KL and Cognitive impairment: On the other hand, the synthesis and release of α-Klotho declines in aging, and because the aforementioned diseases occur mainly during aging, it is to be expected that α-Klotho levels in blood serum and CSF are decreased, as has been shown in several studies involving animal models and in observational studies with humans, where there is a negative association between plasma and CSF concentrations and cognitive impairment.