MAPT and Cognitive impairment: These results in nitric oxide deficiency, decreased calpain nitrosylation, and subsequent activation of calpain and CDK5, promoting cognitive deficits via tau hyperphosphorylation.[10] Interestingly, tau phosphorylation in the neocortex was observed to increase after 4 weeks of HS intake, whereas in the hippocampus, it was not evident until 12 weeks.