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Role of IGF-1 Deficiency in Age-related Impairment of Neurovascular Coupling

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Role of IGF-1 Deficiency in Age-related Impairment of Neurovascular Coupling

 

AUTHORS:

Han Yuan, Assistant Professor, School of Biomedical Engineering, OU
Andriy Yabluchanskiy, Assistant Professor, Department of Geriatric Medicine, OUHSC 

Several aspects of brain function are known to be impaired with increasing age including, learning and memory. By 2050, the number of Americans aged 65 and older is projected to be 88.5 million, more than double its current number of 40.2 million. Foremost among factors that determine quality of life is the ability to live independently, and preserved cognitive function is particularly important in this regard. Evidence from both the clinical literature and animal models has shown that vascular factors have a critical role in age-related cognitive decline by altering cerebral blood flow and thus the availability of oxygen and nutrients for active neurons. Despite its importance in basic and clinical studies, the age-related cellular mechanism(s) underlying neurovascular uncoupling remain unclear.

The overall goal of this seed grant application is to elucidate the mechanistic link between circulating IGF-1 bioavailability and impairment of neurovascular coupling responses in aging. Our recent studies in pre-clinical models show that neurovascular uncoupling and cognitive impairment are causally related. There is strong evidence that in aging endothelial dysfunction plays a critical role in impaired neurovascular coupling. Although vascular causes of age-related cognitive decline are likely preventable, the age-related mechanisms that promote neurovascular uncoupling in humans, which contributes to a significant age-related decline in higher brain function, remain largely unknown. Despite evidence shows that circulating IGF-1 deficiency has a key role in age-related cognitive decline, there is a critical lack of evidence linking IGF-1 deficiency to impaired neurovascular coupling in humans. Therefore, we aim to systematically test the hypothesis that aging IGF-1 deficiency promotes neurovascular uncoupling, altering functional connectivity between interacting brain regions and promoting cognitive decline. We plan to test our hypothesis using human patients recruited via our ongoing collaboration with the Translational Geroscience Laboratory at the Department of Geriatric Medicine of the University of Oklahoma Health Sciences Center. We will utilize simultaneous acquisition of functional near-infrared spectroscopy and electroencephalogram data to comprehensively investigate neurovascular coupling responses in response to established neuronal stimulation protocols. In Aim 1, we will determine the relationship between circulating IGF-1 status and regulation of cerebral blood flow during neural activity in elderly individuals. In Aim 2, we will determine the relationship between circulating IGF-1 status and intrinsic connectivity networks in elderly individuals.