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

The anti-aging protein, α- Klotho, may be involved in cognitive decline and has potential as a surrogate marker that reflects dementia. However, the role of α- Klothoin the brain has not been sufficiently investigated.Here, we investigated the association between α- Klothoand cognitive decline that is associated with cerebral deep white matter lesions (DWMLs).Two hundred-eighty participants (187 males and 93 females, mean age: 70.8 years old) were evaluated for DWMLs, and the Fazekas scale (Grade) was assessed following brain magnetic resonance imaging. A questionnaire concerning lifestyle and neuropsychological tests was administered, and their associations with the blood α- Klotholevel were retrospectively investigated.The α- Klotholevel 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 α- Klotholevel and higher brain function tests including the Mini-Mental State Examinationand 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 α- Klotholevel, 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.A reduced blood α- Klotholevel was correlated with grading of cerebral DWMLs and was accompanied by cognitive decline as an independent risk factor. The α- Klotholevel may serve as a useful clinical index of vascular cognitive impairment.