PROJECT SUMMARY
Post-stroke cognitive impairment is common, particularly in older individuals. Existing knowledge gaps about
mechanisms underpinning poor outcome, particularly in the aged, have been the most significant barriers to
developing novel therapeutic targets and approaches to prevent cognitive decline and progression to Alzheimer’s
disease and related dementias (ADRD). This is especially relevant to health disparity populations, specifically
women and Black demographics. Previous studies of Alzheimer’s disease and mild cognitive impairment,
suggest that the morphological changes of the corpus callosum are related to cognitive measures. Existing data
show that classical neuroimaging biomarkers such as acute infarct volume, location, and white matter
hyperintensity burden have modest prognostic predictive utility in models of post-stroke cognitive function. We
have recently used diffusion tensor imaging in acute stroke patients to show that decreased fractional anisotropy
of the ipsi- and contra-lateral hemispheric normal appearing white matter, as well as the corpus callosum, are
associated with higher stroke scale impairment severity. Additionally, we have also used advanced diffusion
imaging to examine white matter microstructure in midlife individuals with significant vascular risk factors, as well
as Black and women demographics at risk for stroke and cognitive impairment. Our preliminary results suggest
that the corpus callosum and other white matter structures involved in cognition manifest specific diffusion
changes that not only relate to vascular risk factor burden exposure, but also to post-stroke outcome. Our
laboratory has pioneered diffusion MRI acquisition and modeling approaches that are sensitive to not only white
matter anisotropy, but also white matter complexity. As such, we are well poised to comprehensively characterize
the diffusion properties of normal appearing white matter across time and age, in acute stroke patients and their
post-stroke cognitive trajectories. Our established expertise in diffusion imaging and modeling that is sensitive
to white matter complexity in relation to the presence of age-related vascular risk profiles, allows us to
longitudinally examine the unique microstructural properties of the corpus callosum, infarcted and non-infarcted
tissue, and more remote structures on the contralateral non-lesioned hemisphere and their relationship to post-
stroke recovery. It is therefore possible that a deeper understanding of white matter microstructure in the acute
stage after ischemic stroke and its change over time, will enhance prediction models of post-stroke cognitive
recovery and identify novel target for therapeutic interventions. This knowledge will also help our clinicians
provide much needed bed-side prognosis to patients and their families. Our central hypothesis is that after
unilateral ischemic stroke, temporal changes in the diffusion properties of normal appearing white matter of the
corpus callosum specifically, and the white matter across both hemispheres in general, are associated with the
differential patterns of post-stroke age-related cognitive trajectories.