Hostname: page-component-586b7cd67f-l7hp2 Total loading time: 0 Render date: 2024-11-22T04:36:07.106Z Has data issue: false hasContentIssue false

Role of fruit and vegetables in sustaining healthy cognitive function: evidence and issues

Published online by Cambridge University Press:  24 April 2023

Crystal F. Haskell-Ramsay*
Affiliation:
Department of Psychology, Northumbria University, Newcastle upon Tyne, UK
Sarah Docherty
Affiliation:
Department of Psychology, Northumbria University, Newcastle upon Tyne, UK
*
*Corresponding author: Crystal F. Haskell-Ramsay, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Modifiable lifestyle factors, such as improved nutrition, are crucial in maintaining cognitive health in older age. Fruit and vegetables represent healthy and sustainable sources of nutrients with the potential to prevent age-related cognitive decline. The aim of this review is to synthesise the available evidence, from epidemiological and randomised controlled trials (RCT), regarding the role of fruit and vegetables in sustaining healthy cognitive function. Epidemiological studies of combined fruit and vegetable intake suggest that increased consumption may sustain cognition in later life. The evidence appears to be stronger for an association between vegetables and cognition, particularly for green leafy and cruciferous vegetables. Specific benefits shown for berries, citrus fruits, avocado and nuts suggest fruit is worthy of further investigation in relation to cognition. Data from RCT indicate benefits to differing aspects of cognition following citrus and berry fruits, cocoa and peanuts, but the data are limited and there are a lack of studies exploring effects of vegetables. There is growing evidence for an association between fruit and vegetable intake and cognitive function, but this is not always consistent and the data from RCT are limited. Issues in previous research are highlighted, such as strict exclusion criteria, absence of baseline nutritional status data and lack of consideration of individual differences, which may explain the weaker findings from RCT. Inclusion of those most at risk for cognitive decline is recommended in future nutrition and cognition research.

Type
Conference on ‘Food and nutrition: Pathways to a sustainable future’
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
Copyright © The Author(s), 2023. Published by Cambridge University Press on behalf of The Nutrition Society

The world's population is ageing. By 2030, one in six people will be aged 60 years or over(1). However, average health span is not increasing at the same rate as lifespan, as indicated by the increasing prevalence of non-communicable diseases such as CVD and diabetes. Of relevance to this review, dementia has recently emerged as the leading cause of death in the UK. In 2019, one in every fourteen of the UK population aged 65 years and over were diagnosed with dementia(Reference Wittenberg, Barraza-Araiza and Rehill2), and globally this condition affects more than twice as many women as men(Reference Gong, Harris and Lipnicki3). Despite the high prevalence and significant impact of dementia, such as Alzheimer's disease, there are currently no effective pharmaceutical treatments to slow down or reverse disease progression. It is, therefore, imperative that we develop ways to prevent, or at least delay, dementia and maintain cognitive health into older age.

Nutrition represents a crucial modifiable lifestyle factor in the quest to sustain health, including healthy cognitive function. The importance of nutrition is evident from the inverse relationships between non-communicable diseases and adherence to healthy dietary patterns such as the Mediterranean diet, dietary approaches to stop hypertension diet, the Mediterranean-dietary approaches to stop hypertension intervention for neurodegenerative delay, the Nordic diet and the traditional Asian diet(Reference Cena and Calder4). In fact, dietary risks were observed to be the leading cause of disease burden in the United States between 1990 and 2010(Reference Murray, Atkinson and Bhalla5), with a low intake of fruit, vegetables and nuts listed in the top five leading dietary risk factors for death and disability-adjusted life years globally(6). CVD was cited as the leading cause of diet-related death and disability-adjusted life years, highlighting the importance of dietary factors to cardiovascular health. Cardiovascular risk factors are also linked to cognition. For instance, high cholesterol at midlife is associated with an increased risk of vascular dementia(Reference Solomon, Kåreholt and Ngandu7), as well as accelerated cognitive decline, including a specific association for LDL-cholesterol(Reference Ma, Yin and Zhu8). Hypertension has been linked to dementia(Reference Gottesman, Albert and Alonso9), including Alzheimer's disease(Reference Kivipelto, Helkala and Laakso10), as well as steeper cognitive decline(Reference Gottesman, Schneider and Albert11) and poor cognitive function(Reference Launer, Masaki and Petrovitch12). There is also evidence for race(Reference Gottesman, Schneider and Albert11) and sex differences(Reference Gong, Harris and Peters13) in these relationships. Prior to hypertension, arterial stiffness is associated with worse cognitive outcomes in older adults, and in midlife(Reference Tsao, Seshadri and Beiser14). Low-cardiac output, which data from the Framingham Heart Study Offspring Cohort indicate one-third of the general adult population meets clinical criteria for(Reference Jefferson, Beiser and Himali15), is associated with worse cognitive performance(Reference Sabayan, van Buchem and Sigurdsson16). This is potentially mediated by the corresponding cerebral blood flow reductions observed in cardiac dysfunction, which can lead to synaptic dysfunction(Reference Bolay, Gürsoy-Ozdemir and Sara17) and blood–brain barrier permeability(Reference Sage, Van Uitert and Duffy18). Increased risk of dementia(Reference Whitmer, Sidney and Selby19) and accelerated cognitive decline(Reference Hassing, Grant and Hofer20) are also observed in type-2 diabetes, which may be due to increased blood–brain barrier permeability(Reference Van Dyken and Lacoste21). Blood–brain barrier disruption has been linked to inflammation(Reference Varatharaj and Galea22,Reference Huang, Hussain and Chang23) , which can increase the risk of atherosclerosis and insulin resistance(Reference Soysal, Arik and Smith24). Potential mechanisms of increased inflammation in older age and in chronic conditions include changes to gut microbiota and gut permeability(Reference Ferrucci and Fabbri25), which are also linked to brain function(Reference Cryan, O'Riordan and Cowan26) and to mental health conditions including depression(Reference Simpson, Diaz-Arteche and Eliby27). The risk factors outlined all have the potential to be impacted by diet and could therefore represent mechanisms for dietary effects on cognition. Obesity is also associated with a pro-inflammatory state(Reference Ferrucci and Fabbri25), highlighting the role of diet, which is supported by studies showing beneficial effects of anti-inflammatory diets(Reference Molendijk, Molero and Ortuño Sánchez-Pedreño28,Reference Minihane, Vinoy and Russell29) .

In meta-analyses, adherence to the Mediterranean diet was associated with better global cognition both cross-sectionally and longitudinally(Reference Coelho-Júnior, Trichopoulou and Panza30), whilst intervention with a Mediterranean diet was shown to improve cognition when compared to a low-fat control diet(Reference Valls-Pedret, Sala-Vila and Serra-Mir31). One aspect that is common across healthy diet patterns such as the Mediterranean, dietary approaches to stop hypertension and Mediterranean-dietary approaches to stop hypertension intervention for neurodegenerative delay diets, is the recommendation to increase intake of fruit and vegetables. The EAT-Lancet commission report(Reference Willett, Rockström and Loken32), which highlights food as the greatest prospect to optimise health and environmental sustainability, also recommends increased fruit and vegetable intake to improve human and planetary health. A recent review of the EAT-Lancet reference diet and cognition across the life course concluded that the current evidence base is weak, but high fruit and vegetable intake seems to benefit cognition, particularly in older adults(Reference Dalile, Kim and Challinor33).

The aim of this review was to synthesise the evidence for fruit and vegetable intake to sustain cognition in cognitively healthy older adults, and to highlight challenges in this field of research. One issue that is immediately apparent is the use of dementia screening tools, such as the mini-mental state examination, to assess cognition in cognitively healthy older adults. Due to the lack of sensitivity of these screening tools, this review will focus on studies that include measures of cognitive function. One of the most studied aspects of age-related cognitive decline is episodic memory, which reflects the ability to store and subsequently retrieve, and to recognise, previously presented verbal, visual or spatial information. Another aspect of cognition that deteriorates with age is executive function. This involves complex or higher order thinking such as planning, problem solving and reasoning, and is underpinned by working memory as well as information processing. Sustained and selective attention are also important cognitive domains, which respectively reflect the ability to maintain attention on a stimulus or a task for a long period, and the ability to respond to relevant stimuli (targets) whilst ignoring irrelevant stimuli (distractors). One of the difficulties here is that cognitive tasks are often mixed, so there is overlap in terms of the domains involved. For example, the Stroop task involves aspects of executive function whilst also assessing selective attention. (See Table 1 for summary and evaluation of key cognitive domains.)

Table 1. Summary and evaluation of key cognitive domains

In the following sections, data on the relationship between fruit and vegetable intake and cognitive performance are reviewed, followed by a review of randomised controlled trials (RCT) exploring the impact of daily fruit and vegetable intake on cognitive function in healthy older adults.

Epidemiological evidence

Epidemiological studies in this area that have focused on fruit and vegetables as a combined category have shown some positive findings. In the Whitehall II study, consuming <2 portions of fruit and vegetables daily was associated with an increased risk of poor executive function and, to a lesser extent, poorer episodic memory(Reference Sabia, Nabi and Kivimaki34). This association was apparent for fruit and vegetable intake at midlife but was strongest when measured cross-sectionally at 15-year follow-up. The supplementation with antioxidant vitamins and minerals 2 study also showed that higher fruit and vegetable intake was associated with better verbal memory at 13-year follow-up, with specific effects for fruit and for vitamin C-rich fruit and vegetables(Reference Péneau, Galan and Jeandel35). However, in this study the association with executive functioning was negative. One possible explanation for the discrepancy in findings relating to executive function is the classification of verbal fluency as memory tasks in the supplementation with antioxidant vitamins and minerals 2 study(Reference Péneau, Galan and Jeandel35), whereas this was categorised as executive function in the Whitehall II study(Reference Babateen, Shannon and O'Brien36). It is also important to note that in both studies no measure of cognition was taken at baseline, so assessment of cognitive decline was not possible. Support for a relationship between fruit and vegetable intake in late midlife and cognition in later life also comes from the health professionals follow-up study, which showed that higher consumption of both fruit and vegetables was associated with lower odds of poor subjective cognitive function at 18–22-year follow-up(Reference Yuan, Fondell and Bhushan37). Whilst no objective measure was included in this study, the experience of cognitive function subjectively may be particularly important in terms of quality of life. Performance on cognitive tests assessing memory and executive function improved with an increasing intake of fruit and vegetables in the Hordaland health study, with a marked dose-dependent relationship up to about 500 g/d. When analysed separately, fruit consumption was positively associated with performance on three out of five cognitive tests, whereas vegetable consumption was positively associated with performance on four tests(Reference Nurk, Refsum and Drevon38). Interestingly, data from the Boston Puerto Rican health study indicated that greater variety of fruit and vegetable intake but not quantity was associated with better cognition, and this association was strongest for vegetables(Reference Ye, Bhupathiraju and Tucker39).

Studies that have examined the role of vegetables separately from fruit have shown higher intake to be associated with smaller declines in processing speed and global cognitive function. This is despite vegetable intake being associated with lower information processing speed and worse cognitive flexibility at baseline, which may be driven by negative effects of allium (garlic, onion and leek) consumption(Reference Nooyens, Bueno-de-Mesquita and van Boxtel40). Total vegetable intake was also inversely associated with cognitive decline in the nurses' health study, despite no such association for fruit and vegetables combined. The highest intake of vegetable was equivalent to 1⋅5 years less decline at the 2-year follow-up(Reference Kang, Ascherio and Grodstein41). Similarly, those in the highest two quintiles of vegetable intake in the Chicago Health and Aging Project showed a 40 % reduction in decline on a global cognition measure at 6-year follow-up when compared to the lowest quartile intake(Reference Morris, Evans and Tangney42). Moreover, a specific association between cognitive decline and green leafy vegetables was observed(Reference Morris, Evans and Tangney42,Reference Morris, Wang and Barnes43) . This is supported by the nurses' health study showing the greatest benefit for green leafy vegetables, but also a specific benefit for cruciferous vegetable, particularly for episodic memory(Reference Kang, Ascherio and Grodstein41). In the Doetinchem cohort study, higher intake of cabbage was associated with better memory and better global cognitive function at baseline, and with smaller decline in information processing speed at 5-year follow-up, whilst root vegetables were associated with smaller declines in cognitive flexibility and global cognition(Reference Nooyens, Bueno-de-Mesquita and van Boxtel40). Support for the roles of root and cruciferous vegetables also comes from the Hordaland health study showing strongest associations for carrots, and cruciferous vegetables, but also for citrus fruits(Reference Nurk, Refsum and Drevon38).

Effects of specific fruits have been explored with the nurses' health study showing that greater intake of blueberries and strawberries was associated with better episodic memory scores and slower rates of cognitive decline for global cognition, equivalent to up to 2⋅5 years of ageing(Reference Devore, Kang and Breteler44). Consumers of avocado were also shown to have better episodic memory and global cognition than non-consumers(Reference Cheng, Ford and Taylor45). Whilst not always categorised as fruit, a specific benefit has also been shown for tree nuts. The Doetinchem cohort study observed that higher nut intake was related to better global cognition, flexibility, memory and processing speed(Reference Nooyens, Bueno-de-Mesquita and van Boxtel40). Long-term (6-year) nut intake was linked to better global cognition in women aged ≥70 years but not with cognitive decline(Reference O'Brien, Okereke and Devore46) and an association to 5-year cognitive decline in the Doetinchem cohort study was lost following adjustment for cardiovascular risk factors(Reference Nooyens, Bueno-de-Mesquita and van Boxtel40). This indicates a role for cardiovascular effects, which is supported by cognitive improvements shown following Mediterranean diet plus mixed tree nuts in those at high cardiovascular risk(Reference Valls-Pedret, Sala-Vila and Serra-Mir31).

Epidemiological data suggest a relationship between fruit and vegetable intake and cognition. The evidence appears to be stronger for an association between vegetables and cognition than for fruit, which may relate to the common inclusion of fruit juice in the fruit category, despite differences in their fibre content. Since fruit and fruit juice modulate different aspects of immune function, with juice potentially linked to proinflammatory pathway activation(Reference Nicodemus-Johnson and Sinnott47), the inclusion of fruit juice in the fruit category may be concealing effects of whole fruit. Specific benefits shown for berries, citrus fruits, avocado and nuts suggest fruit is worthy of further investigation in relation to cognition; nuts in particular represent a nutrient-dense food with less sugar than other fruits. In terms of vegetables, a specific benefit may be seen for cruciferous or green leafy vegetables. However, this is not consistently shown with one study showing benefits for both(Reference Kang, Ascherio and Grodstein41), whilst others show benefits for one or the other; a specific benefit for cabbage(Reference Nooyens, Bueno-de-Mesquita and van Boxtel40) may indicate that green and leafy vegetables such as kale and savoy cabbage may confer the most favourable effects, potentially due to the high levels of glucosinolates, carotenoids, vitamins, minerals and flavonoids. In an analysis focused on flavonoids, the Lothian birth cohort 1936 study failed to show effects of fruit and/or vegetables(Reference Butchart, Kyle and McNeill48). This potentially highlights the importance of covariates in epidemiological research since relationships between vegetable intake and cognition were lost after controlling for childhood IQ, whilst those for total fruit intake were lost with the additional inclusion of smoking, socio-economic status, education and the apoE 14 allele.

Randomised controlled trials

RCT in this area (see Table 2) have tended to focus on fruit, specifically flavonoid-rich. The effects of orange juice consumption were assessed in a crossover trial of 60–81-year-olds. Cognition was assessed via five episodic memory tasks and six executive function tasks, pre- and post- a 500 ml serving of 305 mg flavanones or placebo for 8 weeks. The findings revealed improvement in global cognitive function, with no effects on episodic memory or executive function when assessed separately(Reference Kean, Lamport and Dodd49). Several studies have also assessed the effects of flavonoid-rich berries. Effects of 12 weeks' tart cherry juice were assessed in 65–80-year-olds on measures of episodic memory, sustained attention, information processing, executive function and subjective memory(Reference Chai, Jerusik and Davis50). Compared to placebo, 480 ml tart cherry juice daily led to fewer errors on an episodic memory task, and shorter movement reaction time, as well as increasing contentment with memory. Two studies have assessed effects of blueberry in older adults(Reference Miller, Hamilton and Joseph51,Reference Whyte, Cheng and Fromentin52) . Twenty-four g/d freeze-dried blueberry extract (equivalent to one cup of fresh blueberries) led to improved episodic memory and executive function in 60–75-year-olds, with no effects on information processing or attention tasks(Reference Miller, Hamilton and Joseph51). Different doses and forms of blueberry have also been assessed in 65–80-year-olds(Reference Whyte, Cheng and Fromentin52). Effects of 500 and 1000 mg wild blueberry powder and 100 mg of a purified extract were assessed on measures of episodic memory, executive function and selective attention. The purified extract led to improved episodic memory and visual memory span at 12 but not 24 weeks, compared to placebo(Reference Whyte, Cheng and Fromentin52). Interestingly, the purified extract contained negligible fat, fibre, vitamin C and sugars, which were present in the other blueberry interventions. This indicates that the observed effects are attributable to the flavonoid content alone rather than a synergy with these other components. The lack of effects at 24 weeks is difficult to explain, particularly as systolic blood pressure was reduced at 12 and 24 weeks, but a tentative explanation is that this is reflective of a practice effect whereby improved strategy in performing the tasks has reduced task sensitivity. Twelve weeks' consumption of 4⋅9 g/d freeze-dried cranberry extract (equivalent to one cup of fresh cranberries) was also shown to improve episodic memory in 50–80-year-olds(Reference Flanagan, Cameron and Sobhan53). Reduced LDL-cholesterol was also shown with some evidence for sex differences in response, as well as increased perfusion in specific regions of the right brain. This is contrary to an earlier study showing no effects of cranberry juice on a range of cognitive measures in healthy older adults(Reference Crews, Harrison and Griffin54). These null findings may be due to the form or dose of cranberry administered, with a 909 ml beverage containing 27 % cranberry juice being delivered, or they could indicate that a 6-week intervention was not sufficient to elicit an effect on cognitive performance in this population.

Table 2. Randomised controlled trials of fruit and vegetable juices and extracts

The effects of cocoa should also be considered here. Whilst not typically thought of as a fruit, cocoa represents the seed of the fruit of the cacao tree and has been studied for potential benefits due to its flavan-3-ol content. In one such study, high flavan-3-ol (993 mg), intermediate flavan-3-ol (520 mg) or low flavan-3-ol control (48 mg) were given for 8 weeks. Improvements to information processing and a measure of executive function were shown following both flavan-3-ol doses and the highest dose also improved verbal fluency(Reference Mastroiacovo, Kwik-Uribe and Grassi55). Importantly, no effects were observed on the mini-mental state examination, highlighting the lack of sensitivity of this measure in short intervention trials of healthy adults. This study also attempted to ascertain the determinants of cognitive change, observing that insulin resistance explained 17 % of cognitive change. Systolic blood pressure and lipid peroxidation were not predictors despite blood pressure and several metabolic markers being improved by the intervention. Another interesting study of cocoa showed that high flavan-3-ol (900 mg) improved novel object recognition reaction time when compared to control. Moreover, the authors reported that the improvement observed following intake of high flavan-3-ol cocoa for 12 weeks was equivalent to three decades of ageing, shifting the slope in expected age-related decline. Imaging data also showed an increase in cerebral blood volume in the dentate gyrus region of the hippocampus and this increase was inversely correlated with reaction time. This indicates a potential mechanism of action for improvements linked to increased blood flow, which may be specific to the hippocampus given the localised effect and the role of the hippocampus in the task assessed(Reference Brickman, Khan and Provenzano56). Significant improvements to global cognition were also observed in healthy elderly following supplementation with 494 mg of cocoa flavan-3-ol for 28 d. Interestingly, increases in serum brain-derived neurotrophic factor levels were also observed(Reference Neshatdoust, Saunders and Castle57).

Studies of nuts have produced mixed findings. In the dual-centre walnuts and healthy ageing study there were no effects of a 2-year walnut intervention(Reference Sala-Vila, Valls-Pedret and Rajaram58). However, a site-specific improvement to global cognition and functional MRI differences indicative of improved neural efficiency in the walnut group were observed following 30–60 g/d walnuts over 2 years. A study assessing effects of 12-week almond consumption failed to find effects on cognition when compared to an isoenergetic carbohydrate-rich snack in overweight and obese older adults, despite improvements to aspects of cardiometabolic health(Reference Coates, Morgillo and Yandell59). However, 12-week peanut consumption was observed to enhance memory, verbal fluency and processing speed, as well as increasing cerebrovascular reactivity and small artery elasticity in healthy overweight adults(Reference Barbour, Howe and Buckley60). Changes in cerebrovascular reactivity in the left middle cerebral artery were also positively correlated with changes in delayed memory and recognition. Although peanuts are legumes and therefore classified as vegetables, they are usually considered in the nut category due to their composition. These nut studies illustrate the issue of implementing a control in studies of whole foods. In two of the studies the control arm consisted of habitual diet minus nuts(Reference Sala-Vila, Valls-Pedret and Rajaram58,Reference Barbour, Howe and Buckley60) , whereas in the other study nuts were compared to an isoenergetic snack(Reference Coates, Morgillo and Yandell59). The first option presents issues in that no intervention is present in the control arm, whereas the snack comparator makes interpreting findings difficult due to potential effects of the composition of the control employed.

RCT of vegetables are less prevalent than fruit, possibly due to the logistics of developing a control for the intervention. Fruit is typically studied in juice form, but vegetable juice is less commonly consumed and is potentially less likely to be accepted by participants where daily intake is required. For instance, there are a number of studies of beetroot juice, but only one of these has included repeated consumption in healthy older adults(Reference Babateen, Shannon and O'Brien36). A 13-week trial in overweight and obese older adults assessed effects of high (800 mg/d), moderate (400 mg/d) and low (200 mg/d) nitrate administered in beetroot juice and compared effects to a nitrate-depleted beetroot juice. Despite a wide array of cognitive tasks, there was no evidence of any effects of beetroot juice on cognition, and no effects on cerebral blood volume as assessed with near IR spectroscopy. This study was designed as a feasibility study and not intended to provide a definitive investigation of the effects of nitrate on cognition and cerebral blood flow, but the null findings are unexpected based upon the available evidence from short-term studies.

Evidence for cognitive benefits of fruit and vegetables from RCT is weaker than epidemiological data. There are generally only one or two RCT per food type, with the strongest evidence for cocoa where three studies exist. Although the available data are limited, the findings are generally positive despite potential issues with short duration of intervention and limited knowledge of optimal dosage. Not all studies show positive effects, the dual-centre walnuts and healthy ageing study(Reference Sala-Vila, Valls-Pedret and Rajaram58) failed to detect effects of a 2-year walnut intervention when analysed in the population as whole. However, subgroup analysis revealed a site-specific improvement. Compared with other sites, participants at the site where improvement was observed, reported lower education and lower intake of the plant n-3, α-linolenic acid(Reference Sala-Vila, Valls-Pedret and Rajaram58). These findings potentially suggest that those at risk, either due to poorer nutrition or poorer education, may be more susceptible to cognitive improvements following a fruit or vegetable intervention. A number of studies(Reference Flanagan, Cameron and Sobhan53,Reference Mastroiacovo, Kwik-Uribe and Grassi55,Reference Brickman, Khan and Provenzano56,Reference Barbour, Howe and Buckley60) indicate increased cerebral blood volume following fruit/legume intervention, as well as improved cardiometabolic markers, and in some cases a correlation between changes in cognition and cerebrovascular/metabolic markers. These findings may suggest that cognitive improvement is more likely in those who are at risk for cardiometabolic dysfunction.

However, RCT assessing effects of diet on cognition often impose strict exclusion criteria such as: no clinically significant coexisting medical conditions, including CVD, cerebrovascular events, neurological disorders, inflammatory diseases, metabolic disorders, gastrointestinal abnormalities, mental illness including depression; no prescription medication; no supplements; no current smokers; no individuals with BMI ≥30 kg/m2. Whilst these criteria are sensible in terms of study design and minimising ‘noise’ from uncontrolled variables, they present a problem in terms of representativeness. For instance, 63 % of adults in England aged 65–74 reported a longstanding health condition in 2018(Reference Conolly and Craig61). In adults aged ≥65, at least 80 % were shown to have taken a prescribed medication in the past week, and more than one in ten took at least eight different prescribed medications per week(Reference Moody, Mindell and Faulding62). Whilst 75 % of 65–74-year-olds were reported to be overweight or obese(Reference Conolly and Craig61). In addition to problems relating to generalisability of findings, these studies create somewhat of a paradox in that they are exploring the importance of nutrition to health yet recruiting unusually healthy people whilst assuming suboptimal nutrition that can be enhanced by intervention.

Nutrition status and self-selection

Inclusion of nutrition status measures, such as dietary intake measures and nutritional biomarkers, in RCT of nutrition interventions on cognition is increasing, but still rare. Failure to measure nutritional status in cognitive studies presents obvious problems in not being able to ascertain if any null findings are due to already optimal status in study participants(Reference Morris and Tangney63). Indeed, post-hoc analyses indicate that beneficial effects of vitamins A, C and certain B-vitamins on cognitive decline may only be shown in those with low baseline intake (for a review see(Reference Morris64)). However, due to self-selection bias, those who volunteer for RCT of nutrition are likely to be health conscious and potentially less likely to display suboptimal nutrition. This is nicely illustrated by the memory and attention supplementation trial where a validated (against blood markers) questionnaire was used to assess diet quality prior to enrolment, aiming for 50 % ‘optimal’ diet (a high intake of fruit, vegetables, legumes, olive oil and nuts, and a lower intake of processed foods) and 50 % suboptimal. Out of 501 volunteers, 461 (74⋅4 %) met the criterion for an ‘optimal’ diet indicative of elevated nutrient status(Reference Young, Gauci and Scholey65). When considered against the statistic that only 5⋅4 % of Australian adults meet the current recommendations for both fruit and vegetable intake, this again highlights the lack of representativeness of cognition-nutrition research volunteers. Since multivitamin use is more common in females and those with healthier lifestyle habits, higher educational attainment, higher socioeconomic status and of lower BMI(Reference Comerford66), it is potentially more likely that those who participate in nutrition research will share similar characteristics. This is supported by evidence from the Monongahela Valley Independent Elders Survey, where those who volunteered to participate were more likely to be women, and had more formal years of education, higher cognitive test scores, higher instrumental activities of daily living ability and lower mortality rates than randomly selected participants(Reference Ganguli, Lytle and Reynolds67). This indicates a further issue with cognitive reserve since those with more years of formal education and who engage in more physical activity are at reduced risk of cognitive decline(Reference Baumgart, Snyder and Carrillo68). Higher cognitive test scores in those who volunteer may also indicate the presence of ceiling effects in study participants, again increasing the likelihood of null findings.

Conclusions

There is growing evidence for an association between fruit and vegetable intake and cognitive function, but this is not always consistent. Some of the differences observed in findings may relate to the populations studied, but also the measures used to assess fruit and vegetable intake – for instance a fruit and vegetable-specific FFQ v. simply asking how many portions of fruit and vegetable are consumed daily, as well as the covariates included in the analyses. Nevertheless, epidemiological support for beneficial effects of fruit and vegetables tends to be stronger than that from RCT. This is not uncommon and is to be expected given the limited information available on dose and duration required to see a measurable effect in RCT. This is further complicated in older populations who may experience issues with absorption of certain micronutrients(Reference Soenen, Rayner and Jones69). Restrictive inclusion/exclusion criteria may also impact findings since those who meet these requirements are likely to be already consuming a healthy diet and may not benefit from additional nutrient intervention. Given the large proportion of older adults who consume a suboptimal diet and who suffer ill health, it is imperative that steps are taken to ensure inclusion in RCT of those most at risk for cognitive decline, who are most likely to receive the greatest benefit. Racial diversity is also lacking in studies of nutrition and cognition, and this is particularly important when considering that race has been shown to modify relationships between cardiovascular factors and cognition(Reference Gottesman, Schneider and Albert11) and between nutrition and cognition(Reference Gu, Guo and Moshfegh70). Sex has also been observed to modify the relationship between nutrition and cognition(Reference Gu, Guo and Moshfegh70), and sex differences in cognition(Reference Herlitz and Rehnman71,Reference Duff and Hampson72) , nutrient requirements(Reference Prentice73) and in pathways by which dietary nutrients and gut microbes modify metabolism and immunity(Reference Israelian and Danska74) all indicate that sex effects should be considered in dietary interventions on cognition, but rarely are. This is particularly important in older adults due to the impact of menopause but also the higher prevalence of dementia in women than men(Reference Cao, Tan and Xu75). Data showing that an increment of 100 g daily of fruit and vegetable consumption is related to approximately 13 % reduction in dementia risk(Reference Jiang, Huang and Song76) highlights the importance of research in this field and the necessity to ensure that those most at risk are included in this research. This review highlights epidemiological evidence for a relationship between fruit and vegetable intake and cognition, which appears to be stronger for vegetables than fruit. However, RCT exploring effects of vegetables on cognition are lacking. Further research is required exploring effects of a range of different fruits and vegetables, including different forms of fruits and vegetables, on cognition, particularly in those at risk for cognitive decline.

Financial Support

This research received no specific grant from any funding agency, commercial or not-for-profit sectors.

Conflict of Interest

None.

Authorship

Both authors contributed to the writing of this manuscript.

References

World Health Organization (2022) Ageing and health. https://wwwwhoint/news-room/fact-sheets/detail/ageing-and-health.Google Scholar
Wittenberg, RHB, Barraza-Araiza, L & Rehill, A (2019) Projections of older people with dementia and costs of dementia care in the United Kingdom, 2019–2040. Care Policy and Evaluation Centre, London School of Economics and Political Science.Google Scholar
Gong, J, Harris, K, Lipnicki, DM et al. (2023) Sex differences in dementia risk and risk factors: individual-participant data analysis using 21 cohorts across six continents from the COSMIC consortium. Alzheimer's Dementia. Epub ahead of print.CrossRefGoogle ScholarPubMed
Cena, H & Calder, PC (2020) Defining a healthy diet: evidence for the role of contemporary dietary patterns in health and disease. Nutrients 12, 334.CrossRefGoogle ScholarPubMed
Murray, CJ, Atkinson, C, Bhalla, K et al. (2013) The state of US health, 1990–2010: burden of diseases, injuries, and risk factors. JAMA 310, 591608.CrossRefGoogle ScholarPubMed
GBD 2017 Diet Collaborators (2019) Health effects of dietary risks in 195 countries, 1990–2017: a systematic analysis for the global burden of disease study 2017. Lancet 393, 19581972.CrossRefGoogle Scholar
Solomon, A, Kåreholt, I, Ngandu, T et al. (2009) Serum total cholesterol, statins and cognition in non-demented elderly. Neurobiol Aging 30, 10061009.CrossRefGoogle ScholarPubMed
Ma, C, Yin, Z, Zhu, P et al. (2017) Blood cholesterol in late-life and cognitive decline: a longitudinal study of the Chinese elderly. Mol Neurodegener 12, 24.CrossRefGoogle ScholarPubMed
Gottesman, RF, Albert, MS, Alonso, A et al. (2017) Associations between midlife vascular risk factors and 25-year incident dementia in the atherosclerosis risk in communities (ARIC) cohort. JAMA Neurol 74, 12461254.CrossRefGoogle ScholarPubMed
Kivipelto, M, Helkala, EL, Laakso, MP et al. (2001) Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study. Br Med J 322, 14471451.CrossRefGoogle ScholarPubMed
Gottesman, RF, Schneider, AL, Albert, M et al. (2014) Midlife hypertension and 20-year cognitive change: the atherosclerosis risk in communities neurocognitive study. JAMA Neurol 71, 12181227.CrossRefGoogle ScholarPubMed
Launer, LJ, Masaki, K, Petrovitch, H et al. (1995) The association between midlife blood pressure levels and late-life cognitive function. The Honolulu-Asia aging study. JAMA 274, 18461851.CrossRefGoogle ScholarPubMed
Gong, J, Harris, K, Peters, SAE et al. (2021) Sex differences in the association between major cardiovascular risk factors in midlife and dementia: a cohort study using data from the UK biobank. BMC Med 19, 110.CrossRefGoogle ScholarPubMed
Tsao, CW, Seshadri, S, Beiser, AS et al. (2013) Relations of arterial stiffness and endothelial function to brain aging in the community. Neurology 81, 984991.CrossRefGoogle ScholarPubMed
Jefferson, AL, Beiser, AS, Himali, JJ et al. (2015) Low cardiac index is associated with incident dementia and Alzheimer disease: the Framingham heart study. Circulation 131, 13331339.CrossRefGoogle ScholarPubMed
Sabayan, B, van Buchem, MA, Sigurdsson, S et al. (2015) Cardiac hemodynamics are linked with structural and functional features of brain aging: the age, gene/environment susceptibility (AGES)-Reykjavik study. J Am Heart Assoc 4, e001294.CrossRefGoogle ScholarPubMed
Bolay, H, Gürsoy-Ozdemir, Y, Sara, Y et al. (2002) Persistent defect in transmitter release and synapsin phosphorylation in cerebral cortex after transient moderate ischemic injury. Stroke 33, 13691375.CrossRefGoogle ScholarPubMed
Sage, JI, Van Uitert, RL & Duffy, TE (1984) Early changes in blood brain barrier permeability to small molecules after transient cerebral ischemia. Stroke 15, 4650.CrossRefGoogle ScholarPubMed
Whitmer, RA, Sidney, S, Selby, J et al. (2005) Midlife cardiovascular risk factors and risk of dementia in late life. Neurology 64, 277281.CrossRefGoogle ScholarPubMed
Hassing, LB, Grant, MD, Hofer, SM et al. (2004) Type 2 diabetes mellitus contributes to cognitive decline in old age: a longitudinal population-based study. J Int Neuropsychol Soc 10, 599607.CrossRefGoogle ScholarPubMed
Van Dyken, P & Lacoste, B (2018) Impact of metabolic syndrome on neuroinflammation and the blood–brain barrier. Front Neurosci 12, 930.CrossRefGoogle ScholarPubMed
Varatharaj, A & Galea, I (2017) The blood–brain barrier in systemic inflammation. Brain Behav Immun 60, 112.CrossRefGoogle ScholarPubMed
Huang, X, Hussain, B & Chang, J (2021) Peripheral inflammation and blood–brain barrier disruption: effects and mechanisms. CNS Neurosci Ther 27, 3647.CrossRefGoogle ScholarPubMed
Soysal, P, Arik, F, Smith, L et al. (2020) Inflammation, frailty and cardiovascular disease. Adv Exp Med Biol 1216, 5564.CrossRefGoogle ScholarPubMed
Ferrucci, L & Fabbri, E (2018) Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol 15, 505522.CrossRefGoogle ScholarPubMed
Cryan, JF, O'Riordan, KJ, Cowan, CSM et al. (2019) The microbiota–gut–brain axis. Physiol Rev 99, 18772013.CrossRefGoogle ScholarPubMed
Simpson, CA, Diaz-Arteche, C, Eliby, D et al. (2021) The gut microbiota in anxiety and depression – a systematic review. Clin Psychol Rev 83, 101943.CrossRefGoogle ScholarPubMed
Molendijk, M, Molero, P, Ortuño Sánchez-Pedreño, F et al. (2018) Diet quality and depression risk: a systematic review and dose-response meta-analysis of prospective studies. J Affect Disord 226, 346354.CrossRefGoogle Scholar
Minihane, AM, Vinoy, S, Russell, WR et al. (2015) Low-grade inflammation, diet composition and health: current research evidence and its translation. Br J Nutr 114, 9991012.CrossRefGoogle ScholarPubMed
Coelho-Júnior, HJ, Trichopoulou, A & Panza, F (2021) Cross-sectional and longitudinal associations between adherence to Mediterranean diet with physical performance and cognitive function in older adults: a systematic review and meta-analysis. Ageing Res Rev 70, 101395.CrossRefGoogle ScholarPubMed
Valls-Pedret, C, Sala-Vila, A, Serra-Mir, M et al. (2015) Mediterranean diet and age-related cognitive decline: a randomized clinical trial. JAMA Intern Med 175, 10941103.CrossRefGoogle ScholarPubMed
Willett, W, Rockström, J, Loken, B et al. (2019) Food in the Anthropocene: the EAT-Lancet Commission on healthy diets from sustainable food systems. Lancet 393, 447492.CrossRefGoogle ScholarPubMed
Dalile, B, Kim, C, Challinor, A et al. (2022) The EAT-Lancet reference diet and cognitive function across the life course. Lancet Planet Health 6, e749ee59.CrossRefGoogle ScholarPubMed
Sabia, S, Nabi, H, Kivimaki, M et al. (2009) Health behaviors from early to late midlife as predictors of cognitive function: the Whitehall II study. Am J Epidemiol 170, 428437.CrossRefGoogle ScholarPubMed
Péneau, S, Galan, P, Jeandel, C et al. (2011) Fruit and vegetable intake and cognitive function in the SU.VI.MAX 2 prospective study. Am J Clin Nutr 94, 12951303.CrossRefGoogle ScholarPubMed
Babateen, AM, Shannon, OM, O'Brien, GM et al. (2022) Incremental doses of nitrate-rich beetroot juice do not modify cognitive function and cerebral blood flow in overweight and obese older adults: a 13-week pilot randomised clinical trial. Nutrients 14, 1052.CrossRefGoogle Scholar
Yuan, C, Fondell, E, Bhushan, A et al. (2019) Long-term intake of vegetables and fruits and subjective cognitive function in US men. Neurology 92, e63e75.CrossRefGoogle ScholarPubMed
Nurk, E, Refsum, H, Drevon, CA et al. (2010) Cognitive performance among the elderly in relation to the intake of plant foods. The Hordaland health study. Br J Nutr 104, 11901201.CrossRefGoogle Scholar
Ye, X, Bhupathiraju, SN & Tucker, KL (2013) Variety in fruit and vegetable intake and cognitive function in middle-aged and older Puerto Rican adults. Br J Nutr 109, 503510.CrossRefGoogle ScholarPubMed
Nooyens, AC, Bueno-de-Mesquita, HB, van Boxtel, MP et al. (2011) Fruit and vegetable intake and cognitive decline in middle-aged men and women: the Doetinchem cohort study. Br J Nutr 106, 752761.CrossRefGoogle ScholarPubMed
Kang, JH, Ascherio, A & Grodstein, F (2005) Fruit and vegetable consumption and cognitive decline in aging women. Ann Neurol 57, 713720.CrossRefGoogle ScholarPubMed
Morris, MC, Evans, DA, Tangney, CC et al. (2006) Associations of vegetable and fruit consumption with age-related cognitive change. Neurology 67, 13701376.CrossRefGoogle ScholarPubMed
Morris, MC, Wang, Y, Barnes, LL et al. (2018) Nutrients and bioactives in green leafy vegetables and cognitive decline: prospective study. Neurology 90, e214ee22.CrossRefGoogle ScholarPubMed
Devore, EE, Kang, JH, Breteler, MM et al. (2012) Dietary intakes of berries and flavonoids in relation to cognitive decline. Ann Neurol 72, 135143.CrossRefGoogle ScholarPubMed
Cheng, FW, Ford, NA & Taylor, MK (2021) US older adults that consume avocado or guacamole have better cognition than non-consumers: national health and nutrition examination survey 2011–2014. Front Nutr 8, 746453.CrossRefGoogle ScholarPubMed
O'Brien, J, Okereke, O, Devore, E et al. (2014) Long-term intake of nuts in relation to cognitive function in older women. J Nutr Health Aging 18, 496502.CrossRefGoogle ScholarPubMed
Nicodemus-Johnson, J & Sinnott, RA (2017) Fruit and juice epigenetic signatures are associated with independent immunoregulatory pathways. Nutrients 9, 752.CrossRefGoogle ScholarPubMed
Butchart, C, Kyle, J, McNeill, G et al. (2011) Flavonoid intake in relation to cognitive function in later life in the Lothian birth cohort 1936. Br J Nutr 106, 141148.CrossRefGoogle ScholarPubMed
Kean, RJ, Lamport, DJ, Dodd, GF et al. (2015) Chronic consumption of flavanone-rich orange juice is associated with cognitive benefits: an 8-wk, randomized, double-blind, placebo-controlled trial in healthy older adults. Am J Clin Nutr 101, 506514.CrossRefGoogle ScholarPubMed
Chai, SC, Jerusik, J, Davis, K et al. (2019) Effect of Montmorency tart cherry juice on cognitive performance in older adults: a randomized controlled trial. Food Funct 10, 44234431.CrossRefGoogle ScholarPubMed
Miller, MG, Hamilton, DA, Joseph, JA et al. (2018) Dietary blueberry improves cognition among older adults in a randomized, double-blind, placebo-controlled trial. Eur J Nutr 57, 11691180.CrossRefGoogle Scholar
Whyte, AR, Cheng, N, Fromentin, E et al. (2018) A randomized, double-blinded, placebo-controlled study to compare the safety and efficacy of low dose enhanced wild blueberry powder and wild blueberry extract (ThinkBlue™) in maintenance of episodic and working memory in older adults. Nutrients 10, 660.CrossRefGoogle ScholarPubMed
Flanagan, E, Cameron, D, Sobhan, R et al. (2022) Chronic consumption of cranberries (Vaccinium macrocarpon) for 12 weeks improves episodic memory and regional brain perfusion in healthy older adults: a randomised, placebo-controlled, parallel-groups feasibility study. Front Nutr 9, 849902.CrossRefGoogle ScholarPubMed
Crews, WD Jr, Harrison, DW, Griffin, ML et al. (2005) A double-blinded, placebo-controlled, randomized trial of the neuropsychologic efficacy of cranberry juice in a sample of cognitively intact older adults: pilot study findings. J Altern Complement Med 11, 305309.CrossRefGoogle Scholar
Mastroiacovo, D, Kwik-Uribe, C, Grassi, D et al. (2015) Cocoa flavanol consumption improves cognitive function, blood pressure control, and metabolic profile in elderly subjects: the cocoa, cognition, and aging (CoCoA) study – a randomized controlled trial. Am J Clin Nutr 101, 538548.CrossRefGoogle ScholarPubMed
Brickman, AM, Khan, UA, Provenzano, FA et al. (2014) Enhancing dentate gyrus function with dietary flavanols improves cognition in older adults. Nat Neurosci 17, 17981803.CrossRefGoogle ScholarPubMed
Neshatdoust, S, Saunders, C, Castle, SM et al. (2016) High-flavonoid intake induces cognitive improvements linked to changes in serum brain-derived neurotrophic factor: two randomised, controlled trials. Nutr Healthy Aging 4, 8193.CrossRefGoogle ScholarPubMed
Sala-Vila, A, Valls-Pedret, C, Rajaram, S et al. (2020) Effect of a 2-year diet intervention with walnuts on cognitive decline. The walnuts and healthy aging (WAHA) study: a randomized controlled trial. Am J Clin Nutr 111, 590600.CrossRefGoogle ScholarPubMed
Coates, AM, Morgillo, S, Yandell, C et al. (2020) Effect of a 12-week almond-enriched diet on biomarkers of cognitive performance, mood, and cardiometabolic health in older overweight adults. Nutrients 12, 1180.CrossRefGoogle ScholarPubMed
Barbour, JA, Howe, PRC, Buckley, JD et al. (2017) Cerebrovascular and cognitive benefits of high-oleic peanut consumption in healthy overweight middle-aged adults. Nutr Neurosci 20, 555562.CrossRefGoogle ScholarPubMed
Morris, MC & Tangney, CC (2011) A potential design flaw of randomized trials of vitamin supplements. JAMA 305, 13481349.CrossRefGoogle ScholarPubMed
Morris, MC (2012) Nutritional determinants of cognitive aging and dementia. Proc Nutr Soc 71(1), 113.CrossRefGoogle ScholarPubMed
Young, LM, Gauci, S, Scholey, A et al. (2020) Self-selection bias: an essential design consideration for nutrition trials in healthy populations. Front Nutr 7, 587983.CrossRefGoogle ScholarPubMed
Comerford, KB (2013) Recent developments in multivitamin/mineral research. Adv Nutr 4, 644656.CrossRefGoogle ScholarPubMed
Ganguli, M, Lytle, ME, Reynolds, MD et al. (1998) Random versus volunteer selection for a community-based study. J Gerontol A Biol Sci Med Sci 53, M39M46.CrossRefGoogle ScholarPubMed
Baumgart, M, Snyder, HM, Carrillo, MC et al. (2015) Summary of the evidence on modifiable risk factors for cognitive decline and dementia: a population-based perspective. Alzheimer's Dementia 11, 718726.CrossRefGoogle ScholarPubMed
Soenen, S, Rayner, CK, Jones, KL et al. (2016) The ageing gastrointestinal tract. Curr Opin Clin Nutr Metab Care 19, 1218.CrossRefGoogle ScholarPubMed
Gu, Y, Guo, J & Moshfegh, AJ (2021) Race/ethnicity and gender modify the association between diet and cognition in U.S. older adults: national health and nutrition examination survey 2011–2014. Alzheimer's Dementia 7, e12128.CrossRefGoogle Scholar
Herlitz, A & Rehnman, J (2008) Sex differences in episodic memory. Curr Dir Psychol Sci 17, 5256.CrossRefGoogle Scholar
Duff, SJ & Hampson, E (2001) A sex difference on a novel spatial working memory task in humans. Brain Cogn 47, 470493.CrossRefGoogle ScholarPubMed
Prentice, A (2021) Sex differences in requirements for micronutrients across the lifecourse. Proc Nutr Soc 80, 356364.CrossRefGoogle ScholarPubMed
Israelian, N & Danska, JS (2017) Sex effects at the ramparts: nutrient- and microbe-mediated regulation of the immune-metabolic interface. Adv Exp Med Biol 1043, 113140.CrossRefGoogle ScholarPubMed
Cao, Q, Tan, CC, Xu, W et al. (2020) The prevalence of dementia: a systematic review and meta-analysis. J Alzheimer's Dis 73, 11571166.CrossRefGoogle ScholarPubMed
Jiang, X, Huang, J, Song, D et al. (2017) Increased consumption of fruit and vegetables is related to a reduced risk of cognitive impairment and dementia: meta-analysis. Front Aging Neurosci 9, 18.CrossRefGoogle Scholar
Figure 0

Table 1. Summary and evaluation of key cognitive domains

Figure 1

Table 2. Randomised controlled trials of fruit and vegetable juices and extracts