Abstract
Background: The effect of diet on age-related brain atrophy is largely unproven.
Objective: To explore the effect of a Mediterranean diet higher in polyphenols and lower in red/processed meat (Green-MED diet) on age-related brain atrophy.
Methods: This 18-month clinical trial longitudinally measured brain structure volumes by magnetic-resonance-imaging using hippocampal-occupancy (HOC) and lateral-ventricle-volume (LVV) expansion scores as neurodegeneration markers. Abdominally obese/dyslipidemic participants were randomly assigned to (1)-healthy dietary guidelines (HDG), (2)-Mediterranean (MED) diet, or (3)-Green-MED diet (MED diet higher in polyphenols and lower in red/processed meat). All subjects received free gym memberships and physical activity guidance. Both MED groups consumed 28g/day walnuts (+440 mg/d polyphenols). The Green-MED group consumed green-tea (3-4 cups/day) and Mankai (Wolffia-globosa strain, 100g frozen-cubes/day) green shake (+800mg/day polyphenols).
Results: Among 284 participants (age=51years; 88% men; BMI=31.2kg/m2; apolipoprotein E‐ε4 genotype=15.7%), 224 (79%) completed the trial with eligible whole-brain MRIs. The pallidum (-4.2%), third ventricle (+3.9%), and LVV (+2.2%) disclosed the largest volume changes. Compared to younger participants, atrophy was accelerated among those ≥ 50 years [HOC change=-1.0±1.4% vs. -0.06±1.1%; 95% confidence-interval (CI):0.6, 1.3; p<0.001; LVV change=3.2±4.5% vs. 1.3±4.1%; 95%CI:-3.1, -0.8;p=0.001]. In subjects ≥50years, HOC decline and LVV expansion were attenuated in both MED groups, with the best outcomes among Green-MED diet participants, as compared to HDG (HOC: -0.8±1.6% vs. -1.3±1.4%;95%CI: -1.5, -0.02;p=0.042, LVV: 2.3±4.7% vs. 4.3±4.5;95%CI;0.3, 5.2;p=0.021). Similar patterns were observed among younger subjects. Improved insulin sensitivity over the trial was the strongest parameter associated with brain atrophy attenuation (p<0.05). Greater Mankai , green-tea and walnuts intake and less red and processed meat were significantly and independently associated with reduced HOC decline (p<0.05). Elevated urinary levels of the Mankai-derived polyphenols: urolithin-A (r=0.24;p=0.013) and tyrosol (r=0.26;p=0.007) were significantly associated with lower HOC decline. Conclusions: A Green-MED, high-polyphenol diet, rich in Mankai, green tea and walnuts and low in red/processed meat is potentially neuroprotective for age-related brain atrophy.