EDUCACIÓN, NUEVAS FORMAS DE SUBJETIVIDAD

risk for CAD

"The secondary pathologic conditions that are made possible and favoured by

primary involution process are many and of great clinical importance, because it is usually through some one of these that the senile individual is kept from achieving a biological death. They fall into several well-defined group: 1) secondary to vascular changes...."A S Warthin, 192878.

The decline in regional brain structure and function in older adults with risks

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posterior brain regions and cognitive domains that are relatively stable during normal

aging. A systematic review of neuroimaging findings from 77 studies that investigated

brain changes related to CAD risk factors in asymptomatic individuals, concluded that

risk factors of hypertension, type II diabetes, obesity and hyperlipidemia, independently

contribute to adverse changes in the structure and function of the brain6. More importantly, an increase in the number of risk factors appears to increase the magnitude

of brain changes6. The impact of CAD risk factors appear to be more regional than global6. In this section, evidence of regional brain atrophy, impaired hemodynamics and abnormal brain metabolism related to CAD and disease risk factors will be briefly

presented.

1.5.1

Changes in brain structure

Regional brain atrophy in the frontal, temporal and parietal gyri are associated

with hypertension193,194, type II diabetes195–197 and obesity6. A voxel-based morphometry (VBM) study of 478 adults aged 60-64 years found an association between hypertension

and decreased GMV in the medial frontal, superior frontal and superior temporal regions

of male subjects, after controlling for effects of age and other vascular disease risk

factors194. In another study of 134 adults from 50-70 years old, higher systolic blood pressure was associated with decrease in GMV in the supplementary motor area, superior

frontal gyrus, anterior cingulate and middle temporal regions in male subjects193. No association between hypertension and brain volume were found among women subjects

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occipital lobes of type II diabetics compared to non-diabetics, and more recently a VBM

study198 found decreased GMV in the temporal and precentral gyri as well.

An increase in white matter lesions and a decrease in regional WM volume are

associated with hypertension199–202and diabetes195,197,198,200,203. Ventricular widening have also been observed in hypertensive204,205 and diabetic206 patients compared to age- matched controls. Even in earlier on in life, higher systolic blood pressure have been

linked to white matter injury and decreased regional GMV in individuals under the age of

50207. However, it appears that higher systolic blood pressure may not be associated with longitudinal changes in brain volume199,208 or in the frequency and severity of white matter lesions200,202,203. Rather, higher diastolic blood pressure in midlife are linked to greater longitudinal decline in GMV208 and increased frequency and severity of white matter lesions200,202.

1.5.2

Changes in brain function

Individuals with uncontrolled or untreated hypertension have been shown to have

regional hypoperfusion in the superior, inferior209 or and orbito-frontal cortices, anterior cingulate, and temporal and occipital regions compared to normotensive controls210–213. Accelerated decline in regional CBF over time has also been observed in hypertensive

adults compared to older normotensive adults211 and could be linked to uncontrolled increases in blood pressure48 and increased arterial stiffness209,214. One study of type II diabetics reported reductions in CBF under resting conditions and during hypercapnia in

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was associated with lower CBF including during hypercapnia195. Another recent study in a larger cohort (541) of middle aged adults, found lower CVR in the cingulate and medial

prefrontal lobe in individuals with elevated blood pressure compared to normotensive

subjects, but no difference in regional CVR in individuals with elevated blood glucose or

blood cholesterol compared to subjects with normal levels73. Hypertension is also associated with significant reductions in CMRglc in the striatum215 and with increased insulin resistance in the frontal, cingulate, parietal and temporal lobes216.

This abnormality in glucose metabolism in diabetics was linked to poor

performance on memory tasks and an activation pattern that seem to demonstrate

compensatory attempts during delayed recall tests216. Impairments in memory as well as in executive control, psychomotor speed and attention are reported in hypertensive

adults193,199,204,212 and in individuals diagnosed with cardiovascular disease217,218. In cardiovascular disease patients, one study demonstrated accelerated decline over time in

visuospatial skills, memory and overall cognitive function, and a linear decline in

language, attention and psychomotor speed217. It is quite possible that cognitive dysfunctions associated with vascular disease are related to cerebral hypoperfusion and

abnormal distribution of CBF during increased demand. For instance, in hypertensive

subjects, decreased CBF in the superior frontal, anterior parietal and temporal was

associated with decreased performance in attention and psychomotor processing212. In addition, during working memory tasks, hypertensive compared to normotensive subjects

had lower increase in posterior parietal CBF219, displayed attempts at recruitment of other cortical regions, and increased contralateral flow220. These regional flow alterations could be mediated by vascular aging that are exacerbated by cardiovascular disease. Cerebral

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hypoperfusion is linked to increased arterial stiffness221, and increased evidence of atherosclerosis214, and is associated with comprised neuronal viability222. In addition, higher carotid intima media thickness and increased pulse wave velocity are linked to

poorer memory performance and lower scores on processing speed and executive

function218,223. However, the pathogenesis of brain alterations associated with cardiovascular disease and disease risk factor are not well known. Equally, it is unclear

what impact cardiovascular disease, specifically diseases of atherosclerotic origin such as

CAD; have on the structural integrity and functional capacity of aging brains.