Arterial stiffness, brain morphology, cognition, and dementia in U.S. Hispanics/Latinos

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Cognitive impairment and Alzheimer's disease and related dementias (ADRD) are pressing public health concerns as the population ages. In the U.S., Hispanics/Latinos have a higher MCI and ADRD risk compared with other population groups, and they are expected to contribute disproportionately to the expected increase in mild cognitive impairment (MCI) and ADRD. Factors explaining this disparity are unknown. Higher central arterial stiffness is posited to alter microvasculature structure and function in the brain contributing to cerebral small vessel disease and with cognitive impairment and risk of ADRD in older white and black adults. No reports to date have examined these associations in a large, diverse Hispanic/Latino population. Similarly, the important roles of sex, obesity, the metabolic syndrome, and type 2 diabetes in these associations have not been assessed. U.S. Hispanics/Latinos have a high burden of cardiometabolic risk factors that are associated with both greater arterial stiffness and risk of ADRD and could contribute to the health disparity in MCI and ADRD. We propose to address these gaps in an ancillary study to the 2019-2022 Visit 3 examination of ~9,297 participants in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), an ongoing cohort study of well-characterized U.S. Hispanic/Latinos. We propose to add pulse wave velocity, a non-invasive arterial stiffness measurement, to participants ≥45 years old during Visit 3 (n ~7,020). All other data will be available from HCHS/SOL and its two ancillary studies. The Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) will provide data on cognitive performance and MCI and dementia classification for cohort members ≥45 years old at Visit 3 (~6,272). INCA-MRI will provide brain magnetic resonance imaging (MRI) data on a sample of cohort members (2017-2019, n ~2,800). The study aims are the following: Aim 1. Estimate the association of central arterial stiffness and cerebral small vessel disease (cerebral white matter hyperintensities, white matter integrity, and infarcts) overall and by sex. Aim 2. Estimate the association of central arterial stiffness and domain-specific cognitive function overall and by sex in participants ≥45 years old. Aim 3. Estimate the association of central arterial stiffness and MCI and ADRD overall and by sex in participants ≥45 years old. For all aims, we will evaluate obesity, the metabolic syndrome, and type 2 diabetes as potential modifiers. This cost-efficient ancillary study will, for the first time, contribute novel information on the association of central arterial stiffness and brain structure and function in a large sample of Hispanic/Latinos, a population burdened with a high levels of metabolic impairments. Additionally, the inclusion of middle-aged adults will provide insights into opportunities for early intervention prior to onset of overt disease. Understanding how arterial stiffness influences cognitive impairment and ADRD will contribute novel information on identifying potential targets for intervention, reducing health disparities, and the promoting cognitive resilience.