Cognitive impairment and Alzheimer's disease and related dementias (ADRD) are pressing public health concerns as the population ages. In the U.S., African Americans have a high risk of ADRD compared with other population groups; however, factors explaining this disparity are unknown. Greater central arterial stiffness is posited to alter microvasculature structure and function in the brain, contributing to cerebral small vessel disease, cognitive impairment, and risk of ADRD. No reports to date have examined these associations in a large, well-characterized African American population. Similarly, the salient roles of sex, type 2 diabetes, and hypertension in these associations have not been addressed, although African Americans have a high burden of cardiometabolic risk factors and hypertension that are associated with both greater arterial stiffness and risk of ADRD. We propose to examine these gaps in an ancillary study to the 2020-2022 Exam 4 of ~2,700 participants, ages 41-104 years, in the Jackson Heart Study (JHS), an ongoing and deeply phenotyped cohort of African Americans. We propose to add pulse wave velocity, a non-invasive arterial stiffness measurement, to all participants during Exam 4. All other data will be available from JHS and Atherosclerosis Risk in Communities-Neurocognitive study (ARIC-NCS). To evaluate temporal change in arterial stiffness, we will leverage existing arterial stiffness measures from those who also participated in the ARIC-NCS Visit 5 (2011- 2013, N=1,078). The study aims are the following:
Aim 1. Estimate the association of central arterial stiffness and the burden of cerebral white matter hyperintensities, subcortical infarcts, and markers of brain atrophy.
Aim 2. Estimate the association of central arterial stiffness and domain-specific cognitive function.
Aim 3. Characterize the 8-year change in central arterial stiffness and its association with the burden of cerebral white matter hyperintensities, subcortical infarcts, and brain volumes at Exam 4 among older adults in participants in both the ARIC-NCS and JHS studies. For all aims, we will evaluate sex, type 2 diabetes, and hypertension as potential effect modifiers. This cost-efficient ancillary study will, for the first time, contribute information on the association of central arterial stiffness and brain structure and function in a large sample of African Americans, a population exposed to high levels of hypertension and metabolic impairments and at risk for ADRD. The inclusion of middle-aged adults and measures of cerebral small vessel disease, cerebral infarcts, and impaired cognitive function will provide insights into opportunities for intervention prior to onset of cognitive impairment or overt ADRD. Understanding how arterial stiffness influences brain health will contribute novel information toward reducing health disparities and promoting cognitive resilience.
This study is focused on the stiffening of the arteries and the associated structural damage to small vessels in the brain and reduced cognitive function that precede cognitive impairment and Alzheimer's disease and related dementias. We propose to add a measure of artery stiffness to the 2020-2022 re-examination of the Jackson Heart Study; information on risk factors, damage to small vessels in the brain and cognitive performance will come from the existing study and as well as measures of artery stiffness in subset of participants that also participated in the 2011-2013 visit of the Atherosclerosis Risk in Communities- Neurocognitive study. This study will provide new information on how stiffening of the arteries relate to brain structure and function in African Americans that can inform efforts to reduce health disparities and to identify potential targets to lower the risk of cognitive impairment and Alzheimer's disease and related dementias.
