A blood-based nutritional risk index explains cognitive enhancement and decline in the multidomain Alzheimer prevention trial

MAPT/DSA Study Group

doi:10.1016/j.trci.2019.11.004

A blood-based nutritional risk index explains cognitive enhancement and decline in the multidomain Alzheimer prevention trial

MAPT/DSA Study Group

Neurology

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

Introduction: Multinutrient approaches may produce more robust effects on brain health through interactive qualities. We hypothesized that a blood-based nutritional risk index (NRI) including three biomarkers of diet quality can explain cognitive trajectories in the multidomain Alzheimer prevention trial (MAPT) over 3-years. Methods: The NRI included erythrocyte n-3 polyunsaturated fatty acids (n-3 PUFA 22:6n-3 and 20:5n-3), serum 25-hydroxyvitamin D, and plasma homocysteine. The NRI scores reflect the number of nutritional risk factors (0–3). The primary outcome in MAPT was a cognitive composite Z score within each participant that was fit with linear mixed-effects models. Results: Eighty percent had at lease one nutritional risk factor for cognitive decline (NRI ≥1: 573 of 712). Participants presenting without nutritional risk factors (NRI=0) exhibited cognitive enhancement (β = 0.03 standard units [SU]/y), whereas each NRI point increase corresponded to an incremental acceleration in rates of cognitive decline (NRI-1: β = −0.04 SU/y, P = .03; NRI-2: β = −0.08 SU/y, P < .0001; and NRI-3: β = −0.11 SU/y, P = .0008). Discussion: Identifying and addressing these well-established nutritional risk factors may reduce age-related cognitive decline in older adults; an observation that warrants further study.

Original language	English (US)
Pages (from-to)	953-963
Number of pages	11
Journal	Alzheimer's and Dementia: Translational Research and Clinical Interventions
Volume	5
DOIs	https://doi.org/10.1016/j.trci.2019.11.004
State	Published - 2019

Keywords

Aging
Biomarkers of diet quality
Cognitive decline
DHA
EPA
Elderly
Homocysteine
Metabolomics
Nutrient biomarkers
Omega-3 fatty acids
Vitamin D

ASJC Scopus subject areas

Clinical Neurology
Psychiatry and Mental health

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10.1016/j.trci.2019.11.004

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@article{0014565734e14a32aa273a60b13e3a55,

title = "A blood-based nutritional risk index explains cognitive enhancement and decline in the multidomain Alzheimer prevention trial",

abstract = "Introduction: Multinutrient approaches may produce more robust effects on brain health through interactive qualities. We hypothesized that a blood-based nutritional risk index (NRI) including three biomarkers of diet quality can explain cognitive trajectories in the multidomain Alzheimer prevention trial (MAPT) over 3-years. Methods: The NRI included erythrocyte n-3 polyunsaturated fatty acids (n-3 PUFA 22:6n-3 and 20:5n-3), serum 25-hydroxyvitamin D, and plasma homocysteine. The NRI scores reflect the number of nutritional risk factors (0–3). The primary outcome in MAPT was a cognitive composite Z score within each participant that was fit with linear mixed-effects models. Results: Eighty percent had at lease one nutritional risk factor for cognitive decline (NRI ≥1: 573 of 712). Participants presenting without nutritional risk factors (NRI=0) exhibited cognitive enhancement (β = 0.03 standard units [SU]/y), whereas each NRI point increase corresponded to an incremental acceleration in rates of cognitive decline (NRI-1: β = −0.04 SU/y, P = .03; NRI-2: β = −0.08 SU/y, P < .0001; and NRI-3: β = −0.11 SU/y, P = .0008). Discussion: Identifying and addressing these well-established nutritional risk factors may reduce age-related cognitive decline in older adults; an observation that warrants further study.",

keywords = "Aging, Biomarkers of diet quality, Cognitive decline, DHA, EPA, Elderly, Homocysteine, Metabolomics, Nutrient biomarkers, Omega-3 fatty acids, Vitamin D",

author = "{MAPT/DSA Study Group} and Bowman, {Gene L.} and Dodge, {Hiroko H.} and Sophie Guyonnet and Nina Zhou and Juliana Donohue and Aline Bichsel and Jeroen Schmitt and Claudie Hooper and Tamas Bartfai and Sandrine Andrieu and Bruno Vellas and Isabelle Carri{\'e} and Laur{\'e}ane Brigitte and Catherine Faisant and Fran{\c c}oise Lala and Julien Delrieu and H{\'e}l{\`e}ne Villars and Emeline Combrouze and Carole Badufle and Audrey Zueras and Christelle Cantet and Christophe Morin and {Van Kan}, {Gabor Abellan} and Charlotte Dupuy and Yves Rolland and C{\'e}line Caillaud and Ousset, {Pierre Jean}",

note = "Funding Information: Disclosures: G.L.B. reports US National Institutes of Health funding; is an unpaid Scientific Advisory Board member of the PROPAG-AGEING EU Horizon 2020 project; H.H.D. reports US National Institutes of Health funding; N.Z. reports no disclosures; S.G. reports no disclosures; the Nestle Institute of Health Sciences employs J.D.; the Nestle Institute of Health Sciences employs A.B.; Nestle Research Center employs J.S.; C.H. reports no disclosures; T.B. reports no disclosures; S.A. reports grants from JPND program, EU-FP7 program, Beaufour Ipsen Pharma, personal fees from Beaufour Ipsen Pharma, Pierre Fabre, Lilly, Nestl?, Sanofi, Servier, MSD, and nonfinancial support from Biogen, Pfizer, Icon, grants from France Alzheimer Association, AMPA Association outside the submitted work; B.V. reports grants from Pierre Fabre, Avid, Exonhit, AbbVie, Lilly, Lundbeck, MSD, Otsuka, Regeneron, Sanofi, Roche, Astra Zeneca, LPG Systems, Nestl?, and Alzheon.MAPT/DSA group refers to MAPT Study Group: Principal investigator: Bruno Vellas (Toulouse); Coordination: Sophie Guyonnet; Project leader: Isabelle Carri?; Clinical research assistant: Laur?ane Brigitte; Investigators: Catherine Faisant, Fran?oise Lala, Julien Delrieu, and H?l?ne Villars; Psychologists: Emeline Combrouze, Carole Badufle, and Audrey Zueras; Methodology, statistical analysis, and data management: Sandrine Andrieu, Christelle Cantet, and Christophe Morin; Multidomain group: Gabor Abellan Van Kan, Charlotte Dupuy, Yves Rolland (physical and nutritional components), C?line Caillaud, Pierre-Jean Ousset (cognitive component), and Fran?oise Lala (preventive consultation). The cognitive component was designed in collaboration with Sherry Willis from the University of Seattle, and Sylvie Belleville, Brigitte Gilbert, and Francine Fontaine from the University of Montreal. Coinvestigators in associated center: Jean-Fran?ois Dartigues, Isabelle Marcet, Fleur Delva, Alexandra Foubert, and Sandrine Cerda (Bordeaux); Marie-No?lle-Cuffi and Corinne Costes (Castres); Olivier Rouaud, Patrick Manckoundia, Val?rie Quipourt, Sophie Marilier, and Evelyne Franon (Dijon); Lawrence Bories, Marie-Laure Pader, Marie-France Basset, Bruno Lapoujade, Val?rie Faure, Michael Li Yung Tong, Christine Malick-Loiseau, and Evelyne Cazaban-Campistron (Foix); Fran?oise Desclaux and Colette Blatge (Lavaur); Thierry Dantoine, C?cile Laubarie-Mouret, Isabelle Saulnier, Jean-Pierre Cl?ment, Marie-Agn?s Picat, Laurence Bernard-Bourzeix, St?phanie Willebois, Il?ana D?sormais, and No?lle Cardinaud (Limoges); Marc Bonnefoy, Pierre Livet, Pascale Rebaudet, Claire G?d?on, Catherine Burdet, Flavien Terracol (Lyon), Alain Pesce, St?phanie Roth, Sylvie Chaillou, and Sandrine Louchart (Monaco); Kristelle Sudres, Nicolas Lebrun, and Nad?ge Barro-Belaygues (Montauban); Jacques Touchon, Karim Bennys, Audrey Gabelle, Aur?lia Romano, Lynda Touati, C?cilia Marelli, and C?cile Pays (Montpellier); Philippe Robert, Franck Le Duff, Claire Gervais, and S?bastien Gonfrier (Nice); Yannick Gasnier and Serge Bordes, Dani?le Begorre, Christian Carpuat, Khaled Khales, Jean-Fran?ois Lefebvre, Samira Misbah El Idrissi, Pierre Skolil, and Jean-Pierre Salles (Tarbes). Magnetic resonance imaging group: Carole Dufouil (Bordeaux), St?phane Leh?ricy, Marie Chupin, Jean-Fran?ois Mangin, and Ali Bouhayia (Paris); Mich?le Allard (Bordeaux); Fr?d?ric Ricolfi (Dijon); Dominique Dubois (Foix); Marie Paule Bonceour Martel (Limoges); Fran?ois Cotton (Lyon); Alain Bonaf? (Montpellier); St?phane Chanalet (Nice); Fran?oise Hugon (Tarbes); Fabrice Bonneville, Christophe Cognard, and Fran?ois Chollet (Toulouse). Positron emission tomography scan group: Pierre Payoux, Thierry Voisin, Julien Delrieu, Sophie Peiffer, and Anne Hitzel (Toulouse); Mich?le Allard (Bordeaux); Michel Zanca (Montpellier); Jacques Monteil (Limoges); Jacques Darcourt (Nice). Medicoeconomics group: Laurent Molinier, H?l?ne Derumeaux, and Nad?ge Costa (Toulouse). Biological sample collection: Sylvie Caspar-Bauguil, Bertrand Perret, and Claire Vinel (Toulouse). Safety management: Pascale Olivier-Abbal. DSA group: Sandrine Andrieu, Christelle Cantet, and Nicola Coley. Funding: Nutrient biomarker and statistical analysis was supported by the Nestle Institute of Health Sciences. The MAPT study was supported by grants from the G?rontop?le of Toulouse, the French Ministry of Health (PHRC 2008, 2009), Pierre Fabre Research Institute (manufacturer of the n-3 supplement), Exhonit Therapeutics SA, and Avid Radiopharmaceuticals Inc. The promotion of this study was supported by the University Hospital Center of Toulouse. The data sharing activity was supported by the Association Monegasque pour la Recherche sur la maladie d'Alzheimer and the UMR 1027 Unit INSERM??University of Toulouse III. Contributions: G.L.B.: conceptualized, designed the study, secured the funding, selected the biomarkers of diet quality and analytical assays, composed the statistical analysis plan, interpreted the data, and drafted and revised the manuscript; H.H.D.: concept and design, composed and conducted the statistical analysis plan, interpreted the data, and revised the manuscript; N.Z.: performed statistical analysis; S.G.: literature review and revised the manuscript; J.D.: literature review and revised the manuscript; A.B.: contributed to the management and coordination of the statistical analysis; J.S.: literature review and revised the manuscript; C.H.: literature review and revised the manuscript; T.B.; S.A.; and B.V.: concept and design, interpreted the data, and revised the manuscript. Funding Information: Funding: Nutrient biomarker and statistical analysis was supported by the Nestle Institute of Health Sciences . The MAPT study was supported by grants from the G{\'e}rontop{\^o}le of Toulouse , the French Ministry of Health (PHRC 2008, 2009), Pierre Fabre Research Institute (manufacturer of the n-3 supplement), Exhonit Therapeutics SA , and Avid Radiopharmaceuticals Inc. The promotion of this study was supported by the University Hospital Center of Toulouse . The data sharing activity was supported by the Association Monegasque pour la Recherche sur la maladie d'Alzheimer and the UMR 1027 Unit INSERM––University of Toulouse III. Publisher Copyright: {\textcopyright} 2019 The Authors",

year = "2019",

doi = "10.1016/j.trci.2019.11.004",

language = "English (US)",

volume = "5",

pages = "953--963",

journal = "Alzheimer's and Dementia: Translational Research and Clinical Interventions",

issn = "2352-8737",

publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - A blood-based nutritional risk index explains cognitive enhancement and decline in the multidomain Alzheimer prevention trial

AU - MAPT/DSA Study Group

AU - Bowman, Gene L.

AU - Dodge, Hiroko H.

AU - Guyonnet, Sophie

AU - Zhou, Nina

AU - Donohue, Juliana

AU - Bichsel, Aline

AU - Schmitt, Jeroen

AU - Hooper, Claudie

AU - Bartfai, Tamas

AU - Andrieu, Sandrine

AU - Vellas, Bruno

AU - Carrié, Isabelle

AU - Brigitte, Lauréane

AU - Faisant, Catherine

AU - Lala, Françoise

AU - Delrieu, Julien

AU - Villars, Hélène

AU - Combrouze, Emeline

AU - Badufle, Carole

AU - Zueras, Audrey

AU - Cantet, Christelle

AU - Morin, Christophe

AU - Van Kan, Gabor Abellan

AU - Dupuy, Charlotte

AU - Rolland, Yves

AU - Caillaud, Céline

AU - Ousset, Pierre Jean

N1 - Funding Information: Disclosures: G.L.B. reports US National Institutes of Health funding; is an unpaid Scientific Advisory Board member of the PROPAG-AGEING EU Horizon 2020 project; H.H.D. reports US National Institutes of Health funding; N.Z. reports no disclosures; S.G. reports no disclosures; the Nestle Institute of Health Sciences employs J.D.; the Nestle Institute of Health Sciences employs A.B.; Nestle Research Center employs J.S.; C.H. reports no disclosures; T.B. reports no disclosures; S.A. reports grants from JPND program, EU-FP7 program, Beaufour Ipsen Pharma, personal fees from Beaufour Ipsen Pharma, Pierre Fabre, Lilly, Nestl?, Sanofi, Servier, MSD, and nonfinancial support from Biogen, Pfizer, Icon, grants from France Alzheimer Association, AMPA Association outside the submitted work; B.V. reports grants from Pierre Fabre, Avid, Exonhit, AbbVie, Lilly, Lundbeck, MSD, Otsuka, Regeneron, Sanofi, Roche, Astra Zeneca, LPG Systems, Nestl?, and Alzheon.MAPT/DSA group refers to MAPT Study Group: Principal investigator: Bruno Vellas (Toulouse); Coordination: Sophie Guyonnet; Project leader: Isabelle Carri?; Clinical research assistant: Laur?ane Brigitte; Investigators: Catherine Faisant, Fran?oise Lala, Julien Delrieu, and H?l?ne Villars; Psychologists: Emeline Combrouze, Carole Badufle, and Audrey Zueras; Methodology, statistical analysis, and data management: Sandrine Andrieu, Christelle Cantet, and Christophe Morin; Multidomain group: Gabor Abellan Van Kan, Charlotte Dupuy, Yves Rolland (physical and nutritional components), C?line Caillaud, Pierre-Jean Ousset (cognitive component), and Fran?oise Lala (preventive consultation). The cognitive component was designed in collaboration with Sherry Willis from the University of Seattle, and Sylvie Belleville, Brigitte Gilbert, and Francine Fontaine from the University of Montreal. Coinvestigators in associated center: Jean-Fran?ois Dartigues, Isabelle Marcet, Fleur Delva, Alexandra Foubert, and Sandrine Cerda (Bordeaux); Marie-No?lle-Cuffi and Corinne Costes (Castres); Olivier Rouaud, Patrick Manckoundia, Val?rie Quipourt, Sophie Marilier, and Evelyne Franon (Dijon); Lawrence Bories, Marie-Laure Pader, Marie-France Basset, Bruno Lapoujade, Val?rie Faure, Michael Li Yung Tong, Christine Malick-Loiseau, and Evelyne Cazaban-Campistron (Foix); Fran?oise Desclaux and Colette Blatge (Lavaur); Thierry Dantoine, C?cile Laubarie-Mouret, Isabelle Saulnier, Jean-Pierre Cl?ment, Marie-Agn?s Picat, Laurence Bernard-Bourzeix, St?phanie Willebois, Il?ana D?sormais, and No?lle Cardinaud (Limoges); Marc Bonnefoy, Pierre Livet, Pascale Rebaudet, Claire G?d?on, Catherine Burdet, Flavien Terracol (Lyon), Alain Pesce, St?phanie Roth, Sylvie Chaillou, and Sandrine Louchart (Monaco); Kristelle Sudres, Nicolas Lebrun, and Nad?ge Barro-Belaygues (Montauban); Jacques Touchon, Karim Bennys, Audrey Gabelle, Aur?lia Romano, Lynda Touati, C?cilia Marelli, and C?cile Pays (Montpellier); Philippe Robert, Franck Le Duff, Claire Gervais, and S?bastien Gonfrier (Nice); Yannick Gasnier and Serge Bordes, Dani?le Begorre, Christian Carpuat, Khaled Khales, Jean-Fran?ois Lefebvre, Samira Misbah El Idrissi, Pierre Skolil, and Jean-Pierre Salles (Tarbes). Magnetic resonance imaging group: Carole Dufouil (Bordeaux), St?phane Leh?ricy, Marie Chupin, Jean-Fran?ois Mangin, and Ali Bouhayia (Paris); Mich?le Allard (Bordeaux); Fr?d?ric Ricolfi (Dijon); Dominique Dubois (Foix); Marie Paule Bonceour Martel (Limoges); Fran?ois Cotton (Lyon); Alain Bonaf? (Montpellier); St?phane Chanalet (Nice); Fran?oise Hugon (Tarbes); Fabrice Bonneville, Christophe Cognard, and Fran?ois Chollet (Toulouse). Positron emission tomography scan group: Pierre Payoux, Thierry Voisin, Julien Delrieu, Sophie Peiffer, and Anne Hitzel (Toulouse); Mich?le Allard (Bordeaux); Michel Zanca (Montpellier); Jacques Monteil (Limoges); Jacques Darcourt (Nice). Medicoeconomics group: Laurent Molinier, H?l?ne Derumeaux, and Nad?ge Costa (Toulouse). Biological sample collection: Sylvie Caspar-Bauguil, Bertrand Perret, and Claire Vinel (Toulouse). Safety management: Pascale Olivier-Abbal. DSA group: Sandrine Andrieu, Christelle Cantet, and Nicola Coley. Funding: Nutrient biomarker and statistical analysis was supported by the Nestle Institute of Health Sciences. The MAPT study was supported by grants from the G?rontop?le of Toulouse, the French Ministry of Health (PHRC 2008, 2009), Pierre Fabre Research Institute (manufacturer of the n-3 supplement), Exhonit Therapeutics SA, and Avid Radiopharmaceuticals Inc. The promotion of this study was supported by the University Hospital Center of Toulouse. The data sharing activity was supported by the Association Monegasque pour la Recherche sur la maladie d'Alzheimer and the UMR 1027 Unit INSERM??University of Toulouse III. Contributions: G.L.B.: conceptualized, designed the study, secured the funding, selected the biomarkers of diet quality and analytical assays, composed the statistical analysis plan, interpreted the data, and drafted and revised the manuscript; H.H.D.: concept and design, composed and conducted the statistical analysis plan, interpreted the data, and revised the manuscript; N.Z.: performed statistical analysis; S.G.: literature review and revised the manuscript; J.D.: literature review and revised the manuscript; A.B.: contributed to the management and coordination of the statistical analysis; J.S.: literature review and revised the manuscript; C.H.: literature review and revised the manuscript; T.B.; S.A.; and B.V.: concept and design, interpreted the data, and revised the manuscript. Funding Information: Funding: Nutrient biomarker and statistical analysis was supported by the Nestle Institute of Health Sciences . The MAPT study was supported by grants from the Gérontopôle of Toulouse , the French Ministry of Health (PHRC 2008, 2009), Pierre Fabre Research Institute (manufacturer of the n-3 supplement), Exhonit Therapeutics SA , and Avid Radiopharmaceuticals Inc. The promotion of this study was supported by the University Hospital Center of Toulouse . The data sharing activity was supported by the Association Monegasque pour la Recherche sur la maladie d'Alzheimer and the UMR 1027 Unit INSERM––University of Toulouse III. Publisher Copyright: © 2019 The Authors

PY - 2019

Y1 - 2019

N2 - Introduction: Multinutrient approaches may produce more robust effects on brain health through interactive qualities. We hypothesized that a blood-based nutritional risk index (NRI) including three biomarkers of diet quality can explain cognitive trajectories in the multidomain Alzheimer prevention trial (MAPT) over 3-years. Methods: The NRI included erythrocyte n-3 polyunsaturated fatty acids (n-3 PUFA 22:6n-3 and 20:5n-3), serum 25-hydroxyvitamin D, and plasma homocysteine. The NRI scores reflect the number of nutritional risk factors (0–3). The primary outcome in MAPT was a cognitive composite Z score within each participant that was fit with linear mixed-effects models. Results: Eighty percent had at lease one nutritional risk factor for cognitive decline (NRI ≥1: 573 of 712). Participants presenting without nutritional risk factors (NRI=0) exhibited cognitive enhancement (β = 0.03 standard units [SU]/y), whereas each NRI point increase corresponded to an incremental acceleration in rates of cognitive decline (NRI-1: β = −0.04 SU/y, P = .03; NRI-2: β = −0.08 SU/y, P < .0001; and NRI-3: β = −0.11 SU/y, P = .0008). Discussion: Identifying and addressing these well-established nutritional risk factors may reduce age-related cognitive decline in older adults; an observation that warrants further study.

AB - Introduction: Multinutrient approaches may produce more robust effects on brain health through interactive qualities. We hypothesized that a blood-based nutritional risk index (NRI) including three biomarkers of diet quality can explain cognitive trajectories in the multidomain Alzheimer prevention trial (MAPT) over 3-years. Methods: The NRI included erythrocyte n-3 polyunsaturated fatty acids (n-3 PUFA 22:6n-3 and 20:5n-3), serum 25-hydroxyvitamin D, and plasma homocysteine. The NRI scores reflect the number of nutritional risk factors (0–3). The primary outcome in MAPT was a cognitive composite Z score within each participant that was fit with linear mixed-effects models. Results: Eighty percent had at lease one nutritional risk factor for cognitive decline (NRI ≥1: 573 of 712). Participants presenting without nutritional risk factors (NRI=0) exhibited cognitive enhancement (β = 0.03 standard units [SU]/y), whereas each NRI point increase corresponded to an incremental acceleration in rates of cognitive decline (NRI-1: β = −0.04 SU/y, P = .03; NRI-2: β = −0.08 SU/y, P < .0001; and NRI-3: β = −0.11 SU/y, P = .0008). Discussion: Identifying and addressing these well-established nutritional risk factors may reduce age-related cognitive decline in older adults; an observation that warrants further study.

KW - Aging

KW - Biomarkers of diet quality

KW - Cognitive decline

KW - DHA

KW - EPA

KW - Elderly

KW - Homocysteine

KW - Metabolomics

KW - Nutrient biomarkers

KW - Omega-3 fatty acids

KW - Vitamin D

UR - http://www.scopus.com/inward/record.url?scp=85077017706&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85077017706&partnerID=8YFLogxK

U2 - 10.1016/j.trci.2019.11.004

DO - 10.1016/j.trci.2019.11.004

M3 - Article

AN - SCOPUS:85077017706

SN - 2352-8737

VL - 5

SP - 953

EP - 963

JO - Alzheimer's and Dementia: Translational Research and Clinical Interventions

JF - Alzheimer's and Dementia: Translational Research and Clinical Interventions

ER -

A blood-based nutritional risk index explains cognitive enhancement and decline in the multidomain Alzheimer prevention trial

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