Neurodegenerative Changes in Post-Stroke Depression

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PROJECT SUMMARY Stroke is one of the leading causes of long-term mortality and disability, affecting nearly 800,000 people in the United States each year. Nearly one-third of stroke victims report post-stroke depression (PSD) after a stroke that significantly affects stroke recovery and is associated with an enormous disability burden and poor quality of life. Post-stroke depression (PSD) is a common and severe complication of cerebrovascular stroke, affecting about one-third of stroke survivors. PSD is associated with poor functional recovery from stroke-related disability, mortality, and poor life quality. The diagnosis and treatment decisions are currently based on clinical evaluation; treatments are not tailored to the brain injury. We hypothesize that identifying specific pathological changes in PSD is the first step towards developing personalized treatments for PSD. Evidence suggests brain anatomical changes (i.e, neurodegeneration - volume loss, microstructures, and disconnections) in prefrontal-limbic circuitry remote from primary stroke lesion and may be causally related to PSD. The primary objectives of this pilot project are to investigate the role of prefrontal-limbic anatomy using MRI and will evaluate synaptic density using a state- of-the-art Positron Emission Tomography (PET) imaging-based synaptic marker. We propose anatomical structural changes and synaptic density losses in prefrontal-limbic circuitry as a biological mechanism underlying PSD. The findings from this study will provide preliminary evidence; (1) if neurodegeneration in the mood-related prefrontal-limbic circuitry underlies depression symptoms, and (2) to develop brain circuit-based neurodegeneration markers underlying neuropsychiatric symptoms in stroke.