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BMC Geriatrics
Published in: BMC Geriatrics 1/2020

Open Access 01-12-2020 | Respiratory Microbiota | Study protocol

Exploring the relationship between Nutrition, gUT microbiota, and BRain AgINg in community-dwelling seniors: the Italian NutBrain population-based cohort study protocol

Authors: Federica Prinelli, Nithiya Jesuthasan, Marco Severgnini, Massimo Musicco, Fulvio Adorni, Maria Lea Correa Leite, Chiara Crespi, Sara Bernini

Published in: BMC Geriatrics | Issue 1/2020

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Abstract

Background

Epidemiological evidence suggests that healthy diet is associated with a slowdown of cognitive decline leading to dementia, but the underlying mechanisms are still partially unexplored. Diet is the main determinant of gut microbiota composition, which in turn impacts on brain structures and functions, however to date no studies on this topic are available. The goal of the present paper is to describe the design and methodology of the NutBrain Study aimed at investigating the association of dietary habits with cognitive function and their role in modulating the gut microbiota composition, and brain measures as well.

Methods/design

This is a population-based cohort study of community-dwelling adults aged 65 years or more living in Northern Milan, Italy. At the point of presentation people are screened for cognitive functions. Socio-demographic characteristics along with lifestyles and dietary habits, medical history, drugs, functional status, and anthropometric measurements are also recorded. Individuals suspected to have cognitive impairment at the screening phase undergo a clinical evaluation including a neurological examination and a Magnetic Resonance Imaging (MRI) scanning (both structural and functional). Stool and blood samples for the gut microbiota analysis and for the evaluation of putative biological markers are also collected. For each subject with a confirmed diagnosis of Mild Cognitive Impairment (MCI), two cognitively intact controls of the same sex and age are visited. We intend to enrol at least 683 individuals for the screening phase and 240 persons for the clinical assessment.

Discussion

The NutBrain is an innovative study that incorporates modern and advanced technologies (i.e. microbiome and neuroimaging) into traditional epidemiologic design. The study represents a unique opportunity to address key questions about the role of modifiable risk factors on cognitive impairment, with a particular focus on dietary habits and their association with gut microbiota and markers of the brain-aging process. These findings will help to encourage and plan lifestyle interventions, for both prevention and treatment, aiming at promoting healthy cognitive ageing.

Trial registration

Trial registration number NCT04461951, date of registration July 7, 2020 (retrospectively registered, ClinicalTrials.​gov).
Appendix
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Literature
1.
Cevenini E, Bellavista E, Tieri P, Castellani G, Lescai F, Francesconi M, Mishto M, Santoro A, Valensin S, Salvioli S, et al. Systems biology and longevity: an emerging approach to identify innovative anti-aging targets and strategies. Curr Pharm Des. 2010;16(7):802–13..PubMedCrossRef
2.
3.
4.
Prince M, Ali GC, Guerchet M, Prina AM, Albanese E, Wu YT. Recent global trends in the prevalence and incidence of dementia, and survival with dementia. Alzheimers Res Ther. 2016;8(1):23.PubMedPubMedCentralCrossRef
5.
6.
Petersen RC, Caracciolo B, Brayne C, Gauthier S, Jelic V, Fratiglioni L. Mild cognitive impairment: a concept in evolution. J Intern Med. 2014;275(3):214–28.PubMedPubMedCentralCrossRef
7.
Ravaglia G, Forti P, Montesi F, Lucicesare A, Pisacane N, Rietti E, Dalmonte E, Bianchin M, Mecocci P. Mild cognitive impairment: epidemiology and dementia risk in an elderly Italian population. J Am Geriatr Soc. 2008;56(1):51–8.PubMedCrossRef
8.
Limongi F, Siviero P, Noale M, Gesmundo A, Crepaldi G, Maggi S. Dementia registry study G: prevalence and conversion to dementia of mild cognitive impairment in an elderly Italian population. Aging Clin Exp Res. 2017;29(3):361–70.PubMedCrossRef
9.
Luck T, Luppa M, Briel S, Riedel-Heller SG. Incidence of mild cognitive impairment: a systematic review. Dement Geriatr Cogn Disord. 2010;29(2):164–75.PubMedCrossRef
10.
Malek-Ahmadi M. Reversion from mild cognitive impairment to Normal cognition: a meta-analysis. Alzheimer Dis Assoc Disord. 2016;30(4):324–30.PubMedCrossRef
11.
Klimova B, Valis M, Kuca K. Cognitive decline in normal aging and its prevention: a review on non-pharmacological lifestyle strategies. Clin Interv Aging. 2017;12:903–10.PubMedPubMedCentralCrossRef
12.
13.
Tucker KL. Nutrient intake, nutritional status, and cognitive function with aging. Ann N Y Acad Sci. 2016;1367(1):38–49.PubMedCrossRef
14.
15.
16.
Alles B, Samieri C, Feart 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(2):207–22.PubMedCrossRef
17.
van de Rest O, Berendsen AA, Haveman-Nies A, de Groot LC. Dietary patterns, cognitive decline, and dementia: a systematic review. Adv Nutr. 2015;6(2):154–68.PubMedPubMedCentralCrossRef
18.
Shakersain B, Santoni G, Larsson SC, Faxen-Irving G, Fastbom J, Fratiglioni L, Xu W. Prudent diet may attenuate the adverse effects of Western diet on cognitive decline. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2016;12(2):100–9.CrossRef
19.
Ozawa M, Shipley M, Kivimaki M, Singh-Manoux A, Brunner EJ. Dietary pattern, inflammation and cognitive decline: the Whitehall II prospective cohort study. Clin Nutr. 2017;36(2):506–12.PubMedPubMedCentralCrossRef
20.
Ozawa M, Ninomiya T, Ohara T, Doi Y, Uchida K, Shirota T, Yonemoto K, Kitazono T, Kiyohara Y. Dietary patterns and risk of dementia in an elderly Japanese population: the Hisayama study. Am J Clin Nutr. 2013;97(5):1076–82.PubMedCrossRef
21.
Granic A, Davies K, Adamson A, Kirkwood T, Hill TR, Siervo M, Mathers JC, Jagger C. Dietary patterns high in red meat, potato, gravy, and butter are associated with poor cognitive functioning but not with rate of cognitive decline in very old adults. J Nutr. 2016;146(2):265–74.PubMedPubMedCentralCrossRef
22.
Martinez-Lapiscina EH, Clavero P, Toledo E, Estruch R, Salas-Salvado J, San Julian B, Sanchez-Tainta A, Ros E, Valls-Pedret C, Martinez-Gonzalez MA. Mediterranean diet improves cognition: the PREDIMED-NAVARRA randomised trial. J Neurol Neurosurg Psychiatry. 2013;84(12):1318–25.PubMedCrossRef
23.
Valls-Pedret C, Sala-Vila A, Serra-Mir M, Corella D, de la Torre R, Martinez-Gonzalez MA, Martinez-Lapiscina EH, Fito M, Perez-Heras A, Salas-Salvado J, et al. Mediterranean diet and age-related cognitive decline: a randomized clinical trial. JAMA Intern Med. 2015;175(7):1094–103.PubMedCrossRef
24.
Moll van Charante EP, Richard E, Eurelings LS, van Dalen JW, Ligthart SA, van Bussel EF, Hoevenaar-Blom MP, Vermeulen M, van Gool WA: Effectiveness of a 6-year multidomain vascular care intervention to prevent dementia (preDIVA): a cluster-randomised controlled trial. Lancet 2016, 388(10046):797–805.
25.
Andrieu S, Guyonnet S, Coley N, Cantet C, Bonnefoy M, Bordes S, Bories L, Cufi MN, Dantoine T, Dartigues JF, et al. Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial. Lancet Neurol. 2017;16(5):377–89.PubMedCrossRef
26.
Ngandu T, Lehtisalo J, Solomon A, Levalahti E, Ahtiluoto S, Antikainen R, Backman L, Hanninen T, Jula A, Laatikainen T, et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015;385(9984):2255–63.PubMedCrossRef
27.
Smith PJ, Blumenthal JA, Babyak MA, Craighead L, Welsh-Bohmer KA, Browndyke JN, Strauman TA, Sherwood A. Effects of the dietary approaches to stop hypertension diet, exercise, and caloric restriction on neurocognition in overweight adults with high blood pressure. Hypertension. 2010;55(6):1331–8.PubMedCrossRef
28.
Blumenthal JA, Smith PJ, Welsh-Bohmer K, Babyak MA, Browndyke J, Lin PH, Doraiswamy PM, Burke J, Kraus W, Hinderliter A, et al. Can lifestyle modification improve neurocognition? Rationale and design of the ENLIGHTEN clinical trial. Contemporary clinical trials. 2013;34(1):60–9.PubMedCrossRef
29.
Tussing-Humphreys L, Lamar M, Blumenthal JA, Babyak M, Fantuzzi G, Blumstein L, Schiffer L, Fitzgibbon ML. Building research in diet and cognition: the BRIDGE randomized controlled trial. Contemporary clinical trials. 2017;59:87–97.PubMedPubMedCentralCrossRef
30.
31.
Horie N. Caloric Restriction in Obese Patients With Mild Cognitive Impairment: Effects on Adiposity CaC.
32.
Lam V, Hackett M, Takechi R: Antioxidants and Dementia Risk: Consideration through a Cerebrovascular Perspective. Nutrients 2016, 8(12).
33.
Morris MC. Symposium 1: vitamins and cognitive development and performance nutritional determinants of cognitive aging and dementia. Proc Nutr Soc. 2012;71:1–13.PubMedCrossRef
34.
Rogers GB, Keating DJ, Young RL, Wong ML, Licinio J, Wesselingh S. From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways. Mol Psychiatry. 2016;21(6):738–48.PubMedPubMedCentralCrossRef
35.
Scheperjans F, Aho V, Pereira PA, Koskinen K, Paulin L, Pekkonen E, Haapaniemi E, Kaakkola S, Eerola-Rautio J, Pohja M, et al. Gut microbiota are related to Parkinson's disease and clinical phenotype. Movement disorders : official journal of the Movement Disorder Society. 2015;30(3):350–8.CrossRef
36.
Manderino L, Carroll I, Azcarate-Peril MA, Rochette A, Heinberg L, Peat C, Steffen K, Mitchell J, Gunstad J. Preliminary evidence for an association between the composition of the gut microbiome and cognitive function in neurologically healthy older adults. Journal of the International Neuropsychological Society : JINS. 2017;23(8):700–5.PubMedCrossRef
37.
Bajaj JS, Ahluwalia V, Steinberg JL, Hobgood S, Boling PA, Godschalk M, Habib S, White MB, Fagan A, Gavis EA, et al. Elderly patients have an altered gut-brain axis regardless of the presence of cirrhosis. Sci Rep. 2016;6:38481.PubMedPubMedCentralCrossRef
38.
Caracciolo B, Xu W, Collins S, Fratiglioni L. Cognitive decline, dietary factors and gut-brain interactions. Mech Ageing Dev. 2014;136-137:59–69.PubMedCrossRef
39.
40.
Foster JA, Lyte M, Meyer E, Cryan JF: Gut Microbiota and Brain Function: An Evolving Field in Neuroscience. Int J Neuropsychopharmacol 2016, 19(5).
41.
Tengeler AC, Kozicz T, Kiliaan AJ. Relationship between diet, the gut microbiota, and brain function. Nutr Rev. 2018;76(8):603–17.PubMedCrossRef
42.
43.
Pistollato F, Cano SS, Elio I, Vergara MM, Giampieri F, Battino M. The use of neuroimaging to assess associations among diet, nutrients, metabolic syndrome, and Alzheimer's disease. Journal of Alzheimer's disease : JAD. 2015;48(2):303–18.PubMedCrossRef
44.
Bonk J. A road map for the recruitment and retention of older adult participants for longitudinal studies. J Am Geriatr Soc. 2010;58(Suppl 2):S303–7.PubMedCrossRef
45.
Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, Ainsworth BE, Pratt M, Ekelund U, Yngve A, Sallis JF, et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003;35(8):1381–95.PubMedCrossRef
46.
Nucci M, Mapelli D, Mondini S. Cognitive reserve index questionnaire (CRIq): a new instrument for measuring cognitive reserve. Aging Clin Exp Res. 2012;24(3):218–26.PubMed
47.
Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. The Gerontologist. 1969;9(3):179–86.PubMedCrossRef
48.
Katz S. Assessing self-maintenance: activities of daily living, mobility, and instrumental activities of daily living. J Am Geriatr Soc. 1983;31(12):721–7.PubMedCrossRef
49.
WC W: Nurses’ Health Study Dietary questionnaire: appendix 5–1. In: In Nutritional Epidemiology, 2nd edition edn. Edited by Press. NYOU; 1998 pp. 95–97.
50.
Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2011;7(3):270–9.CrossRef
51.
Magni E, Binetti G, Bianchetti A, Rozzini R, Trabucchi M. Mini-mental state examination: a normative study in Italian elderly population. Eur J Neurol. 1996;3(3):198–202.PubMedCrossRef
52.
Frasson P, Ghiretti R, Catricala E, Pomati S, Marcone A, Parisi L, Rossini PM, Cappa SF, Mariani C, Vanacore N, et al. Free and cued selective reminding test: an Italian normative study. Neurol Sci. 2011;32(6):1057–62.PubMedCrossRef
53.
Novelli G, Papagno, C., Capitani, E., and Laiacona, M. : Tre test clinici di ricerca e produzione lessicale. Taratura su sogetti normali. Archivio di psicologia, neurologia e psichiatria. In., edn.; 1986.
54.
Caffarra P, Vezzadini G, Dieci F, Zonato F, Venneri A. Rey-Osterrieth complex figure: normative values in an Italian population sample. Neurol Sci. 2002;22(6):443–7.PubMedCrossRef
55.
Appollonio I, Leone M, Isella V, Piamarta F, Consoli T, Villa ML, Forapani E, Russo A, Nichelli P. The frontal assessment battery (FAB): normative values in an Italian population sample. Neurol Sci. 2005;26(2):108–16.PubMedCrossRef
56.
Carlesimo GA, Caltagirone C, Gainotti G. The mental deterioration battery: normative data, diagnostic reliability and qualitative analyses of cognitive impairment. The Group for the Standardization of the mental deterioration battery. Eur Neurol. 1996;36(6):378–84.PubMedCrossRef
57.
Giovagnoli AR, Del Pesce M, Mascheroni S, Simoncelli M, Laiacona M, Capitani E. Trail making test: normative values from 287 normal adult controls. Ital J Neurol Sci. 1996;17(4):305–9.PubMedCrossRef
58.
Sartori G, and Job, R. : The oyster with four legs: A neuropsychological study on the interaction of visual and semantic information. Cognitive Neuropsychology. 1988 5((1):105–132.
59.
LS. R: the CES-D scale: a self-report depression scale for research in the general population. . Appl Psychol Meas 1977, 1(3):385–401.
60.
Guigoz Y, Vellas B. The mini nutritional assessment (MNA) for grading the nutritional state of elderly patients: presentation of the MNA, history and validation. Nestle Nutrition workshop series Clinical & performance programme. 1999;1:3–11 discussion 11-12.CrossRef
61.
62.
Wenham PR, Price WH, Blandell G. Apolipoprotein E genotyping by one-stage PCR. Lancet. 1991;337(8750):1158–9.PubMedCrossRef
63.
Consolandi C, Turroni S, Emmi G, Severgnini M, Fiori J, Peano C, Biagi E, Grassi A, Rampelli S, Silvestri E, et al. Behcet's syndrome patients exhibit specific microbiome signature. Autoimmun Rev. 2015;14(4):269–76.PubMedCrossRef
64.
Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, Fierer N, Pena AG, Goodrich JK, Gordon JI, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010;7(5):335–6.PubMedPubMedCentralCrossRef
65.
Wang Q, Garrity GM, Tiedje JM, Cole JR. Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl Environ Microbiol. 2007;73(16):5261–7.PubMedPubMedCentralCrossRef
66.
Lozupone C, Lladser ME, Knights D, Stombaugh J, Knight R. UniFrac: an effective distance metric for microbial community comparison. ISME J. 2011;5(2):169–72.PubMedCrossRef
67.
Sachdev PS, Lipnicki DM, Kochan NA, Crawford JD, Thalamuthu A, Andrews G, Brayne C, Matthews FE, Stephan BC, Lipton RB, et al. The prevalence of mild cognitive impairment in diverse geographical and Ethnocultural regions: the COSMIC collaboration. PLoS One. 2015;10(11):e0142388.PubMedPubMedCentralCrossRef
68.
Leite ML. Applying compositional data methodology to nutritional epidemiology. Stat Methods Med Res. 2016;25(6):3057–65.PubMedCrossRef
69.
Leite MLC, Prinelli F. A compositional data perspective on studying the associations between macronutrient balances and diseases. Eur J Clin Nutr. 2017.
70.
Cornelis MC, Hu FB: Systems Epidemiology: A New Direction in Nutrition and Metabolic Disease Research. Curr Nutr Rep 2013, 2(4).
Metadata
Title
Exploring the relationship between Nutrition, gUT microbiota, and BRain AgINg in community-dwelling seniors: the Italian NutBrain population-based cohort study protocol
Authors
Federica Prinelli
Nithiya Jesuthasan
Marco Severgnini
Massimo Musicco
Fulvio Adorni
Maria Lea Correa Leite
Chiara Crespi
Sara Bernini
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Geriatrics / Issue 1/2020
Electronic ISSN: 1471-2318
DOI
https://doi.org/10.1186/s12877-020-01652-2

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