In view of the biochemical, pharmacological, morphological and electrophysiological evidence here reported in hippocampal primary neurons and in the hippocampus of mice, these results suggest that orexin antagonism by conventional pharmacological insomnia treatments may be beneficial in subjects with mild-to-moderate age-related cognitive decline associated with sleep disturbances to delay or limit neurodegenerative injuries. This evidence concerns the gene HCRT and insomnia.