Hila Zelicha

Obesity is a pressing global concern, prompting the implementation of comprehensive lifestyle modifications to aid weight reduction and management. Despite the efficacy of various interventions in initiating weight loss and mitigating associated health conditions, relapse rates remain alarmingly high. Acknowledging the significance of psychological and behavioral factors in long-term weight management, this prospective study explores the predictive role of executive functions within a lifestyle intervention context. One hundred and fifty-nine participants from the DIRECT-PLUS clinical trial completed executive functions tasks at baseline, assessing three core functions: Shifting, Inhibition (measured by Antisaccade task), and Decision under Load. Participants were randomly assigned to one of three diet groups: one active control group and two Mediterranean diet groups. All groups participated in an 18-month lifestyle intervention. Hierarchical regressions with cross-validation were used to analyse the predictive relationship between executive functions and weight loss at 6 and 18 months. Initial weight loss was significantly predicted by the diet type, with both Mediterranean diet groups showing positive effects at 6 months, which diminished by 18 months. All three executive functions significantly predicted 6-month weight loss, with only Antisaccade performance improving the model’s prediction. At 18 months, Antisaccade remained the only significant predictor. These findings suggest that Inhibition, as measured by Antisaccade, plays an important role in predicting both short-term weight loss and long-term weight maintenance. The results underscore the potential of targeting executive functions, particularly Inhibition, to enhance sustained weight loss efforts.

Objective: The objective of this study was to explore the effects of a green Mediterranean (green‐MED) diet, which is high in dietary polyphenols and green plant‐based protein and low in red/processed meat, on cardiovascular disease and inflammation‐related circulating proteins and their associations with cardiometabolic risk parameters.Methods: In the 18‐month weight loss trial Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT‐PLUS), 294 participants with abdominal obesity were randomized to basic healthy dietary guidelines, Mediterranean (MED), or green‐MED diets. Both isocaloric MED diet groups consumed walnuts (28 g/day), and the green‐MED diet group also consumed green tea (3–4 cups/day) and green shakes (Mankai plant shake, 500 mL/day) and avoided red/processed meat. Proteome panels were measured at three time points using Olink CVDII.Results: At baseline, a dominant protein cluster was significantly related to higher phenotypic cardiometabolic risk parameters, with the strongest associations attributed to magnetic resonance imaging‐assessed visceral adiposity (false discovery rate of 5%). Overall, after 6 months of intervention, both the MED and green‐MED diets induced improvements in cardiovascular disease and proinflammatory risk proteins (p < 0.05, vs. healthy dietary guidelines), with the green‐MED diet leading to more pronounced beneficial changes, largely driven by dominant proinflammatory proteins (IL‐1 receptor antagonist protein, IL‐16, IL‐18, thrombospondin‐2, leptin, prostasin, galectin‐9, and fibroblast growth factor 21; adjusted for age, sex, and weight loss; p < 0.05). After 18 months, proteomics cluster changes presented the strongest correlations with visceral adiposity reduction.Conclusions: Proteomics clusters may enhance our understanding of the favorable effect of a green‐MED diet that is enriched with polyphenols and low in red/processed meat on visceral adiposity and cardiometabolic risk.

Objective: High BMI, which poorly represents specific fat depots, is linked to poorer cognition and higher dementia risk, with different associations between sexes. This study examined associations of abdominal fat depots with cognition and brain volumes and whether sex modifies this association.Methods: A total of 204 healthy middle‐aged offspring of Alzheimer's dementia patients (mean age = 59.44, 60% females) underwent abdominal magnetic resonance imaging to quantify hepatic, pancreatic, visceral, and subcutaneous adipose tissue and to assess cognition and brain volumes.Results: In the whole sample, higher hepatic fat percentage was associated with lower total gray matter volume (β = −0.17, p < 0.01). Primarily in males, higher pancreatic fat percentage was associated with lower global cognition (males: β = −0.27, p = 0.03; females: β = 0.01, p = 0.93) executive function (males: β = −0.27, p = 0.03; females: β = 0.02, p = 0.87), episodic memory (males: β = −0.28, p = 0.03; females: β = 0.07, p = 0.48), and inferior frontal gyrus volume (males: β = −0.28, p = 0.02; females: β = 0.10, p = 0.33). Visceral and subcutaneous adipose tissue was inversely associated with middle frontal and superior frontal gyrus volumes in males and females.Conclusions: In middle‐aged males at high Alzheimer's dementia risk, but not in females, higher pancreatic fat was associated with lower cognition and brain volumes. These findings suggest a potential sex‐specific link between distinct abdominal fat with brain health.

Background: High body mass index (BMI) has been consistently linked to poorer cognition and higher dementia risk, with different associations in males and females. However, BMI does not represent well specific fat depots. We examined in middle‐aged adults at high Alzheimer’s dementia (AD) risk, whether regional abdominal adiposity is associated with cognitive functioning and brain indices and whether sex modifies these associations.Methods: 204 healthy Israeli middle‐aged AD offspring (59.44 [SD = 7.60] years old, 60% females) underwent abdominal Magnetic Resonance Imaging (MRI) to quantify hepatic, pancreatic, and peripheral fat %‐visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). A broad cognitive battery defined global cognition and specific cognitive domains (episodic memory, working memory, executive functions, and language). A subsample of 142 participants had brain MRI to assess regional brain volumes (total gray matter [GM], hippocampus, and inferior, middle, and superior frontal gyrus [IFG, MFG, and SFG, respectively]). Partial correlations examined associations of regional abdominal adiposity with cognitive functioning, and brain indices, adjusting for age, sex, education, BMI, and time interval between abdominal MRI and the dependent variable. Fisher‐z transformation compared partial correlations between males and females.Results: In the whole sample, the only significant association was of higher hepatic fat % with lower GM volume (r = ‐264, p = 0.003), with similar associations in males and females. Only in males, higher pancreatic fat % was associated with lower global cognitive functioning (Males: r = ‐.276, p = .028; Females: r = 0.009, p = 0.93), executive functioning (Males: r = ‐0.267, p = 0.034; Females: r = 0.015, p = 0.87) and episodic memory (Males: r = ‐0.278, p = 0.027; Females: r = 0.068, p = 0.484) as well as with lower IFG volume (Males: r = ‐0.343, p = .017; Females: r = 0.117; p = 0.326). Also only in males, higher VAT% was associated with SFG volume (Males: r = .261, p = .045; Females: r = ‐0.198; p = 0.091).Conclusion: In middle‐aged males, but not in females, at high AD risk, regional abdominal adiposity, primarily pancreatic fat, was associated with lower cognitive functioning and lower AD‐related brain volumes. Results suggest sex differences in the contributions of fat to brain and cognitive aging. Since fat % is modifiable, these results may suggest that interventions to decrease distinct fats for the advancement of brain health must be sex‐specific.

Background: Obesity negatively impacts multiple bodily systems, including the central nervous system. Retrospective studies that estimated chronological age from neuroimaging have found accelerated brain aging in obesity, but it is unclear how this estimation would be affected by weight loss following a lifestyle intervention.Methods: In a sub-study of 102 participants of the Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT-PLUS) trial, we tested the effect of weight loss following 18 months of lifestyle intervention on predicted brain age based on magnetic resonance imaging (MRI)-assessed resting-state functional connectivity (RSFC). We further examined how dynamics in multiple health factors, including anthropometric measurements, blood biomarkers, and fat deposition, can account for changes in brain age.Results: To establish our method, we first demonstrated that our model could successfully predict chronological age from RSFC in three cohorts (n=291;358;102). We then found that among the DIRECT-PLUS participants, 1% of body weight loss resulted in an 8.9 months’ attenuation of brain age. Attenuation of brain age was significantly associated with improved liver biomarkers, decreased liver fat, and visceral and deep subcutaneous adipose tissues after 18 months of intervention. Finally, we showed that lower consumption of processed food, sweets and beverages were associated with attenuated brain age.Conclusions: Successful weight loss following lifestyle intervention might have a beneficial effect on the trajectory of brain aging.Funding: The German Research Foundation (DFG), German Research Foundation - project number 209933838 - SFB 1052; B11, Israel Ministry of Health grant 87472511 (to I Shai); Israel Ministry of Science and Technology grant 3-13604 (to I Shai); and the California Walnuts Commission 09933838 SFB 105 (to I Shai).

Proximal aortic stiffness (PAS) reflects arterial aging and is strongly associated with increased cardiovascular risk. Plant-rich, specifically Mediterranean-style, diets are associated with reduced cardiovascular risk. The effect of dietary interventions on PAS remains unclear. We randomized participants with abdominal-obesity/dyslipidemia to healthy-dietary-guidelines (HDG), Mediterranean, or green-Mediterranean diets combined with physical activity (PA). Both Mediterranean diets were similarly hypocaloric and included 28g/day walnuts. The green-Mediterranean group also consumed green tea (3–4 cups/day) and a Wolffia-globosa (Mankai) plant green-shake. PAS was estimated based on aortic-arch pulse-wave-velocity using magnetic resonance imaging (MRI) at baseline and after 18-months. Among 294 participants [age=51±10.6 years, body-mass-index 31.3±4.0 kg/m², PAS = 6.1±2.7 m/sec, retention rate = 89.8%], 281 had valid PAS measurements. Higher PAS was mostly associated with aging, hypertension, dyslipidemia, diabetes, and increased visceral adiposity (p<0.05 for all). After 18-months of intervention, all diet groups significantly reduced their PAS ([HDG: −4.8% (interquartile-range [IQR]: −22.3 to 8.7); Mediterranean: −7.3%, IQR (−20.8 to 11.9); green-Mediterranean: −14.0%, IQR (−27.0 to 2.4); p<0.05 for within-groups changes). Green-Mediterranean dieters had significantly greater PAS reduction than HDG dieters (p=0.007), also after controlling for age, sex, baseline-PAS, and Δweight. Further adjustment to baseline dyslipidemia, diabetes, and hypertension also revealed significant differences in PAS reduction between green-Mediterranean and Mediterranean groups (p=0.027). Specifically, greater green tea consumption was associated with greater PAS regression (p=0.04). ΔPAS was significantly associated with improvements in Δlow-density-lipoprotein cholesterol and Δtotal-cholesterol (p<0.05, multivariable models). All lifestyle intervention showed aortic age regression as compared to the expected (1.8±0.14 years vs.: HDG: −2.9±7.5 years; MED: −4.1±7.4 years; green-MED:-4.9±8.0 years; p<0.001). Higher PAS is strongly related to aging and is associated with traditional cardiovascular risk factors. Lifestyle intervention promotes PAS reduction. Green-Mediterranean diet may be associated with more remarkable aortic rejuvenation. Type of funding sources: Foundation. Main funding source(s): The Deutsche Forschungsgemeinschaft (DFG, German Research Foundation); the Israel Ministry of Health Figure 1. PAS (%) changes across study groups