PuSH - Publikationsserver des Helmholtz Zentrums München: Glycemic control contributes to the neuroprotective effects of mediterranean and green-mediterranean diets on brain age; the DIRECT PLUS brain-MRI randomized controlled trial.

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Pachter, D.* ; Kaplan, A.* ; Tsaban, G.* ; Zelicha, H.* ; Meir, A.Y.* ; Rinott, E.* ; Levakov, G.* ; Salti, M.* ; Yovell, Y.* ; Huhn, S.* ; Beyer, F.* ; Witte, V.* ; Kovacs, P.* ; von Bergen, M.* ; Ceglarek, U.* ; Blüher, M. ; Stumvoll, M.* ; Hu, F.B.* ; Stampfer, M.J.* ; Friedman, A.* ; Shelef, I.* ; Avidan, G.* ; Shai, I.

Glycemic control contributes to the neuroprotective effects of mediterranean and green-mediterranean diets on brain age; the DIRECT PLUS brain-MRI randomized controlled trial.

Am. J. Clin. Nutr. 120, 1029-1036 (2024)

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BACKGROUND: We recently reported that Mediterranean (MED) and green-MED diets significantly attenuated age-related brain atrophy by ∼50% within 18 months. OBJECTIVE: To explore the contribution of specific diet-induced parameters to brain volume deviation from chronological age. METHODS: A post-hoc analysis of the 18-month DIRECT-PLUS trial, where participants were randomly assigned to: (1)-healthy-dietary-guidelines (HDG); (2)-MED diet; or (3)-green-MED diet, high in polyphenols and low in red meat. Both MED groups consumed 28g walnuts/day (+440mg/day polyphenols). The green-MED group further consumed green-tea (3-4 cups/day) and Mankai green shake (Wolffia-globosa aquatic plant) (+800mg/day polyphenols). We collected blood samples through the intervention and followed brain structure volumes by magnetic-resonance-imaging (MRI). We used hippocampal-occupancy (HOC) score (hippocampal and inferior-lateral-ventricle volumes ratio) as a neurodegeneration marker and brain age proxy. We applied multivariate-linear-regression models. RESULTS: Of 284 participants (88% male; age=51.1years; BMI=31.2kg/m²; HbA1c=5.48%; APOE-ε4 genotype=15.7%), 224 completed the trial with eligible whole-brain MRIs. Individuals with higher HOC-deviations (i.e., younger brain age) presented lower body weight (r=-0.204;95%CI[-0.298,-0.101]), waist-circumference (r=-0.207;95%CI[-0.310,-0.103]), diastolic (r=-0.186;95%CI[-0.304,-0.072]), and systolic blood pressure (r=-0.189;95%CI[-0.308,-0.061]), insulin (r=-0.099;95%CI[-0.194,-0.004]) and HbA1c (r=-0.164;95%CI[-0.337,-0.006]) levels. After 18 months, greater changes in HOC-deviations (i.e., brain-age decline attenuation) were independently associated with improved HbA1c (β=-0.254;95%CI[-0.392,-0.117]), HOMA-IR (β=-0.200;95%CI[-0.346,-0.055]) fasting glucose (β=-0.155;95%[CI -0.293,-0.016]), and s-CRP (β=-0.153;95%[CI -0.296,-0.010]). Improvement in diabetes status was associated with greater HOC-deviation changes compared to either no change in diabetes status (0.010;95%CI]0.002,0.019[) or with an unfavorable change (0.012;95%CI]0.002,0.023]). A decline in HbA1c is further associated with greater deviation changes in the Thalamus, Caudate nucleus, and Cerebellum (p<0.05). Greater consumption of Mankai and green-tea (green-MED diet components) were associated with greater HOC-deviation changes beyond weight loss. CONCLUSIONS: Glycemic control contributes to the neuroprotective effects of the MED and green-MED diets on brain age. Polyphenols-rich diet components as Mankai and green-tea may contribute to a more youthful brain age. TRIAL-REGISTRATION-CLINICAL-TRIALS-IDENTIFIER: NCT03020186 URL OF REGISTRATION: https://clinicaltrials.gov/study/NCT03020186.

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