Caloric Restriction in Older Adults-Differential Effects of Weight Loss and Reduced Weight on Brain Structure and Function.

Dietary modifications such as caloric restriction (CR) have been suggested as a means to improve memory and prevent age-related decline. However, it is unclear whether those effects remain stable over time or are related specifically to negative energy balance during the weight loss phase of CR. Using a randomized interventional design, we investigated changes in recognition memory and neural correlates in postmenopausal obese women (n = 19): 1) after intense weight loss in the course of a 12-week low-caloric diet (reduced body weight and negative energy balance) and 2) after having sustained the reduced weight over 4 more weeks (reduced body weight, but energy balance equilibrium). Participants were contrasted to a control group (n = 18) instructed not to change dietary habits. In the CR group, we found improved recognition memory, paralleled by increased gray matter volume in inferior frontal gyrus and hippocampus, and augmented hippocampal resting-state functional connectivity to parietal areas. Moreover, effects were specific for transient negative energy balance and could not be detected after subsequent weight maintenance. Our data demonstrate for the first time in humans that beneficial effects of CR on brain structure and function are due to weight loss rather than an overall reduced weight.

Combined omega-3 fatty acids, aerobic exercise and cognitive stimulation prevents decline in gray matter volume of the frontal, parietal and cingulate cortex in patients with mild cognitive impairment.

Previous studies in older adults suggested beneficial effects of omega-3 fatty acid (FA) supplementation, aerobic exercise, or cognitive stimulation on brain structure and function. However, combined effects of these interventions in patients suffering from mild cognitive impairment (MCI) are unknown. Using a randomized interventional design, we evaluated the effect of combined omega-3 FA supplementation, aerobic exercise and cognitive stimulation (target intervention) versus omega-3 FA supplementation and non-aerobic exercise (control intervention) on cognitive function and gray matter volume in patients with MCI. Moreover, we analyzed potential vascular, metabolic or inflammatory mechanisms underlying these effects. Twenty-two MCI patients (8 females; 60-80years) successfully completed six months of omega-3 FA intake, aerobic cycling training and cognitive stimulation (n=13) or omega-3 FA intake and non-aerobic stretching and toning (n=9). Before and after the interventions, cognitive performance, magnetic resonance imaging of the brain at 3T (n=20), intima-media thickness of the internal carotid artery and serum markers of glucose control, lipid and B-vitamin metabolism, and inflammation were assessed. Intervention-related changes in gray matter volume of Alzheimer's disease (AD)-related brain regions, i.e., frontal, parietal, temporal and cingulate cortex were examined using voxel-based morphometry of high resolution T1-weighted images. After the intervention period, significant differences emerged in brain structure between groups: Gray matter volume decreased in the frontal, parietal and cingulate cortex of patients in the control intervention, while gray matter volume in these areas was preserved or even increased after the target intervention. Decreases in homocysteine levels in the target intervention group were associated with increases in gray matter volume in the middle frontal cortex (p=0.010). No significant differences in cognitive performance or other vascular, metabolic and inflammatory parameters were observed between groups. This pilot study provides preliminary evidence that omega-3 FA intake combined with aerobic exercise and cognitive stimulation prevents atrophy in AD-related brain regions in MCI patients, compared to omega-3 FA intake plus the control condition of stretching and toning. These promising findings should now be validated in a larger interventional trial.