{"id":"https://openalex.org/G3897366751","display_name":"Vascular Effects on Normal Neural and Cognitive Aging","description":"PROJECT NARRATIVE The present proposal examines a vascular hypothesis of aging which investigates the role of general vascular risk factors, such as hypertension, and specific cerebrovascular mechanisms such as hypoperfusion, in shaping the course of neural and cognitive aging within a normal aging model. Understanding the contributions of vascular health to successful, as well as pathological aging is fundamentally important given both the prevalence of vascular risk in the aging population, and its amenability to prevention and treatment. __SpecificAimsTextDelimiter__  A. SPECIFIC AIMS: Even normal aging is marked by detrimental changes in the integrity of brain structure and function, and a corresponding decline in cognitive abilities. However, considerable individual differences in the aging trajectory exist; some individuals maintain sharp mental acuity well into old age, while others show significant decline. The mechanisms driving these differences are manifold, but vascular risk may be one of the most salient among them. One of the most common vascular risk factors, hypertension, modifies brain structure and has a negative impact on age-sensitive cognitive skills (e.g., Raz, Rodrigue & Acker, 2003). Moreover, hypertension present at mid-life increases the risk for dementia (Kivipelto, et al., 2002). Successful and efficient maintenance of brain function and cognition depends upon reliable delivery of oxygen and nutrients via the blood supply (Edvinsson & Krause, 2002). Consequently, neurocognitive function is particularly vulnerable to changes in the vascular system, such as decreased cerebral perfusion, that can occur with aging. Chronic hypoperfusion may precipitate a metabolic energy crisis, which promotes neurodegeneration and abnormal processing of amyloid precursor protein resulting in \u00bf-amyloid deposition (de la Torre, 2008). Thus, early detection of CBF decline with aging may be an important earlier predictor of subsequent cognitive deterioration. It is unclear, however, if CBF declines are harbingers of pathological aging, or if decreased perfusion predicts cognitive decline in healthy aging as well.  Thus, the overall goal of my research program is to examine a vascular hypothesis of aging which investigates the role of general vascular risk factors, such as hypertension, and specific cerebrovascular mechanisms such as hypoperfusion, in shaping the course of normal neural and cognitive aging. The proposed K99 phase focuses on the hypothesis that age-related alteration in regional brain perfusion predicts decline in cognitive performance, as well as examines the modifying effects of hypertension on neural activity in a functional MRI paradigm. The R00 phase extends the study of the impact of vascular health on neural and cognitive decline by examining vascular predictors of \u00bf-amyloid deposition in normal aging. K99 Aim 1. To evaluate prefrontal hypoperfusion as an early mechanism of age-related declines in processing speed, working memory and long-term memory in normal aging. To achieve this aim, we will measure regional perfusion in the four lobes, with the expectation that age-related decreases in perfusion will be most pronounced in the frontal regions. Three age-sensitive domains of cognition will be examined to determine the specificity of the perfusion effects. Given the importance of prefrontal function in multiple cognitive processes we hypothesize that perfusion deficits to the prefrontal region will exert adverse effects on all three cognitive domains. In contrast, we hypothesize that medial temporal perfusion deficits will show selective effects on memory performance, but not on other age-sensitive domains. K99 Aim 2. To determine if essential hypertension, a known correlate of hypoperfusion and a significant vascular risk factor, affects functional brain activation patterns observed in otherwise healthy, older adults. Even treated hypertension has adverse effects on cognition and brain structure, but the effects of hypertension on brain function in fMRI studies is an open question. Functional activation patterns in hypertensive vs. demographically matched normotensive control participants will be compared in an fMRI task that examines degree of neural specificity. We hypothesize that hypertensives will show decreased neural specialization to specific categories compared to normotensive older adults. In addition, we hypothesize that middle-aged hypertensive participants will already show decreased specialization (i.e., dedifferentiation) similar to the pattern typically observed in the older group, thus exhibiting an accelerated course of aging. K99 Aim 3. To collect preliminary data to test the hypothesis that hypertension exacerbates \u00bf -amyloid deposition. Hypertensive participants will show greater magnitude and extent of amyloid burden than a normotensive, demographically matched control group. This aim serves to ensure thorough training in this methodology and to provide published results on which to base the R00 projects . R00 Aim 4 . To examine the associations among vascular risk, hypoperfusion and \u00bf-amyloid deposition in normal cognitive aging. During the R00 phase, I propose to prospectively recruit groups of middle and older aged adults who are either completely healthy, or have hypertension to examine differences in perfusion, \u00bf-amyloid, and cognition. First, I will gauge the contribution of hypoperfusion (by vascular risk group) in predicting amyloid burden. Second, I will examine whether perfusion or amyloid is a more sensitive predictor of impairment in three age-sensitive domains of cognition. Third, I will examine whether the proposed relationship among perfusion, \u00bf-amyloid and cognition is selective to vascular risk. Hypothesis 1: Decreased regional perfusion will be associated with greater amyloid burden, and this association will be stronger in the hypertensive group; Hypothesis 2: If indeed hypoperfusion is a precursor to amyloid accumulation, then hypoperfusion will be the more sensitive predictor of cognition in middle-aged adults. In contrast, I expect amyloid burden to be a stronger predictor of cognitive decline in older adults. Hypothesis 3: The associations among perfusion, \u00bf-amyloid and cognition will be stronger in individuals with vascular risk factors, lending support to the idea that vascular risk is an important instigator of cognitive decline.","funder_award_id":"R00AG036848","funder":{"id":"https://openalex.org/F4320337337","display_name":"National Institute on Aging","doi":"10.13039/100000049"},"funded_outputs":["https://openalex.org/W1570796039","https://openalex.org/W1964311148","https://openalex.org/W1987110004","https://openalex.org/W1990321340","https://openalex.org/W2001462170","https://openalex.org/W2037403969","https://openalex.org/W2085386918","https://openalex.org/W2101800098","https://openalex.org/W2113525383","https://openalex.org/W2129932089","https://openalex.org/W2143828545","https://openalex.org/W2160565960","https://openalex.org/W2162069510","https://openalex.org/W2461521134","https://openalex.org/W2539685118","https://openalex.org/W2555261974","https://openalex.org/W2566910879","https://openalex.org/W2575975340","https://openalex.org/W2605672284","https://openalex.org/W2665919687","https://openalex.org/W2776495092","https://openalex.org/W2782431358","https://openalex.org/W2789964425","https://openalex.org/W2792211318","https://openalex.org/W2886694005","https://openalex.org/W2889850836","https://openalex.org/W2898117636","https://openalex.org/W2901512353","https://openalex.org/W2962952924","https://openalex.org/W2971074351","https://openalex.org/W2979971971","https://openalex.org/W3002519818","https://openalex.org/W3033577168","https://openalex.org/W3045899671","https://openalex.org/W3086501880","https://openalex.org/W3089416312","https://openalex.org/W3095446109","https://openalex.org/W3098797936","https://openalex.org/W3111326831","https://openalex.org/W3164235448","https://openalex.org/W4283832862","https://openalex.org/W4396667471","https://openalex.org/W4404555795","https://openalex.org/W7045440543"],"funded_outputs_count":44,"parent_awards":[],"sub_awards":[],"sub_awards_count":0,"amount":null,"currency":"USD","amount_usd":null,"amount_usd_basis":null,"recipients":[],"recipient_countries":[],"recipient_regions":[],"research_scope":{"is_research":true,"basis":"funder_default","tier":1},"funding_type":"research","funder_scheme":"R00","start_date":"2010-09-30","end_date":"2016-05-31","start_year":2010,"end_year":2016,"landing_page_url":"https://reporter.nih.gov/project-details/8726263","doi":null,"provenance":"nih_exporter","lead_investigator":{"given_name":"KAREN M","family_name":"RODRIGUE","orcid":null,"role_start":null,"affiliation":{"name":"UNIVERSITY OF TEXAS DALLAS","country":"UNITED STATES","ids":null}},"co_lead_investigator":null,"investigators":null,"works_api_url":"https://api.openalex.org/works?filter=awards.id:G3897366751","primary_topic":null,"topics":null,"institution_awarded":[{"id":"https://openalex.org/I162577319","display_name":"The University of Texas at Dallas","ror":"https://ror.org/049emcs32","country_code":"US","type":"education","lineage":["https://openalex.org/I162577319"]},{"id":"https://openalex.org/I182980787","display_name":"University of Dallas","ror":"https://ror.org/00v3ak792","country_code":"US","type":"education","lineage":["https://openalex.org/I182980787"]},{"id":"https://openalex.org/I87573096","display_name":"University of North Texas at Dallas","ror":"https://ror.org/01n51v443","country_code":"US","type":"education","lineage":["https://openalex.org/I87573096"]}],"updated_date":"2026-10-30T03:00:55.000Z","created_date":"2026-10-09T19:56:01.000Z"}