In our cross-sectional findings, higher daily intake of vegetables, (MUFA + PUFA):SFA ratio, and moderate alcohol consumption were associated with a decreased OR of MCI and a-MCI (but not na-MCI). The OR of MCI decreased with higher intake of fruit and increasing MeDi score, but the trends were not statistically significant. The longitudinal findings showed a 25% reduced risk of MCI or dementia in subjects in the upper tertile of the MeDi score at baseline, but the association did not reach statistical significance.
Our findings are consistent with those of other investigators. High vegetable intake was associated with a slower rate of cognitive decline in the Chicago Health and Aging Project [32
]; high intake of β-carotene, flavonoids, vitamins C and E, thiamine, and folate from dietary fruit and vegetables was associated with a lower risk of AD in the Rotterdam Study [33
] and with better Mini-Mental State Exam (MMSE) scores [34
]. Moderate alcohol intake has also been associated with a reduced incidence of dementia [35
], a decreased OR of MCI [37
], reduced progression of MCI to dementia [37
], a lower risk of poor cognitive function [39
], and higher MMSE scores [34
]. The effects of fruits and vegetables, PUFA, MUFA, and moderate alcohol intake have been attributed to beneficial antioxidant effects on cerebrovascular disease risk and amyloid pathology. The adverse association of high caloric intake with MCI has also been observed with AD [40
]. The association of dietary factors with MCI subtypes has not been evaluated. Our observation of associations of higher intake of vegetables and of higher MUFA:SFA and (MUFA + PUFA):SFA ratios with a-MCI is interesting and raises questions about the role of dietary factors in the pathogenesis of MCI and AD. However, given the cross-sectional design, the implications and relevance are not clear. We will examine these associations further in our longitudinal study of the cohort when we have a larger number of events and longer duration of follow-up.
Our preliminary longitudinal studies suggest that a high MeDi score is beneficial even in our cohort, but we may have had inadequate power to detect significant associations, possibly due to a low adherence to the MeDi. Lower adherence in our cohort is suggested by the comparison of our sample with 2 Mediterranean [8
] and 2 US samples [9
] where a significant association of MeDi score with cognition has been observed (table ). Overall, daily intake of vegetables, fruit, and fish was lower, and red meat intake was higher than in 1 of the US samples. The MUFA:SFA ratio was low compared to 1 Greek sample, 1 US sample, and was also lower than a ratio of 2 for participants in the Italian Longitudinal Study of Aging [11
Distribution of components of the MeDi in the current study and other studies
Low adherence to MeDi in a community may limit the ability to detect a significant dose-response association of the MeDi score with cognition. Since the median intakes in a sample are used to determine the cutpoints for computing the MeDi score, a score in 1 community may not reflect intakes in a community with very different dietary habits [11
]. Other cultural differences in the foods may also affect studies involving the MeDi score. For example, availability of fruits and vegetables year-round is different in Mediterranean regions than in a Midwestern US community.
Relatively few investigators have used the whole diet approach such as the MeDi to assess the impact of diet on cognitive function. In these studies, higher adherence to a MeDi was associated with decreasing cognitive decline assessed from the MMSE [31
], with prevalent AD [43
], a reduced risk of AD and slower cognitive decline [9
], and a reduced risk of AD mortality [44
], and with a borderline reduced risk of MCI incidence and MCI conversion to dementia [10
]. It is evident that different measures of cognition were used, and MCI criteria were retrospectively applied in some cases. However, the widespread health benefits of the MeDi are well noted. These include beneficial effects on survival [8
], cardiovascular risk factors and outcomes [5
], cancer [45
], and inflammation [46
]. Nonetheless, additional longitudinal studies are needed to confirm the associations with MCI in a population-based setting using reliable and valid ascertainment of both dietary exposure and MCI using specified criteria for MCI at the time of evaluation as in the present study. A longer duration of follow-up in our cohort may demonstrate significant associations.
Potential limitations of our findings include the possibility of recall bias in this elderly cohort, and our failure to validate the questionnaire in our cohort. Any effect of recall bias is likely to be minimal, and reporting of dietary intake is likely to be valid for the following reasons: (a) we excluded subjects with dementia who are unlikely to report valid dietary intake; (b) participants did not know about their cognitive status, reducing the potential for biased reporting; (c) MCI cases were very mild, with a median CDR sum of boxes of only 1.0 (interquartile range = 0.5–1.5), and (d) the results remained the same after excluding subjects in the lowest 5% of the memory domain score who could have provided unreliable data (data not presented). Also, others have observed that assessment of dietary intake over a longer period (prior 1 year) may be less susceptible to bias than short-term recall [47
]. The modest differences between included and excluded subjects raises the question of potential nonparticipation bias. We addressed this by assigning included subjects who had the characteristics of the excluded subjects a heavier weight in all the logistic models to account for the propensity to participate in the study. The results were similar to those that were not adjusted for propensity to participate. The cross-sectional study design prevents our ability to assess causal associations. Given the number of tests assessed in the study, there is a potential for type 2 errors; a Bonferroni correction would require a p value of ≤0.004 for statistical significance. At this p value, the associations between the upper tertile of the (MUFA + PUFA):SFA ratio and total energy intake would remain statistically significant, but the other associations would no longer be significant. The preliminary longitudinal data based on the small number of incident events suggest a benefit of a higher MeDi score for MCI or dementia. Longitudinal follow-up of the sample will enable us to obtain more reliable estimates and will increase our power to detect significant associations. The findings may be generalizable to communities with similar demographic characteristics.
Our study has several strengths. The study sample was randomly selected from the community, thus reducing the potential for referral, selection, or volunteer bias. We used a previously validated questionnaire to ascertain dietary intake of foods. In addition to a whole-diet approach, we also assessed the association of individual components of the MeDi with MCI, and with MCI subtypes, and observed differences across the subtypes. The assessment of MCI was made using information from 3 independent evaluators, and the diagnosis of MCI or normal cognition was made by consensus, at the time of the evaluation, and was based on previously specified criteria. Our findings provide insight into the dietary habits of a Midwestern US community, and suggest that in this elderly cohort, adherence to a MeDi may be low. Despite this, we demonstrated beneficial associations of certain dietary components with MCI, and our preliminary longitudinal studies suggest that a high MeDi score may be beneficial. Thus, findings from our study and other studies provide insights into the role of the MeDi and components of this diet as a potential target for intervention in clinical trials to prevent MCI, and ultimately reduce the burden of dementia.