Neural Correlates of Visuospatial Working Memory in Healthy Young Adults at Risk for Hypertension

Abstract

Family history of hypertension (FH+) has been associated with subtle deficits in cognitive function. In search of an early marker that may identify individuals predisposed to developing cognitive difficulties, we employed fMRI to test for FH+ related differences in hemodynamic response to a working memory challenge in healthy young adults with intact working memory. Fourteen healthy adults (ages 18 to 40 years) participated in an fMRI study of working memory. Seven of the participants were FH+. Groups were matched for working memory performance. Relative to FH− controls, FH+ participants exhibited lower 2-Back-related activation in the right inferior parietal lobule and the right inferior temporal gyrus as well as significantly more deactivation in the posterior cingulate cortex. These results indicate that FH+ is associated with subtle changes in visuospatial attention even in healthy young adults.

Functional MR Imaging Evidence of Altered Functional Activation in Metabolic Syndrome

“…In the past, a higher task-related BOLD response at comparable levels of performance in patients with MS, HIV, and genetic risk for AD relative to healthy controls has been observed and interpreted as compensatory overactivation 25,46,47 ; however, the opposite trend (ie, lower task-related activation at similar levels of performance) has been noted in patients at high risk for cardiovascular and cerebrovascular disease. 42,[48][49][50] On the basis these observations, it may be that early in the vascular disease process, subclinical reductions in vascular responsivity and endothelial function result in lower, yet sufficient, amounts of oxygen being delivered to activated neurons, thus producing a lower BOLD response to a cognitive challenge despite intact behavioral performance. 48,49 As vascular problems worsen, further declines in cerebrovascular reactivity and microvascular damage likely lead to vascular cognitive impairment.…”

“…42,[48][49][50] On the basis these observations, it may be that early in the vascular disease process, subclinical reductions in vascular responsivity and endothelial function result in lower, yet sufficient, amounts of oxygen being delivered to activated neurons, thus producing a lower BOLD response to a cognitive challenge despite intact behavioral performance. 48,49 As vascular problems worsen, further declines in cerebrovascular reactivity and microvascular damage likely lead to vascular cognitive impairment. Support is provided by a growing body of literature documenting that peripheral cardiovascular dysfunction is related to poor cerebrovascular health and diminished cognitive function in older patients with cardiovascular disease.…”

Vascular Functions and Brain Integrity in Midlife: Effects of Obesity and Metabolic Syndrome

“…The final study samples were diverse (less than 60% non-Hispanic Caucasian), well educated (average education level = 15 years), and cognitively intact (average Mini-Mental State Examination score, MMSE > 26 out of 30). We found that the intensity of working memory-related brain activation diminished with the development of metabolic and cardiovascular disorders as early as midlife, even when cognitive performance was still within normal limits [11,12,22,25,30]. These disorders included obesity, hypertension, metabolic syndrome, and frank cardiovascular diseases.…”

“…Lower brain activity in expected taskrelated brain regions [11,12,24,25], greater brain activity in expected task-related brain regions [15,17,19], significant recruitment of unexpected brain regions [43,44], and suspension of unrelated brain activity [22,23] have all been reported among normally performing at-risk individuals. Ubiquitous interpretations of diminished BOLD response to a cognitive challenge as both cognitive efficiency and impairment have limited our ability to extrapolate mechanisms through interpretations of isolated fMRI findings.…”

“…Since this noninvasive tool can map subtle alterations in cerebral blood flow in response to changes in regional energy demands related to neuronal function [20], it has the potential to detect early signs of brain reorganization in response to developing neuropathology. Increased activation in expected task-related brain regions in at-risk groups [15,17,19], bilateral recruitment of brain areas for the successful completion of normally lateralized tasks [21], and decreased potentially distracting activation (e.g., in areas devoted to self-monitoring) [22,23] have all been proposed as potential signs of compensation for diminishing brain function. Coupled with well-targeted behavioral challenges that unmask early cognitive inefficiencies and compensation, fMRI can be invaluable for timely identification of obesity-related brain vulnerability as well.…”