Individuals with dementia and neurodegenerative diseases (NDDs) often suffer from cardiovascular diseases (CVDs). Neuroinflammation driven by conditions involved in CVDs is linked to disruptions in the central nervous system triggering immune reactions, perpetuating an “inflammatory-like” environment. The Mediterranean diet (MedDiet), known for its anti-inflammatory and antioxidant properties, has been proposed as a key factor to attenuate these risks. Blood nuclear cell samples were collected from 134 participants of the PREDIMED trial, which randomized participants to three diets: one supplemented with extra-virgin olive oil (MedDiet-EVOO), another with nuts (MedDiet-Nuts), and a low-fat control diet. These samples were analyzed at baseline and 12-month follow-up to assess the impact of these dietary interventions on gene expression markers. We first selected target genes by analyzing intersections between NDD and CVD associations. Significant gene expression changes from baseline to 12 months were observed in the participants allocated to the MedDiet-EVOO, particularly in CDKN2A, IFNG, NLRP3, PIK3CB, and TGFB2. Additionally, TGFB2 expression changed over time in the MedDiet-Nuts group. Comparative analyses showed significant differences in TGFB2 between MedDiet-EVOO and control, and in NAMPT between MedDiet-Nuts and control. Longitudinal models adjusted for different covariates also revealed significant effects for TGFB2 and NAMPT. In conclusion, our results suggest that one year of traditional MedDiet, especially MedDiet-EVOO, modulates gene expression associated with CVD risk and NDDs in older adults at high CV risk.

In this study, we investigated gene expression related to cholesterol efflux receptors in individuals at high cardiovascular risk undergoing Mediterranean dietary interventions. Through transcriptomic analysis, we examined samples from two randomized controlled trials: PREDIMED and PREDIMED‐Plus, with 151 and 89 elderly adults, respectively. Blood cells were isolated at baseline and after a 12‐month intervention. In the PREDIMED trial, participants followed different Mediterranean diets: one supplemented with extra‐virgin olive oil (traditional Mediterranean diet enriched with extra‐virgin olive oil [MedDiet‐EVOO]), another with nuts (MedDiet enriched with nuts MedDiet‐Nuts [MedDiet‐Nuts]), and a low‐fat control diet. The PREDIMED‐Plus trial compared an energy‐reduced Mediterranean diet (Er‐MedDiet) with physical activity to an ad libitum Mediterranean diet. Over time, mild but significant upregulation of genes like ATP binding cassette subfamily A member 1 (ABCA1), retinoid X receptor alpha (RXRA), retinoid X receptor beta (RXRB), and Nuclear Receptor Subfamily 1 Group H Member 3 (NR1H3) was observed in response to MedDiet‐EVOO, MedDiet‐Nuts, and Er‐MedDiet. Notably, RXRA expression was higher in both MedDiet‐EVOO and MedDiet‐Nuts compared to the control diet. Differences in gene expression, particularly RXRA, ATP binding cassette subfamily G member 1 (ABCG1), NR1H3, and Peroxisome Proliferator Activated Receptor Delta (PPARD), were evident between MedDiet‐Nuts and the control diet. In the PREDIMED‐Plus trial, no significant differences in gene expression were found between dietary groups. Principal component analysis (PCA) and linear discriminant analysis (LDA) showed overlapping gene expression profiles across different Mediterranean diet interventions. In conclusion, our study highlights the cardiovascular health benefits of long‐term adherence to a Mediterranean diet, both normocaloric and hypocaloric, primarily reflected by mild upregulation of cholesterol efflux‐related genes—specifically involving RXRA, RXRB, ABCA1, ABCG1, Nuclear Receptor Subfamily 1 Group H Member 2(NR1H2), and PPARD—among elderly adults at high cardiovascular risk. This suggests a potential mechanism by which these diets may exert cardiovascular protective effects.

The Mediterranean diet, featuring sourdough bread, shows promise in managing metabolic syndrome. This study explored the effects of two sourdough breads, with differing fermentation times but similar nutritional profiles, on inflammation, satiety, and gut microbiota composition in adults with metabolic syndrome. In a double-blind clinical trial, participants were randomized to consume either Elias Boulanger^® long-fermentation (48 h) sourdough bread (EBLong) or Elias Boulanger^® short-fermentation (2 h) sourdough bread (EBShort) over a two-month period. We assessed clinical parameters, inflammatory biomarkers, satiety-related hormones, and the richness and abundance of gut microbiota at baseline and follow-up. The participants included 31 individuals (mean age, 67, 51.6% female). EBShort was associated with reduced levels of soluble intercellular adhesion molecule (sICAM), and all participants, regardless of the intervention, exhibited a decrease in sICAM and diastolic pressure from baseline (p < 0.017). At follow-up, plasminogen activator inhibitor-1 (PAI-1) levels were lower in EBShort (−744 pg/mL; 95%CI: −282 to −1210 pg/mL) compared to EBLong. No differences in microbiota richness or abundance were observed. EBShort bread was effective in reducing some inflammation markers. The consumption of sourdough bread may offer potential benefits in reducing inflammation markers in individuals with metabolic syndrome; however, longer fermentation times did not show additional benefits.

Background: Peripheral artery disease (PAD) is a major vascular condition often overlooked in prevention strategies. We aimed to evaluate the association between cardiovascular health, measured by Life’s Simple 7 (LS7), and the risk of PAD in a high-risk Mediterranean population. Methods: This prospective analysis included 7122 participants from the PREDIMED study (Prevención con Dieta Mediterránea) at high cardiovascular risk but free of cardiovascular disease at baseline. LS7 scores (0–14 points) were calculated using seven metrics: smoking status, body mass index, physical activity, blood pressure, total cholesterol, glucose metabolism, and adherence to the Mediterranean diet. Participants were categorized into inadequate (0–5), average (6–8), and optimal (9–14) cardiovascular health. Multivariable Cox regression models and Nelson–Aalen curves assessed the association between LS7 and PAD incidence over a median 4.8-year follow-up. A meta-analysis combining these results with three prior studies was also performed. Results: A total of 87 incident PAD cases were identified. Compared to participants with inadequate cardiovascular health, those with average and optimal LS7 scores exhibited significantly lower PAD risk (adjusted hazard ratio [HR] 0.37; 95% confidence interval [CI]: 0.22–0.61, and HR 0.25; 95% CI: 0.10–0.65, respectively). Each one-point increase in the LS7 score (range 0 to 14) was associated with an 22% lower PAD risk (HR 0.78; 95% CI: 0.68–0.90). The meta-analysis yielded a pooled HR of 0.81 (95% CI: 0.76–0.87), confirming consistent inverse associations across populations. Conclusions: Greater adherence to LS7 metrics is associated with a significantly reduced risk of PAD in high-risk Mediterranean individuals. Promoting LS7 adherence may represent an effective strategy for preventing both cardiovascular disease and PAD.

Mediterranean diet, featuring sourdough bread, shows promise in managing metabolic syndrome. This study explored the effects of two sourdough breads with differing fermentation times but similar nutritional profiles on inflammation, satiety, and gut microbiota composition in adults with metabolic syndrome. The double-blind clinical trial randomized participants to consume over two-months Elias Boulanger® long fermentation (48h) sourdough bread (EBLong) or Elias Boulanger® short fermentation (2h) sourdough bread (EBShort). We assessed clinical parameters, inflammatory- and satiety-related biomarkers; and richness and abundance of gut microbiota at baseline and follow-up. 31 individuals (mean age: 67, 55.7% female) participated. EBShort was associated with reduced soluble intercellular adhesion molecule (sICAM) levels, and irrespective of the adjudicated intervention, all participants had a decrease in sICAM and diastolic pressure relative to baseline (p<0.017). At follow-up, plasminogen activator inhibitor-1 (PAI-1) levels were lower in EBShort (-744 pg/mL; 95%CI: -282 to -1210 pg/mL) compared to EBLong. High-quality sourdough bread may offer mild benefits in blood pressure and inflammation for those with metabolic syndrome, however, only EBLong was associated to reduced Enterobacteriaceae abundance. Further research is needed to understand potential benefits and mechanisms of sourdough bread in managing metabolic syndrome and improving cardiovascular health.

Associations of lipid profiles, including qualitative and functional high-density lipoprotein (HDL) traits, and cholesterol-related biomarkers with incident dementia and Alzheimer’s disease (AD), remain unclear. In this regard, older adults at high cardiovascular risk are at particularly high risk of developing dementia. The aim is to evaluate whether these biomarkers are associated with the incidence of dementia and AD in older adults at high cardiovascular (CV) risk. In a case–cohort study, we selected 106 incident dementia cases (82 AD) and a random subcohort of 201 non-cases. We quantified (baseline and at one-year), lipid profile; HDL-mediate cholesterol efflux capacity in a model of human neurons; HDL-mediated anti-inflammatory protection in a model of brain endothelial cells; 24S-hydroxycholesterol and apolipoprotein E. Multivariable-adjusted Cox models were addressed. HDL cholesterol was inversely associated, whereas triglycerides directly associated, with dementia and AD incidence. Higher HDL-mediated cholesterol efflux was inversely associated with dementia (HR 0.64, 95% confidence interval (CI) 0.45–0.91) and AD (HR 0.52, 0.35–0.76). Greater HDL-mediated endothelial protection was associated with lower dementia and AD incidence (HR 0.68, 95% CI 0.47 to 0.99 and HR 0.61, 95% CI 0.41 to 0.91, respectively). A one-year increase in 24S-hydroxycholesterol was associated with a higher incidence of any dementia (HR 2.38, 1.33–4.27) and AD (HR 2.24, 1.11–4.53). Enhanced HDL functional properties ex vivo, in preclinical models using human brain cells, together with lower levels of 24S-hydroxycholesterol, are inversely associated with the incidence of dementia and AD, highlighting these factors as promising prognostic targets in older adults at high CV risk.