TY - JOUR
T1 - Glycemic control contributes to the neuroprotective effects of Mediterranean and green-Mediterranean diets on brain age
T2 - the DIRECT PLUS brain-magnetic resonance imaging randomized controlled trial
AU - Pachter, Dafna
AU - Kaplan, Alon
AU - Tsaban, Gal
AU - Zelicha, Hila
AU - Meir, Anat Yaskolka
AU - Rinott, Ehud
AU - Levakov, Gidon
AU - Salti, Moti
AU - Yovell, Yoram
AU - Huhn, Sebastian
AU - Beyer, Frauke
AU - Witte, Veronica
AU - Kovacs, Peter
AU - von Bergen, Martin
AU - Ceglarek, Uta
AU - Blüher, Matthias
AU - Stumvoll, Michael
AU - Hu, Frank B.
AU - Stampfer, Meir J.
AU - Friedman, Alon
AU - Shelef, Ilan
AU - Avidan, Galia
AU - Shai, Iris
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/9/14
Y1 - 2024/9/14
N2 - 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.
AB - 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.
KW - aging
KW - brain age
KW - dietary intervention
KW - glycemic control
KW - green-Mediterranean
KW - hippocampal occupancy score
KW - polyphenols
UR - http://www.scopus.com/inward/record.url?scp=85205807488&partnerID=8YFLogxK
U2 - 10.1016/j.ajcnut.2024.09.013
DO - 10.1016/j.ajcnut.2024.09.013
M3 - Article
C2 - 39284453
AN - SCOPUS:85205807488
SN - 0002-9165
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
ER -