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Purpose While the benefits of adopting a more plant-based diet for sustainability and animal welfare are clear, its long-term health impacts, including the impact on cognitive ageing, are limited studied. Therefore, we investigated the associations between plant-based diet adherence and cognitive ageing. Methods Data from a previous intervention study involving community-dwelling adults aged ≥ 65 years were analysed at baseline (n = 658) and after 2-year follow-up (n = 314). Global and domain-specific cognitive functioning were assessed at both timepoints. Overall, healthful and unhealthful plant-based dietary indices were calculated from a 190-item food frequency questionnaire. Multivariate-adjusted linear regression models were applied to test for associations. Results After full-adjustment, higher overall adherence to a plant-based diet was not associated with global cognitive function (difference in Z-score, tertile 1 versus 3 [95% CI]: 0.04 [− 0.05, 0.13] p = 0.40) or cognitive change (− 0.04 [− 0.11, 0.04], p = 0.35). Similarly, healthful and unhealthful plant-based diet indices were not associated with cognitive functioning (respectively p = 0.48; p = 0.87) or change (respectively p = 0.21, p = 0.33). Interestingly, we observed fish consumption to influence the association between plant-based diet adherence and cognitive functioning (p-interaction = 0.01), with only individuals with a fish consumption of ≥ 0.93 portion/week benefitting from better overall plant-based diet adherence (β per 10-point increment [95% CI]: 0.12 [0.03, 0.21] p = 0.01). Conclusion We did not demonstrate associations of a more plant-based diet with cognitive ageing. However, possibly such association exists in a subpopulation with higher fish intake. This would be in line with earlier observations that diets rich in plant foods and fish, such as the Mediterranean diet, may be beneficial for cognitive ageing. Trial registration Registered at clinicaltrials.gov (NCT00696514) on June 12, 2008.

The response to lifestyle intervention studies is often heterogeneous, especially in older adults. Subtle responses that may represent a health gain for individuals are not always detected by classical health variables, stressing the need for novel biomarkers that detect intermediate changes in metabolic, inflammatory, and immunity-related health. Here, our aim was to develop and validate a molecular multivariate biomarker maximally sensitive to the individual effect of a lifestyle intervention; the Personalized Lifestyle Intervention Status (PLIS). We used 1 H-NMR fasting blood metabolite measurements from before and after the 13-week combined physical and nutritional Growing Old TOgether (GOTO) lifestyle intervention study in combination with a fivefold cross-validation and a bootstrapping method to train a separate PLIS score for men and women. The PLIS scores consisted of 14 and four metabolites for females and males, respectively. Performance of the PLIS score in tracking health gain was illustrated by association of the sex-specific PLIS scores with several classical metabolic health markers, such as BMI, trunk fat%, fasting HDL cholesterol, and fasting insulin, the primary outcome of the GOTO study. We also showed that the baseline PLIS score indicated which participants respond positively to the intervention. Finally, we explored PLIS in an independent physical activity lifestyle intervention study, showing similar, albeit remarkably weaker, associations of PLIS with classical metabolic health markers. To conclude, we found that the sex-specific PLIS score was able to track the individual short-term metabolic health gain of the GOTO lifestyle intervention study. The methodology used to train the PLIS score potentially provides a useful instrument to track personal responses and predict the participant's health benefit in lifestyle interventions similar to the GOTO study.