We propose this project as part of a larger R01 submission to the US NIH for June 2025. Understanding and reducing Alzheimer’s disease and related dementias (ADRD) in acute myocardial infarction (MI) survivors is an urgent health priority and a critical research area. Acute MI is a major ADRD risk factor. However, the mechanisms for post-MI ADRD are unclear. This knowledge is vital to developing effective treatments for reducing ADRD in MI survivors. Aims 1 and 2 will examine how post-MI vascular risk factor (VRF) and inflammatory levels contribute to ADRD in a pooled cohort of US studies. Aim 3 will examine the role of cerebral small vessel disease in post-MI ADRD. VRFs put MI survivors at higher risk for stroke and cerebral small vessel disease-postulated mechanisms for AMI-related ADRD. Defining the role of cerebral small vessel disease in post-MI ADRD will identify intervention targets.
Aim: Clarify the relationships between cerebral small vessel disease’s magnetic resonance imaging (MRI) markers with post-MI ADRD. We will explore the roles of incident stroke and heart failure. We will use the UK Biobank dataset. Hypothesis: Higher cerebral small vessel disease burden is associated with greater post-MI ADRD.
The primary cerebral small vessel disease measure is the time-dependent mean total WMHV measure assessed on T2-weighted fluid-attenuated inversion recovery images. The secondary cerebral small vessel dis-ease measure is the time-dependent mean total fractional anisotropy (FA) measure assessed on diffusion tensor images. FA reflects white matter microstructural integrity and is a more sensitive early-stage marker of white matter injury than WMHV. To test the Hypothesis, there is a significant effect of time-dependent cumulative mean cerebral small vessel disease on post-MI ADRD risk after adjusting for other covariates, we will use Cox proportional regression models for time to incident ADRD.