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Title: Cerebral blood volume and vasodilation are independently diminished by aging and hypertension: A near infrared spectroscopy study

Author
item SHAUL, MERAV - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item HALLACOGLU, BERTAN - Tufts University
item SASSAROLI, ANGELO - Tufts University
item Shukitt-Hale, Barbara
item FANTINI, SERGIO - Tufts University
item ROSENBERG, IRWIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item TROEN, ARON - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Alzheimer's Disease
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/19/2014
Publication Date: N/A
Citation: N/A

Interpretive Summary: The integrity of brain blood vessels is essential for the proper functioning of brain tissue. Increasingly, the brain vasculature is recognized to be an active player not only in the progression of cognitive decline, but possibly in its initiation as well. Structural changes in brain vasculature causing a decrease in adequate blood supply to the brain have been suggested to be promoted partly by aging, but also by high blood pressure (hypertension), a leading treatable cause of cognitive decline. In this study, we aimed to detect the changes in brain blood circulation associated with age and hypertension, and inquired whether decreased blood flow as a result of the natural processes of aging would be exacerbated by chronic hypertension. To this end, we used Near Infrared Spectroscopy (NIRS) which allows one to record in real time the cerebral blood volume (CBV) and assess the response of brain blood vessels to respiratory challenges. The impact of age and hypertension were evaluated by monitoring Normotensive Wistar-Kyoto (WKY) rats and Spontaneous-Hypertensive (SHR) rats at 4-months of age and repeating these measurements on the same animals at 16-months of age. Results showed that cerebral blood volume decreased markedly with age in both normotensive and hypertensive animals. Chronic hypertension, however, did not significantly aggravate this age-related decrease in CBV. In contrast, constriction of the blood vessels was already apparent in the hypertensive rats from a young age and further worsened by middle-age. The ability of absolute NIRS to distinguish between different properties and changes in brain vascular circulation in life may allow early detection and intervention to preserve cerebrovascular health with age.

Technical Abstract: Senescent changes in brain microvascular circulation may cause or contribute to age-related cognitive decline. Such changes are promoted partly by aging, but also by chronic hypertension, a leading treatable cause of cognitive decline. We aimed to non-invasively detect in vivo the senescent changes in brain microvascular circulation associated with age and hypertension, and inquired whether decrements driven by aging would be exacerbated by chronic hypertension. In this longitudinal study, absolute Near Infrared Spectroscopy (NIRS) was used to quantify in vivo cerebral blood volume (CBV) and assess the hemodynamic response to a hypercapnic respiratory challenge in normotensive Wistar-Kyoto (WKY) and Spontaneous-Hypertensive (SHR) rats. The impact of age and hypertension were evaluated by repeating these measurements on the same animals at 4- and 16-months of age. CBV decreased markedly with age in both strains, from 4.5+/-0.2 to 2.6+/-0.1ml/100gr tissue, on average. Chronic hypertension, however, did not significantly exacerbate this age-related decrease in CBV (-48.1+/-3.7% in WKYs vs. -53.3+/-5.4% in SHRs). In contrast, vasoreactivity was already impaired in the young hypertensive rats (delta VMR 0.017+/-0.014 in young SHRs vs. 0.042+/-0.005 in young WKYs) and further worsened by middle-age (delta VMR 0.011+/-0.017 middle-aged SHRs). Whereas a decrease in brain blood volume correlated with age but not hypertension, vasodilatory capacity was diminished due to hypertension but did not appear affected by age alone. The ability of absolute NIRS to distinguish between such senescent changes in brain (micro)vascular circulation in life may allow early detection and intervention to preserve cerebrovascular health with age.