| Summary: | Abstract Alzheimer’s disease is a progressive neurodegenerative disorder with no cure, making preventive strategies crucial. Dietary interventions, particularly the Mediterranean (MeDi) and MIND diets, have been associated with reduced cognitive decline, but their long-term comparative effects remain underexplored. To compare the long-term neuroprotective effects of the Mediterranean and MIND diets in healthy individuals and AD patients, assess dietary adherence and cognitive function relationships, and investigate the impact of micronutrients on cognitive biomarkers. A 5-year prospective cohort study was conducted with 1500 participants (750 healthy controls, 750 AD patients). Dietary adherence was assessed using validated dietary screening tools. Cognitive function was evaluated via MMSE and MoCA scores, while biomarkers (amyloid-beta, tau, NfL, CRP, IL-6, TNF-α, polyphenols, omega-3, and B vitamins) were measured through blood and CSF samples. Machine learning techniques were utilized to analyze dietary patterns and predict cognitive trajectories. Higher adherence to both diets was associated with significantly better cognitive scores (p < 0.0001), lower amyloid-beta, tau, and NfL levels, and reduced inflammatory markers (CRP, IL-6, TNF-α). The MIND diet showed a slightly stronger association with cognitive protection than MeDi. Micronutrients such as polyphenols, omega-3, and B vitamins correlated with improved cognitive performance. Genetic analysis suggested that APOE-ε4 carriers may experience variable responses to dietary interventions. The Mediterranean and MIND diets provide significant neuroprotection against cognitive decline and AD progression. While both diets confer benefits, the MIND diet demonstrated a marginally greater impact on cognitive preservation. These findings underscore the importance of dietary interventions as non-pharmacological strategies for AD prevention and management. Further research is needed to optimize dietary recommendations based on genetic predisposition and metabolic factors.
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