Association between α-Klotho and Deep White Matter Lesions in the Brain: A Pilot Case Control Study Using Brain MRI.

Background: The anti-aging protein, alpha-Klotho, may be involved in cognitive decline and has potential as a surrogate marker that reflects dementia. However, the role of alpha-Klotho in the brain has not been sufficiently investigated. Objective: Here, we investigated the association between alpha-Klotho and cognitive decline that is associated with cerebral deep white matter lesions (DWMLs). Methods: Two hundred-eighty participants (187 males and 93 females, mean age: 70.8 years old) were evaluated forDWMLs, and the Fazekas scale (Grade) was assessed following brain magnetic resonance imaging. Aquestionnaire concerning lifestyle and neuropsychological tests was administered, and their associations with the blood alpha-Klotho level were retrospectively investigated. Results: The alpha-Klotho level was 685.1 pg/mL in Grade 0 (68 subjects), 634.1 in G1 (134), 596.0 in G2 (62), and 571.6 in G3 (16), showing that the level significantly decreased with advanced grades. Significant correlations were noted between the alpha-Klotho level and higher brain function tests including the Mini-Mental State Examination and word fluency tests (p < 0.05). When a 90th percentile value of the level in the G0 group (400 pg/mL) or lower was defined as a low alpha-Klotho level, the odds ratio of the high-grade G3 group was 2.9 (95% confidence interval: 1.4-7.8) (after correction for age, sex, hypertension, and chronic kidney disease), which was significant. Conclusion: A reduced blood alpha-Klotho level was correlated with grading of cerebral DWMLs and was accompanied by cognitive decline as an independent risk factor. The alpha-Klotho level may serve as a useful clinical index of vascular cognitive impairment.