Curiosity-Based Interventions Increase Everyday Functioning Score But Not Serum BDNF Levels in a Cohort of Healthy Older Adults

Abstract

An enriched environment is effective in stimulating learning and memory in animal models as well as in humans. Environmental enrichment increases brain-derived neurotrophic factor (BDNF) in aged rats and reduces levels of Alzheimer-related proteins in the blood, including amyloid-β (Aβ) peptides and misfolded toxic forms of tau. To address whether stimulation of curiosity, which is a form of enrichment, may provide a buffer against Alzheimer's disease (AD), we measured levels of biomarkers associated with AD at baseline and after a 6-week intervention in older adults (>65 years of age) randomized to one of three different intervention conditions. Specifically, in this pilot study, we tested the effectiveness of a traditional, structured learning environment compared to a self-motivated learning environment designed to stimulate curiosity. There were no significant differences from baseline to post-intervention in any of the groups for Aβ42/Aβ40 ratio or t-tau (total-tau) plasma levels. Serum BDNF levels decreased significantly in the control group. Interestingly, individuals who had the lowest serum BDNF levels at baseline experienced significantly higher increases in BDNF over the course of the 6-week intervention compared to individuals with higher serum BDNF levels at baseline. As expected, older individuals had lower MoCA scores. Years of education correlated negatively with Aβ levels, suggesting a protective effect of education on levels of this toxic protein. ECog scores were negatively correlated with BDNF levels, suggesting that better performance on the ECog questionnaire was associated with higher BDNF levels. Collectively, these findings did not suggest that a 6-week cognitive training intervention focused on curiosity resulted in significant alterations in blood biomarkers but showed interesting correlations between cognitive scores and BDNF levels, further supporting the role of this trophic factor in brain health in older adults.

Keywords: Alzheimer’s disease; amyloid; brain-derived neurotrophic factor; curiosity; memory; t-tau.

FIGURE 1

Change in Aβ42/Aβ40 ratio, t-tau and BDNF levels from baseline to post-intervention. (A) Change in plasma Aβ42/Aβ40 ratio from baseline to post-intervention in the curiosity group (shown in green), traditional group (shown in purple) and control group (shown in black). Although the control group exhibited a steeper decline, an ANCOVA did not reveal any significant group difference. (B) Change in plasma t-tau levels (pg/ml) from baseline to post-intervention in the curiosity group, traditional group and control group. No significant group difference was found. (C) Change in serum BDNF levels (ng/ml) from baseline to post-intervention in the curiosity group, traditional group and control group. BDNF levels decreased significantly in the control group (p = 0.01). However, there were no significant differences in BDNF concentration between the three intervention groups. All data were analyzed using ANCOVA with post-hoc Bonferroni adjustment. Data are represent as mean ± SEM.

FIGURE 2

Change in serum BDNF levels from baseline to post-intervention. Each bar depicts the change in BDNF level (in ng/mL) between the post-intervention value and the baseline value for each participant in the curiosity group (shown in green), the traditional group (shown in purple), and the control group (shown in black). A higher proportion of participants in the two intervention groups experienced an increased in BDNF levels, suggesting that both interventions resulted in a positive change in BDNF levels.

FIGURE 3

Changes in serum BDNF levels from baseline to post-intervention depend on baseline levels of BDNF. The total cohort of participants was stratified in three groups according to their baseline BDNF levels using tertiles. BDNF change was significantly higher (p = 0.012) in individuals with lower BDNF at baseline (1st tertile, shown in red) compared to individuals with higher levels of BDNF at baseline (2nd tertile, shown in grey; 3rd tertile, shown in grey). Data were analyzed using a one-way ANOVA with post-hoc Bonferroni adjustment. Error bars represent the SEM.