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This study investigated the relationship among cerebral amyloid\u2010\u03b2 (A\u03b2) deposition, VD, and cognitive decline. We enrolled 92 participants, including 47\u2009AD patients and 45 healthy control (HC) participants. VD across retinal subregions was quantified using deep learning\u2010based fundus photography, and cerebral A\u03b2 deposition was measured with 18<\/jats:sup>F\u2010florbetapir (18<\/jats:sup>F\u2010AV45) PET\/MRI. Using the minimum bounding circle of the optic disc as the diameter (papilla\u2010diameter, PD), VD (total, 0.5\u20131.0 PD, 1.0\u20131.5 PD, 1.5\u20132.0 PD, 2.0\u20132.5 PD) was calculated. Standardized uptake value ratio (SUVR) for A\u03b2 deposition was computed for global and regional cortical areas, using the cerebellar cortex as the reference region. Cognitive performance was assessed with the Mini\u2010Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Pearson correlation, multiple linear regression, and mediation analyses were used to explore A\u03b2 deposition, VD, and cognition. AD patients exhibited significantly lower VD in all subregions compared to HC (p<\/jats:italic>\u2009<\u20090.05). Reduced VD correlated with higher SUVR in the global cortex and a decline in cognitive abilities (p<\/jats:italic>\u2009<\u20090.05). Mediation analysis indicated that VD influenced MMSE and MoCA through SUVR in the global cortex, with the most pronounced effects observed in the 1.0\u20131.5 PD range. Retinal VD is associated with cognitive decline, a relationship primarily mediated by cerebral A\u03b2 deposition measured via 18<\/jats:sup>F\u2010AV45 PET. These findings highlight the potential of retinal VD as a biomarker for early detection in AD.<\/jats:p>","DOI":"10.1002\/hbm.70310","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T13:04:36Z","timestamp":1754312676000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cerebral Amyloid Deposition With 18<\/sup>F<\/scp>\u2010Florbetapir PET<\/scp> Mediates Retinal Vascular Density and Cognitive Impairment in Alzheimer's Disease"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1675-5606","authenticated-orcid":false,"given":"Zhigeng","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Radiology and Nuclear Medicine Xuanwu Hospital, Capital Medical University Beijing China"},{"name":"Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics Beijing China"},{"name":"Key Laboratory of Neurodegenerative Diseases 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