Caloric restriction improves memory in elderly humans

Abstract

Animal studies suggest that diets low in calories and rich in unsaturated fatty acids (UFA) are beneficial for cognitive function in age. Here, we tested in a prospective interventional design whether the same effects can be induced in humans. Fifty healthy, normal- to overweight elderly subjects (29 females, mean age 60.5 years, mean body mass index 28 kg/m(2)) were stratified into 3 groups: (i) caloric restriction (30% reduction), (ii) relative increased intake of UFAs (20% increase, unchanged total fat), and (iii) control. Before and after 3 months of intervention, memory performance was assessed under standardized conditions. We found a significant increase in verbal memory scores after caloric restriction (mean increase 20%; P < 0.001), which was correlated with decreases in fasting plasma levels of insulin and high sensitive C-reactive protein, most pronounced in subjects with best adherence to the diet (all r values < -0.8; all P values <0.05). Levels of brain-derived neurotrophic factor remained unchanged. No significant memory changes were observed in the other 2 groups. This interventional trial demonstrates beneficial effects of caloric restriction on memory performance in healthy elderly subjects. Mechanisms underlying this improvement might include higher synaptic plasticity and stimulation of neurofacilitatory pathways in the brain because of improved insulin sensitivity and reduced inflammatory activity. Our study may help to generate novel prevention strategies to maintain cognitive functions into old age.

Fig. 1.

Flow-chart of the study. 50 healthy elderly subjects were initially included in the study and performed baseline measurements of physiological parameters, fasting serum levels, and memory tests (session I). Based on age, sex, and BMI, subjects were stratified into 3 groups to follow either a specific diet, namely caloric restriction (n = 20, group 1) or unsaturated fatty acids (UFA) enhancement (n = 20, group 2), or not to change previous eating habits (control, n = 10). Dietary instructions were provided by clinical dieticians. One women from group 1 was not available for posttesting. After a period of 3 months, participants again underwent measurements of physiological parameters, fasting serum levels, and memory tests (session II). At baseline, after 6 and after 12 weeks, subjects additionally completed nutrition diaries over 7 consecutive days.

Fig. 2.

Percentage changes in weight (black bars), BMI (gray bars), and changes in unsaturated fatty acids (UFA)-to-saturated fatty acids (SFA) ratio (striped bars) after caloric restriction (group 1), UFA enhancement (group 2), and control condition. Note that caloric restriction led to a significant decrease in weight, BMI, and UFA enhancement to a significant increase in the UFA-to-SFA-ratio. Error bars indicate standard error. ***, P < 0.001; **, P < 0.01 according to ANOVA_RM posthoc testings.

Fig. 3.

Percentage memory scores normalized to baseline values before and after caloric restriction (dashed line), unsaturated fatty acid (UFA) enhancement (dotted line), and control (solid line). Note that after caloric restriction, a highly significant improvement in memory scores can be seen. Baseline memory scores were not significantly different. Dots give means, bars indicate standard error. ***, P < 0.001.

Fig. 4.

Inverse correlation (Spearman, r = −0.81, P = 0.014) between changes in insulin levels and memory score improvements after caloric restriction in those subjects with best adherence to the diet (n = 9). Line indicates regression fit.

Fig. 5.

Inverse correlation (Spearman, r = −0.83, P = 0.005) between changes in high sensitive C-reactive protein (hs-CRP) and memory score improvements after caloric restriction in those subjects with best adherence to the diet (n = 9). Line indicates regression fit.