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Title: Association between MPV and Cerebral Vascular Ischemic Burden in Mild to Moderate Alzheimers’s Disease Running Title: MPV and Ischemic Burden in AD ABSTRACT Objective: Vascular pathologies and chronic neuroinflammation play an important role in Alzheimer's Disease(AD). Increased platelet activity, which underlies the pathophysiology of atherosclerosis and systemic inflammation, has been reported several times in the setting of AD. However, the relationship between this increase and neuroimaging correlates has not been studied yet. This study aims to evaluate the relationship between mean platelet volume (MPV), as a reliable indicator of platelet activity, and vascular ischemic burden in neuroimaging of AD. Material- Method: Medical records of mild-moderate AD cases diagnosed in our dementia outpatient clinic between 2021-2022 were retrospectively reviewed. Patients were classified as having "mild" or "severe" vascular ischemic burden on MRI. Clinical findings and platelet markers were compared between the groups. Multivariate regression was applied for potential confounders regarding vascular ischemic burden. Results: Out of 59 patients, 36 had 'mild' and 23 had 'severe' ischemic burden. Demographic and clinical features were similar; however, MPV was significantly higher in the group with severe ischemia (p:0.013). Multivariate analysis revealed an independent association between MPV and ischemic burden. An MPV value of ≥8.7 fL had a sensitivity of 69.6% and a specificity of 61% for the presence of severe burden. Discussion: Our results highlight the role of platelet activation in the vascular pathogenesis of AD. During the early evaluation of AD, increased MPV can serve as a marker to determine the high-risk group in terms of cerebral ischemic burden. This might enable close monitoring and timely management of high-risk patients regarding the development of vascular morbidities. Keywords: Alzheimer's Disease, mean platelet volume, MPV, vascular ischemic burden, inflammation

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