Hypertension is associated with cognitive impairment even in the absence of dementia. These vascular-related mild cognitive impairments are undetected and are commonly characterized by executive dysfunction. To date, no specific treatment is available for executive mild cognitive impairment which is associated with poor outcomes in hypertension. The PI has recently completed, with support from a K23 award, a preparatory pilot study (n=47) to test the feasibility, safety and effect size of candesartan, an angiotensin receptor blocker, compared to hydrochlorothiazide and lisinopril, in individuals with hypertension and mild cognitive impairment characterized by executive dysfunction. Our preliminary analysis which was recently accepted for publication in the Archives of Internal Medicine, suggests that, independent of blood pressure, candesartan is superior to other antihypertensives in preserving executive function. Candesartan was also associated with an increase in cerebral blood flow velocity that only reached significance in those with low flow velocity at baseline (n=23). We hypothesized based on these data to further test the effect of angiotensin receptor blockers on cognitive function by conducting a 1-year double blind randomized active-control trial of candesartan vs. lisinopril in 160 individuals with hypertension and evidence of mild cognitive impairment in the executive domain.
The specific aims of this proposal are to investigate the effects of candesartan on executive function decline and on change in cerebral perfusion, cerebrovascular reserve and microvascular brain injury. We also aim at Identifying potential underlying mechanisms related to vascular structure and function by which candesartan may affect the cognitive and cerebrovascular outcomes. Participants will be recruited from the greater Los Angeles Area and evaluated at the University of Southern California. Cognitive tests that assess executive function and other cognitive domains will be administered at baseline and 12 months after treatment. Neuroimaging which includes perfusion (continuous arterial spin labeling) and micro-structure (diffusion tensor imaging), carotid ultrasound (carotid intima-media thickness), and endothelial and vascular inflammatory markers will be performed at baseline and after 12 months of treatment. This trial will shed more light onto the potential therapeutic effects of angiotensin receptor blockers on executive dysfunction and related vascular brain injury. This project will also improve our understanding of the possible mechanisms of action of this class of antihypertensives.
Hypertension is associated with a pattern of cognitive decline characterized by executive dysfunction. Although great advances have been made in treating hypertension, cognitive decline is on the rise. This study investigates the effect and mechanism of action of an angiotensin receptor blocker compared to an angiotensin converting enzyme inhibitor (an antihypertensive medication) on executive function and related cognitive domains. The effects of this medication will also be assessed based on cerebral circulatory function and structure.
|Shokouhi, Mahsa; Qiu, Deqiang; Samman Tahhan, Ayman et al. (2018) Differential Associations of Diastolic and Systolic Pressures With Cerebral Measures in Older Individuals With Mild Cognitive Impairment. Am J Hypertens 31:1268-1277|
|Hajjar, Ihab; Hayek, Salim S; Goldstein, Felicia C et al. (2018) Oxidative stress predicts cognitive decline with aging in healthy adults: an observational study. J Neuroinflammation 15:17|
|Hammadah, Muhammad; Al Mheid, Ibhar; Wilmot, Kobina et al. (2017) Telomere Shortening, Regenerative Capacity, and Cardiovascular Outcomes. Circ Res 120:1130-1138|
|Chand, Ganesh B; Wu, Junjie; Qiu, Deqiang et al. (2017) Racial Differences in Insular Connectivity and Thickness and Related Cognitive Impairment in Hypertension. Front Aging Neurosci 9:177|
|Chand, Ganesh B; Wu, Junjie; Hajjar, Ihab et al. (2017) Interactions of the Salience Network and Its Subsystems with the Default-Mode and the Central-Executive Networks in Normal Aging and Mild Cognitive Impairment. Brain Connect 7:401-412|
|Fleischer, C C; Wu, J; Qiu, D et al. (2017) The Brain Thermal Response as a Potential Neuroimaging Biomarker of Cerebrovascular Impairment. AJNR Am J Neuroradiol 38:2044-2051|
|Chand, Ganesh B; Wu, Junjie; Hajjar, Ihab et al. (2017) Interactions of Insula Subdivisions-Based Networks with Default-Mode and Central-Executive Networks in Mild Cognitive Impairment. Front Aging Neurosci 9:367|
|Hajjar, Ihab; Goldstein, Felicia C; Martin, Greg S et al. (2016) Roles of Arterial Stiffness and Blood Pressure in Hypertension-Associated Cognitive Decline in Healthy Adults. Hypertension 67:171-5|
|Hajjar, Ihab; Wharton, Whitney; Mack, Wendy J et al. (2016) Racial Disparity in Cognitive and Functional Disability in Hypertension and All-Cause Mortality. Am J Hypertens 29:185-93|
|Hajjar, Ihab; Goldstein, Felicia C; Waller, Edmund K et al. (2016) Circulating Progenitor Cells is Linked to Cognitive Decline in Healthy Adults. Am J Med Sci 351:147-52|
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