European Journal of Clinical Nutrition (2014) 68, 1241–1244 © 2014 Macmillan Publishers Limited All rights reserved 0954-3007/14 www.nature.com/ejcn
REVIEW
Mediterranean diet interventions to prevent cognitive decline—opportunities and challenges JV Woodside, NE Gallagher, CE Neville and MC McKinley Cognitive decline has a profound impact on the health and quality of life of older people and their caregivers. Exploring mechanisms to delay cognitive decline has become an urgent economic priority, given the projected changes in population demographics. Systematic reviews and meta-analyses of observational studies suggest that adherence to a Mediterranean Diet (MD) is associated with reduced cognitive decline, but such an observation needs to be tested in randomised controlled trials. Intervention evidence is currently limited, and future studies need to be adequately powered, with careful attention given to choice of participants, outcomes being assessed, study duration and strategies to achieve compliance. Alongside these studies, consideration has to be given to how best promote and encourage dietary change in older people in general, and particularly in those experiencing the early stages of cognitive decline, as there may be specific factors that need to be considered when designing lifestyle behaviour change interventions in this group. European Journal of Clinical Nutrition (2014) 68, 1241–1244; doi:10.1038/ejcn.2014.178; published online 3 September 2014
INTRODUCTION In the developed world, as life expectancy increases and the birth rate declines, the proportion of older people is increasing. The number of people aged over 60 years is expected to rise from 605 million in 2000 to 2 billion in 2050, accounting for approximately one-fifth of the worldwide population in 2050.1 As the proportion of older people increases, so will the incidence of chronic diseases and the proportion of the population living with disability. Therefore, health and social policy makers will need to strive to overcome the challenges which this ageing population presents. Healthy or successful ageing is defined as the ability to maintain three key behaviours: low risk of disease and disease-related disability, high mental and physical function and active engagement of life.2 Strategies that reduce age-related morbidity and reduce chronic disease prevalence are therefore important for healthy or successful ageing, and are likely to have financial and societal benefits. The avoidance of malnutrition is known to contribute to the health of older people and helps recovery from illness.3 Dietary factors have also been suggested to have a role in chronic disease prevention4,5 and to promote healthy ageing. The increasing prevalence of cognitive decline and dementia, and the impact on health-care systems is a major concern as the population ages. In 2010, it was estimated that there were 35.6 million people with dementia worldwide and it has been predicted that this figure will approximately double every 20 years.6 It has also been suggested that between 5 and 20% of older people have mild cognitive impairment (MCI) of some form at any one time, although the figure depends on how MCI is defined.7 DIET AND COGNITIVE DECLINE Individual dietary components The role of diet in cognitive decline has become topical, and has been systematically reviewed.8 Several nutrients have been
examined, including B vitamins, anti-oxidant vitamins and bioactive compounds, and fat,8 yet the most recent systematic review of factors associated with prevention of cognitive decline in later life found the overall quality of evidence to be low, largely because of a relative absence of randomised controlled trials (RCTs).9,10 Mediterranean diet One dietary pattern that has received much recent attention, because of consistent observational associations with reduced risk of cardiovascular disease and diabetes,11 and recent confirmation by RCT evidence,12,13 is the Mediterranean diet (MD). The MD has been described as a pattern that emphasises a high intake of fruits, vegetables, bread, other forms of cereals, potatoes, beans, nuts and seeds. It includes olive oil as a major fat source, dairy products, fish and poultry are consumed in low-to-moderate amounts, eggs are consumed zero to four times weekly and little red meat is consumed.14 Wine is consumed in low-to-moderate amounts with meals. While there is no single MD, and geographic variations of the MD exist, in general, the MD is reminiscent of typical food patterns of many regions in Greece and southern Italy in the early 1960s. The MD has been proposed as an alternative, palatable, beneficial lifestyle change.15 Adherence to an MD is most commonly measured through the use of a score (Mediterranean Diet Score (MDS) and includes key foods consumed as part of the diet. The exact composition of the score used in epidemiological studies varies depending on the dietary data available, and the population studied.14,16–18 The use of samplespecific medians to assign scores means that similar scores can be obtained by populations with very different dietary intake and actual adherence to the MD.17,19 Similarly, the multi-component nature of the dietary score means that the same MDS can be obtained by individuals consuming quite different combinations of foods.17 A final concern in the assessment of adherence to the
Centre for Public Health, Queen’s University Belfast, Belfast, UK. Correspondence: Professor JV Woodside, Centre for Public Health, Institute of Clinical Science B, Queen’s University Belfast, Grosvenor Road, Belfast BT12 6BJ, UK. E-mail: [email protected] Received 10 July 2014; accepted 12 July 2014; published online 3 September 2014
Mediterranean diet and cognitive decline JV Woodside et al
1242 MD concerns relates to the reliance of dietary assessment methods, such as the food frequency questionnaire or 24 h recall, on memory, which may make them inappropriate data collection tools to use with older populations or in those who are already experiencing cognitive decline. A biomarker-based or biomarker/ questionnaire combined approach to assess adherence to the MD may be more appropriate in such populations and would be a useful adjunct in epidemiological studies. EVIDENCE FOR A LINK BETWEEN MD AND COGNITIVE DECLINE There are plausible mechanisms, for example, metabolic, antioxidative and anti-inflammatory, by which an MD may reduce cognitive decline, including those which are common to vascular diseases, and those which are non-vascular.20 A number of observational studies have examined whether adherence to an MD is associated with a reduced risk of cognitive decline, development of MCI or development of Alzheimer’s disease, and these studies have been subjected to systematic review and metaanalysis. An early meta-analysis pooled studies regardless of the outcome assessed, and suggested that an increase in MDS of two points was associated with a 13% reduction (95% confidence interval 0.81, 0.94) in risk of neurodegenerative diseases, and no significant heterogeneity was observed across studies (I2 = 0%, P = 0.73).11 A more recent systematic review examined cognitive function, rates of cognitive decline, risk of MCI and risk of Alzheimer’s disease separately. Twelve eligible papers were identified (eleven observational studies and one RCT), which were based on seven unique cohorts. There was considerable methodological heterogeneity and limited statistical power due to a relatively short duration of follow-up in some studies, but, despite this, reasonably consistent patterns of associations were observed. A higher adherence to MD was associated with better cognitive function, lower rates of cognitive decline and reduced risk of Alzheimer’s disease in 9/12 studies. However, the results for MCI were inconsistent. The authors acknowledged the relative lack of observational analyses and the heterogeneity in exposure and outcome assessment, suggesting that future studies need to adopt more coherent and uniform methodology to facilitate more meaningful pooled analysis in the future. The need for long-term RCTs was also highlighted.21 Since this systematic review, three further prospective cohort studies have been published. The Women’s Antioxidant Cardiovascular Study demonstrated no association between consuming an MD and cognitive decline in women who were at high risk of cardiovascular disease.22 Similarly, no association between MD and trajectories of repeated cognitive scores was shown among participants in the Women’s Health Study.23 However, over an 11-year follow-up, higher levels of adherence to the MD were associated with higher levels of cognitive function in the Cache County Study on Memory, Health and Ageing.24 Therefore, moderately consistent evidence for a protective association between increased MD adherence and reduced cognitive decline exists. However, there is some heterogeneity in the evidence to date, which may reflect methodological differences in the assessment of diet and cognitive outcomes, follow-up time and number of clinical events, which all impact on the power of the individual studies. The evidence base would be strengthened by RCT evidence, which, to date, is extremely limited. One study examined the effect of an MD over 10 days in healthy young female volunteers.25 No consistent changes in cognitive function were observed, although significant improvements in self-rated vigour, alertness and contentment were demonstrated.25 The generalisability of this intervention to older populations is questionable. A more relevant study design, a sub-study of the larger PREDIMED trial, examined the effect of a MD with extra-virgin European Journal of Clinical Nutrition (2014) 1241 – 1244
olive oil or nuts on cognition, assessed using the Mini Mental State Examination and Clock Drawing Test. These cognitive tests were not conducted at baseline, which is an obvious methodological weakness, but participants allocated to the two MD groups demonstrated higher Mini Mental State Examination and Clock Drawing Test scores compared with the control group after 6.5 years of nutritional intervention.26 This is the first RCT of MD and cognitive function carried out over a long intervention duration and, despite the lack of baseline data, and the relatively crude cognitive assessment, this study suggests that an MD can have a positive effect on cognition. More RCT evidence is needed, however, the methodological weaknesses in studies to date highlights the need to carefully consider the design of future trials to improve the quality of the evidence in this field.27 CONDUCTING FOOD AND WHOLE DIET INTERVENTION STUDIES IN OLDER PEOPLE Conducting intervention studies with whole foods and whole diets is more complex than a single nutrient intervention, which can, for example, in the case of micronutrients, be delivered in a pill form using a placebo control for comparison. In food-based or whole diet studies, notable design issues include the selection of an appropriate control group, and determining whether the intervention can be blinded, or at least the end point assessment blinded. Giving careful consideration to methods to encourage and measure compliance is also important. Guidelines on the design, conduct and reporting of food-based studies now exist,28 and these should be examined when developing such studies. The design of interventions will depend on whether the trials are of efficacy (which are certainly required initially), or, perhaps when the evidence base is more advanced, designed to develop and test interventions to promote long-term behaviour change in the target group. For efficacy studies examining the effect of the MD on cognition, design issues to be considered will include the baseline levels of cognitive function and MD adherence of the participants, the outcomes to be assessed, and, based on that outcome selection, the duration that will be required to demonstrate an effect. Outcome selection should consider an evaluation of mechanisms by which an MD intervention is likely to act,20 and possible outcomes include neuropsychological or cognitive testing, assessment of biomarkers or use of imaging, as well as the clinical diagnosis of MCI or dementia. It has been suggested that MCI, as a potentially reversible stage of decline, may be an optimum stage at which to intervene with preventive therapies, such as the MD.17,29 Study duration is an important consideration, as ensuring participants comply with a dietary intervention can be challenging, particularly in the long term. Therefore, while considering study duration, the minimum increase in MDS to be achieved must be pre-specified, and strategies and methods put in place to encourage and measure compliance. For example, in the PREDIMED study the intervention included the delivery of key foods to participants, along with regular meetings with a dietitian, but the more intensive the dietary intervention (aimed at improving compliance), the more costly the intervention will become. The required duration of studies may be reduced with the development of novel biomarkers of Alzheimer’s disease risk.30 Other study design issues that need to be considered include the advice that will be given to the control group, and how to ensure blinding of outcome assessment, as blinding of group assignment will not be possible. As a multi-component dietary intervention, it may also be appropriate to monitor other lifestyle behaviours over the course of the study (for example, physical activity) and to measure both weight and overall diet, as it is likely that MD advice may affect many aspects of diet. Indeed, including MD components may displace other foods from the diet, leading © 2014 Macmillan Publishers Limited
Mediterranean diet and cognitive decline JV Woodside et al
to an overall improvement in diet quality.31 Similarly, advice to change diet may, inadvertently, also lead to changes in other lifestyle behaviours. A final consideration when designing MD intervention studies is that the effect of adopting the diet patterns on outcomes may depend on genetic background, particularly apoE genotype.32 A number of researchers have highlighted general study design issues for primary prevention trials of dementia.33–35 Encouraging behaviour change in older people presents many challenges. The ageing process is accompanied by physical, emotional and psychological changes that can decrease food intake.36 This decrease in food intake is commonly associated with a reduction in diet quality. In particular, older people who are in hospital or in residential care are at great risk of malnutrition,37 which is associated with increased morbidity and mortality.38 Physiological factors affecting an older person’s diet include a loss of appetite (with slower gastric emptying and higher satiety levels), sensory changes in taste and smell, which can result in appetite loss, vision loss, which affects ability to buy and prepare food, and poor dental health, which can reduce the ability to eat certain foods.39 Furthermore, the presence of other factors, including chronic diseases such as diabetes and arthritis, can reduce an older person’s ability to prepare and cook healthy meals,40 and reduced gastrointestinal function can impair absorption of nutrients.41 Also, certain medications can impair the senses of taste and smell to adversely affect appetite.38 Psychological factors such as depression, grief, loneliness and social isolation can also negatively affect dietary intake in older people.42 Cognitive decline itself can interfere with the eating patterns of an older person.43,44 As well as these issues, social and economic factors, including income, knowledge and cooking ability can affect diet,45 while mobility issues can affect shopping habits and resulting dietary intake. Therefore, a range of factors including medical, physiological, psychological, social and economic factors can influence an older person’s diet, and interventions to change behaviours must consider the impact of these factors on the likely success of any intervention, including one promoting MD adherence. Few studies have examined barriers to healthy eating and views on healthy eating in older people. Fewer still have focused on those with the early stages of cognitive decline. One qualitative study in MCI patients observed a lack of awareness of the potential lifestyle-cognitive link in patients, and a reluctance to mention this link from health professionals, because of a lack of clinical trial evidence and lack of confidence in their ability to deliver lifestyle advice. Discussion with MCI patients suggested that they would favour a staged or gradual approach to the delivery of information to help with retention of information. However, as for the general population, patients with MCI varied in their willingness to even attempt lifestyle change and in the level of support they felt they would need to make lifestyle changes.46 Similar findings regarding a lack of knowledge about the link between nutrition and cognitive health have been demonstrated in the United States,47 as has the need for a multifaceted approach to educate older people about lifestyle and cognitive health.48 Finally, a demonstrated concern about declining cognitive health49 supports the need for the development of strategies to try to support lifestyle change to delay cognitive decline. CONCLUSION Strategies to encourage healthy ageing are becoming increasingly important to public health. Observational evidence suggests a possible association between increased adherence to the MD and reduced risk of cognitive decline, but studies are heterogeneous in populations studied, dietary assessment and in the outcomes measured, and therefore further well-designed studies are © 2014 Macmillan Publishers Limited
1243 required. In addition, such observational evidence would be strengthened by RCTs to test the efficacy of such an intervention. Such evidence is currently non-existent, and future studies need to be well designed, adequately powered, with careful choice of participants, study duration, outcomes to be assessed, and strategies to maximise compliance. Alongside these studies, consideration has to be given to how best promote and encourage dietary change in older people in general, and particularly those who are experiencing the first stages of cognitive decline. CONFLICT OF INTEREST The authors declare no conflict of interest.
REFERENCES 1 World Health Organisation Ageing and Life Course. [Online] Available from http://www.who.int/world-health-day/2012/toolkit/background/en/ (accessed on 5/3/14). 2 Krondl M, Coleman P, Lau D. Helping older adults meet nutritional challenges. J Nutr Elder 2008; 27: 205–220. 3 Ahmed T, Haboubi N. Assessment and management of nutrition in older people and its importance to health. Clin Interv Aging 2010; 5: 207–216. 4 Mente A, Irvine EJ, Honey RJ, Logan AG. Urinary potassium is a clinically useful test to detect a poor quality diet. J Nutr 2009; 139: 743–749. 5 World Cancer Research Fund Diet and Cancer Report. Available from http://www. dietandcancerreport.org/ (accessed on 5/3/14). 6 Alzheimer’s Disease International Dementia Statistics. [Online] Available from http://www.alz.co.uk/research/statistics. (accessed on 5/3/14). 7 Alzheimer’s Society Mild cognitive impairment Factsheet. [Online] Available from http://www.alzheimers.org.uk/site/scripts/documents_info.php?documentID = 120. (accessed on 5/3/14). 8 Gillette-Guyonnet S, Abellan van Kan G, Andrieu S, Barberger Gateau P, Berr C, Bonnefoy M et al. IANA task force on nutrition and cognitive decline with aging. J Nutr Health Aging 2007; 11: 132–142. 9 Plassman BL, Williams JW, Burke JR, Holsinger T, Benjamin S. Systematic review: factors associated with risk for and possible prevention of cognitive decline in later life. Ann Intern Med 2010; 153: 182–193. 10 Daviglus ML, Plassman BL, Pirzada A, Bell CC, Bowen PE, Burke JR et al. Risk factors and preventive interventions for Alzheimer disease: state of the science. Arch Neurol 2011; 68: 1185–1190. 11 Sofi F, Abbate R, Gensini GF, Casini A. Accruing evidence on benefits of adherence to the Mediterranean diet on health: an updated systematic review and meta-analysis. Am J Clin Nutr 2010; 92: 1189–1196. 12 Salas-Salvadó J, Bulló M, Babio N, Martínez-González MÁ, Ibarrola-Jurado N, Basora J et al. PREDIMED Study Investigators. Reduction in the incidence of type 2 diabetes with the Mediterranean diet: results of the PREDIMED-Reus nutrition intervention randomized trial. Diabetes Care 2011; 34: 14–19. 13 Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med 2013; 368: 1279–1290. 14 Bach-Faig A, Berry EM, Lairon D, Reguant J, Trichopoulou A, Dernini S. Mediterranean diet pyramid today. Science and cultural updates. Public Health Nutr 2011; 14: 2274–2284. 15 Kris-Etherton P, Eckel RH, Howard BV St, Jeor S, Bazzarre TL. Nutrition Committee Population Science Committee and Clinical Science Committee of the American Heart Association. AHA Science Advisory: Lyon Diet Heart Study: Benefits of a Mediterranean-style, National Cholesterol Education Program/American Heart Association step I dietary pattern on cardiovascular disease. Circulation 2001; 103: 1823–1825. 16 Trichopoulou A, Costacou T, Bamia C, Trichopoulos D. Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med 2003; 348: 2599–2608. 17 Féart C, Samieri C, Allès B, Barberger-Gateau P. Potential benefits of adherence to the Mediterranean diet on cognitive health. Proc Nutr Soc 2013; 72: 140–152. 18 Milà-Villarroel R, Bach-Faig A, Puig J, Puchal A, Farran A, Serra-Majem L, Carrasco JL. Comparison and evaluation of the reliability of indexes of adherence to the Mediterranean diet. Public Health Nutr 2011; 14: 2338–2345. 19 Allès B, Samieri C, Féart C, Jutand MA, Laurin D, Barberger-Gateau P. Dietary patterns: a novel approach to examine the link between nutrition and cognitive function in older individuals. Nutr Res Rev 2012; 25: 207–222.
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1244 20 Frisardi V, Panza F, Seripa D, Imbimbo BP, Vendemiale G, Pilotto A, Solfrizzi V. Nutraceutical properties of Mediterranean diet and cognitive decline: possible underlying mechanisms. J Alzheimers Dis 2010; 22: 715–740. 21 Lourida I, Soni M, Thompson-Coon J, Purandare N, Lang IA, Ukoumunne OC, Llewellyn DJ. Mediterranean diet, cognitive function, and dementia: a systematic review. Epidemiology 2013; 24: 479–489. 22 Vercambre MN, Grodstein F, Berr C, Kang JH. Mediterranean diet and cognitive decline in women with cardiovascular disease or risk factors. J Acad Nutr Diet 2012; 112: 816–823. 23 Samieri C, Grodstein F, Rosner BA, Kang JH, Cook NR, Manson JE et al. Mediterranean diet and cognitive function in older age. Epidemiology 2013; 24: 490–499. 24 Wengreen H, Munger RG, Cutler A, Quach A, Bowles A, Corcoran C et al. Prospective study of dietary approaches to stop hypertension- and mediterranean-style dietary patterns and age-related cognitive change: the Cache County Study on Memory, Health and Aging. Am J Clin Nutr 2013; 98: 1263–1271. 25 McMillan L, Owen L, Kras M, Scholey A. Behavioural effects of a 10-day Mediterranean diet. Results from a pilot study evaluating mood and cognitive performance. Appetite 2011; 56: 143–147. 26 Martínez-Lapiscina EH, Clavero P, Toledo E, Estruch R, Salas-Salvadó J, San Julián B et al. Mediterranean diet improves cognition: the PREDIMED-NAVARRA randomised trial. J Neurol Neurosurg Psychiatry 2013; 84: 1318–1325. 27 Scarmeas N. Mediterranean food for thought? J Neurol Neurosurg Psychiatry 2013; 84: 1297. 28 Welch RW, Antoine JM, Berta JL, Bub A, de Vries J, Guarner F et al. Guidelines for the design, conduct and reporting of human intervention studies to evaluate the health benefits of foods. Br J Nutr 2011; 106: S3–S15. 29 Burgener SC, Buettner LL, Beattie E, Rose KM. Effectiveness of community-based, nonpharmacological interventions for early-stage dementia: conclusions and recommendations. J Gerontol Nurs 2009; 35: 50–57. 30 Gu Y, Scarmeas N. Dietary patterns in Alzheimer’s Disease and cognitive aging. Curr Alzheimer Rev 2011; 8: 510–519. 31 Zazpe I, Sanchez-Tainta A, Estruch R, Lamuela-Raventos RM, Schröder H, Salas-Salvado J et al. A large randomized individual and group intervention conducted by registered dietitians increased adherence to Mediterranean-type diets: the PREDIMED study. J Am Diet Assoc 2008; 108: 1134–1144. 32 Hanson AJ, Bayer-Carter JL, Green PS, Montine TJ, Wilkinson CW, Baker LD et al. Effect of apolipoprotein E genotype and diet on apolipoprotein E lipidation and amyloid peptides: randomized clinical trial. JAMA Neurol 2013; 70: 972–980. 33 Luchsinger JA, Mayeux R. Dietary factors and Alzheimer's disease. Lancet Neurol 2004; 3: 579–587. 34 Coley N, Andrieu S, Gardette V, Gillette-Guyonnet S, Sanz C, Vellas B, Grand A. Dementia prevention: methodological explanations for inconsistent results. Epidemiol Rev 2008; 30: 35–66.
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35 Andrieu S, Coley N, Aisen P, Carrillo MC, DeKosky S, Durga J et al. Methodological issues in primary prevention trials for neurodegenerative dementia. J Alzheimers Dis 2009; 16: 235–270. 36 Chapman IM, MacIntosh CG, Morley JE, Horowitz M. The anorexia of ageing. Biogerontology 2002; 3: 67–71. 37 Williamson C. Dietary factors and in older people. Br J Community Nurs 2009; 14: 422–426. 38 Clarke DM, Wahlqvist ML, Strauss BJ. Undereating and undernutrition in old age: integrating bio-psychosocial aspects. Age Ageing 1998; 27: 527–534. 39 Sheiham A, Steele JG, Marcenes W, Finch S, Walls AW. The impact of oral health on stated ability to eat certain foods; findings from the National Diet and Nutrition Survey of Older People in Great Britain. Gerodontology 1999; 16: 11–20. 40 Sharpe DL, Huston SJ, Finke MS. Factors affecting nutritional adequacy among single elderly women. Family Econ Nutr Rev 2003; 15: 74–82. 41 Parker BA, Chapman IM. Food intake and ageing—the role of the gut. Mech Ageing Dev 2004; 125: 859–866. 42 German L, Kahana C, Rosenfeld V, Zabrowsky I, Wiezer Z, Fraser D, Shahar DR. Depressive symptoms are associated with food insufficiency and nutritional deficiencies in poor community-dwelling elderly people. J Nutr Health Aging 2011; 15: 3–7. 43 Watson R. Measuring feeding difficulty in patients with dementia: perspectives and problems. J Adv Nurs 1993; 18: 25–31. 44 Bucht G, Sandman PO. Nutritional aspects of dementia, especially Alzheimer’s disease. Age Ageing 1990; 19: S32–S36. 45 De Morais C, Oliveira B, Afonso C, Lumbers M, Raats M, de Almeida MDV. Nutritional risk of European elderly. Eur J Clin Nutr 2013; 67: 1215–1219. 46 Neville CE, McCourt HJ, McKinley MC, Lowis C, Barrett SL, McGuinness B et al. Encouraging lifestyle behaviour change in mild cognitive impairment patients: development of appropriate educational material. Aging Ment Health 2013; 17: 276–286. 47 Wilcox S, Sharkey JR, Matthews AE, Laditka JN, Laditka SB, Logsdon RG et al. Perceptions and beliefs about the role of physical activity and nutrition on brain health in older adults. Gerontologist 2009; 49: S61–S71. 48 Friedman DB, Laditka JN, Hunter R, Ivey SL, Wu B, Laditka SB et al. Getting the message out about cognitive health: a cross-cultural comparison of older adults’ media awareness and communication needs on how to maintain a healthy brain. Gerontologist 2009; 49: S50–S60. 49 Connell CM, Scott Roberts J, McLaughlin SJ. Public opinion about Alzheimer disease among blacks, Hispanics, and whites: results from a national survey. Alzheimer Dis Assoc Disord 2007; 21: 232–240.
© 2014 Macmillan Publishers Limited
REVIEW
Mediterranean diet interventions to prevent cognitive decline—opportunities and challenges JV Woodside, NE Gallagher, CE Neville and MC McKinley Cognitive decline has a profound impact on the health and quality of life of older people and their caregivers. Exploring mechanisms to delay cognitive decline has become an urgent economic priority, given the projected changes in population demographics. Systematic reviews and meta-analyses of observational studies suggest that adherence to a Mediterranean Diet (MD) is associated with reduced cognitive decline, but such an observation needs to be tested in randomised controlled trials. Intervention evidence is currently limited, and future studies need to be adequately powered, with careful attention given to choice of participants, outcomes being assessed, study duration and strategies to achieve compliance. Alongside these studies, consideration has to be given to how best promote and encourage dietary change in older people in general, and particularly in those experiencing the early stages of cognitive decline, as there may be specific factors that need to be considered when designing lifestyle behaviour change interventions in this group. European Journal of Clinical Nutrition (2014) 68, 1241–1244; doi:10.1038/ejcn.2014.178; published online 3 September 2014
INTRODUCTION In the developed world, as life expectancy increases and the birth rate declines, the proportion of older people is increasing. The number of people aged over 60 years is expected to rise from 605 million in 2000 to 2 billion in 2050, accounting for approximately one-fifth of the worldwide population in 2050.1 As the proportion of older people increases, so will the incidence of chronic diseases and the proportion of the population living with disability. Therefore, health and social policy makers will need to strive to overcome the challenges which this ageing population presents. Healthy or successful ageing is defined as the ability to maintain three key behaviours: low risk of disease and disease-related disability, high mental and physical function and active engagement of life.2 Strategies that reduce age-related morbidity and reduce chronic disease prevalence are therefore important for healthy or successful ageing, and are likely to have financial and societal benefits. The avoidance of malnutrition is known to contribute to the health of older people and helps recovery from illness.3 Dietary factors have also been suggested to have a role in chronic disease prevention4,5 and to promote healthy ageing. The increasing prevalence of cognitive decline and dementia, and the impact on health-care systems is a major concern as the population ages. In 2010, it was estimated that there were 35.6 million people with dementia worldwide and it has been predicted that this figure will approximately double every 20 years.6 It has also been suggested that between 5 and 20% of older people have mild cognitive impairment (MCI) of some form at any one time, although the figure depends on how MCI is defined.7 DIET AND COGNITIVE DECLINE Individual dietary components The role of diet in cognitive decline has become topical, and has been systematically reviewed.8 Several nutrients have been
examined, including B vitamins, anti-oxidant vitamins and bioactive compounds, and fat,8 yet the most recent systematic review of factors associated with prevention of cognitive decline in later life found the overall quality of evidence to be low, largely because of a relative absence of randomised controlled trials (RCTs).9,10 Mediterranean diet One dietary pattern that has received much recent attention, because of consistent observational associations with reduced risk of cardiovascular disease and diabetes,11 and recent confirmation by RCT evidence,12,13 is the Mediterranean diet (MD). The MD has been described as a pattern that emphasises a high intake of fruits, vegetables, bread, other forms of cereals, potatoes, beans, nuts and seeds. It includes olive oil as a major fat source, dairy products, fish and poultry are consumed in low-to-moderate amounts, eggs are consumed zero to four times weekly and little red meat is consumed.14 Wine is consumed in low-to-moderate amounts with meals. While there is no single MD, and geographic variations of the MD exist, in general, the MD is reminiscent of typical food patterns of many regions in Greece and southern Italy in the early 1960s. The MD has been proposed as an alternative, palatable, beneficial lifestyle change.15 Adherence to an MD is most commonly measured through the use of a score (Mediterranean Diet Score (MDS) and includes key foods consumed as part of the diet. The exact composition of the score used in epidemiological studies varies depending on the dietary data available, and the population studied.14,16–18 The use of samplespecific medians to assign scores means that similar scores can be obtained by populations with very different dietary intake and actual adherence to the MD.17,19 Similarly, the multi-component nature of the dietary score means that the same MDS can be obtained by individuals consuming quite different combinations of foods.17 A final concern in the assessment of adherence to the
Centre for Public Health, Queen’s University Belfast, Belfast, UK. Correspondence: Professor JV Woodside, Centre for Public Health, Institute of Clinical Science B, Queen’s University Belfast, Grosvenor Road, Belfast BT12 6BJ, UK. E-mail: [email protected] Received 10 July 2014; accepted 12 July 2014; published online 3 September 2014
Mediterranean diet and cognitive decline JV Woodside et al
1242 MD concerns relates to the reliance of dietary assessment methods, such as the food frequency questionnaire or 24 h recall, on memory, which may make them inappropriate data collection tools to use with older populations or in those who are already experiencing cognitive decline. A biomarker-based or biomarker/ questionnaire combined approach to assess adherence to the MD may be more appropriate in such populations and would be a useful adjunct in epidemiological studies. EVIDENCE FOR A LINK BETWEEN MD AND COGNITIVE DECLINE There are plausible mechanisms, for example, metabolic, antioxidative and anti-inflammatory, by which an MD may reduce cognitive decline, including those which are common to vascular diseases, and those which are non-vascular.20 A number of observational studies have examined whether adherence to an MD is associated with a reduced risk of cognitive decline, development of MCI or development of Alzheimer’s disease, and these studies have been subjected to systematic review and metaanalysis. An early meta-analysis pooled studies regardless of the outcome assessed, and suggested that an increase in MDS of two points was associated with a 13% reduction (95% confidence interval 0.81, 0.94) in risk of neurodegenerative diseases, and no significant heterogeneity was observed across studies (I2 = 0%, P = 0.73).11 A more recent systematic review examined cognitive function, rates of cognitive decline, risk of MCI and risk of Alzheimer’s disease separately. Twelve eligible papers were identified (eleven observational studies and one RCT), which were based on seven unique cohorts. There was considerable methodological heterogeneity and limited statistical power due to a relatively short duration of follow-up in some studies, but, despite this, reasonably consistent patterns of associations were observed. A higher adherence to MD was associated with better cognitive function, lower rates of cognitive decline and reduced risk of Alzheimer’s disease in 9/12 studies. However, the results for MCI were inconsistent. The authors acknowledged the relative lack of observational analyses and the heterogeneity in exposure and outcome assessment, suggesting that future studies need to adopt more coherent and uniform methodology to facilitate more meaningful pooled analysis in the future. The need for long-term RCTs was also highlighted.21 Since this systematic review, three further prospective cohort studies have been published. The Women’s Antioxidant Cardiovascular Study demonstrated no association between consuming an MD and cognitive decline in women who were at high risk of cardiovascular disease.22 Similarly, no association between MD and trajectories of repeated cognitive scores was shown among participants in the Women’s Health Study.23 However, over an 11-year follow-up, higher levels of adherence to the MD were associated with higher levels of cognitive function in the Cache County Study on Memory, Health and Ageing.24 Therefore, moderately consistent evidence for a protective association between increased MD adherence and reduced cognitive decline exists. However, there is some heterogeneity in the evidence to date, which may reflect methodological differences in the assessment of diet and cognitive outcomes, follow-up time and number of clinical events, which all impact on the power of the individual studies. The evidence base would be strengthened by RCT evidence, which, to date, is extremely limited. One study examined the effect of an MD over 10 days in healthy young female volunteers.25 No consistent changes in cognitive function were observed, although significant improvements in self-rated vigour, alertness and contentment were demonstrated.25 The generalisability of this intervention to older populations is questionable. A more relevant study design, a sub-study of the larger PREDIMED trial, examined the effect of a MD with extra-virgin European Journal of Clinical Nutrition (2014) 1241 – 1244
olive oil or nuts on cognition, assessed using the Mini Mental State Examination and Clock Drawing Test. These cognitive tests were not conducted at baseline, which is an obvious methodological weakness, but participants allocated to the two MD groups demonstrated higher Mini Mental State Examination and Clock Drawing Test scores compared with the control group after 6.5 years of nutritional intervention.26 This is the first RCT of MD and cognitive function carried out over a long intervention duration and, despite the lack of baseline data, and the relatively crude cognitive assessment, this study suggests that an MD can have a positive effect on cognition. More RCT evidence is needed, however, the methodological weaknesses in studies to date highlights the need to carefully consider the design of future trials to improve the quality of the evidence in this field.27 CONDUCTING FOOD AND WHOLE DIET INTERVENTION STUDIES IN OLDER PEOPLE Conducting intervention studies with whole foods and whole diets is more complex than a single nutrient intervention, which can, for example, in the case of micronutrients, be delivered in a pill form using a placebo control for comparison. In food-based or whole diet studies, notable design issues include the selection of an appropriate control group, and determining whether the intervention can be blinded, or at least the end point assessment blinded. Giving careful consideration to methods to encourage and measure compliance is also important. Guidelines on the design, conduct and reporting of food-based studies now exist,28 and these should be examined when developing such studies. The design of interventions will depend on whether the trials are of efficacy (which are certainly required initially), or, perhaps when the evidence base is more advanced, designed to develop and test interventions to promote long-term behaviour change in the target group. For efficacy studies examining the effect of the MD on cognition, design issues to be considered will include the baseline levels of cognitive function and MD adherence of the participants, the outcomes to be assessed, and, based on that outcome selection, the duration that will be required to demonstrate an effect. Outcome selection should consider an evaluation of mechanisms by which an MD intervention is likely to act,20 and possible outcomes include neuropsychological or cognitive testing, assessment of biomarkers or use of imaging, as well as the clinical diagnosis of MCI or dementia. It has been suggested that MCI, as a potentially reversible stage of decline, may be an optimum stage at which to intervene with preventive therapies, such as the MD.17,29 Study duration is an important consideration, as ensuring participants comply with a dietary intervention can be challenging, particularly in the long term. Therefore, while considering study duration, the minimum increase in MDS to be achieved must be pre-specified, and strategies and methods put in place to encourage and measure compliance. For example, in the PREDIMED study the intervention included the delivery of key foods to participants, along with regular meetings with a dietitian, but the more intensive the dietary intervention (aimed at improving compliance), the more costly the intervention will become. The required duration of studies may be reduced with the development of novel biomarkers of Alzheimer’s disease risk.30 Other study design issues that need to be considered include the advice that will be given to the control group, and how to ensure blinding of outcome assessment, as blinding of group assignment will not be possible. As a multi-component dietary intervention, it may also be appropriate to monitor other lifestyle behaviours over the course of the study (for example, physical activity) and to measure both weight and overall diet, as it is likely that MD advice may affect many aspects of diet. Indeed, including MD components may displace other foods from the diet, leading © 2014 Macmillan Publishers Limited
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to an overall improvement in diet quality.31 Similarly, advice to change diet may, inadvertently, also lead to changes in other lifestyle behaviours. A final consideration when designing MD intervention studies is that the effect of adopting the diet patterns on outcomes may depend on genetic background, particularly apoE genotype.32 A number of researchers have highlighted general study design issues for primary prevention trials of dementia.33–35 Encouraging behaviour change in older people presents many challenges. The ageing process is accompanied by physical, emotional and psychological changes that can decrease food intake.36 This decrease in food intake is commonly associated with a reduction in diet quality. In particular, older people who are in hospital or in residential care are at great risk of malnutrition,37 which is associated with increased morbidity and mortality.38 Physiological factors affecting an older person’s diet include a loss of appetite (with slower gastric emptying and higher satiety levels), sensory changes in taste and smell, which can result in appetite loss, vision loss, which affects ability to buy and prepare food, and poor dental health, which can reduce the ability to eat certain foods.39 Furthermore, the presence of other factors, including chronic diseases such as diabetes and arthritis, can reduce an older person’s ability to prepare and cook healthy meals,40 and reduced gastrointestinal function can impair absorption of nutrients.41 Also, certain medications can impair the senses of taste and smell to adversely affect appetite.38 Psychological factors such as depression, grief, loneliness and social isolation can also negatively affect dietary intake in older people.42 Cognitive decline itself can interfere with the eating patterns of an older person.43,44 As well as these issues, social and economic factors, including income, knowledge and cooking ability can affect diet,45 while mobility issues can affect shopping habits and resulting dietary intake. Therefore, a range of factors including medical, physiological, psychological, social and economic factors can influence an older person’s diet, and interventions to change behaviours must consider the impact of these factors on the likely success of any intervention, including one promoting MD adherence. Few studies have examined barriers to healthy eating and views on healthy eating in older people. Fewer still have focused on those with the early stages of cognitive decline. One qualitative study in MCI patients observed a lack of awareness of the potential lifestyle-cognitive link in patients, and a reluctance to mention this link from health professionals, because of a lack of clinical trial evidence and lack of confidence in their ability to deliver lifestyle advice. Discussion with MCI patients suggested that they would favour a staged or gradual approach to the delivery of information to help with retention of information. However, as for the general population, patients with MCI varied in their willingness to even attempt lifestyle change and in the level of support they felt they would need to make lifestyle changes.46 Similar findings regarding a lack of knowledge about the link between nutrition and cognitive health have been demonstrated in the United States,47 as has the need for a multifaceted approach to educate older people about lifestyle and cognitive health.48 Finally, a demonstrated concern about declining cognitive health49 supports the need for the development of strategies to try to support lifestyle change to delay cognitive decline. CONCLUSION Strategies to encourage healthy ageing are becoming increasingly important to public health. Observational evidence suggests a possible association between increased adherence to the MD and reduced risk of cognitive decline, but studies are heterogeneous in populations studied, dietary assessment and in the outcomes measured, and therefore further well-designed studies are © 2014 Macmillan Publishers Limited
1243 required. In addition, such observational evidence would be strengthened by RCTs to test the efficacy of such an intervention. Such evidence is currently non-existent, and future studies need to be well designed, adequately powered, with careful choice of participants, study duration, outcomes to be assessed, and strategies to maximise compliance. Alongside these studies, consideration has to be given to how best promote and encourage dietary change in older people in general, and particularly those who are experiencing the first stages of cognitive decline. CONFLICT OF INTEREST The authors declare no conflict of interest.
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