Cognitive decline, associated with aging, is a serious public health concern, given the increasing prevalence of neurodegenerative diseases as people are living longer and the proportion of older persons worldwide continues to rise rapidly (United Nations et al., 2020). Globally, dementia affects an estimated 50 million people, and this prevalence is projected to increase over 130 million by 2050 (World Health Organization [WHO], 2019). Epidemiological studies further suggest a negative interaction of aging and obesity with cognitive dysfunction (Kanaya et al., 2009; Hassing et al., 2010). With the prevalence of overweight and obesity affecting an estimated 30% of the adult population and more, there are additional adverse implications for cognition health (Ng et al., 2014; Balasubramanian et al., 2020). Cognitive decline carries a significant social and economic burden, given cognitive impairment and dementia are strong predictors of functional disability and dependence (Petersen et al., 2001). Cognitive decline is a normal part of the aging process; however, the rate of decline may vary depending on the differences in genetic and lifestyle-related factors (Wu et al., 2020).

The potential of modifiable lifestyle factors is important as there are no effective pharmacological agents identified for the improvement of cognition or delay of the progression of cognitive decline (Petersen et al., 2018). Diet is a key lifestyle risk factor. Individual nutrients and foods have been inconsistently associated with cognitive function, including some vitamins, carotenoids, long-chain n-3 polyunsaturated fatty acids (PUFAs), such as seafood, and whole foods rich in polyphenols, such as fruits and vegetables, nuts, olive oil, and coffee (Rutjes et al., 2018; Ammar et al., 2020; Brainard et al., 2020). As food is consumed as part of a dietary pattern, it is important to consider the interactions and associations of whole dietary approaches. Three dietary patterns, in particular, are hypothesized to have a beneficial impact on cognitive function: the Mediterranean diet (MedDiet), the Dietary Approaches to Stop Hypertension (DASH), and the MedDiet-DASH Intervention for Neurodegenerative Delay (MIND). The MedDiet and DASH are currently promoted for their cardiovascular benefits (Arnett et al., 2019) yet may also be advisable to benefit cognition in themselves and because of the association of vascular risk factors with dementia risk (Gottesman et al., 2017).

Epidemiological studies and clinical trials have shown a relationship between adherence to MedDiet and cognitive function (Loughrey et al., 2017; Wu and Sun, 2017), and the World Health Organization (WHO) has included this dietary pattern in their guidelines for risk reduction of cognitive decline and dementia; however, the strength of the recommendation is considered conditional (World Health Organization [WHO], 2019). A hybrid of the MedDiet and DASH diet, the MIND diet, is also being promoted for brain health, albeit it has been less extensively investigated in relation to cognition and other cardiometabolic health outcomes (van den Brink et al., 2019). At any rate, dietary recommendations for preventing cognitive decline are still not widely accepted in guidelines due to conflicting and limited evidence. The MedDiet, DASH, and MIND dietary patterns each represent a modifiable lifestyle practice that could aid cognitive performance, yet further evidence is needed to inform cognitive guideline recommendations, as well as assess whether changes may be observed in a period of 2 years.

The aim of this study was to prospectively examine the relationship between baseline adherence to a priori dietary patterns, assessed using the MedDiet, DASH, and MIND dietary patterns scores, with 2-year changes in cognitive performance in a large sample of community-dwelling older adults with overweight or obesity at high cardiovascular disease risk.

Figure 1 provides the flow diagram of participants. This study included a total of 6,647 participants (mean age 65 years, 48% women). Table 1 provides the baseline characteristics of the participants overall and shows the categories representing the lowest and highest adherence to each of the a priori dietary pattern scores at baseline. The median (range) of dietary adherence scores for the lowest and highest tertiles of each of the three assessed dietary patterns were 6 (1–7) and 10 (10–14) for the MedDiet (lowest possible score 0, highest possible score 14), respectively; 19 (8–21) and 30 (27–38) for DASH (lowest possible score 8, highest possible score 40), respectively; and 8 (2.5–8.5) and 10.5 (10.0–13.5) for MIND (lowest possible score 0, highest possible score 15), respectively.

A higher percentage of women (P ≤ 0.001), older age (P < 0.001), higher physical activity (P < 0.001), and a tendency toward lower BMI, although not clinically significant (P ≤ 0.05), were observed in the highest adherence tertiles for all three dietary patterns. In the DASH and MIND patterns, lower percentages of daily energy intake and current smokers (both P < 0.001) were also observed in the highest adherence tertiles of these patterns. Furthermore, higher adherence to the DASH and MIND diets were associated with less alcohol intake (P < 0.001) and depression (P = 0.001), respectively. For the MedDiet, a lower percentage of participants with depressive symptoms, higher alcohol, and total energy (all P < 0.01) was observed in the highest adherence tertile compared with the lowest adherence tertile.

Figure 2 and Supplementary Table 1 show the β coefficients (95% CIs) associated with 2-year changes in cognitive assessment z-scores across tertiles of a priori dietary pattern adherence scores. Results of the fully adjusted linear regression models show a significant association between highest adherence to the MedDiet and 2-year changes in MMSE (β: 0.070; 95% CI: 0.014, 0.175, P-trend = 0.011), TMT-A (β: −0.054; 95% CI: −0.110, −0.002, P-trend = 0.047), and TMT-B (β: −0.062; 95% CI: −0.116, −0.007, P-trend = 0.024). Adherence to the MIND diet was significantly associated with 2-year changes in DST-B (β: 0.058; 95% CI: 0.002, 0.114, P-trend = 0.045). No other significant beneficial associations with changes in cognitive performance measured by the different neuropsychological test batteries were observed between adherence to the MedDiet, MIND, or DASH dietary patterns. Conversely, significant associations were observed in the crude models with greater 2-year increases in the DASH diet being associated with lower performance in all nine cognitive tests. Sensitivity analyses, which included assessing only participants with baseline MMSE scores above 23 (as scores 23 and below suggest possible mild dementia or worse), or the addition of alcohol as a potential confounder in the model, did not significantly modify the findings (data not shown). The only modification observed was that including total alcohol intake in the model slightly, but non-significantly, mitigated any negative associations observed between adherence to the DASH diet and changes in cognitive function. Figure 3 shows the impact of all 14 food components of the MedDiet on changes of each individual cognitive test. Of these components, olive oil used as the primary oil was found to be positively associated with changes in global cognitive function, as well as changes in the two DSTs (both forward recall P = 0.007 and backward recall P ≤ 0.001). Nut intake was significantly and positively associated with an increase in CDT performance (P = 0.034) and trended toward beneficially impacting changes in MMSE score (P = 0.069). Red wine was also significantly associated with changes in various cognitive function assessments, yet indicating converse findings, where red wine intake may have a beneficial relationship with changes in TMT-A (P = 0.004), TMT-B (P = 0.006), and DST-b (P = 0.020), and a negative association with changes in VFT-a (P = 0.048). Likewise, preferably consuming white meat as opposed to red or processed meat showed conflicting findings where a beneficial association was observed with changes in DST-f (P = 0.001) and negatively associated with changes in CDT (P = 0.001). Fish and shellfish intake was negatively associated with changes in DST-b (P = 0.008). Analyses investigating the DASH and MIND diets showed similar associations with nut consumption and wine intake. Additionally, when assessed within the context of the MIND diet, lower consumption of confectionery products was associated with improvements in 2-year changes in GCF (P = 0.007), VFT-a (P = 0.019), TMT-a (P = 0.011), DST-b (P = 0.042), and higher red meat intake was associated with worsening changes in TMT-a (P = 0.001) and TMT-b (P = 0.014) scores.

Table 2 presents the quantity of intake of various dietary components overall and by tertile of dietary pattern adherence score and shows differences between the dietary patterns. When assessing the MedDiet adherence, 94.7% of participants within the highest adherence tertile used olive oil as their primary oil with a mean intake level of 47.4 ± 14.7 g/day, nut intake was 19.9 ± 18.2 g/day, and red wine consumption was on average 59.4 ± 98.1 g/day.

This study examined the PREDIMED-Plus trial as a longitudinal, observational cohort to evaluate the relationship between adherence to a priori dietary patterns and changes in cognitive performance in community-dwelling older adults with overweight or obesity and at high cardiovascular disease risk. Findings suggested that the MedDiet may support cognitive function in older age as significant beneficial associations were observed between greater adherence to the MedDiet with favorable cognitive changes in MMSE, TMT-A, and TMT-B assessments over the follow-up period of 2 years. This represented better general cognitive function, as well as executive function specifically attention and processing speed and cognitive flexibility in those with higher adherence to a MedDiet. Findings also indicated that the MIND diet may be associated with better working memory based on higher adherence being related to higher DST-b assessment. However, the DASH diet was not beneficially associated with 2-year changes in cognitive function in this population with overweight or obesity at high cardiovascular disease risk. The observed advantageous associations between adherence to the MedDiet and cognition align with previous findings presented in systematic reviews and meta-analyses of observational studies suggesting associations between MedDiet adherence with slower cognitive decline, lower risk of dementia (especially Alzheimer’s disease), and reduced conversion of mild cognitive impairment to Alzheimer’s disease (Singh et al., 2014; Loughrey et al., 2017; Wu and Sun, 2017). Recently, a meta-analysis including nine prospective cohort studies reported that high adherence to the MedDiet was associated with a 21% risk reduction in pooled cognitive disorders, in addition to a dose-response with positive findings almost exclusively limited to higher MedDiet adherence (Wu and Sun, 2017). Furthermore, neuroimaging evaluations have found evidence in favor of a protective effect (Karstens et al., 2019). Nevertheless, it is interesting to highlight that previous prospective cohort studies generally had 4 or more years of follow-up, many of which were conducted in relatively healthy, non-Mediterranean populations, with many of the cognitive assessments using screening tests based on criteria to discriminate overall mild cognitive impairment or dementia. Our study also found a positive association between higher adherence to MedDiet and a screening test (MMSE) but also showed specific beneficial associations for executive functioning, including attention and processing speed (TMT-A) and cognitive flexibility (TMT-B). Conversely, a systematic review of randomized controlled trials (nine reports, five unique trials) showed inconsistent findings when comparing a MedDiet with either a waiting list, usual diet, or a low-fat control group for a duration ranging from 10 days to 6.5 years on cognition or brain morphology and function (Radd-Vagenas et al., 2018). However, the authors stated that significant and clinically meaningful effect sizes were found for cognitive composites in the largest and most robust trial, with a duration of 4.1 years, conducted within the context of the PREDIMED trial (Valls-Pedret et al., 2015). Furthermore, in a more recent analysis of a smaller sub-cohort of the PREDIMED-Plus trial evaluating cognition, higher adherence to an energy-reduced MedDiet was associated with greater improvements in memory; however, interpretation of these findings was related to the interplay with weight loss (Soldevila-Domenech et al., 2021). In this study population, we did not find an association for the GCF, which may be explained by the short duration (2 years) and by the broad neuropsychological battery utilized compared with other studies. However, the present findings further support the MedDiet for better cognition while suggesting that beneficial associations may be observable within a shorter timeframe and have applicability for populations at greater risk of cognitive decline (older, with overweight or obesity, and at high risk of cardiovascular disease), which could have implications for improving quality of life. In particular, obesity and its comorbidities are associated with accelerated cognitive decline and impaired cognitive performance including neurodegenerative pathologies, such as dementia, in later life (Dye et al., 2017).

While a significant association was seen in the present analyses with the MedDiet and MIND diet within a shorter follow-up duration with some cognitive function assessments compared with other prospective cohort studies that have been conducted, this relationship was not found with the DASH diet. While MedDiet has been associated with a lower risk of cognitive impairment, it has not always been associated with a slower decline in cognitive function (Keenan et al., 2020). Inconsistent findings have previously been observed with the DASH diet (van den Brink et al., 2019). However, MIND dietary adherence has been associated with better cognitive function across various domains in a systematic review of 13 MIND studies (9 cohorts, 3 cross-sectional, and 1 RCT) evaluating cognitive functioning in older adults (Kheirouri and Alizadeh, 2021). The observed discrepancies with present findings may be related to differences in the types of foods consumed by the study population, and a potential threshold effect related to the amount of each food component consumed, as well as the cognitive tests performed.

The analyzed three dietary patterns each have plant-based foundations, with moderate to high amounts of fish and dairy products, yet they differ in the types and amounts of each dietary component. The MedDiet is typically characterized by high consumption of olive oil, fruits, vegetables, legumes, nuts, cereals, and unsaturated fatty acids; low consumption of meat and saturated fatty acids; low to moderate consumption of dairy products; moderate to high consumption of fish; and a regular, but moderate, intake of wine (Sánchez-Sánchez et al., 2020). The DASH diet shares many similarities yet differs in recommending low-fat dairy and low sodium, besides having fewer specifications (Fung et al., 2008). Based on these two dietary patterns, the MIND diet was developed combining Mediterranean and DASH aspects and incorporating purported neuroprotective foods such as green leafy vegetables and berries (Morris et al., 2015a,b). A potential explanation for our discordant findings may be due to differences in the use of olive oil as the primary oil between tertiles of adherence. In our sample, the use of olive oil was clearly linked with a beneficial association in the GCF composite, as well epidemiological and clinical evidence have suggested improved cognition with olive oil (Millman et al., 2021; Theodore et al., 2021). With any dietary pattern, in addition to observing associations with specific food components, there is also the potential for synergistic effects (Schulz et al., 2021). The present findings suggest such effects given the observed associations for MedDiet with MMSE and TMT-A and TMT-B or the MIND diet with DST-b did not appear to be fully explained by any one component of the dietary pattern; however, further investigation is warranted.

In older Spanish adults with overweight or obesity, higher adherence to the MedDiet may help mitigate the risk of cognitive decline, specifically as it relates to general and executive cognitive functioning, even over a short (2-year) period.

Data described in the manuscript, code book, and analytic code will be made available upon request pending application and approval of the PREDIMED-Plus Steering Committee. There are restrictions on the availability of data for the PREDIMED-Plus trial, due to the signed consent agreements around data sharing, which only allow access to external researchers for studies following the project purposes. Requestors wishing to access the PREDIMED-Plus trial data used in this study can make a request to the PREDIMED-Plus trial Steering Committee chair: (JS-S, jordi.salas@urv.cat). The request will then be passed to members of the PREDIMED-Plus Steering Committee for deliberation.

The study was conducted in accordance with the principles of the Declaration of Helsinki. The respective Institutional Review Board (IRB) of all study centres approved the study protocol. The trial was registered at the International Standard Randomized Controlled Trial in 2014 (ISRCTNwww.isrctn.com/ISRCTN8989887089898870). All participants provided written informed consent.

MAM-G, DC, JS-S, MF, JAM, AMA-G, JW, JV, DR, JL-M, RE, FJT, JL, JLS-M, AB-C, JAT, VMS, XP, MD-R, PM-M, JV, CV, LD, and ER (all the principal PREDIMED-Plus investigators) contributed to the study concept and design and to data extraction from the participants in the PREDIMED-Plus trial, with SKN, NB, and JS-S, contributing to the study concept and design of the present analyses. SKN, NB, CG-M, NB-T and JS-S performed the statistical analyses. SKN, NB and JS-S drafted the manuscript. All authors reviewed the manuscript for important intellectual content and approved the final version to be published.

SKN was a volunteer member of the not-for profit group Plant Based Canada. JS-S reported receiving research support from the Instituto de Salud Carlos III, Ministerio de Educación y Ciencia, Departament de Salut Pública de la Generalitat de Catalunya, the European Commission, the United States National Institutes of Health; receiving consulting fees or travel expenses from Danone, California Walnut Commission, Eroski Foundation, Instituto Danone, Nestle, and Abbott Laboratories, receiving non-financial support from Hojiblanca, Patrimonio Comunal Olivarero, the California Walnut Commission, Almond Board of California, La Morella Nuts, Pistachio Growers, and Borges SA; serving on the board of and receiving grant support through his institution from the International Nut and Dried Foundation and the Eroski Foundation; and grants and personal fees from Instituto Danone; Serving in the Board of Danone Institute International. DC reported receiving grants from Instituto de Salud Carlos III. RE reported receiving grants from Instituto de Salud Carlos III, Fundación Dieta Meditarránea and Cerveza y Salud and olive oil for the trial from Fundación Patrimonio Comunal Olivarero and personal fees from Brewers of Europe, Fundación Cerveza y Salud, Interprofesional del Aceite de Oliva, Instituto Cervantes in Albuquerque, Milano and Tokyo, Pernod Ricard, Fundación Dieta Mediterránea (Spain), Wine and Culinary International Forum and Lilly Laboratories; non-financial support from Sociedad Española de Nutrición and Fundación Bosch y Gimpera; and grants from Uriach Laboratories. ER reports grants, personal fees, non-financial support, and others from California Walnut Commission, during the conduct of the study; grants, personal fees, non-financial support and other from Alexion; grants from Amgen and Pfizer; grants, personal fees and other from Sanofi Aventis; personal fees, non-financial support and other from Ferrer International, Danone and Merck Sharp and Dohme, personal fees and other from Amarin, outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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