Research Area: Cognitive Health

Pachter, D., A. Kaplan, G. Tsaban, H. Zelicha, A.Y. Meir, E. Rinott, G. Levakov, M. Salti, Y. Yovell, S. Huhn, F. Beyer, V. Witte, P. Kovacs, M. von Bergen, U. Ceglarek, M. Blüher, M. Stumvoll, F.B. Hu, M.J. Stampfer, A. Friedman, I. Shelef, G. Avidan, I. Shai, 2024. 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. Am J Clin Nutr. 120(5):1029-1036. doi: 10.1016/j.ajcnut.2024.09.013.

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.

 

Lázaro, I., O. Grau-Rivera, M. Suárez-Calvet, K. Fauria, C. Minguillón, M. Shekari, C. Falcón, M. García-Prat, J. Huguet, J.L. Molinuevo, J.D. Gispert, A. Sala-Vila, 2024. Omega-3 blood biomarkers relate to brain glucose uptake in individuals at risk of Alzheimer’s disease dementia. Alzheimers Dement (Amst). 16(3):e12596. https://doi.org/10.1002/dad2.12596

Introduction: Brain glucose hypometabolism is a preclinical feature of Alzheimer’s disease (AD). Dietary omega-3 fatty acids promote brain glucose metabolism, but clinical research is incipient. Circulating omega-3s objectively reflect their dietary intake. Methods: This was a cross-sectional study in 320 cognitively unimpaired participants at increased risk of AD dementia. Using lipidomics, we determined blood docosahexaenoic (DHA) and alpha-linolenic (ALA) acid levels (omega-3s from marine and plant origin, respectively). We assessed brain glucose metabolism using [18-F]-fluorodeoxyglucose (FDG) positron emission tomography (PET). Results: Blood ALA directly related to FDG uptake in brain areas known to be affected in AD. Stronger associations were observed in apolipoprotein E ε4 carriers and homozygotes. For DHA, significant direct associations were restricted to amyloid beta-positive tau-positive participants. Discussion: Blood omega-3 directly relate to preserved glucose metabolism in AD-vulnerable brain regions in individuals at increased risk of AD dementia. This adds to the benefits of omega-3 supplementation in the preclinical stage of AD dementia. Highlights: Blood omega-3s were related to brain glucose uptake in participants at risk of Alzheimer’s disease (AD) dementia. Complementary associations were observed for omega-3 from marine and plant sources. Foods rich in omega-3 might be useful in early features of AD.

Ayala-Aldana, N., A. Pinar-Martí, M. Ruiz-Rivera, S. Fernández-Barrés, D. Romaguera, J. Casanova-Mollà, N. Solà-Valls, J. Julvez, 2024. Original article: adolescent dietary patterns derived using principal component analysis and neuropsychological functions: a cross-sectional analysis of Walnuts Smart Snack cohort. Eur Child Adolesc Psychiatry. 2024 Sep 18. https://doi.org/10.1007/s00787-024-02577-6

A balanced diet is relevant for neuropsychological functioning. We aimed to analyze the association between dietary patterns and neuropsychological outcomes in a sample of healthy adolescents of the Walnuts Smart Snack (WSS) cohort from Barcelona city. We performed principal components analysis (PCA) to determine dietary patterns in the adolescent sample using a food frequency questionnaire (60 items). Multiple linear regression models were performed to analyze the association between PCA dietary patterns with neuropsychological outcomes: Strengths and Difficulties (SDQ) externalizing and internalizing scores, Attention Network Test (ANT) Impulsivity Index and Emotional Recognition Task (ERT) scores. We additionally adjusted the models for child sex, age, body mass index (BMI), physical activity and maternal education. Six dietary patterns were identified in PCA analyses. “low consumption of calorie-dense foods” dietary pattern had a negative association (protective) with the both SDQ outcomes (p value < 0.001) and “Nuts” dietary pattern showed a negative (protective) association with impulsivity index (β1= −24.60, 95% CI = −36.80, −12.41, p value < 0.001). Overall, our main results suggest that healthy dietary patterns, including higher intakes of “nuts” and a preference of “low consumption of calorie-dense foods” dietary patterns, could provide a beneficial association with neuropsychological functions during the adolescence period. The associations may include improvements of externalizing and internalizing problem symptoms, and impulsivity.