Effect of the NU-AGE Diet on Cognitive Functioning in Older Adults: A Randomized Controlled Trial

Anna Marseglia, Weili Xu, Laura Fratiglioni, Cristina Fabbri, Agnes A M Berendsen, Agata Bialecka-Debek, Amy Jennings, Rachel Gillings, Nathalie Meunier, Elodie Caumon, Susan Fairweather-Tait, Barbara Pietruszka, Lisette C P G M De Groot, Aurelia Santoro, Claudio Franceschi, Anna Marseglia, Weili Xu, Laura Fratiglioni, Cristina Fabbri, Agnes A M Berendsen, Agata Bialecka-Debek, Amy Jennings, Rachel Gillings, Nathalie Meunier, Elodie Caumon, Susan Fairweather-Tait, Barbara Pietruszka, Lisette C P G M De Groot, Aurelia Santoro, Claudio Franceschi

Abstract

Background: Findings from animal and epidemiological research support the potential neuroprotective benefits from healthy diets. However, to establish diet-neuroprotective causal relations, evidence from dietary intervention studies is needed. NU-AGE is the first multicenter intervention assessing whether a diet targeting health in aging can counteract the age-related physiological changes in different organs, including the brain. In this study, we specifically investigated the effects of NU-AGE's dietary intervention on age-related cognitive decline. Materials and Methods: NU-AGE randomized trial (NCT01754012, clinicaltrials.gov) included 1279 relatively healthy older-adults, aged 65-79 years, from five European centers. Participants were randomly allocated into two groups: "control" (n = 638), following a habitual diet; and, "intervention" (n = 641), given individually tailored dietary advice (NU-AGE diet). Adherence to the NU-AGE diet was measured over follow-up, and categorized into tertiles (low, moderate, high). Cognitive function was ascertained at baseline and at 1-year follow-up with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD)-Neuropsychological Battery and five additional domain-specific single cognitive tests. The raw scores from the CERAD subtests [excluding the Mini-Mental State Examination (MMSE)] and the single tests were standardized into Z-scores. Global cognition (measured with MMSE and CERAD-total score), and five cognitive domains (perceptual speed, executive function, episodic memory, verbal abilities, and constructional praxis) were created. Cognitive changes as a function of the intervention were analyzed with multivariable mixed-effects models. Results: After the 1-year follow-up, 571 (89.1%) controls and 573 (89.8%) from the intervention group participated in the post-intervention assessment. Both control and intervention groups showed improvements in global cognition and in all cognitive domains after 1 year, but differences in cognitive changes between the two groups were not statistically significant. However, participants with higher adherence to the NU-AGE diet showed statistically significant improvements in global cognition [β 0.20 (95%CI 0.004, 0.39), p-value = 0.046] and episodic memory [β 0.15 (95%CI 0.02, 0.28), p-value = 0.025] after 1 year, compared to those adults with lower adherence. Discussion: High adherence to the culturally adapted, individually tailored, NU-AGE diet could slow down age-related cognitive decline, helping to prevent cognitive impairment and dementia.

Keywords: cognitive decline; dietary intervention; episodic memory; healthy diet; multicenter; neuroprotective; randomized controlled trial.

Figures

Figure 1
Figure 1
Estimated trajectories of change in global and domain-specific cognitive function 1-year after randomization by group. The figure shows the changes in global cognition (A), perceptual speed (B), executive functions (C), episodic memory (D), verbal abilities (E), and constructional praxis (F) in the control group [n = 641; (reference); black solid line] vs. intervention group (n = 638; gray dash line). Mixed-effect models were adjusted for baseline age, sex, education, country, and interviewer. The trajectories were plotted using the mean values of the covariates. CTS, CERAD total score.
Figure 2
Figure 2
Estimated trajectories of change in global cognition (A) and episodic memory (B) among participants in the intervention group (n = 638) with low (first tertile, reference) to high (third tertile) adherence levels to the NU-AGE dietary intervention. Mixed-effect models were adjusted for baseline age, sex, education, country, and interviewer. The trajectories were plotted using the mean values of the covariates. CTS, CERAD total score.

References

    1. Babcock H., Levy L. (1940). Revision of the Babcock Examination for Measuring Efficiency of Mental Functioning. Chicago: Stoelting.
    1. Berendsen A., Santoro A., Pini E., Cevenini E., Ostan R., Pietruszka B., et al. (2014). Reprint of: a parallel randomized trial on the effect of a healthful diet on inflammageing and its consequences in European elderly people: design of the NU-AGE dietary intervention study. Mech. Ageing Dev. 136–137, 14–21. 10.1016/j.mad.2014.03.001
    1. Boccardi V., Calvani R., Limongi F., Marseglia A., Mason A., Noale M., et al. (2018). Consensus paper on the “executive summary of the international conference on mediterranean diet and health: a lifelong approach”, an italian initiative supported by the mediterranean diet foundation and the menarini foundation. Nutrition 51–52, 38–45. 10.1016/j.nut.2017.12.002
    1. Calabrese V., Santoro A., Monti D., Crupi R., Di Paola R., Latteri S., et al. . (2017). Aging and Parkinson's Disease: Inflammaging, neuroinflammation and biological remodeling as key factors in pathogenesis. Free Radic. Biol. Med. 115, 80–91. 10.1016/j.freeradbiomed.2017.10.379
    1. Caracciolo B., Xu W., Collins S., Fratiglioni L. (2014). Cognitive decline, dietary factors and gut-brain interactions. Mech. Ageing Dev. 136–137, 59–69. 10.1016/j.mad.2013.11.011
    1. Chandler M. J., Lacritz L. H., Hynan L. S., Barnard H. D., Allen G., Deschner M., et al. . (2005). A total score for the CERAD neuropsychological battery. Neurology 65, 102–106. 10.1212/01.wnl.0000167607.63000.38
    1. Cherbuin N., Anstey K. J. (2012). The Mediterranean diet is not related to cognitive change in a large prospective investigation: the PATH through life study. Am. J. Geriatr. Psychiatry 20, 635–639. 10.1097/JGP.0b013e31823032a9
    1. Dernini S., Berry E. M. (2015). Mediterranean diet: from a healthy diet to a sustainable dietary pattern. Front. Nutr. 2:15. 10.3389/fnut.2015.00015
    1. Devore E. E., Kang J. H., Breteler M. M., Grodstein F. (2012). Dietary intakes of berries and flavonoids in relation to cognitive decline. Ann. Neurol. 72, 135–143. 10.1002/ana.23594
    1. Dickerson B. C., Eichenbaum H. (2010). The episodic memory system: neurocircuitry and disorders. Neuropsychopharmacology 35, 86–104. 10.1038/npp.2009.126
    1. Dubois B., Feldman H. H., Jacova C., Cummings J. L., Dekosky S. T., Barberger-Gateau P., et al. . (2010). Revising the definition of Alzheimer's disease: a new lexicon. Lancet Neurol. 9, 1118–1127. 10.1016/S1474-4422(10)70223-4
    1. Féart C., Samieri C., Rondeau V., Amieva H., Portet F., Dartigues J. F., et al. . (2009). Adherence to a Mediterranean diet, cognitive decline, and risk of dementia. JAMA 302, 638–648. 10.1001/jama.2009.1146
    1. Folstein M. F., Folstein S. E., McHugh P. R. (1975). “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 12, 189–198. 10.1016/0022-3956(75)90026-6
    1. Fried L. P., Tangen C. M., Walston J., Newman A. B., Hirsch C., Gottdiener J., et al. . (2001). Frailty in older adults: evidence for a phenotype. J. Gerontol. A Biol. Sci. Med. Sci. 56, M146–M156. 10.1093/gerona/56.3.M146
    1. Fusco D., Colloca G., Lo Monaco M. R., Cesari M. (2007). Effects of antioxidant supplementation on the aging process. Clin. Interv. Aging 2, 377–387.
    1. Gillette-Guyonnet S., Secher M., Vellas B. (2013). Nutrition and neurodegeneration: epidemiological evidence and challenges for future research. Br. J. Clin. Pharmacol. 75, 738–755. 10.1111/bcp.12058
    1. Gray S. L., Anderson M. L., Hubbard R. A., LaCroix A., Crane P. K., McCormick W., et al. . (2013). Frailty and incident dementia. J. Gerontol. A Biol. Sci. Med. Sci. 68, 1083–1090. 10.1093/gerona/glt013
    1. Gu Y., Brickman A. M., Stern Y., Habeck C. G., Razlighi Q. R., Luchsinger J. A., et al. . (2015). Mediterranean diet and brain structure in a multiethnic elderly cohort. Neurology 85, 1744–1751. 10.1212/WNL.0000000000002121
    1. Heneka M. T., Carson M. J., El Khoury J., Landreth G. E., Brosseron F., Feinstein D. L., et al. . (2015). Neuroinflammation in Alzheimer's disease. Lancet Neurol. 14, 388–405. 10.1016/S1474-4422(15)70016-5
    1. Hooshmand B., Lökk J., Solomon A., Mangialasche F., Miralbell J., Spulber G., et al. . (2014). Vitamin D in relation to cognitive impairment, cerebrospinal fluid biomarkers, and brain volumes. J. Gerontol. A Biol. Sci. Med. Sci. 69, 1132–1138. 10.1093/gerona/glu022
    1. Jacka F. N., Cherbuin N., Anstey K. J., Sachdev P., Butterworth P. (2015). Western diet is associated with a smaller hippocampus: a longitudinal investigation. BMC Med. 13:215. 10.1186/s12916-015-0461-x
    1. Jacobs D. R., Jr., Gross M. D., Tapsell L. C. (2009). Food synergy: an operational concept for understanding nutrition. Am. J. Clin. Nutr. 89, 1543S−1548S. 10.3945/ajcn.2009.26736B
    1. Kanerva N., Kaartinen N. E., Schwab U., Lahti-Koski M., Männistö S. (2014). The Baltic Sea Diet Score: a tool for assessing healthy eating in Nordic countries. Public Health Nutr. 17, 1697–1705. 10.1017/S1368980013002395
    1. Knight A., Bryan J., Murphy K. (2016a). Is the Mediterranean diet a feasible approach to preserving cognitive function and reducing risk of dementia for older adults in Western countries? New insights and future directions. Ageing Res. Rev. 25, 85–101. 10.1016/j.arr.2015.10.005
    1. Knight A., Bryan J., Wilson C., Hodgson J. M., Davis C. R., Murphy K. J. (2016b). The Mediterranean diet and cognitive function among healthy older adults in a 6-month randomised controlled trial: the medley study. Nutrients 8:E579. 10.3390/nu8090579
    1. Laukka E. J., Lövdén M., Herlitz A., Karlsson S., Ferencz B., Pantzar A., et al. . (2013). Genetic effects on old-age cognitive functioning: a population-based study. Psychol. Aging 28, 262–274. 10.1037/a0030829
    1. Lezak M. D., Howieson D. B., Bigler E. D., Tranel D. (2012). Neuropsychological Assessment. New York, NY: Oxford University Press.
    1. Liu Z., Zhou T., Ziegler A. C., Dimitrion P., Zuo L. (2017). Oxidative stress in neurodegenerative diseases: from molecular mechanisms to clinical applications. Oxid. Med. Cell. Longev. 2017:2525967. 10.1155/2017/2525967
    1. Mangialasche F., Kivipelto M., Mecocci P., Rizzuto D., Palmer K., Winblad B., et al. . (2010). High plasma levels of vitamin E forms and reduced Alzheimer's disease risk in advanced age. J. Alzheimers. Dis. 20, 1029–1037. 10.3233/JAD-2010-091450
    1. Mangialasche F., Solomon A., Kåreholt I., Hooshmand B., Cecchetti R., Fratiglioni L., et al. . (2013). Serum levels of vitamin E forms and risk of cognitive impairment in a Finnish cohort of older adults. Exp. Gerontol. 48, 1428–1435. 10.1016/j.exger.2013.09.006
    1. Martucci M., Ostan R., Biondi F., Bellavista E., Fabbri C., Bertarelli C., et al. . (2017). Mediterranean diet and inflammaging within the hormesis paradigm. Nutr. Rev. 75, 442–455. 10.1093/nutrit/nux013
    1. Morris J. C., Heyman A., Mohs R. C., Hughes J. P., Van Belle G., Fillenbaum G., et al. . (1989). The Consortium to establish a registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer's disease. Neurology 39, 1159–1165. 10.1212/WNL.39.9.1159
    1. Morris M. C. (2016). Nutrition and risk of dementia: overview and methodological issues. Ann. N. Y. Acad. Sci. 1367, 31–37. 10.1111/nyas.13047
    1. Morris M. C., Tangney C. C., Wang Y., Sacks F. M., Barnes L. L., Bennett D. A., et al. . (2015). MIND diet slows cognitive decline with aging. Alzheimers. Dement. 11, 1015–1022. 10.1016/j.jalz.2015.04.011
    1. Ostan R., Lanzarini C., Pini E., Scurti M., Vianello D., Bertarelli C., et al. . (2015). Inflammaging and cancer: a challenge for the Mediterranean diet. Nutrients 7, 2589–2621. 10.3390/nu7042589
    1. Prince M., Wimo A., Guerchet M., Ali G. C., Wu Y. T., Prina M. (2015). World Alzheimer Report 2015—the Global Impact of Dementia: an Analysis of Prevalence, Incidence, Cost and Trends. (Alzheimer's Disease International, London: ).
    1. Psaltopoulou T., Kyrozis A., Stathopoulos P., Trichopoulos D., Vassilopoulos D., Trichopoulou A. (2008). Diet, physical activity and cognitive impairment among elders: the EPIC-Greece cohort (European Prospective Investigation into Cancer and Nutrition). Public Health Nutr. 11, 1054–1062. 10.1017/S1368980007001607
    1. Psaltopoulou T., Sergentanis T. N., Panagiotakos D. B., Sergentanis I. N., Kosti R., Scarmeas N. (2013). Mediterranean diet, stroke, cognitive impairment, and depression: a meta-analysis. Ann. Neurol. 74, 580–591. 10.1002/ana.23944
    1. Salthouse T. A., Babcock R. L. (1991). Decomposing adult age differences in working memory. Dev. Psychol. 27, 763–776. 10.1037/0012-1649.27.5.763
    1. Samieri C., Grodstein F., Rosner B. A., Kang J. H., Cook N. R., Manson J. E., et al. . (2013a). Mediterranean diet and cognitive function in older age. Epidemiology 24, 490–499. 10.1097/EDE.0b013e318294a065
    1. Samieri C., Okereke O. I., E Devore E., Grodstein F. (2013b). Long-term adherence to the Mediterranean diet is associated with overall cognitive status, but not cognitive decline, in women. J. Nutr. 143, 493–499. 10.3945/jn.112.169896
    1. Santoro A., Pini E., Scurti M., Palmas G., Berendsen A., Brzozowska A., et al. (2014). Combating inflammaging through a Mediterranean whole diet approach: the NU-AGE project's conceptual framework and design. Mech. Ageing Dev. 136–137, 3–13. 10.1016/j.mad.2013.12.001
    1. Scarmeas N., Stern Y., Mayeux R., Luchsinger J. A. (2006). Mediterranean diet, Alzheimer disease, and vascular mediation. Arch. Neurol. 63, 1709–1717. 10.1001/archneur.63.12.noc60109
    1. Segarra A. B., Ruiz-Sanz J. I., Ruiz-Larrea M. B., Ramírez-Sánchez M., de Gasparo M., Banegas I., et al. . (2011). The profile of fatty acids in frontal cortex of rats depends on the type of fat used in the diet and correlates with neuropeptidase activities. Horm. Metab. Res. 43, 86–91. 10.1055/s-0030-1269855
    1. Shakersain B., Santoni G., Larsson S. C., Faxén-Irving G., Fastbom J., Fratiglioni L., et al. . (2016). Prudent diet may attenuate the adverse effects of Western diet on cognitive decline. Alzheimers. Dement. 12, 100–109. 10.1016/j.jalz.2015.08.002
    1. Singh B., Parsaik A. K., Mielke M. M., Erwin P. J., Knopman D. S., Petersen R. C., et al. . (2014). Association of mediterranean diet with mild cognitive impairment and Alzheimer's disease: a systematic review and meta-analysis. J. Alzheimers. Dis. 39, 271–282. 10.3233/JAD-13083
    1. Siscovick D. S., Fried L., Mittelmark M., Rutan G., Bild D., O'leary D. H. (1997). Exercise intensity and subclinical cardiovascular disease in the elderly. The Cardiovascular Health Study. Am. J. Epidemiol. 145, 977–986. 10.1093/oxfordjournals.aje.a009066
    1. Smith P. J., Blumenthal J. A., Babyak M. A., Craighead L., Welsh-Bohmer K. A., Browndyke J. N., et al. . (2010). Effects of the dietary approaches to stop hypertension diet, exercise, and caloric restriction on neurocognition in overweight adults with high blood pressure. Hypertension 55, 1331–1338. 10.1161/HYPERTENSIONAHA.109.146795
    1. Solfrizzi V., Custodero C., Lozupone M., Imbimbo B. P., Valiani V., Agosti P., et al. . (2017). Relationships of dietary patterns, foods, and micro- and macronutrients with Alzheimer's Disease and late-life cognitive disorders: a systematic review. J. Alzheimers. Dis. 59, 815–849. 10.3233/JAD-170248
    1. Sousa-Santos A. R., Afonso C., Moreira P., Padrão P., Santos A., Borges N., et al. . (2018). Weakness: the most frequent criterion among pre-frail and frail older Portuguese. Arch. Gerontol. Geriatr. 74, 162–168. 10.1016/j.archger.2017.10.018
    1. Tangney C. C., Kwasny M. J., Li H., Wilson R. S., Evans D. A., Morris M. C. (2011). Adherence to a Mediterranean-type dietary pattern and cognitive decline in a community population. Am. J. Clin. Nutr. 93, 601–607. 10.3945/ajcn.110.007369
    1. Tangney C. C., Li H., Wang Y., Barnes L., Schneider J. A., Bennett D. A., et al. . (2014). Relation of DASH- and Mediterranean-like dietary patterns to cognitive decline in older persons. Neurology 83, 1410–1416. 10.1212/WNL.0000000000000884
    1. Taylor H. L., Jacobs D. R., Jr., Schucker B., Knudsen J., Leon A. S., Debacker G. (1978). A questionnaire for the assessment of leisure time physical activities. J. Chronic Dis. 31, 741–755. 10.1016/0021-9681(78)90058-9
    1. Trichopoulou A., Kyrozis A., Rossi M., Katsoulis M., Trichopoulos D., La Vecchia C., et al. . (2015). Mediterranean diet and cognitive decline over time in an elderly Mediterranean population. Eur. J. Nutr. 54, 1311–1321. 10.1007/s00394-014-0811-z
    1. Valls-Pedret C., Sala-Vila A., Serra-Mir M., Corella D., De La Torre R., Martínez-González MÁ M. A., et al. . (2015). Mediterranean diet and age-related cognitive decline: a randomized clinical trial. JAMA Intern. Med. 175, 1094–1103. 10.1001/jamainternmed.2015.1668
    1. Vitale G., Salvioli S., Franceschi C. (2013). Oxidative stress and the ageing endocrine system. Nat. Rev. Endocrinol. 9, 228–240. 10.1038/nrendo.2013.29
    1. Winblad B., Amouyel P., Andrieu S., Ballard C., Brayne C., Brodaty H., et al. . (2016). Defeating Alzheimer's disease and other dementias: a priority for European science and society. Lancet Neurol. 15, 455–532. 10.1016/S1474-4422(16)00062-4
    1. Yannakoulia M., Kontogianni M., Scarmeas N. (2015). Cognitive health and Mediterranean diet: just diet or lifestyle pattern? Ageing Res. Rev. 20, 74–78. 10.1016/j.arr.2014.10.003
    1. Zazzo R. (1974). Test Des deux Barrages. Actualités Pédagogiques et Psychologiques, Vol. 7 Neuchâtel: Delachaux et Nestlé.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever