Serum α-Klotho levels correlate with episodic memory changes related to cardiovascular exercise in older adults

Aerobic exercise is a potential life-style intervention to delay cognitive decline and neurodegeneration. Elevated serum levels of the anti-aging protein α-Klotho (αKL) are a potential mediating factor of exercise benefits on cognition. Here, we examined in older adults how exercise-related changes of αKL levels in serum relate to changes in cerebral blood flow (CBF), hippocampal volumes and episodic memory. We analyzed data from a previously published intervention study in which forty cognitively healthy subjects were pseudo-randomly assigned to either a cardiovascular exercise group (treadmill training, n=21) or control group (indoor progressive-muscle relaxation/stretching, n=19). 3-Tesla gadolinium perfusion imaging was used to track hippocampal CBF changes and high resolution 7-Tesla-T1-images were used to track hippocampal volume changes. Changes in episodic memory performance were measured using the complex figure test (CFT). Longitudinal changes were compared between groups and analyzed with a multiple linear regression approach. CFT and hippocampal volume changes significantly predicted changes in serum αKL levels. For CFT, this effect was found in the exercise but not the control group. Collectively the data suggest that αKL level increases induced by exercise can be associated with improved hippocampal function in older adults.