Glycemic control contributes to the neuroprotective effects of Mediterranean and green-Mediterranean diets on brain age: the DIRECT PLUS brain-magnetic resonance imaging randomized controlled trial

Dafna Pachter, Alon Kaplan, Gal Tsaban, Hila Zelicha, Anat Yaskolka Meir, Ehud Rinott, Gidon Levakov, Moti Salti, Yoram Yovell, Sebastian Huhn, Frauke Beyer, Veronica Witte, Peter Kovacs, Martin von Bergen, Uta Ceglarek, Matthias Blüher, Michael Stumvoll, Frank B. Hu, Meir J. Stampfer, Alon FriedmanIlan Shelef, Galia Avidan, Iris Shai

Research output: Contribution to journalArticlepeer-review

Abstract

Background: We recently reported that Mediterranean (MED) and green-MED diets significantly attenuated age-related brain atrophy by ∼50% within 18 mo. Objective: The objective of this study was to explore the contribution of specific diet-induced parameters to brain-volume deviation from chronologic age. Methods: A post hoc analysis of the 18-mo DIRECT PLUS trial, where participants were randomly assigned to the following groups: 1) healthy dietary guidelines, 2) MED diet, or 3) green-MED diet, high in polyphenols, and low in red meat. Both MED groups consumed 28 g walnuts/d (+440 mg/d polyphenols). The green-MED group further consumed green tea (3–4 cups/d) and Mankai green shake (Wolffia globosa aquatic plant) (+800 mg/d 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 = 51.1 y; body mass index = 31.2 kg/m2; hemoglobin A1c (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% confidence interval (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), 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 mo, 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 c-reactive protein (β = –0.153; 95% CI: –0.296, –0.010). Improvement in diabetes status was associated with greater HOC deviation changes than 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 was 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. This trial was registered at clinicaltrials.gov at clinicaltrials.gov as NCT03020186.

Original languageEnglish
JournalAmerican Journal of Clinical Nutrition
Early online date14 Sep 2024
DOIs
StateE-pub ahead of print - 14 Sep 2024
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2024 The Authors

Keywords

  • aging
  • brain age
  • dietary intervention
  • glycemic control
  • green-Mediterranean
  • hippocampal occupancy score
  • polyphenols

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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