As the population continues to age, the incidence of dementia is dramatically increasing, resulting in an urgent need to identify risk factors for abnormal brain aging and dementia. Alterations in cardiac function influence systemic blood flow, which impacts cerebral blood flow homeostasis as demonstrated by animal models. Such changes in cerebral blood flow homeostasis may pose a risk for accelerating age-related brain injury. Our preliminary research suggests that cardiac function is related to markers of maladaptive brain aging. It is not yet clear if cardiac function accelerates neuroimaging or cognitive markers of cerebrovascular or Alzheimer's disease among aging individuals with mild cognitive impairment (MCI). Individuals with MCI are at increased risk for cognitive progression and susceptible to more rapid abnormal brain aging when concomitant vascular disease is present. Our proposed study will examine relations between cardiac function and maladaptive brain aging and provide important information for developing novel strategies to delay the progression from MCI to dementia. Using a prospective observational matched design, we will cross-sectionally and longitudinally relate cardiac function to neuroimaging and cognitive markers of early Alzheimer's disease and cerebrovascular changes among aging adults with MCI and age-, sex-, and race-matched cognitively normal adults. Clinical or subclinical cardiac dysfunction may be due to complex systemic mechanisms that are preventable or treatable, such as enhanced inflammatory markers and insulin resistance, or genetic factors, such as apolipoprotein E. Therefore, we will consider systemic and genetic factors as potential mediating mechanisms in relations between cardiac function and brain aging. The proposed study leverages an existing Alzheimer's Association funded study directed by the principal investigator, the participant registry of our NIA-funded Boston University Alzheimer's Disease Center, a recent American Recovery &Reinvestment Act supplement grant focused on African American recruitment and retention, and the unique resources afforded by our local Clinical and Translational Science Institute housing the General Clinical Research Unit.

Public Health Relevance

The incidence of dementia is dramatically increasing, and in the absence of effective therapies, there is an urgent need to identify risk factors and prevention strategies. Our preliminary data suggest cardiac function may be an unrecognized risk factor for maladaptive brain aging. The proposed project will generate evidence to support the development of novel strategies for delaying dementia onset and progression.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
3R01AG034962-04S2
Application #
8890405
Study Section
Program Officer
Silverberg, Nina B
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Neurology
Type
Schools of Medicine
DUNS #
City
Nashville
State
TN
Country
United States
Zip Code
37212
Lane, Elizabeth M; Hohman, Timothy J; Jefferson, Angela L et al. (2016) Insulin-like growth factor binding protein-2 interactions with Alzheimer's disease biomarkers. Brain Imaging Behav :
Jefferson, Angela L; Gifford, Katherine A; Acosta, Lealani Mae Y et al. (2016) The Vanderbilt Memory & Aging Project: Study Design and Baseline Cohort Overview. J Alzheimers Dis 52:539-59
Hohman, Timothy J; Bell, Susan P; Jefferson, Angela L et al. (2015) The role of vascular endothelial growth factor in neurodegeneration and cognitive decline: exploring interactions with biomarkers of Alzheimer disease. JAMA Neurol 72:520-9
Gifford, Katherine A; Liu, Dandan; Damon, Stephen M et al. (2015) Subjective memory complaint only relates to verbal episodic memory performance in mild cognitive impairment. J Alzheimers Dis 44:309-18
Jefferson, Angela L; Gifford, Katherine A; Damon, Stephen et al. (2015) Gray & white matter tissue contrast differentiates Mild Cognitive Impairment converters from non-converters. Brain Imaging Behav 9:141-8
Gifford, Katherine A; Liu, Dandan; Hohman, Timothy J et al. (2015) A Mutual Self- and Informant-Report of Cognitive Complaint Correlates with Neuropathological Outcomes in Mild Cognitive Impairment. PLoS One 10:e0141831
Jefferson, Angela L; Beiser, Alexa S; Seshadri, Sudha et al. (2015) APOE and mild cognitive impairment: the Framingham Heart Study. Age Ageing 44:307-11
Hohman, Timothy J; Samuels, Lauren R; Liu, Dandan et al. (2015) Stroke risk interacts with Alzheimer's disease biomarkers on brain aging outcomes. Neurobiol Aging 36:2501-8
Jefferson, Angela L; Beiser, Alexa S; Himali, Jayandra J et al. (2015) Low cardiac index is associated with incident dementia and Alzheimer disease: the Framingham Heart Study. Circulation 131:1333-9
Hohman, Timothy J; Chibnik, Lori; Bush, William S et al. (2015) GSK3β Interactions with Amyloid Genes: An Autopsy Verification and Extension. Neurotox Res 28:232-8

Showing the most recent 10 out of 16 publications