In a prospective study with 262 first-ever ischaemic stroke patients (average age: 67.4), plasma Klotho concentration was inversely associated with the presence of WMH lesions, PVS, lacunes, total SVD burden and disease progression, though not microbleeds, possibly suggesting different pathological mechanisms underlying the protective involvement of Klotho proteins in distinct radiologic manifestations of SVD [161]. This evidence concerns the gene KL and snowflake vitreoretinal degeneration.