The effect of casein hydrolysate intake on cerebral neural regulation during cognitive tasks in the elderly

Exp Gerontol. 2022 Aug;165:111853. doi: 10.1016/j.exger.2022.111853. Epub 2022 May 26.


Human and animal studies have shown that casein peptide (casein hydrolysate) has positive effects on cognitive function. This double-blind randomized controlled study aimed to investigate whether single ingestion of casein peptide could affect cognitive function (executive function) and cognitive neural activity in healthy older adults. We assigned 47 participants to one of the three dietary supplements as follows: casein peptide (TMP, n = 15), casein (TMC, n = 16), and indigestible dextrin (TMF, n = 16). Dietary supplements were ingested 30 min before starting the experiment; moreover, neural activity while performing the task-switching reaction time (SWT) trial was assessed through functional magnetic resonance imaging (fMRI). Additionally, we used a visual analog scale (VAS) test to assess the pre- and post-test feeling and mood. Regarding the parameters of the SWT trial, there were no significant among-group differences in the reaction time, accuracy rate, and %SwitchCost. Contrastingly, the fMRI experiment revealed among-group differences in the main effects in the medial frontal gyrus, Supplementary motor cortex (SMC), posterior cingulate gyrus (PCg), and amygdala (Amyg). Specifically, there was a significant decrease in the neural activities in the SMC and PCg in the TMP group than in the other two groups. Moreover, there was a significant increase in the neural activity in the Amyg in the TMP group compared with the TMF, but not the TMC, group. Furthermore, the VAS score was significantly higher in the TMP group than in the other two groups. There were no recorded adverse outcomes. Our findings suggested that TMP ingestion by older adults could temporarily suppress complementary neural activity in specific brain regions involved in executive functions, as well as default mode network activity, which could improve cognitive neural activities.

Keywords: Casein hydrolysate; Cognitive function; Functional magnetic resonance imaging; Neural activity.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Brain*
  • Caseins* / pharmacology
  • Cognition
  • Humans
  • Magnetic Resonance Imaging / methods


  • Caseins
  • casein hydrolysate