Edited by:
Reviewed by:
*Correspondence:
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Cognitive impairment is an important public health concern, with a prevalence that is expected to rise with the population aging. It is a transitional stage between normal aging and dementia. Interventions may be particularly effective at earlier stages of disease development, which offer an opportunity for reducing the public health burden of Alzheimer’s disease (AD) and other dementias through early detection and prevention (
A number of epidemiologic researches and animal models have found associations between dietary components and age-related cognitive impairment and dementia (
We followed the guidelines published by the Meta-analysis of Observational Studies in Epidemiology (MOOSE) group to complete the meta-analysis (Supplementary Table
A study was eligible for inclusion if the following criteria were met: (1) examination of dietary consumption of fruit and/or vegetables as the variable of interest; (2) determination of incidence of cognitive impairment or dementia as the outcome of interest; and (3) reporting the relative risks of cognitive impairment or dementia calculated according to the highest category with the lowest category of fruit and/or vegetables consumption, and their 95% confidence intervals (CIs). The studies about animal experiment, mechanistic research, and review research were excluded.
Two researchers independently extracted the following data from each publication: author, country, study design, sample size, disease type (cognitive impairment or dementia), number of cases, age, disease ascertainment, exposure variable (fruit, vegetable, or fruit and vegetable), exposure assessment, risk estimates with CIs, and factors adjusted for. The most adjusted estimate was included when a study reported more than one risk estimate. The quality of each study was assessed by two researchers, using the Newcastle-Ottawa Scale recommended by
We performed meta-analyses of risk estimates for cognitive impairment and dementia comparing the highest category of exposure of fruit and vegetables with the lowest category. We pooled the data on cognitive impairment and dementia together, since there were limited studies on each single disease. Dose–response meta-analyses of fruit and vegetable consumption and risk of cognitive impairment and dementia were then conducted using methods previously reported (
We used a fixed effects model to estimate the pooled ORs and 95% CI if there was no evidence of heterogeneity; otherwise, a random effect model was used. The
Of the 359 citations identified from database searches, nine articles met the inclusion criteria and were included in the meta-analysis, including five cohort studies (
Characteristics of included studies in the systematic review and meta-analysis.
Study | Country | Study design | Sample size | Follow-up duration (years) | Disease type, number of cases | Age (years), mean/range | Disease ascertainment | Exposure variable | Exposure assessment | Factors adjusted for |
---|---|---|---|---|---|---|---|---|---|---|
France | Cohort | 8,085 | 3.5 | Dementia, 281 | NR/≥65 | Neurological exam, DSM-IV, and NINCDS-ADRDA | F+V | FFQ | Age, gender, education, city, income, marital status, ApoE genotype, BMI, and diabetes | |
Hong Kong, China | Cross-sectional | 3,670 | – | Cognitive impairment, 877 | 72.4/≥65 | CSI-D | F+V | FFQ | Age, BMI, PASE, energy intake, educational level, Hong Kong ladder, community ladder, smoking status, alcohol use, No. of ADLs, GDS category, self-reported history of DM, hypertension, and CVD/stroke | |
China | Cohort | 5,691 | NR | Cognitive impairment, 1,306 | 82.9/≥65 | MMSE | Fruit | Interviewer-administrated questionnaire | None | |
Vegetable | Age, gender, marital status, financial status, residential area, BMI, hypertension, diabetes, smoking, alcohol, tea drinking, and exercise habits | |||||||||
Sweden | Cohort | 3,779 | 31.5 | Dementia, 335 | 48.3/42–71 | DSM-IV and NINCDS-ADRDA | F+V | The Swedish Twin Registry 1967 questionnaire | Age at cognitive screening, gender, education, smoking, alcohol drinking, angina pectoris, BMI, total food compared to others, marital status, and exercise | |
Hong Kong, China | Cross-sectional | 285 | – | Dementia, 146 | 70.5/≥60 | DSM-IV and CDR | F+V | Mini-Nutritional Assessment (Chinese version) | Age, sex, and education | |
France | Cohort | 1,433 | 7.3 | Mild cognitive impairment or dementia, 405 | 72.5/≥65 | Standardized interview incorporating cognitive testing | F+V | Nutritional questionnaires | Age and sex | |
United States | Cross-sectional | 1,233 | – | Mild cognitive impairment, 163 | NR/70–89 | CDR, the Short Test of Mental Status, the Hachinski Scale, and neurological examination. | Fruit and vegetable | Modified Block 1995 Revision of the Health Habits and History Questionnaire | Age, years of education, total energy, sex, ApoE 𝜀4, stroke, coronary heart disease, and depressive symptoms | |
France | Cohort | 4,809 | 13.0 | Recent cognitive impairment, 598 | NR/76-82 | Observed Cognitive Deterioration Scale | Fruit and vegetable | Diet history questionnaire | Age, education level, BMI, physical activity, daily energy intake, smoking, supplement of vitamin D and/or Ca, supplement of other vitamins or minerals, use of postmenopausal hormones, history of depression, history of cancer, history of CHD, history of stroke, history of diabetes mellitus, history of hypertension, and history of hypercholesterolaemia | |
Taiwan, China | Cross-sectional | 2,119 | – | Cognitive impairment, 472 | 73.3/≥65 | MMSE | F+V | Questionnaire for lifestyle | Age, gender, educational level, marital status, social support, hyperlipidemia, stroke, physical function, depressive symptoms, self-rated health, cigarette smoking, leisure-time physical activity, coffee intake, tea intake, multivitamin intake, and BMI. |
Subgroup analysis for studies included in the analysis.
Subgroup analysis | Pooled OR (95% CI), |
|
---|---|---|
Risk estimates of cognitive impairment and dementia | ||
≥65 years | 12 | 0.80 (0.71–0.91); |
< years | 3 | 0.79 (0.51–1.21); |
Female | 4 | 0.82 (0.64–1.06); |
Male | 2 | 1.18 (0.85–1.63); |
Combined | 9 | 0.71 (0.66–0.78); |
Europe | 7 | 0.84 (0.70–0.99); |
United States | 2 | 0.78 (0.58–1.04); |
China | 6 | 0.71 (0.64–0.78); |
Cohort | 9 | 0.80 (0.69–0.92); |
Cross-sectional | 6 | 0.80 (0.67–0.95); |
Full marks | 7 | 0.91 (0.81–1.02); |
Not full marks | 8 | 0.71 (0.65–0.77); |
Cognitive impairment | 10 | 0.82 (0.72–0.93); |
Dementia | 5 | 0.73 (0.54–0.83); |
FFQ | 3 | 0.79 (0.65–0.96); |
Others | 12 | 0.79 (0.69–0.91); |
Only four estimates from three individual studies were included in the dose–response meta-analysis, because there were only two categories of fruit and vegetable consumption in other studies, and dose–response meta-analysis requires data for the distribution of cases and person-time across at least three categories of exposure (
Visual assessment of funnel plots (
We have quantitatively assessed the relation between fruit and vegetable consumption and risk of cognitive impairment and dementia through a meta-analysis of existing epidemiological studies. Evidence from the literature is mixed. Some studies indicate that fruit and vegetable intake has a protective effect on global cognitive performance (
Our findings extend the results of a previous systematic review (
Epidemiological and animal investigations support the protective effect of fruit and vegetables against cognitive impairment and dementia. The brain is extremely susceptible to oxidative damage (
In subgroup analyses, we found that there was a statistically significant inverse association between fruit and vegetable consumption and cognitive impairment and dementia risk in participants with mean age over 65 years, but not in those with mean age less than 65 years. This may be because that the incidence of cognitive impairment and dementia increases sharply with the age grows. Thus, the protective effects of fruit and vegetables against cognitive impairment and dementia are more prominent among the older populations. Notably, the null inverse association in younger participants might also result from the limited number of included studies. More studies are warranted to investigate the potential difference between the different age groups. In the subgroup analysis of geographic location, we found the pooled OR for China was much smaller than that for Europe and the United States (0.71 with 95% CI 0.64–0.78, 0.84 with 95% CI 0.64–0.78, and 0.78 with 95% CI 0.58–1.04 for China, Europe, and the United States, respectively). This means that the protective effects of fruit and vegetables against cognitive impairment and dementia are stronger for Chinese populations than the Western populations. This may be explained by the different dietary patterns and food preparation methods between Chinese and Western populations. Firstly, the proportion of saturated fat-rich food is higher in the Western dietary pattern, which may increase the risk of cognitive impairment and dementia as discussed above. Secondly, in Western world, people mainly eat raw vegetables, such as in the form of salad, while the Chinese populations often eat cooked, steamed, or boiled vegetables. Usually, people tend to eat more vegetables after being cooked, and the cooked vegetables can be more easily digested because the cell wall of raw vegetables is relatively harder, which will increase the burden of digestion. In addition, studies show that the nutritional quality increases in all cooked vegetables because of matrix softening and increased extractability of compounds, which could be partially converted into more antioxidant chemical species (
The strengths of the present meta-analysis include the considerable number of studies and subjects included, as well as the acceptable methodologic quality of the studies on which the analysis is based. The study has several limitations. Firstly, a substantial heterogeneity across studies was apparent in the meta-analysis. The heterogeneity was not accounted by age, sex, geographic location, study design, disease type, and dietary assessment method. However, the subgroup analysis for study quality score reduced the heterogeneity, which means the study quality is a main source of heterogeneity. Secondly, the assessment for fruit and vegetable consumption is mostly based on self-reported habits, and such data are subject to recall errors. In addition, there were many other differences among studies, including dietary assessment methods, the variety of fruit or vegetables investigated, the definition of the reference group, and the choice of exposure categories. These differences could affect the estimation of the true relation. Thirdly, the meta-analysis is based on observational studies, which leaves the possibility that potential confounders cannot be ruled out, affect the relation between fruit and vegetable consumption and risk of cognitive impairment and dementia. A meta-analysis is not able to solve problems with confounding that may be inherent in the included studies. However, most studies have made adjustment of major confounding factors, which should reduce the potential bias due to the dietary and lifestyle factors. Finally, due to the limited studies, we combined consumption of fruit and vegetable together as the exposure variable and cognitive impairment and dementia together as the outcome. The effects of fruit and vegetable separately on cognitive impairment or dementia should be further investigated in future studies.
This meta-analysis indicates significant inverse association between fruit and vegetable consumption and risk of cognitive impairment and dementia. The risk of cognitive impairment and dementia was reduced by 20% for a higher consumption of fruit and vegetables, and by 13% for an increment of 100 g per day of fruit and vegetable consumption. For further studies, based on our findings, we suggest that the investigators should improve the standardization of various dietary assessment methods, which may make the results more accurate and conceivable. Furthermore, the use of genetic and biological makers as surrogate end points in the future studies should help to clarify the cause and effect relationship that link fruit and vegetable consumption and cognitive impairment and dementia.
ZZ designed the study. JH, DS, and RD collected the data. XJ performed all analyses. XJ, JH, JW, and ZZ wrote the manuscript. All authors contributed to writing of this manuscript.
The 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.
This study is supported by Education Department of Sichuan Province (13ZB0267), projects by Luzhou Municipal Science and Technology Bureau & Luzhou Medical College (14JC0181 and 2013LZLY-J52), and Science and Technology Department of Sichuan Province (2014SZ0071).
The Supplementary Material for this article can be found online at: