Stroke Impact on Progression of Alzheimer's (SIPA)

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Stroke and the most commonly occurring dementia, Alzheimer's disease (AD), share overlapping pathophysiology. Vascular comorbidities and cerebral arterial disease substantially contribute to the risk for both stroke and AD; more importantly, AD frequently co-exists with cerebrovascular disease. The application of MRI for hyperacute stroke now provides an unprecedented and unique opportunity to study how acute ischemic stroke (AIS) impacts the progression of ADRD in patients who already have a diagnosis of AD. We propose a prospective observational study of 50 patients with mild AD/MCI who present to the emergency department at Memorial Hermann hospital with AIS within 24 hrs of symptom onset. These patients will undergo a hyperacute multimodal MRI in the emergency department and then 24-48 hrs afterwards followed by serial cognitive, biomarker, and imaging assessments up to 1 year. As part of specific aim 1, we will measure the effect of AIS on the rate of clinical disease progression in patients with mild ADRD. We will create a carefully matched cohort of control patients with early-stage AD but without stroke derived from the placebo groups of recent randomized clinical trials testing new therapies for AD to determine how AIS accelerates disease progression on cognitive testing. In specific aim 2, we will measure the effect of AIS on the rate of neurodegeneration in patients with mild ADRD by measuring various imaging markers of regional and total brain volumetric analyses as well as degeneration of selective white matter tracts on quantitative MRI. Subhoc analyses will focus on the impact of infarct growth and perfusion changes in hyperacute stroke with subsequent degeneration of grey matter and selected white matter tracts. For comparative analyses, we will create a matched cohort control group derived from the Alzheimer's Disease Neuroimaging (ADNI) dataset. In aim 3, we will measure biomarkers of neurodegeneration in patients with AIS and mild AD/MCI: plasma β- amyloid ratios (42:40), total tau, and P-tau18, neurofilament light chain, and GFAP. We will assess the relationships between serum biomarkers and disease progression. This study will help to identify which AD patients will have a more accelerated trajectory of disease progression and neurodegeneration after a stroke. The results will be critical for subsequent studies to identify biomarkers that predict disease progression in these patients.