Intern Med 33:1721-1728
Walker, Keenan A; Windham, B Gwen; Power, Melinda C et al. (2018) The association of mid-to late-life systemic inflammation with white matter structure in older adults: The Atherosclerosis Risk in Communities Study. Neurobiol Aging 68:26-33
Iadecola, Costantino; Gottesman, Rebecca F (2018) Cerebrovascular Alterations in Alzheimer Disease. Circ Res 123:406-408
Walker, Keenan A; Power, Melinda C; Hoogeveen, Ron C et al. (2017) Midlife Systemic Inflammation, Late-Life White Matter Integrity, and Cerebral Small Vessel Disease: The Atherosclerosis Risk in Communities Study. Stroke 48:3196-3202

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