Mediterranean Diet Adherence and Risk of Cognitive Decline in Older Adults: The PREDIMED-Plus Cognitive Substudy

Background

The Mediterranean diet has been associated with reduced cardiovascular risk, but evidence for its neuroprotective effects remains inconsistent. The PREDIMED-Plus trial provides a unique opportunity to evaluate the relationship between dietary intervention and cognitive trajectories in a large, well-characterized cohort of older adults. We aimed to assess whether Mediterranean diet adherence reduces the rate of cognitive decline over a 5-year follow-up period.

Methods

We conducted a prospective analysis of 6,874 participants aged 55 to 75 years enrolled in the PREDIMED-Plus cognitive substudy. Participants were randomized to an energy-restricted Mediterranean diet supplemented with extra-virgin olive oil or mixed nuts versus a control diet with standard dietary advice. Cognitive function was assessed at baseline and annually using a validated neuropsychological battery including the Mini-Mental State Examination (MMSE), Clock Drawing Test, and Trail Making Tests A and B. The primary outcome was the composite cognitive score change over 5 years. Linear mixed-effects models adjusted for age, sex, education, APOE genotype, physical activity, and cardiovascular risk factors.

Results

After a median follow-up of 4.8 years, participants in the Mediterranean diet group showed significantly less decline in the composite cognitive score compared with controls (between-group difference: 0.62 points; 95% CI, 0.34-0.90; P<0.001). The protective association was strongest for executive function (Trail Making Test B difference: -8.4 seconds; P=0.002) and global cognition (MMSE difference: 0.8 points; P<0.001). Benefits were more pronounced among APOE e4 carriers (interaction P=0.03) and participants aged 65 years or older. Higher plasma levels of hydroxytyrosol, a polyphenol marker of olive oil intake, correlated with better cognitive trajectories (r=0.24; P<0.001).

Conclusions

Among older adults at elevated cardiovascular risk, a Mediterranean dietary intervention enriched with extra-virgin olive oil was associated with significantly slower cognitive decline over 5 years, particularly among those with genetic susceptibility to Alzheimer disease.