Abstract
Background/Aims
Various foods have been shown to be associated with cognitive outcomes. As individual food items are not consumed in isolation, we examined the association between dietary patternsand cognitive function, with special attention to the role of education in this association.
Methods
Analyses were carried out on 4,693 stroke-free white European participants of the Whitehall II study. Two dietary patterns were determined using principal component analysis: a ‘whole food’ and a ‘processed food’ pattern. Cognitive function was assessed using a battery of 5 tests.
Results
After adjustment for demographic, behavioral and health measures, higher intake of ‘whole food’ diet was associated with lower and high consumption of ‘processed food’ with higher odds of cognitive deficit. However, adjustment for education significantly attenuated most of these associations.
Conclusions
Education, through its role as a powerful confounder, shapes the relationship between dietary patterns and cognitive deficit in a healthy middle-aged UK cohort.
Key Words: Nutrition, Cognitive functions, Population-based study, Education
Introduction
Cognitive impairment and dementia are among the most prevalent of the aging-related pathologies and the world faces an increase in both the number of elderly people and lifespan at the oldest ages [1]. The association between nutrition and cognition has increasingly been investigated in the last decade [2, 3]. Studies on single nutrients or foods associated with cognition constitute the large majority of the literature [3], while studies that examine the associations with dietary patterns are limited [3, 4].
A number of factors, sociodemographic, health behaviors and chronic diseases, are associated both with nutrition and cognition [5], making it important to consider them as potential confounders in the analysis of the association between nutrition and cognition. The role of education may be important as it has been shown to shape food choices [6, 7]. Further, there is extensive evidence to suggest that high education might delay or protect from cognitive impairment [8,9,10,11]. As the onset of dementia is insidious with the underlying pathologies believed to be active many years before clinical expression, it is important to examine risk factors for cognitive deficit and decline earlier than in elderly populations. The objective of this study was to examine the association between nutrition typologies, rather than ‘single nutrients’, and cognition in a middle-aged population. A further objective was to investigate the influence of sociodemographic factors, health behaviors and health measures on this association, with special attention to the role of education.
Subjects and Methods
Study Population
The target population for the Whitehall II study was all London-based office staff, aged 35–55 years, working in 20 civil service departments. The cohort consisted of 10,308 participants at the first phase in 1985 [12]. A total of 6,767 participants completed the phase 7 medical examination (2002–2004). Analyses in this study were restricted to the 4,693 white European participants with data on cognitive function, dietary assessments and all covariates at phase 7. Black (n = 93) and Asian (n = 197) participants were excluded due to differences in eating behavior. We also excluded participants with self-reported stroke or transient ischemic attack (n = 120).
After complete description of the study to the subjects, written informed consent was obtained. The University College London ethics committee approved the study.
Dietary Assessment
A machine-readable Food Frequency Questionnaire (FFQ) [13] based on one used in the US Nurses Health study [14] was sent to the participants. The food list (127 items) in the FFQ was anglicized, and foods commonly eaten in the UK were added [15]. A common unit or portion size for each food was specified, and participants were asked how often, on average, they had consumed that amount of the item during the previous year. Response to all items was on a 9-point scale, ranging from ‘never or less than once per month’ to ‘six or more times per day’. The selected frequency category for each food item was converted to a daily intake.
According to the nutrient profile and culinary use of food items, the 127 items of the FFQ were grouped in 37 predefined food groups (by adding food items within each group; Appendix 1). Dietary patterns were identified using principal component analysis of these 37 groups. The factors were rotated by an orthogonal transformation (varimax rotation function in SAS; SAS Institute, Cary, N.C., USA) to achieve a simple structure, allowing greater interpretability. Two dietary patterns were identified using multiple criteria: the diagram of eigenvalues, the scree plot, the interpretability of the factors and the percentage of variance explained by the factors (table 1). The factor score for each pattern was calculated by summing intakes of all food groups weighted by their factor loadings. Factor loadings represent correlation coefficients between the food groups and particular patterns. The first pattern was heavily loaded by high intake of vegetables, fruits, dried legume and fish, labeled the ‘whole food’ pattern. The second pattern, labeled ‘processed food’, was heavily loaded by high consumption of sweetened desserts, chocolates, fried food, processed meat, pies, refined grains, high-fat dairy products, margarine and condiments. Each participant received a factor score for each identified pattern. Factor analysis does not group individuals into clusters; instead, all individuals contribute to both factors and it is the homogeneity between food items that defines the factors. To assess the validity of the dietary patterns resulting from this a posteriori food grouping, we performed the principal component analyses using the 127 individual food items, and the results obtained were similar.
Table 1.
‘Whole food' pattern | ‘Processed food’ pattern | |
---|---|---|
Leafy vegetables | 0.68 | – |
Other vegetables | 0.67 | – |
Cruciferous vegetables | 0.57 | – |
Tomatoes | 0.55 | – |
Fruits | 0.53 | – |
Fish | 0.46 | – |
Salad dressing | 0.43 | – |
Peas and dried legume | 0.42 | – |
Desserts/biscuits | – | 0.55 |
Chocolate and sweets | – | 0.50 |
Fried food | – | 0.49 |
Processed meats | – | 0.46 |
Quiche/pie | – | 0.45 |
Margarine | – | 0.44 |
Refined grain | – | 0.41 |
High-fat dairy products | – | 0.41 |
Condiments | – | 0.41 |
The two dietary patterns were identified using principal component analysis. Factor loadings issued from orthogonal rotation represent the correlation between the factors and individual items from the food group.
The factor score for each pattern was calculated by summing intakes of the 37 predefined food groups (see Appendix 1) weighted by their factor loadings. In order to simplify interpretation of the two patterns, values <0.40 were not listed in the table.
Cognitive Function
The cognitive test battery [16] consisted of 5 standard tasks chosen to comprehensively evaluate cognitive functioning in white-collar middle-aged adults, ensuring that the tests did not create problems with ceiling effects. High scores on all tests denote better performance. The first was a 20-word free-recall test of short-term verbal memory. Participants were presented with a list of 20 one- or two-syllable words at 2-second intervals and were then asked to recall in writing as many of the words as they could, in any order; they had 2 min to do so. Next was the AH4-I[17], composed of a series of 65 verbal and mathematical reasoning items of increasing difficulty. This test of inductive reasoning measures the ability to identify patterns and infer principles and rules. Participants had 10 min to complete this section. This was followed by the Mill Hill Vocabulary Test[18] that assesses knowledge of verbal meaning and encompasses the ability to recognize and comprehend words. We used this test in its multiple format, which consists of a list of 33 stimulus words ordered by increasing difficulty and 6 response choices. Finally, we used two measures of verbal fluency: phonemic and semantic [19]. Phonemic fluency was assessed via ‘s’ words and semantic fluency via ‘animal’ words. Subjects were asked to recall in writing as many words beginning with ‘s’ and as many animal names as they could. One minute was allowed for each test of fluency. Test-retest reliability of these measures was estimated from a reexamination on a subsample of 556 participants who returned for a medical examination within a month of their original screening. These estimates for the various tests are as follows: r = 0.58 for the short-term verbal memory, r = 0.87 for the AH4-I, r = 0.85 for the Mill Hill Vocabulary Test, r = 0.68 for the phonemic fluency and r = 0.71 for the semantic fluency test.
Covariates
Sociodemographic variables consisted of age, gender, marital status (married or cohabited, single, divorced, widowed) and education, regrouped into 5 levels (no formal education, lower secondary education, higher secondary education, university degree, higher university degree). Health behaviors measured were smoking habits (nonsmoker, former, current smoker) and physical activity, converted into MET scores [20] and categorized as ‘mildly energetic’ (MET values below 3), ‘moderately energetic’ (MET values ranging from 3 to 6) and ‘vigorous’ (MET values of 6 or above) physical activity. Health status was ascertained by prevalence of coronary heart disease (CHD), based on clinically verified events and included nonfatal myocardial infarction and definite angina as described previously [21], diabetes (diagnosed according to WHO definition), hypertension (systolic/diastolic blood pressure ≥140/90 mm Hg or use of hypertensive drugs), dyslipidemia (low-density lipoprotein cholesterol ≥4.1 mmol/l or use of lipid-lowering drugs), BMI and mental health (using the 30-item General Health Questionnaire) [22].
Statistical Analysis
Cognitive deficit was defined as performances in the worst sex-specific quintile. Among men (women), this corresponded to scores ≤5 (5) for memory, ≤39 (31) for reasoning, ≤24 (21) for vocabulary, and ≤13 (12) for phonemic and semantic fluency. Logistic regression was used to model the association between the tertiles on the two factors representing the two dietary patterns and cognitive deficit. In the first model (M1), the analyses were adjusted for sex, age and energy intake. In the fully adjusted model (M2), the analyses were further adjusted for marital status, health behaviors and health measures. All the analyses were carried out first without and then after adjustment for education. Interaction between dietary patterns and education was also tested, and analyses of the association between dietary patterns and cognition stratified by education (by grouping no formal education and lower secondary education together and levels above higher secondary education) were performed. All analyses were conducted with the use of SAS software, version 9 (SAS Institute).
Results
Compared to the 6,767 stroke-free participants still alive at phase 7, participants included in the analyses (n = 4,693) were less likely to be women (26.2 vs. 39.2%) or to have no academic qualifications or lower secondary education (30.7 vs. 45.0%).
Sample characteristics as a function of the tertiles of the two dietary patterns, ‘whole food’ and ‘processed food’, are shown in table 2. Tables 3 and 4 show the association between the tertiles of the ‘whole food’ (table 3) and ‘processed food’ (table 4) dietary patterns and cognitive deficit, defined as performance in the worst quintile for each cognitive test. In analyses unadjusted for education, being in the highest tertile of the ‘whole food’ dietary pattern was associated with lower odds of deficit on all cognitive tests (table 3). On the other hand, participants with high intake of ‘processed food’ compared to those with a low intake had higher odds of cognitive deficit for reasoning (odds ratio, OR = 1.55; 95% confidence interval, CI = 1.21–1.98), vocabulary (OR = 2.36; 95% CI = 1.84–3.04), phonemic (OR = 1.70; 95% CI = 1.33–2.19) and semantic fluency (OR = 1.58; 95% CI = 1.25–2.01), but not for memory (OR = 1.26; 95% CI = 0.95–1.67) in analyses adjusted for marital status, health behaviors and health status (M2, table 4). However, adjustment for education attenuated all associations. The lower odds of cognitive deficit associated with higher intake of ‘whole food’ only remained significant for vocabulary (OR = 0.75; 95% CI = 0.60–0.92) and semantic fluency (OR = 0.72; 95% CI = 0.59–0.88) (table 3). Similarly, the higher odds of cognitive deficit associated with greater intake of ‘processed food’ remained significant for vocabulary (OR = 1.63; 95% CI = 1.25–2.13) and phonemic fluency (OR = 1.34; 95% CI = 1.04–1.74) (table 4).
Table 2.
‘Whole food’ ‘dietary pattern |
‘Processed food’ dietary pattern |
|||||||
---|---|---|---|---|---|---|---|---|
tertile 1a (n = 1,564) | tertile 2a (n = 1,565) | tertile 3a (n = 1,564) | p for trend | tertile 1a (n = 1,564) | tertile 2a (n = 1,565) | tertile 3a (n = 1,564) | p for trend | |
Women, % | 24.2 | 24.3 | 30.1 | <10–4 | 38.5 | 25.2 | 14.9 | <10–4 |
Ageb, years | 60.7 (5.9) | 61.1 (6.0) | 61.3 (5.9) | 0.02 | 60.9 (5.8) | 61.0 (5.9) | 61.2 (6.2) | 0.45 |
Single or divorced, % | 24.1 | 17.3 | 16.3 | <10–4 | 20.9 | 17.6 | 19.2 | <10–4 |
No academic qualification, % | 13.0 | 8.6 | 6.9 | <10–4 | 8.2 | 8.8 | 8.2 | 0.05 |
Current smoker, % | 14.7 | 9.3 | 8.6 | <10–4 | 9.4 | 10.9 | 12.3 | 0.02 |
Low level of physical activity, % | 19.7 | 12.7 | 11.5 | <10–4 | 15.5 | 14.1 | 14.4 | 0.59 |
Diabetic, % | 5.9 | 5.9 | 5.9 | 0.98 | 4.8 | 6.8 | 5.9 | 0.06 |
With hypertension, % | 34.6 | 35.8 | 36.8 | 0.45 | 36.1 | 36.9 | 34.3 | 0.32 |
Dyslipidemic, % | 39.2 | 38.9 | 37.4 | 0.54 | 39.8 | 40.0 | 35.7 | 0.02 |
With CHD, % | 6.3 | 7.1 | 6.6 | 0.64 | 6.1 | 6.3 | 7.5 | 0.22 |
BMIb | 26.6 (4.3) | 26.5 (4.0) | 26.5 (4.2) | 0.48 | 26.3 (4.4) | 26.6 (4.1) | 26.6 (4.0) | 0.17 |
GHQ scoreb | 77.1 (15.8) | 77.6 (15.3) | 78.3 (15.0) | 0.09 | 77.5 (16.2) | 78.5 (14.5) | 77.0 (15.4) | 0.02 |
Total energyb, kcal/day | 1,927 (568) | 2,186 (551) | 2,489 (666) | <10–4 | 1,723 (405) | 2,115 (393) | 2,765 (596) | <10–4 |
GHQ = General Health Questionnaire.
Tertiles 1, 2 and 3 represent individuals in the lowest, intermediate and highest thirds of the dietary factor score.
For continuous variables, means with standard deviation in parentheses were given.
Table 3.
Without adjustment for education |
After adjustment for education |
||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
T1a | T2a |
T3a |
p for trend |
T1a | T2a |
T3a |
p for trend |
||||||
OR | OR | 95% CI | OR | 95% CI | OR | OR | 95% CI | OR | 95% CI | ||||
Memory | M1 | 1 | 0.79 | 0.65–0.97 | 0.67 | 0.54–0.84 | 0.002 | 1 | 0.87 | 0.71–1.07 | 0.78 | 0.62–0.98 | 0.09 |
M2 | 1 | 0.85 | 0.69–1.05 | 0.74 | 0.59–0.93 | 0.03 | 1 | 0.93 | 0.75–1.15 | 0.85 | 0.68–1.08 | 0.42 | |
Reasoning | M1 | 1 | 0.68 | 0.57–0.82 | 0.64 | 0.53–0.77 | <10–4 | 1 | 0.81 | 0.67–0.98 | 0.85 | 0.70–1.05 | 0.08 |
M2 | 1 | 0.73 | 0.61–0.88 | 0.69 | 0.57–0.84 | 0.0002 | 1 | 0.86 | 0.71–1.04 | 0.92 | 0.75–1.13 | 0.31 | |
Vocabulary | M1 | 1 | 0.68 | 0.57–0.81 | 0.55 | 0.45–0.67 | <10–4 | 1 | 0.84 | 0.70–1.02 | 0.78 | 0.63–0.96 | 0.04 |
M2 | 1 | 0.68 | 0.56–0.81 | 0.54 | 0.44–0.66 | <10–4 | 1 | 0.82 | 0.68–1.00 | 0.75 | 0.60–0.92 | 0.02 | |
Phonemic fluency | M1 | 1 | 0.77 | 0.64–0.92 | 0.72 | 0.59–0.88 | 0.002 | 1 | 0.87 | 0.72–1.05 | 0.89 | 0.73–1.10 | 0.32 |
M2 | 1 | 0.83 | 0.69–1.00 | 0.80 | 0.66–0.98 | 0.06 | 1 | 0.94 | 0.77–1.13 | 0.98 | 0.80–1.21 | 0.77 | |
Semantic fluency | M1 | 1 | 0.66 | 0.56–0.79 | 0.57 | 0.47–0.68 | <10–4 | 1 | 0.75 | 0.63–0.90 | 0.70 | 0.57–0.85 | 0.0004 |
M2 | 1 | 0.69 | 0.58–0.82 | 0.59 | 0.50–0.72 | <10–4 | 1 | 0.78 | 0.65–0.93 | 0.72 | 0.59–0.88 | 0.002 |
M1 = Adjusted for age, sex and energy intake; M2 = model 1 + adjusted for marital status, health behavior (smoking habits, physical activity) and health status (diabetes, hypertension, CHD, dyslipidemia, BMI and mental health); T = tertile.
Tertiles 1, 2 and 3 represent individuals in the lowest, intermediate and highest thirds of the dietary factor score.
Table 4.
Without adjustment for education |
After adjustment for education |
||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
T1a | T2a |
T3a |
p for trend | T1a | T2a |
T3a |
p for trend | ||||||
OR | OR | 95% CI | OR | 95% CI | OR | OR | 95% CI | OR | 95% CI | ||||
Memory | M1 | 1 | 1.17 | 0.94–1.46 | 1.40 | 1.06–1.85 | 0.06 | 1 | 1.06 | 0.85–1.32 | 1.15 | 0.87–1.55 | 0.61 |
M2 | 1 | 1.13 | 0.91–1.41 | 1.26 | 0.95–1.67 | 0.26 | 1 | 1.03 | 0.83–1.29 | 1.06 | 0.79–1.41 | 0.92 | |
Reasoning | M1 | 1 | 1.37 | 1.13–1.66 | 1.68 | 1.31–2.14 | <10–4 | 1 | 1.14 | 0.93–1.39 | 1.15 | 0.89–1.49 | 0.43 |
M2 | 1 | 1.34 | 1.10–1.62 | 1.55 | 1.21–1.98 | 0.001 | 1 | 1.12 | 0.91–1.37 | 1.09 | 0.84–1.42 | 0.55 | |
Vocabulary | M1 | 1 | 1.62 | 1.33–1.96 | 2.45 | 1.92–3.14 | <10–4 | 1 | 1.33 | 1.08–1.63 | 1.63 | 1.25–2.13 | 0.001 |
M2 | 1 | 1.58 | 1.30–1.92 | 2.36 | 1.84–3.04 | <10–4 | 1 | 1.31 | 1.07–1.62 | 1.63 | 1.25–2.13 | 0.001 | |
Phonemic fluency | M1 | 1 | 1.26 | 1.04–1.53 | 1.83 | 1.43–2.35 | <10–4 | 1 | 1.10 | 0.90–1.34 | 1.42 | 1.10–1.83 | 0.02 |
M2 | 1 | 1.23 | 1.01–1.49 | 1.70 | 1.33–2.19 | 10–4 | 1 | 1.07 | 0.88–1.32 | 1.34 | 1.04–1.74 | 0.06 | |
Semantic fluency | M1 | 1 | 1.21 | 1.00–1.45 | 1.68 | 1.33–2.12 | <10–4 | 1 | 1.04 | 0.86–1.26 | 1.28 | 1.00–1.63 | 0.10 |
M2 | 1 | 1.17 | 0.97–1.42 | 1.58 | 1.25–2.01 | 0.0005 | 1 | 1.02 | 0.84–1.24 | 1.23 | 0.96–1.57 | 0.17 |
M1 = Adjusted for age, sex and energy intake; M2 = model 1 + adjusted for marital status, health behavior (smoking habits, physical activity) and health status (diabetes, hypertension, CHD, dyslipidemia, BMI and mental health); T = tertile.
Tertiles 1, 2 and 3 represent individuals in the lowest, intermediate and highest thirds of the dietary factor score.
The interaction term between the dietary patterns and education (by grouping no formal education and lower secondary education together and levels above higher secondary education) did not provide any evidence for a moderating effect for education (all p values between 0.12 and 0.89). In analyses stratified by education, there was no evidence of different associations between diet and cognition in the different education groups (results not shown).
Discussion
We examined associations between two distinct dietary patterns, i.e. ‘whole food’ (rich in fruit, vegetables, dried legume and fish) and ‘processed food’ (rich in processed meat, chocolates, sweet desserts, fried food, refined cereals and high-fat dairy products), and cognitive deficit in a middle-aged population. In the fully adjusted models, but without taking into account the influence of education, our results suggested that the ‘whole food’ pattern was associated with lower and the ‘processed food’ pattern with increased odds of cognitive deficit. However, adjustment for education considerably attenuates these associations, suggesting that education is an important confounder in the association between nutrition and cognition.
While dietary patterns have been investigated inrelation to several chronic diseases such as cardiovascular diseases [23], or diabetes [24], studies on the relation between dietary patterns and cognitive functioning are less frequent. One exception is a recent study [4] that examined the association between dietary pattern, using dietary indices, and the risk of Alzheimer's disease and cognitive decline in an elderly population. They showed that high adherence to a Mediterranean diet [25] decreased the risk of cognitive decline and Alzheimer's disease in a nondemented, multiethnic elderly cohort (n = 2,258, mean age 77.2 ± 6.6 years). This association remained significant after adjustment for education. The use of an ‘a priori’ definition like the Mediterranean score presents the inconvenience of weighting equally the underlying individual food component categories, which, in turn, are composed of a number of food constituents. Using an ‘a posteriori’ factor analysis, our results, unadjusted for education, support those reported using the Mediterranean diet [4] by suggesting that a diet rich in fruits, vegetable and fish is associated with lower odds of cognitive deficit while a diet rich in processed meat, chocolates and sweeteners, desserts, fried food, refined grains and high-fat dairy products is associated with greater odds of cognitive deficit.
In our analysis, the diet and cognition relationship remained unchanged after adjustment for sex, age, energy intake, marital status, physical activity, smoking habits, chronic diseases (diabetes, dyslipidemia, CHD, hypertension), BMI and mental health. Our finding, before adjustment for education, of a relationship between the ‘whole food’ dietary pattern and cognitive deficit is supported, partly, by results of two prospective studies that found high intake of vegetables to be associated with a slower rate of cognitive decline at older ages [26, 27]. The beneficial effect of fruits and vegetables on cognition could be a result of high amounts of antioxidants in these foods. However, the literature on the association between antioxidant levels in the blood or estimated from food intake and cognitive performances or dementia is inconsistent and dependent on the specific nutrient examined [28]. Our ‘whole food’ dietary pattern also included a high intake of fish and there is consistent evidence to support this finding. Many studies have shown high fish consumption to be associated with low incidence of dementia [29, 30] including Alzheimer's diseases [29,30,31], slower cognitive decline in elderly [32, 33] and lower cognitive impairment in a middle-aged population [34]. The protective effects of fish consumption has been traditionally attributed to its high content in long-chain omega-3 polyunsaturated fatty acids which are a major component of neuron membranes and have vascular and anti-inflammatory properties [35]. Then, the association between the ‘whole food’ diet and cognition observed in our study could be explained by the cumulative and synergic effect of nutrients from different sources of foods rather than by the effect of one isolated nutrient.
The ‘processed food’ factor described in our study was highly loaded by sweets, desserts, fried food, processed food, refined grain products and high-fat dairy products and was very close to the ‘Western’ pattern defined in the American population [36] which has been shown to be correlated with markers of systemic inflammation [37]. Several lines of investigation have suggested that inflammation is involved in the pathogenesis of dementia [38,39,40,41,42]. However, the association between inflammation and cognition is still under debate [43] and more studies are needed to better understand the associationbetween the ‘processed food’ intake, inflammation process and cognition.
In this middle-aged British population, we showed education to influence the relationship between dietary pattern and cognition. The test for interaction suggests that it does not moderate the association between dietary factors and cognition, in that the diet-cognition association is similar in high- and low-education groups. The attenuation of the diet-cognition association after adjustment for education is a statistical result and could suggest two things. One, that education mediates the association between dietary factors and cognition in that dietary factors influence education which then influences cognition. However, the first part of this causal chain is unlikely as education was assessed prior to the dietary measures, and it appears unlikely that dietary factors influence education in this way. The second explanation for the substantially attenuated association between dietary patterns and cognition is that education acts as a confounder. Previous research shows that education is linked to dietary behavior [6, 7], the exposure being considered here and cognition [8,9,10,11], the outcome. Thus, we argue that education plays an important confounding role in the association between dietary patterns and cognition. The fact that this effect for education is evident after adjustment for multiple covariates is remarkable, particularly as Whitehall II is a white-collar middle-aged cohort.
The confounder role of education could work in several ways. One, education is associated with dietary habits and nutrient intake. Low education is associated with poor health behaviors, smoking, and less regular physical activity. Thus, participants with lower education have less healthy eating patterns compared to those with higher education. Furthermore, there is some evidence to show that lower socioeconomic position, of which education is a measure, is associated with purchase of foods that are cheaper per unit of energy rather than foods rich in protective nutrients [44,45,46,47]. Finally, low education is also related to poorer health-related nutrition knowledge [6, 7] which determines food choice. Second, education as a risk factor of cognitive impairment could confound the diet-cognition relationship. Low education has been shown to be associated with increased risk of dementia [8,9,10,11]. These observations are supported by the cognitive reserve hypothesis [48, 49], which stipulates that cognitive reserve delays the onset of clinical manifestations of dementia.
Our study has several potential limitations. First, the use of a semi-quantitative food questionnaire, only on specific foods, is recognized to be less precise than dietary assessment using a diary questionnaire. However, in this study population, at a previous wave of data collection, we have shown that nutrient intakes estimated by the FFQ method were well correlated with biomarker levels and with intake estimates from the generally more accurate 7-day diary [13]. Second, the cross-sectional framework of the analyses makes it impossible to draw causal inferences on the association between nutrition and cognition. Third, Whitehall II study participants are office-based civil servants, who are not fully representative of the British population [12, 50]. Finally, the factor analysis approach used to identify these patterns involves several arbitrary decisions such as the consolidation of food items into food groups, the number of factors extracted, the methods of rotation or labeling of the factors [51].
Despite these limitations, by considering an overall diet approach rather than a ‘single’ nutrient or food approach, our study is the first to show, in a middle-aged general population, that education, through its role as a powerful confounder, shapes the relationship between the two dietary patterns – ‘whole food’ and ‘processed food’ pattern – and cognitive function.
Acknowledgements
The authors thank all of the participating civil service departments and their welfare, personnel, and establishment officers; the British Occupational Health and Safety Agency; the British Council of Civil Service Unions; all participating civil servants in the Whitehall II study, and all members of the Whitehall II study team. The Whitehall II study has been supported by grants from the British Medical Research Council (MRC); the British Heart Foundation; the British Health and Safety Executive; the British Department of Health; the National Heart, Lung, and Blood Institute (grant HL36310); the National Institute on Aging (grant AG13196); the Agency for Health Care Policy and Research (grant HS06516), and the John D. and Catherine T. MacArthur Foundation Research Networks on Successful Midlife Development and Socioeconomic Status and Health. A.S.-M. is supported by a ‘European Young Investigator Award’ from the European Science Foundation. M.G.M. is supported by an MRC research professorship. The sponsors did not participate in thedesign and conduct of the study; collection, management, analysis, and interpretation of the data, or preparation, review, or approvalof the manuscript.
Appendix 1
Red meat | Beef, beef burgers, pork, lamb |
---|---|
Poultry | Chicken or other poultry |
Processed meats | Bacon, ham, corned beef, spam, luncheon meats, sausages |
Organ meat | Liver |
Fish | White fish, oily fish and shellfish |
Refined grain | White bread and rolls, cream cracker, cheese biscuits, crisp bread, refined grain ready-to-eat cereals, white pasta, white rice |
Whole grain | Brown bread and rolls, wholemeal bread and rolls, wholemeal pasta, brown rice, whole grain ready-to-eat cereals |
Eggs | Eggs |
Butter | Butter |
Margarine | Margarines, spread |
High-fat dairy | Full cream milk, Channel Island milk, coffee whitener, single or clotted cream, cheese, ice cream |
Low-fat dairy | Skimmed milk, sterilized milk, dried milk, yoghurt, cottage cheese |
Soya product | Soya milk, tofu, soya bean curd, soya meat, TVP, veggie-burger |
Liqueurs/spirits | Port, sherry, liqueurs, spirits |
Wine | Wine |
Beer | Beers, ciders |
Hot drinks | Tea, regular coffee, decaffeinated coffee, cocoa, hot chocolate, chicory |
Fruits | Apples, pears, oranges, mandarins, grapefruit, bananas, grapes, melon, peaches, plums, apricots, strawberries, raspberries, tinned fruit, dried fruits |
Fruit juice | 100% real fruit juice |
Leafy vegetables | Spinach, salads |
Cruciferous vegetables | Broccoli, kales, Brussels sprouts, cabbage, cauliflower, coleslaw |
Other vegetables | Carrots, marrow, courgettes, parsnip, leeks, mushroom, peppers, onion, garlic |
Tomatoes | Tomatoes |
Peas and dried legume | Beans, peas, baked beans, dried lentils |
Soup | Vegetable soup, meat soup |
Nuts | Peanuts, other nuts, peanut butter |
Potatoes | Boiled, mashed potatoes, jacket potatoes, potato salad |
Quiche/pie | Quiche, meat pie |
Pizza/lasagne | Pizza, lasagne |
Fried food | Chips or French fries, roast potatoes, fish fingers, fried fish in batter |
Snacks | Crisps |
Desserts/biscuits | Sweet biscuits, cakes, buns, pastries, fruit pies, tarts, crumbles, milk pudding, sponge puddings |
Chocolate and sweets | Chocolate bars, sweets, toffees, sugar added to tea, coffee, jam, marmalade, honey |
Sugar beverages | Fizzy soft drinks, fruit squash |
Low-calorie beverages | Low-calorie or diet fizzy soft drinks |
Condiments | Sauce, tomato ketchup, pickles, marmites |
Salad dressing | French vinaigrette, salad cream |
References
- 1.World Health Organization . Active Ageing: A Policy Framework. Madrid: World Health Organization; 2002. [PubMed] [Google Scholar]
- 2.Luchsinger JA, Mayeux R. Dietary factors and Alzheimer's disease. Lancet Neurol. 2004;3:579–587. doi: 10.1016/S1474-4422(04)00878-6. [DOI] [PubMed] [Google Scholar]
- 3.Van Dyk K, Sano M. The impact of nutrition on cognition in the elderly. Neurochem Res. 2007;32:893–904. doi: 10.1007/s11064-006-9241-5. [DOI] [PubMed] [Google Scholar]
- 4.Scarmeas N, Stern Y, Tang MX, et al. Mediterranean diet and risk for Alzheimer's disease. Ann Neurol. 2006;59:912–921. doi: 10.1002/ana.20854. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Berr C, Akbaraly TN, Nourashemi F, et al. Epidemiology of dementia. Presse Med. 2007;36:1431–1441. doi: 10.1016/j.lpm.2007.04.022. [DOI] [PubMed] [Google Scholar]
- 6.Parmenter K, Waller J, Wardle J. Demographic variation in nutrition knowledge in England. Health Educ Res. 2000;15:163–174. doi: 10.1093/her/15.2.163. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Wardle J, Parmenter K, Waller J. Nutrition knowledge and food intake. Appetite. 2000;34:269–275. doi: 10.1006/appe.1999.0311. [DOI] [PubMed] [Google Scholar]
- 8.Ngandu T, von Strauss E, Helkala EL, et al. Education and dementia: what lies behind the association? Neurology. 2007;69:1442–1450. doi: 10.1212/01.wnl.0000277456.29440.16. [DOI] [PubMed] [Google Scholar]
- 9.Roe CM, Xiong C, Miller JP, et al. Education and Alzheimer disease without dementia: support for the cognitive reserve hypothesis. Neurology. 2007;68:223–228. doi: 10.1212/01.wnl.0000251303.50459.8a. [DOI] [PubMed] [Google Scholar]
- 10.Scarmeas N, Albert SM, Manly JJ, et al. Education and rates of cognitive decline in incident Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2006;77:308–316. doi: 10.1136/jnnp.2005.072306. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Stern Y, Gurland B, Tatemichi TK, et al. Influence of education and occupation on the incidence of Alzheimer's disease. Jama. 1994;271:1004–1010. [PubMed] [Google Scholar]
- 12.Marmot MG, Smith GD, Stansfeld S, et al. Health inequalities among British civil servants: the Whitehall II study. Lancet. 1991;337:1387–1393. doi: 10.1016/0140-6736(91)93068-k. [DOI] [PubMed] [Google Scholar]
- 13.Brunner E, Stallone D, Juneja M, et al. Dietary assessment in Whitehall II: comparison of 7 d diet diary and food-frequency questionnaire and validity against biomarkers. Br J Nutr. 2001;86:405–414. doi: 10.1079/bjn2001414. [DOI] [PubMed] [Google Scholar]
- 14.Willett WC, Sampson L, Stampfer MJ, et al. Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol. 1985;122:51–65. doi: 10.1093/oxfordjournals.aje.a114086. [DOI] [PubMed] [Google Scholar]
- 15.Bingham SA, Gill C, Welch A, et al. Validation of dietary assessment methods in the UK arm of EPIC using weighed records, and 24-hour urinary nitrogen and potassium and serum vitamin C and carotenoids as biomarkers. Int J Epidemiol. 1997;26(suppl 1):S137–S151. doi: 10.1093/ije/26.suppl_1.s137. [DOI] [PubMed] [Google Scholar]
- 16.Singh-Manoux A, Marmot M. High blood pressure was associated with cognitive function in middle-age in the Whitehall II study. J Clin Epidemiol. 2005;58:1308–1315. doi: 10.1016/j.jclinepi.2005.03.016. [DOI] [PubMed] [Google Scholar]
- 17.Heim AW. AH 4 group test of general intelligence ASE. Windsor: NFER-Nelson; 1970. [Google Scholar]
- 18.Raven J. Guide to Using the Mill Hill Vocabulary Scale with Progressive Matrices. London: HK Lewis; 1965. [Google Scholar]
- 19.Borkowski J, Benton A, Spreen O. Word fluency and brain damage. Neuropsychologica. 1967;5:135–140. [Google Scholar]
- 20.Ainsworth BE, Haskell WL, Leon AS, et al. Compendium of physical activities: classification of energy costs of human physical activities. Med Sci Sports Exerc. 1993;25:71–80. doi: 10.1249/00005768-199301000-00011. [DOI] [PubMed] [Google Scholar]
- 21.Singh-Manoux A, Britton A, Kivimaki M, et al. Socioeconomic status moderates the association between carotid intima-media thickness and cognition in midlife: Evidence from the Whitehall II study. Atherosclerosis. 2008;197:541–548. doi: 10.1016/j.atherosclerosis.2007.08.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Goldberg D. The Detection of Psychiatric Illness by Questionnaire. London: Oxford University Press; 1972. [Google Scholar]
- 23.Hu FB, Rimm EB, Stampfer MJ, et al. Prospective study of major dietary patterns and risk of coronary heart disease in men. Am J Clin Nutr. 2000;72:912–921. doi: 10.1093/ajcn/72.4.912. [DOI] [PubMed] [Google Scholar]
- 24.van Dam RM, Rimm EB, Willett WC, et al. Dietary patterns and risk for type 2 diabetes mellitus in US men. Ann Intern Med. 2002;136:201–209. doi: 10.7326/0003-4819-136-3-200202050-00008. [DOI] [PubMed] [Google Scholar]
- 25.Trichopoulou A, Costacou T, Bamia C, et al. Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med. 2003;348:2599–2608. doi: 10.1056/NEJMoa025039. [DOI] [PubMed] [Google Scholar]
- 26.Kang JH, Ascherio A, Grodstein F. Fruit and vegetable consumption and cognitive decline in aging women. Ann Neurol. 2005;57:713–720. doi: 10.1002/ana.20476. [DOI] [PubMed] [Google Scholar]
- 27.Morris MC, Evans DA, Tangney CC, et al. Associations of vegetable and fruit consumption with age-related cognitive change. Neurology. 2006;67:1370–1376. doi: 10.1212/01.wnl.0000240224.38978.d8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Akbaraly T. Etude des facteurs biologiques nutritionnels dans le vieillissement cerebral. Kremlin-Bicêtre: Faculté de Médecine du Kremlin-Bicêtre; 2006. [Google Scholar]
- 29.Barberger-Gateau P, Letenneur L, Deschamps V, et al. Fish, meat, and risk of dementia: cohort study. Bmj. 2002;325:932–933. doi: 10.1136/bmj.325.7370.932. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Kalmijn S, Launer LJ, Ott A, et al. Dietary fat intake and the risk of incident dementia in the Rotterdam Study. Ann Neurol. 1997;42:776–782. doi: 10.1002/ana.410420514. [DOI] [PubMed] [Google Scholar]
- 31.Morris MC, Evans DA, Bienias JL, et al. Consumption of fish and n–3 fatty acids and risk of incident Alzheimer disease. Arch Neurol. 2003;60:940–946. doi: 10.1001/archneur.60.7.940. [DOI] [PubMed] [Google Scholar]
- 32.Morris MC, Evans DA, Tangney CC, et al. Fish consumption and cognitive decline with age in a large community study. Arch Neurol. 2005;62:1849–1853. doi: 10.1001/archneur.62.12.noc50161. [DOI] [PubMed] [Google Scholar]
- 33.van Gelder BM, Tijhuis M, Kalmijn S, et al. Fish consumption, n–3 fatty acids, and subsequent 5-y cognitive decline in elderly men: the Zutphen Elderly Study. Am J Clin Nutr. 2007;85:1142–1147. doi: 10.1093/ajcn/85.4.1142. [DOI] [PubMed] [Google Scholar]
- 34.Kalmijn S, van Boxtel MP, Ocke M, et al. Dietary intake of fatty acids and fish in relation to cognitive performance at middle age. Neurology. 2004;62:275–280. doi: 10.1212/01.wnl.0000103860.75218.a5. [DOI] [PubMed] [Google Scholar]
- 35.Yehuda S, Rabinovitz S, Carasso RL, et al. The role of polyunsaturated fatty acids in restoring the aging neuronal membrane. Neurobiol Aging. 2002;23:843–853. doi: 10.1016/s0197-4580(02)00074-x. [DOI] [PubMed] [Google Scholar]
- 36.Hu FB. Dietary pattern analysis: a new direction in nutritional epidemiology. Curr Opin Lipidol. 2002;13:3–9. doi: 10.1097/00041433-200202000-00002. [DOI] [PubMed] [Google Scholar]
- 37.Lopez-Garcia E, Schulze MB, Fung TT, et al. Major dietary patterns are related to plasma concentrations of markers of inflammation and endothelial dysfunction. Am J Clin Nutr. 2004;80:1029–1035. doi: 10.1093/ajcn/80.4.1029. [DOI] [PubMed] [Google Scholar]
- 38.Campbell IL, Stalder AK, Chiang CS, et al. Transgenic models to assess the pathogenic actions of cytokines in the central nervous system. Mol Psychiatry. 1997;2:125–129. doi: 10.1038/sj.mp.4000225. [DOI] [PubMed] [Google Scholar]
- 39.Ho GJ, Drego R, Hakimian E, et al. Mechanisms of cell signaling and inflammation in Alzheimer's disease. Curr Drug Targets Inflamm Allergy. 2005;4:247–256. doi: 10.2174/1568010053586237. [DOI] [PubMed] [Google Scholar]
- 40.Eikelenboom P, Veerhuis R. The importance of inflammatory mechanisms for the development of Alzheimer's disease. Exp Gerontol. 1999;34:453–461. doi: 10.1016/s0531-5565(99)00022-4. [DOI] [PubMed] [Google Scholar]
- 41.Schmidt R, Schmidt H, Curb JD, et al. Early inflammation and dementia: a 25-year follow-up of the Honolulu-Asia Aging Study. Ann Neurol. 2002;52:168–174. doi: 10.1002/ana.10265. [DOI] [PubMed] [Google Scholar]
- 42.Engelhart MJ, Geerlings MI, Meijer J, et al. Inflammatory proteins in plasma and the risk of dementia: the Rotterdam study. Arch Neurol. 2004;61:668–672. doi: 10.1001/archneur.61.5.668. [DOI] [PubMed] [Google Scholar]
- 43.Schram MT, Euser SM, de Craen AJ, et al. Systemic markers of inflammation and cognitive decline in old age. J Am Geriatr Soc. 2007;55:708–716. doi: 10.1111/j.1532-5415.2007.01159.x. [DOI] [PubMed] [Google Scholar]
- 44.Davey Smith G, Brunner E. Socioeconomic differentials in health: the role of nutrition. Proc Nutr Soc. 1997;56:75–90. doi: 10.1079/pns19970011. [DOI] [PubMed] [Google Scholar]
- 45.Dowler E. Budgeting for food on a low income in the UK: the case of lone-parent families. Food Policy. 1997;22:405–417. [Google Scholar]
- 46.James WP, Nelson M, Ralph A, et al. Socioeconomic determinants of health. The contribution of nutrition to inequalities in health. BMJ. 1997;314:1545–1549. doi: 10.1136/bmj.314.7093.1545. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 47.Stallone DD, Brunner EJ, Bingham SA, et al. Dietary assessment in Whitehall II: the influence of reporting bias on apparent socioeconomic variation in nutrient intakes. Eur J Clin Nutr. 1997;51:815–825. doi: 10.1038/sj.ejcn.1600491. [DOI] [PubMed] [Google Scholar]
- 48.Katzman R. Education and the prevalence of dementia and Alzheimer's disease. Neurology. 1993;43:13–20. doi: 10.1212/wnl.43.1_part_1.13. [DOI] [PubMed] [Google Scholar]
- 49.Stern Y. What is cognitive reserve? Theory and research application of the reserve concept. J Int Neuropsychol Soc. 2002;8:448–460. [PubMed] [Google Scholar]
- 50.Marmot M, Brunner E. Cohort Profile: the Whitehall II study. Int J Epidemiol. 2005;34:251–256. doi: 10.1093/ije/dyh372. [DOI] [PubMed] [Google Scholar]
- 51.Martinez ME, Marshall JR, Sechrest L. Invited commentary: Factor analysis and the search for objectivity. Am J Epidemiol. 1998;148:17–19. doi: 10.1093/oxfordjournals.aje.a009552. [DOI] [PubMed] [Google Scholar]