Energy Restriction Enhances Adult Hippocampal Neurogenesis-Associated Memory after Four Weeks in an Adult Human Population with Central Obesity; a Randomized Controlled Trial

Abstract

Adult neurogenesis, the generation of new neurons throughout life, occurs in the subventricular zone of the dentate gyrus in the human hippocampal formation. It has been shown in rodents that adult hippocampal neurogenesis is needed for pattern separation, the ability to differentially encode small changes derived from similar inputs, and recognition memory, as well as the ability to recognize previously encountered stimuli. Improved hippocampus-dependent cognition and cellular readouts of adult hippocampal neurogenesis have been reported in daily energy restricted and intermittent fasting adult mice. Evidence that nutrition can significantly affect brain structure and function is increasing substantially. This randomized intervention study investigated the effects of intermittent and continuous energy restriction on human hippocampal neurogenesis-related cognition, which has not been reported previously. Pattern separation and recognition memory were measured in 43 individuals with central obesity aged 35-75 years, before and after a four-week dietary intervention using the mnemonic similarity task. Both groups significantly improved pattern separation (P = 0.0005), but only the intermittent energy restriction group had a significant deterioration in recognition memory. There were no significant differences in cognitive improvement between the two diets. This is the first human study to investigate the association between energy restriction with neurogenesis-associated cognitive function. Energy restriction may enhance hippocampus-dependent memory and could benefit those in an ageing population with declining cognition. This study was registered on ClinicalTrials.gov (NCT02679989) on 11 February 2016.

Keywords: adult hippocampal neurogenesis; ageing; cognition; energy restriction; intermittent fasting; pattern separation; randomized controlled trial; recognition memory.

Figure 1

CONSORT (Consolidated Standards of Reporting Trials) diagram for the Met-IER study (Metabolic effects of Intermittent Energy Restriction). IER: intermittent energy restriction; CER: continuous energy restriction.

Figure 2

Energy restriction improves pattern separation regardless of method. (a) There is no significant difference between IER and CER in pattern separation and recognition memory performance, as measured by LDI and REC scores, respectively. However, the IER group had a significant reduction in REC score (P = 0.007), which was not observed in the CER group. (b) When the groups are treated as a single cohort, there is a significant increase in LDI score (P = 0.0005). Significance at P < 0.05. ** P < 0.01, *** P < 0.001. IER: intermittent energy restriction; CER: continuous energy restriction LDI: lure discrimination index; REC: recognition.