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Nutritional Epidemiology

Intake of Flavonoid-Rich Wine, Tea, and Chocolate by Elderly Men and Women Is Associated with Better Cognitive Test Performance^1–3,

⁴ Department of Nutrition, University of Oslo, 0316 Oslo, Norway; ⁵ Oxford Project to Investigate Memory and Ageing and Department of Physiology, Anatomy and Genetics, University of Oxford, OX1 3QX Oxford, United Kingdom; ⁶ Department of Public Health and Primary Health Care, University of Bergen, 5020 Bergen, Norway; ⁷ NKS Olaviken Hospital for Old Age Psychiatry, 5306 Erdal, Norway; and ⁸ Department of Geriatric Medicine, Norwegian Centre for Dementia Research, Ullevål University Hospital, 0407 Oslo, Norway

^* To whom correspondence should be addressed. E-mail: david.smith{at}pharm.ox.ac.uk.

	ABSTRACT

TOP ABSTRACT Introduction Methods Results Discussion LITERATURE CITED

 
In a cross-sectional study, we examined the relation between intake of 3 common foodstuffs that contain flavonoids (chocolate, wine, and tea) and cognitive performance. 2031 participants (70–74 y, 55% women) recruited from the population-based Hordaland Health Study in Norway underwent cognitive testing. A cognitive test battery included the Kendrick Object Learning Test, Trail Making Test, part A (TMT-A), modified versions of the Digit Symbol Test, Block Design, Mini-Mental State Examination, and Controlled Oral Word Association Test. Poor cognitive performance was defined as a score in the highest decile for the TMT-A and in the lowest decile for all other tests. A self-reported FFQ was used to assess habitual food intake. Participants who consumed chocolate, wine, or tea had significantly better mean test scores and lower prevalence of poor cognitive performance than those who did not. Participants who consumed all 3 studied items had the best test scores and the lowest risks for poor test performance. The associations between intake of these foodstuffs and cognition were dose dependent, with maximum effect at intakes of 10 g/d for chocolate and 75–100 mL/d for wine, but approximately linear for tea. Most cognitive functions tested were influenced by intake of these 3 foodstuffs. The effect was most pronounced for wine and modestly weaker for chocolate intake. Thus, in the elderly, a diet high in some flavonoid-rich foods is associated with better performance in several cognitive abilities in a dose-dependent manner.

	Introduction

TOP ABSTRACT Introduction Methods Results Discussion LITERATURE CITED

Polyphenols are abundant micronutrients in our plant-derived foods and are powerful antioxidants. Fruits and beverages such as tea, red wine, cocoa, and coffee are major dietary sources of polyphenols. The largest subclass of dietary polyphenols is flavonoids (8,9). A significant inverse relationship between dementia or cognitive performance and the intake of flavonoids has been reported (9–11).

Wine and tea are flavonoid-rich beverages that may have dual effects on health and cognitive function. Moderate alcohol consumption is associated with better cognitive function (12) and reduced risk of Alzheimer's disease and dementia in general (4,10,12–15). In contrast, heavy alcohol intake has been considered to be one of many causes of dementia (4,12). Tea consumption is associated with a reduced risk of cognitive impairment (16,17) and of cognitive decline (17) and components in green tea may be associated with neuroprotection (5,9). But in cellular models, a dual action of tea polyphenols, e.g. (-) epigallocatechin-3-gallate, on cell survival has also been demonstrated: they protect at low micromolar concentrations, whereas they become pro-oxidant and pro-apoptotic at concentrations over 10–20 µmol/L (18).

Dark chocolate, like other cocoa products, may contain greater amounts of flavonoids, depending on the processing, per serving than teas and red wines (19). Acute (20) as well as chronic (21) ingestion of flavanol-rich cocoa is associated with increased blood flow to cerebral gray matter and it has been suggested that cocoa flavanols might be beneficial in conditions with reduced cerebral blood flow, including dementia and stroke (21).

The aim of this study was to examine the relation of the performance, in a variety of cognitive tests, to habitual intake during the previous year of certain types of flavonoid-rich food intake (chocolate, wine, and tea). A subset of elderly participants within the Hordaland Health Study (HUSK)⁹ afforded the opportunity to examine these issues among >2000 older men and women.

	Methods

TOP ABSTRACT Introduction Methods Results Discussion LITERATURE CITED

 
    Study population. The HUSK study was conducted from 1997 to 1999 as a collaboration between the University of Bergen, University of Oslo, local health services and the Norwegian Institute of Public Health. Details of the study and of recruitment to the Cognitive Sub-study has been described previously (22,23). Briefly, a total of 2841 participants out of 3341 attendees in the HUSK born in 1925–1927 were invited to participate in cognitive tests; 2197 (77.3%) of these agreed and constitute the Cognitive Sub-study. In this report, we have confined the analysis to cross-sectional data for 2031 (71.5%) individuals who also completed a FFQ.

All participants gave their written, informed consent. The study protocol was approved by the Regional Committee for Medical Research Ethics of Western Norway.

    Data collection. Cognitive testing was performed at the study location by trained nurses after the standard cardiovascular examinations of the National Health Screening Service were completed. The cognitive test battery included 6 tests (24): Kendrick Object Learning test (KOLT; episodic memory) (25); Trail Making test, part A (TMT-A) (26); a modified version of Digit Symbol test (m-DST; perceptual speed) (27); Block Design, short form (m-BD; visuospatial skills) (27); a modified version of the Mini-Mental State Examination (m-MMSE; global cognition) (28); and an abridged version of Controlled Oral Word Association test (S-task) (access to semantic memory) (29).

    Dietary habits. To asses the habitual food consumption, a comprehensive FFQ created at the Department of Nutrition, University of Oslo (30,31) was handed out on the day of examination, filled out later at home by the participants, and then mailed to the HUSK Project Centre in Bergen. The FFQ has been validated in several previous studies, including the correlation between self-reported dietary intake of fish and essential (n-3) fatty acids in plasma phospholipids among 579 men and women (31) and 14-d weighed diet records with the intakes calculated from the FFQ in a group of 38 elderly women (30). The questionnaire included 169 food items that were grouped according to Norwegian meal patterns. It was designed to obtain information on usual food intake during the last year. The frequency of consumption was given per day, week, or month. The portion sizes were defined as follows: chocolate (type not specified), 60 g (the approximate amount in a standard chocolate bar in Norway); wine (type not specified), 1 glass (120 mL); and tea [an infusion of the leaves of Camellia sinensis (the most common type at the end of the 1990s in Norway was black tea)], 1 cup (200 mL). Precise information on the type of chocolate consumed was not recorded, but at that time in Norway, the most common type purchased was milk chocolate.

Dichotomous variables were created considering individuals who reported the use of chocolate, wine, or tea, whereas all others reporting that they never consumed the actual product were considered nonusers. To identify the individuals who never had these items and individuals who consumed at least 1 or 2 or all of them, all dichotomous variables were combined. The amount of each item in g or mL/d and total energy intake were calculated by using a food database and software system developed at the Department of Nutrition, University of Oslo (Kostberegningssystem, version 3.2, University of Oslo, Norway).

    Covariates. The FFQ also included questions about dietary supplement intake, in which the product names of the most used supplements in Norway were considered. Use of dietary supplements was reported as "seasonal use" (during the whole year or only winter half of the year), frequency per week, and amount per time.

Self-reported information on diabetes and history of myocardial infarction, angina pectoris, stroke, thrombosis, phlebitis, and hypertension was recorded in 1992–1993 and 1997–1999. On the basis of information from both surveys, the participants were categorized as with or without a history of cardiovascular disease (CVD) (including the diseases and conditions mentioned above). About four-fifths (79%) of the self-reported CVD cases were validated with hospitalization records used in our earlier study (32), whereas the remaining 21% of CVD cases were presumably less severe and did not require hospitalization or occurred before 1992.

Educational level was self-reported and recorded in 5 categories: primary school (9 y), vocational secondary school (10–12 y), theoretical secondary school (10–12 y), college or university 4 y, and university of 4 y. Smoking was considered in 3 categories: nonsmokers, ex-smokers, and current smokers (including daily smoking of cigarettes, cigars, cigarillos, or pipe). The depression score was assessed by a 7-item subscale for depression from the Hospital Anxiety and Depression Scale (33). Intake of coffee was reported as the number of cups (120 mL) consumed per day.

    Statistical analysis. Cutoff points for poor cognitive test scores were set at about the 10th percentile of the cognitive test score, except for the TMT-A, where the 90th percentile was used. Preliminary analyses showed that cognitive test scores and intake of chocolate, wine, and tea were significantly correlated with 1 or more of the following background variables: sex, education, use of vitamin supplements, coffee intake, smoking status, history of CVD, diabetes, depression score, and total energy intake (Supplemental Table 1). Although the depression score was significantly correlated with most of the cognitive test scores, it made little difference when introduced in the statistical models and because inclusion of the depression score significantly reduced the numbers of participants due to missing data, it was excluded from final models. The results were almost identical when the use of vitamin supplements such as multivitamins, folate, B vitamins (not specified), and vitamins C, D, and E was included as covariates in separate variables or was combined into 1 variable. Consequently, in the present paper, the use of all these vitamin supplements was combined. Similarly, inclusion of coffee intake as a covariate in statistical models made very little difference and is therefore omitted from the final models. Thus, the final fully adjusted models used throughout the present paper were controlled for sex, education, history of CVD, smoking status, vitamin supplement use, diabetes, and total energy intake. Due to potential over-adjustment, we selected both a simple (sex-adjusted) model and a fully adjusted model in the table presenting mean values of cognitive test scores and when demonstrating dose-response associations. Given the narrow age range, adjustment for age did not change the results and has not been included.

For comparison between the groups of chocolate, wine, and tea intake, the ² test or ANOVA was used. Estimated mean values of cognitive scores by combined intake of chocolate, wine, and tea, adjusted according to our final model of cofactors, were obtained from the univariate ANOVA, and risk ratios for poor cognitive test performance (based on cross-sectional data on habitual consumption of chocolate, wine, and tea during the previous year) were obtained from logistic regression analysis. Gaussian generalized additive regression models, as implemented in S-PLUS 6.2 for Windows (Insightful Corporation), were used to generate graphic representations of the dose-response relationships using a sex-adjusted model. On the vertical axis, the model generates a reference value of 0 that approximately corresponds to the value of cognitive test score associated with the mean of the average intake of flavonoid-rich food in g or mL/d for all participants. Multiple linear regression analyses were used to examine significant associations between the cognitive test scores and average chocolate, wine, and tea intake using both a sex-adjusted model and a model adjusted for the variables referred to in the final model. Except for generalized additive models, all statistical analyses were performed using SPSS, 12.0 for Windows. P-values < 0.05 were considered significant.

	Results

TOP ABSTRACT Introduction Methods Results Discussion LITERATURE CITED

 
Mean intakes among the 2031 participants were 3.8 (95% CI: 3.5, 4.2) g/d for chocolate, 22 (20, 25) mL/d for wine, and 222 (209, 235) mL/d for tea. When nonconsumers were excluded, the mean intakes doubled: 7.5 (6.9, 8.1) g/d for chocolate (n = 1036), 51 (46, 57) mL/d for wine (n = 882), and 417 (399, 435) mL/d for tea (n = 827). Approximately 30% of total tea intake was attributed to herbal tea [mean intake, 68 (60, 76) mL/d; mean intake among tea drinkers, 127 (114, 141) mL/d].

The proportion of wine drinkers was higher in men than in women, whereas the proportion of tea drinkers was higher among women than men (Table 1). The use of vitamin supplements was more frequent, and total energy intake and educational level (9 y) were higher among chocolate, wine, and tea consumers than nonconsumers. Current smoking was more prevalent among those who did not drink tea, whereas there were more ex-smokers among wine drinkers than among nondrinkers. Wine and tea drinkers drank less coffee than nondrinkers. Chocolate users had lower prevalence of CVD history and diabetes than nonusers and the prevalence of diabetes was lower among wine drinkers than nondrinkers.

The multiple-adjusted mean values of various cognitive tests and the risk ratios for poor cognitive test performance are presented in Table 3 in relation to how many of the 3 flavonoid-rich foods (chocolate, wine, or tea) were consumed. For each of the 6 cognitive tests, the test performance improved as an increasing number of these products were consumed.

In the sex-adjusted models, independent of cognitive test, the risk for poor performance decreased significantly among consumers of chocolate, wine, and tea when compared with nonconsumers (data not shown). In the fully adjusted models, the strongest risk-reducing effect for poor cognitive performance was related to wine intake: compared with nondrinkers, the wine drinkers had a 41–53% reduced risk for poor test performance in all 6 cognitive tests (Table 4). Among the chocolate eaters, the risk-reducing effect in 4 out of 6 tests (TMT-A, m-DST, m-MMSE, and S-task) remained significant when the models were controlled for multiple risk factors, but the tea drinkers had significantly reduced risk for poor performance only in the TMT-A and S-task.

View larger version (32K): [in this window] [in a new window]   FIGURE 1  Associations between different cognitive tests scores and intake of chocolate, wine, and tea obtained by Gaussian generalized additive regression models. Solid lines are the estimated dose-response curves; shaded areas represent the 95% CI. P-values are from corresponding multiple linear regression analyses. P1-values are adjusted for gender and P2-values are adjusted for sex, education, vitamin supplement use (multivitamins, folate, and vitamins B, C, D, or E), smoking status, history of CVD, diabetes, and total energy intake. The data for the highest 2.5 percentile of chocolate, wine, and tea intake are not included.

To determine whether the effect of particular flavonoid-rich foods on cognitive performance is independent, we repeated all statistical models adding chocolate, wine, and tea as covariates. This did not affect our results; all significant associations remained, except for the fully adjusted linear association (Fig. 1) between tea and S-task (P-value changed to 0.080).

	Discussion

TOP ABSTRACT Introduction Methods Results Discussion LITERATURE CITED

 
In a population-based study of elderly people, we showed that habitual intake of flavonoid-rich foods such as chocolate, wine, and tea is associated with better cognitive performance. The associations were dose dependent and applied for most of the cognitive tests used in the study. The associations were also additive in the sense that the risk of poor cognition was lower the greater the number of the 3 flavonoid-rich foods consumed the previous year.

Although elderly Norwegians were modest in their habitual wine consumption (50% of users drank <1 glass/wk and 5% drank >1 glass/d), the strongest beneficial effect on cognitive test performance was related to wine intake. Earlier studies have shown that light-to-moderate alcohol consumption might have a protective effect on cognitive impairment compared with total abstention or heavy consumption (1,12,34–36). The most potent effects have been attributed to wine intake, because in several studies, moderate wine drinkers have shown strikingly low OR of 0.15–0.19 for Alzheimer's disease and dementia compared with nondrinkers (12,15,34,35). In our study, all wine consumers were grouped together, independent of dose, but the effect of wine intake was still evident (OR varied from 0.46 to 0.57 depending on cognitive test). Furthermore, we observed a plateau effect of wine at an intake of 0.5 glass/d, which is comparable with the protective effect of moderate intake observed in the studies cited above. Because there were few people who reported high wine intake in our population (14 reported consuming >4 glasses/d), we could not study the effect of heavy consumption.

Several mechanisms by which moderate wine consumption might protect against cognitive impairment have been proposed, including reduced cardiovascular risk, antiinflammatory effects, and the antioxidant actions of its flavonoids (12,35,36). However, moderate wine intake may be a marker of a healthier diet or of a complex set of favorable social and lifestyle factors (15,34,37), which themselves are protective for cognitive impairment. In our study, we have tried to adjust for potentially relevant factors, but we cannot exclude the possibility of residual confounding.

Cocoa products are particularly rich sources of flavonoids, although this is influenced by the processing during manufacture (19). Due to a high antioxidant capacity, cocoa products have been promoted as having several beneficial properties (mainly cardiovascular). Even very modest consumption of chocolate may significantly contribute to total polyphenol intake (38). However, a recent clinical trial (39) did not find any beneficial effects of short-term (6 wk) dark chocolate and cocoa consumption on cardiovascular outcomes or on neuropsychological tests. In our study, we found that habitual chocolate users performed better in all cognitive tests and had significantly reduced risk for poor test performance in most tests, whereas the mean intake of chocolate among users was as little as <8 g/d. Moreover, a maximum beneficial effect on cognitive performance was gained at a mean intake of chocolate of 10 g/d. The real effect of polyphenols in chocolate may be even stronger, because not all chocolates are equally good sources of flavonoids and the type of chocolate consumed was not specified in our study. In the US and Europe, milk chocolate is the most popular form, but this contains less cocoa mass than dark chocolate and therefore contains fewer polyphenols (40).

Green tea polyphenols have been promoted as therapeutic agents claimed to alter brain aging processes and as possible neuroprotective agents in progressive neurodegenerative diseases (18). There have been 2 recent studies on the association between tea intake and dementia or cognitive impairment in humans. In a cross-sectional study, Kuriyama et al. (16) found inverse dose-response relations between consumption of green tea and the prevalence of cognitive impairment and a weak relation between consumption of black tea and cognitive impairment. However, a strong inverse relationship was found by Ng et al. (17) between consumption of black tea and both cognitive impairment and cognitive decline. Although the flavonoid content in typical black (31%, wt:wt) and green (33%, wt:wt) tea is similar, there is a significant difference in catechins: 9% in black tea and 30% in green tea (41). The favorable properties ascribed to tea consumption may be due to catechins and their derivatives (18,41,42) that are recognized as multifunctional compounds for neuroprotection. Although we did not record the type of tea consumed, black tea comprised 96% of the total tea imported into Norway in 1999 (43).

Food components are often studied in isolation, but the benefit achieved via food intake may depend not only on the individual component but on the milieu in which it is taken (1). Consistently, we found that the cognitive test scores improved and the risk for poor test performance decreased with the number of different flavonoid-rich items (chocolate, wine, and tea) consumed. Because plateau effects were observed individually for wine and chocolate intake (Fig. 1), the additive effect may reflect confounding by unknown lifestyle factors or it may reflect the presence of other substances that enhance the protective effects of flavonoids.

The strengths of our study include a large population-based sample with 6 different tests to study cognitive performance and the use of a well-validated FFQ. One limitation of dietary studies is error in the estimates of nutrients (4). Thus, it is possible to over- or underestimate true associations with outcomes if the type of certain foods was not specified, i.e. if the person preferred dark chocolate to milk chocolate or red wine to white wine or green tea to black tea. There was also no indication of whether individuals preferred weak or strong tea. With regard to alcohol consumption, underreporting by individuals is common and especially the information based on quantity-frequency data has such a tendency (44). Thus, observed relations are, if anything, probably an underestimation of the true effect, if there is one.

Because 77% of the study attendees volunteered for cognitive testing, the possibility of recruitment bias should be considered. Several differences between participants who did and those who did not undergo cognitive testing have been reported earlier (45). For flavonoid-rich food intake, the participants in the cognitive substudy drank more wine and tea than nonparticipants: mean wine intake was 12 [95% CI: 11, 13] vs. 7 [6, 8] mL/d (P < 0.001) and mean tea intake was 154 [143, 165] vs. 129 [114, 143] mL/d (P = 0.007). The difference in chocolate intake was only 0.5 g/d: 3.8 [3.5, 4.1] g/d vs. 3.3 [2.8, 3.7] g/d, respectively, among participants and nonparticipants (P = 0.071). Cognition in the elderly is shaped by long-term exposures (46,47). Thus, a major limitation of our study is the cross-sectional design, even though the questionnaire involved food intake over the previous year. Furthermore, participants with impaired cognition may have altered their diet as a consequence of a change in their cognitive status. In addition, self-reported dietary data collected from participants who are cognitively impaired or demented may be less reliable. However, because the participants in the present study were not seriously impaired, we do not think this had a major impact on our findings. Also, foods are not consumed individually but as part of a diet and therefore confounding by other food items is always an issue in studies using dietary assessments.

In conclusion, in a population-based study, we showed that intake of flavonoid-rich food, including chocolate, wine, and tea, is associated with better performance across several cognitive abilities and that the associations are dose dependent. However, these results should be considered with caution, because they were based on food-based analyses of population data and so we cannot conclude that the observed dietary benefits are truly associated with the flavonoids in chocolate, wine, or tea. We suggest that further studies should directly examine the flavonoid status and take into account other bioactive dietary substances in these foods.

	ACKNOWLEDGMENTS

 
We thank Elfrid Blomdal (University of Bergen, Norway), Gunnar Åmlid, and Dr. Kari Solvoll (University of Oslo, Norway) for their excellent support with the literature and the questionnaires.

	FOOTNOTES

 
¹ Supported by the Charles Wolfson Charitable Trust, the Norman Collisson Foundation (United Kingdom), the Advanced Research Programme of Norway, the Johan Throne Holst Foundation for Nutrition Research, University of Oslo.

² Author disclosures: E. Nurk, H. Refsum, C. A. Drevon, G. S. Tell, H. A. Nygaard, K. Engedal, and A. D. Smith, no conflicts of interest.

³ Supplemental Table 1 is available with the online posting of this paper at jn.nutrition.org.

⁹ Abbreviations used: CVD, cardiovascular disease; HUSK, Hordaland Health Study; KOLT, Kendrick Object Learning Test; m-BD, a short form of Block Design; m-DST, a modified version of Digit Symbol Test; m-MMSE, a modified version of the Mini-Mental State Examination; OR, odds ratio; S-task, an abridged version of Controlled Oral Word Association Test; TMT-A, part A from the Trail Making Test.

Manuscript received 26 June 2008. Initial review completed 29 August 2008. Revision accepted 21 October 2008.

	LITERATURE CITED

TOP ABSTRACT Introduction Methods Results Discussion LITERATURE CITED

 

1. Van Dyk K, Sano M. The impact of nutrition on cognition in the elderly. Neurochem Res. 2007;32:893–904.[CrossRef][Medline]

2. Rosenberg IH, Miller JW. Nutritional factors in physical and cognitive functions of elderly people. Am J Clin Nutr. 1992;55:S1237–43.[Medline]

3. Selhub J, Bagley LC, Miller J, Rosenberg IH. B vitamins, homocysteine, and neurocognitive function in the elderly. Am J Clin Nutr. 2000;71:S614–20.

4. Luchsinger JA, Mayeux R. Dietary factors and Alzheimer's disease. Lancet Neurol. 2004;3:579–87.[CrossRef][Medline]

5. Frank B, Gupta S. A review of antioxidants and Alzheimer's disease. Ann Clin Psychiatry. 2005;17:269–86.[CrossRef][Medline]

6. Ancelin ML, Christen Y, Ritchie K. Is antioxidant therapy a viable alternative for mild cognitive impairment? Examination of the evidence. Dement Geriatr Cogn Disord. 2007;24:1–19.[Medline]

7. Smith AD. The worldwide challenge of the dementias: a role for B vitamins and homocysteine? Food Nutr Bull. 2008;29:S143–72.[Medline]

8. Manach C, Scalbert A, Morand C, Rémésy C, Jiménez L. Polyphenols: food sources and bioavailability. Am J Clin Nutr. 2004;79:727–47.[Abstract/Free Full Text]

9. Ramassamy C. Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: a review of their intracellular targets. Eur J Pharmacol. 2006;545:51–64.[CrossRef][Medline]

10. Commenges D, Scotet V, Renaud S, Jacqmin-Gadda H, Barberger-Gateau P, Dartigues JF. Intake of flavonoids and risk of dementia. Eur J Epidemiol. 2000;16:357–63.[CrossRef][Medline]

11. Letenneur L, Proust-Lima C, Le Gouge A, Dartigues JF, Barberger-Gateau P. Flavonoid intake and cognitive decline over a 10-year period. Am J Epidemiol. 2007;165:1364–71.[Abstract/Free Full Text]

12. de Lorimier AA. Alcohol, wine, and health. Am J Surg. 2000;180:357–61.[CrossRef][Medline]

13. Lindsay J, Laurin D, Verreault R, Hebert R, Helliwell B, Hill GB, McDowell I. Risk factors for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging. Am J Epidemiol. 2002;156:445–53.[Abstract/Free Full Text]

14. Larrieu S, Letenneur L, Helmer C, Dartigues JF, Barberger-Gateau P. Nutritional factors and risk of incident dementia in the PAQUID longitudinal cohort. J Nutr Health Aging. 2004;8:150–4.[Medline]

15. Mehlig K, Skoog I, Guo X, Schutze M, Gustafson D, Waern M, Ostling S, Bjorkelund C, Lissner L. Alcoholic beverages and incidence of dementia: 34-year follow-up of the prospective population study of women in Göteborg. Am J Epidemiol. 2008;167:684–91.[Abstract/Free Full Text]

16. Kuriyama S, Hozawa A, Ohmori K, Shimazu T, Matsui T, Ebihara S, Awata S, Nagatomi R, Arai H, et al. Green tea consumption and cognitive function: a cross-sectional study from the Tsurugaya Project 1. Am J Clin Nutr. 2006;83:355–61.[Abstract/Free Full Text]

17. Ng TP, Feng L, Niti M, Kua EH, Yap KB. Tea consumption and cognitive impairment and decline in older Chinese adults. Am J Clin Nutr. 2008;88:224–31.[Abstract/Free Full Text]

18. Mandel SA, Avramovich-Tirosh Y, Reznichenko L, Zheng H, Weinreb O, Amit T, Youdim MB. Multifunctional activities of green tea catechins in neuroprotection. Modulation of cell survival genes, iron-dependent oxidative stress and PKC signaling pathway. Neurosignals. 2005;14:46–60.[CrossRef][Medline]

19. Ding EL, Hutfless SM, Ding X, Girotra S. Chocolate and prevention of cardiovascular disease: a systematic review. Nutr Metab (Lond). 2006;3:2.[CrossRef][Medline]

20. Francis ST, Head K, Morris PG, Macdonald IA. The effect of flavanol-rich cocoa on the fMRI response to a cognitive task in healthy young people. J Cardiovasc Pharmacol. 2006;47 Suppl 2:S215–20.[CrossRef][Medline]

21. Fisher NDL, Sorond FA, Hollenberg NK. Cocoa flavanols and brain perfusion. J Cardiovasc Pharmacol. 2006;47 Suppl 2:S210–4.[CrossRef][Medline]

22. HUSK. Recruitment into the cognitive sub-study of the Hordaland Homocysteine Study [cited 2008 May 16]. Available from: www.uib.no/isf/husk/Vedlegg_dokumenter/Cognitive_Sub_study.pdf.

23. Refsum H, Nurk E, Smith AD, Ueland PM, Gjesdal CG, Bjelland I, Tverdal A, Tell GS, Nygard O, et al. The Hordaland Homocysteine Study: a community-based study of homocysteine, its determinants, and associations with disease. J Nutr. 2006;136:S1731–40.[Abstract/Free Full Text]

24. Nurk E, Drevon CA, Refsum H, Solvoll K, Vollset SE, Nygard O, Nygaard HA, Engedal K, Tell GS, et al. Cognitive performance among the elderly and dietary fish intake: the Hordaland Health Study. Am J Clin Nutr. 2007;86:1470.[Abstract/Free Full Text]

25. Kendrick DC. Kendrick cognitive tests for the elderly. Windsor (UK): NFER-NELSON Publishing Company Ltd; 1985.

26. Reitan RM. Validity of the trail making test as an indicator of organic brain damage. Percept Mot Skills. 1958;8:271–6.[Medline]

27. Wechsler D. Wechsler Adult Intelligence Scale-revised. New York: Psychological Corporation; 1981.

28. Folstein MF, Folstein SE, McHugh PR. Mini-mental state" A practical method for grading the cognitive state of patients for clinician. J Psychiatr Res. 1975;12:189–98.[CrossRef][Medline]

29. Benton A, Hamsher K. Multilingual aphasia examination. (IA): AJA Associates; 1989.

30. Nes M, Andersen LF, Solvoll K, Sandstad B, Hustvedt BE, Lovo A, Drevon CA. Accuracy of a quantitative food frequency questionnaire applied in elderly Norwegian women. Eur J Clin Nutr. 1992;46:809–21.[Medline]

31. Andersen LF, Solvoll K, Drevon CA. Very-long-chain (n-3)fatty acids as biomarkers for intake of fish and (n-3)fatty acid concentrates. Am J Clin Nutr. 1996;64:305–11.[Abstract/Free Full Text]

32. Nurk E, Tell GS, Vollset SE, Nygård O, Refsum H, Ueland PM. Plasma total homocysteine and hospitalizations for cardiovascular disease. The Hordaland Homocysteine Study. Arch Intern Med. 2002;162:1374–81.[Abstract/Free Full Text]

33. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67:361–70.[Medline]

34. Solfrizzi V, D'Introno A, Colacicco AM, Capurso C, Del Parigi A, Baldassarre G, Scapicchio P, Scafato E, Amodio M, et al. Alcohol consumption, mild cognitive impairment, and progression to dementia. Neurology. 2007;68:1790–9.[Abstract/Free Full Text]

35. Letenneur L. Risk of dementia and alcohol and wine consumption: a review of recent results. Biol Res. 2004;37:189–93.[Medline]

36. Stampfer MJ, Kang JH, Chen J, Cherry R, Grodstein F. Effects of moderate alcohol consumption on cognitive function in women. N Engl J Med. 2005;352:245–53.[Abstract/Free Full Text]

37. Ruidavets JB, Bataille V, Dallongeville J, Simon C, Bingham A, Amouyel P, Arveiler D, Ducimetiere P, Ferrieres J. Alcohol intake and diet in France, the prominent role of lifestyle. Eur Heart J. 2004;25:1153–62.[Abstract/Free Full Text]

38. Scalbert A, Williamson G. Dietary intake and bioavailability of polyphenols. J Nutr. 2000;130:S2073–85.[Abstract/Free Full Text]

39. Crews WD Jr, Harrison DW, Wright JW. A double-blind, placebo-controlled, randomized trial of the effects of dark chocolate and cocoa on variables associated with neuropsychological functioning and cardiovascular health: clinical findings from a sample of healthy, cognitively intact older adults. Am J Clin Nutr. 2008;87:872–80.[Abstract/Free Full Text]

40. Cooper KA, Donovan JL, Waterhouse AL, Williamson G. Cocoa and health: a decade of research. Br J Nutr. 2008;99:1–11.[Medline]

41. Wiseman SA, Balentine DA, Frei B. Antioxidants in tea. Crit Rev Food Sci Nutr. 1997;37:705–18.[Medline]

42. Weinreb O, Mandel S, Amit T, Youdim MBH. Neurological mechanisms of green tea polyphenols in Alzheimer's and Parkinson's diseases. J Nutr Biochem. 2004;15:506–16.[CrossRef][Medline]

43. Statistics Norway. National economy and external trade. [cited 2008 May 16]. Available from: http://statbank.ssb.no/statistikkbanken/Default_FR.asp?PXSid=0&nvl=true&PLanguage=0&tilside=selectvarval/define.asp&Tabellid=03057.

44. Koppes LLJ, Twisk JWR, Snel J, Kemper HCG. Concurrent validity of alcohol consumption measurement in a ‘healthy’ population; quantity-frequency questionnaire v. dietary history interview. Br J Nutr. 2002;88:427–34.[Medline]

45. Nurk E, Refsum H, Tell GS, Engedal K, Vollset SE, Ueland PM, Nygaard HA, Smith AD. Plasma total homocysteine and memory in the elderly: the Hordaland Homocysteine Study. Ann Neurol. 2005;58:847–57.[CrossRef][Medline]

46. Launer LJ. The epidemiologic study of dementia: a life-long quest? Neurobiol Aging. 2005;26:335–40.[CrossRef][Medline]

47. Whalley LJ, Dick FD, McNeill G. A life-course approach to the aetiology of late-onset dementias. Lancet Neurol. 2006;5:87–96.[CrossRef][Medline]

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