As the population ages, cognitive decline and Alzheimer's disease (AD) are becoming increasingly important public health issues. Mild cognitive impairment (MCI) is considered a precursor to AD, and early identification of MCI and effective management of risk factors associated with conversion from MCI to dementia is an important step in managing the public health crisis of AD. Unfortunately, MCI is an unstable diagnostic construct, and key predictors of conversion and reversion are poorly understood. Multiple vascular factors and prevalent cardiovascular disease are known risks for the development of AD, so a plausible predictor of diagnostic fluctuations in MCI is the presence of concomitant micro vascular disease in the brain. This proposal will leverage the existing and robust dataset from the Alzheimer's Disease Neuroimaging Initiative to examine neuroimaging markers of micro vascular and microstructural tissue changes in the white matter with cognitive trajectory among cognitively normal older adults and individuals with MCI. We will (1) assess how stable versus progressive cerebral micro vascular disease and micro structural changes in white matter affect maladaptive cognitive aging over time and (2) assess the mediating effect of baseline systemic vascular disease (using a vascular health index) in the longitudinal relation between micro vascular and micro structural white matter changes and diagnostic conversion and cognitive trajectory. Insights regarding complex relations between systemic vascular disease and micro vascular or microstructural changes in the brain have important public health implications because they will contribute to early identification of a vulnerable population at high risk for cognitive progression. Furthermore, because vascular risk factors can be modified over the life course to reduce the burden of cerebrovascular disease in older adults, this vulnerable population would benefit most from novel strategies to delay or prevent progression, which is particularly valuable in light of the aging of the population and increasing prevalence of AD.

Public Health Relevance

The incidence of dementia is dramatically increasing, and in the absence of effective therapies, there is an urgent need to identify vascular risk factors and prevention strategies. The proposed project will provide insights regarding complex relations between systemic vascular disease, micro vascular and micro structural changes on brain MRI, and early identification of a vulnerable population at risk for cognitive progression to aid in early identification and risk reduction strategies.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL111516-01
Application #
8220394
Study Section
Behavioral Medicine, Interventions and Outcomes Study Section (BMIO)
Program Officer
Reid, Diane M
Project Start
2012-03-27
Project End
2017-02-28
Budget Start
2012-03-27
Budget End
2013-02-28
Support Year
1
Fiscal Year
2012
Total Cost
$390,000
Indirect Cost
$140,000
Name
Vanderbilt University Medical Center
Department
Neurology
Type
Schools of Medicine
DUNS #
004413456
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; Dumitrescu, Logan; Cox, Nancy J et al. (2016) Genetic resilience to amyloid related cognitive decline. Brain Imaging Behav :
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
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

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