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/m2) 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

The disparity between the chronological age of an individual and their brain-age measured based on biological information has the potential to offer clinically relevant biomarkers of neurological syndromes that emerge late in the lifespan. While prior brain-age prediction studies have relied exclusively on either structural or functional brain data, here we investigate how multimodal brain-imaging data improves age prediction. Using cortical anatomy and whole-brain functional connectivity on a large adult lifespan sample (N=2354, age 19-82), we found that multimodal data improves brain-based age prediction, resulting in a mean absolute prediction error of 4.29 years. Furthermore, we found that the discrepancy between predicted age and chronological age captures cognitive impairment. Importantly, the brain-age measure was robust to confounding effects: head motion did not drive brain-based age prediction and our models generalized reasonably to an independent dataset acquired at a different site (N=475). Generalization performance was increased by training models on a larger and more heterogeneous dataset. The robustness of multimodal brain-age prediction to confounds, generalizability across sites, and sensitivity to clinically-relevant impairments, suggests promising future application to the early prediction of neurocognitive disorders.

Dietary habits such as caloric restriction or nutrients that mimic these effects may exert beneficial effects on brain aging. The plant-derived polyphenol resveratrol has been shown to increase memory performance in primates; however, interventional studies in older humans are lacking. Here, we tested whether supplementation of resveratrol would enhance memory performance in older adults and addressed potential mechanismsunderlyingthiseffect.Twenty-threehealthyoverweightolderindividualsthatsuccessfullycompleted26weeksofresveratrolintake (200 mg/d) were pairwise matched to 23 participants that received placebo (total n ϭ 46, 18 females, 50 -75 years). Before and after the intervention/control period, subjects underwent memory tasks and neuroimaging to assess volume, microstructure, and functional connectivity (FC) of the hippocampus, a key region implicated in memory functions. In addition, anthropometry, glucose and lipid metabolism, inflammation, neurotrophic factors, and vascular parameters were assayed. We observed a significant effect of resveratrol on retention of words over 30 min compared with placebo (p ϭ 0.038). In addition, resveratrol led to significant increases in hippocampal FC, decreases in glycated hemoglobin (HbA1c) and body fat, and increases in leptin compared with placebo (all p Ͻ 0.05). Increases in FC between the left posterior hippocampus and the medial prefrontal cortex correlated with increases in retention scores and with decreases in HbA1c (all p Ͻ 0.05). This study provides initial evidence that supplementary resveratrol improves memory performance in association with improved glucose metabolism and increased hippocampal FC in older adults. Our findings offer the basis for novel strategies to maintain brain health during aging.

No abstract