Abstract
Intact cognitive function is the best predictor of quality of life and functional ability in older age. Thus, preventing cognitive decline is central to any effort to guarantee successful aging for our growing population of elderly. The purpose of the work discussed in this outlook paper is to bridge knowledge from basic and clinical neuroscience with the aim of improving how we understand, predict, and treat age- and disease-related cognitive impairment. Over the past six years, our research team has focused on intermediate neuroimaging phenotypes of brain vulnerability in midlife and isolating the underlying physiological mechanisms. The ultimate goal of this work was to pave the road for the development of early interventions to enhance cognitive function and preserve brain integrity throughout the lifespan.
Highlights
The most rapidly rising threat to brain health in US adults is the clustering of obesity, high blood pressure, elevated fasting glucose, and abnormal lipid metabolism in a single individual, a condition known as metabolic syndrome
A staggering 34–45% of US adults currently fulfill criteria for metabolic syndrome [1]. These numbers are alarming as metabolic syndrome is associated with increased risk for cardiovascular disease and diabetes [2], and with current cognitive dysfunction and risk for future cognitive decline, over and above the detrimental effects of its components [3,4,5,6,7,8,9,10]
Our work demonstrates that obesity/metabolic syndrome may lead to cognitive decline through two potential pathways (Figure 3): a vascular pathway whereby obesity promotes the development of insulin resistance, which, in turn, interferes with cerebral endothelial function, leading to unfavorable alterations in the cerebrovascular response to a mental challenge and eventually to cognitive decline [11, 12]
Summary
The most rapidly rising threat to brain health in US adults is the clustering of obesity, high blood pressure, elevated fasting glucose, and abnormal lipid metabolism in a single individual, a condition known as metabolic syndrome. A staggering 34–45% of US adults currently fulfill criteria for metabolic syndrome [1]. These numbers are alarming as metabolic syndrome is associated with increased risk for cardiovascular disease and diabetes [2], and with current cognitive dysfunction and risk for future cognitive decline, over and above the detrimental effects of its components [3,4,5,6,7,8,9,10]. The goal of our work over the past six years has been to explore the underlying neural mechanisms of midlife brain vulnerability related to peripheral vascular and metabolic disturbances, before clinically significant and permanent cognitive dysfunction has developed. Our team has endeavored to solve this problem through combining sophisticated behavioral analyses with modern neuroimaging techniques
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