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Introduction: Cortical superficial siderosis (cSS) refers to deposition of blood breakdown products along the cerebral cortex, causing characteristic staining patterns seen with iron-sensitive MRI techniques. Cortical superficial siderosis is a relatively rare disorder, but has been linked to cerebral amyloid angiopathy and Alzheimer’s disease. The objective of this study was to determine the frequency and natural history of cSS in the general elderly population.Methods: MRI scans from the Mayo Clinic Study of Aging (MCSA), an ongoing population-based study of elderly residents in Olmsted County, Minnesota, were reviewed by neuroradiologists. Participants with cSS were identified based on linear pattern of hypointensity on gradient recalled echo imaging consistent with cSS. Exclusion criteria were: 1) MRI findings not consistent with cSS or 2) alternative explanation for MRI findings (such as aneurysmal subarachnoid hemorrhage, intracranial surgery, or trauma). Additional data abstracted included extent of cSS, presence of cerebral microbleeds, and clinical outcome.Results: Eleven out of 1,441 participants had MRI scans showing cSS (0.8%). When stratified by age, the frequency was 0.4% in those 50 to 70 years old and 1.1% in those over 70 years old. Six participants had only focal involvement of cSS (restricted to three or fewer sulci) and five had disseminated involvement (affecting more than three sulci). Microbleeds were seen in four of five (80%) participants with disseminated cSS, but none with focal cSS. Five participants (2 focal, 3 disseminated cSS) had follow up MRI scans, with an average follow up of 25 months. There was no further hemorrhage in those with focal cSS. However, all three participants with disseminated cSS experienced additional hemorrhage: one with new microbleeds, one with new microbleeds and lobar hemorrhage, and one with sulcal subarachnoid hemorrhage and lobar hemorrhage.Conclusion: Although rare, cSS may be encountered in the general elderly population. Extent of involvement of cSS and concomitant microbleeds may be important risk factors for progression of disease and intracerebral hemorrhage. The clinical significance of focal cSS occurring in the absence of microbleeds requires further investigation.