TY - JOUR
T1 - Specific nutritional biomarker profiles in mild cognitive impairment and subjective cognitive decline are associated with clinical progression
T2 - the NUDAD Project
AU - de Leeuw, Francisca A.
AU - van der Flier, Wiesje M.
AU - Tijms, Betty M.
AU - Scheltens, Philip
AU - Mendes, Vera M.
AU - Manadas, Bruno
AU - Bierau, Jörgen
AU - van Wijk, Nick
AU - van den Heuvel, Ellen G.H.M.
AU - Mohajeri, M. Hasan
AU - Teunissen, Charlotte E.
AU - Kester, Maartje I.
N1 - Funding Information:
Funding sources: The NUDAD project is funded by NWO-FCB (project number 057-14-004), and Francisca de Leeuw and Maartje Kester are appointed on this project. Research of the Alzheimer Center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. The Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. The clinical database structure was developed with funding from Stichting Dioraphte. Docosahexaenoic acid and total omega-3 fatty acids measurements were funded by Biobanking and Biomolecular Resource Research Infrastructure (BBMRI)-NL (NWO 184.021.007). Theobromine measurements were supported by Fundação para a Ciência e a Tecnologia (FCT) [POCI-01-0145-FEDER-007440 (strategic project UID/NEU/04539/2019), UID/BIM/04773/2013, PEst-C/SAU/LA0001/2013-2014, POCI-01-0145-FEDER-016428 (ref.: SAICTPAC/0010/2015), POCI-01-0145-FEDER-30943 (ref.: PTDC/MEC-PSQ/30943/2017)], PTDC/MED-NEU/27946/2017 and co-financed by “COMPETE Programa Operacional Factores de Competitividade,” QREN; the European Union (FEDER—Fundo Europeu de Desenvolvimento Regional) and by the National Mass Spectrometry Network (RNEM) (POCI-01-0145-FEDER-402-022125).N.v.W. is an employee of Nutricia Research; E.H. is an employee of FrieslandCampina, a dairy company; H.M. is an advisor to the life science and medical industry and a lecturer at the University of Zurich. During the course of the present work, he was an employee of DSM. P.S. has received consultancy/speaker fees (paid to the institution) from Novartis, Vivoryon, Genentech, and EIP Pharma. C.T. received grants from the European Commission, the Dutch Research Council (ZonMW), Association of Frontotemporal Dementia / Alzheimer's Drug Discovery Foundation, The Weston Brain Institute, Alzheimer Nederland. C.T. has a collaboration contract with ADx Neurosciences, performed contract research, or received grants from Probiodrug, Biogen, Esai, Toyama, Janssen Prevention Center, Boehringer, AxonNeurosciences, Fujirebio, EIP Farma, PeopleBio, and Roche. Research programs of W.v.d.F. have been funded by ZonMw, NWO, EU-FP7, EU-JPND, Alzheimer Nederland, CardioVascular Onderzoek Nederland, Health∼Holland, Topsector Life Sciences & Health, Stichting Dioraphte, Gieskes-Strijbis fonds, Stichting Equilibrio, Pasman Stichting, Biogen MA Inc, Boehringer Ingelheim, Life-MI, AVID, Roche BV, Janssen Stellar, and Combinostics. W.v.d.F. holds the Pasman chair. W.v.d.F. has performed contract research for Biogen MA Inc and Boehringer Ingelheim. W.v.d.F. has been an invited speaker at Boehringer Ingelheim and Biogen MA Inc. W.v.d.F. is recipient of a donation by Stichting Equilibrio and of a ZonMW Memorabel grant (#733050814). All funding is paid to her institution. F.d.L., B.T., V.M., B.M., J.B., and M.K. report no conflict of interest.
Funding Information:
Funding sources: The NUDAD project is funded by NWO-FCB (project number 057-14-004), and Francisca de Leeuw and Maartje Kester are appointed on this project. Research of the Alzheimer Center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. The Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds . The clinical database structure was developed with funding from Stichting Dioraphte . Docosahexaenoic acid and total omega-3 fatty acids measurements were funded by Biobanking and Biomolecular Resource Research Infrastructure (BBMRI)-NL (NWO 184.021.007). Theobromine measurements were supported by Fundação para a Ciência e a Tecnologia (FCT) [POCI-01-0145-FEDER-007440 (strategic project UID/NEU/04539/2019), UID/BIM/04773/2013, PEst-C/SAU/LA0001/2013-2014, POCI-01-0145-FEDER-016428 (ref.: SAICTPAC/0010/2015), POCI-01-0145-FEDER-30943 (ref.: PTDC/MEC-PSQ/30943/2017)], PTDC/MED-NEU/27946/2017 and co-financed by “COMPETE Programa Operacional Factores de Competitividade,” QREN; the European Union (FEDER— Fundo Europeu de Desenvolvimento Regional ) and by the National Mass Spectrometry Network (RNEM) (POCI-01-0145-FEDER-402-022125).
Funding Information:
N.v.W. is an employee of Nutricia Research; E.H. is an employee of FrieslandCampina, a dairy company; H.M. is an advisor to the life science and medical industry and a lecturer at the University of Zurich. During the course of the present work, he was an employee of DSM. P.S. has received consultancy/speaker fees (paid to the institution) from Novartis, Vivoryon, Genentech, and EIP Pharma. C.T. received grants from the European Commission , the Dutch Research Council (ZonMW), Association of Frontotemporal Dementia / Alzheimer's Drug Discovery Foundation , The Weston Brain Institute , Alzheimer Nederland . C.T. has a collaboration contract with ADx Neurosciences, performed contract research, or received grants from Probiodrug , Biogen , Esai , Toyama , Janssen Prevention Center , Boehringer , AxonNeurosciences , Fujirebio , EIP Farma , PeopleBio , and Roche . Research programs of W.v.d.F. have been funded by ZonMw , NWO , EU-FP7 , EU-JPND , Alzheimer Nederland , CardioVascular Onderzoek Nederland , Health∼Holland , Topsector Life Sciences & Health , Stichting Dioraphte , Gieskes-Strijbis fonds , Stichting Equilibrio , Pasman Stichting , Biogen MA Inc , Boehringer Ingelheim , Life-MI , AVID , Roche BV , Janssen Stellar , and Combinostics . W.v.d.F. holds the Pasman chair. W.v.d.F. has performed contract research for Biogen MA Inc and Boehringer Ingelheim. W.v.d.F. has been an invited speaker at Boehringer Ingelheim and Biogen MA Inc. W.v.d.F. is recipient of a donation by Stichting Equilibrio and of a ZonMW Memorabel grant (#733050814). All funding is paid to her institution. F.d.L., B.T., V.M., B.M., J.B., and M.K. report no conflict of interest.
Publisher Copyright:
© 2019 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
PY - 2020/10
Y1 - 2020/10
N2 - Objectives: Nutritional insufficiencies have been associated with cognitive impairment. Understanding whether nutritional biomarker levels are associated with clinical progression could help to design dietary intervention trials. This longitudinal study examined a panel of nutritional biomarkers in relation to clinical progression in patients with subjective cognitive decline (SCD) or mild cognitive impairment (MCI). Design, setting and participants: We included 299 patients without dementia (n = 149 SCD; age 61 ± 10 years, female 44%, n = 150 MCI; age 66 ± 8 years, female 38%). Median (interquartile range) follow-up was 3 (2-5) years. Methods: We measured 28 nutritional biomarkers in blood and 5 in cerebrospinal fluid (CSF), associated with 3 Alzheimer's disease pathologic processes: vascular change (lipids), synaptic dysfunction (homocysteine-related metabolites), and oxidative stress (minerals and vitamins). Nutritional biomarker associations with clinical progression to MCI/dementia and cognitive decline based on the Mini-Mental State Examination score were evaluated using Cox proportional hazard models and linear mixed models. We used partial least squares Cox models (PLS-Cox) to examine nutritional biomarker profiles associated with clinical progression. Results: In the total group, high high-density lipoprotein (HDL) levels were associated with clinical progression and cognitive decline. In SCD, high folate and low bilirubin levels were associated with cognitive decline. In MCI, low CSF S-adenosylmethionine (SAM) and high theobromine were associated with clinical progression to dementia and high HDL, cholesterol, iron, and 1,25(OH)2 vitamin D were associated with cognitive decline. PLS-Cox showed 1 profile for SCD, characterized by high betaine and folate and low zinc associated with clinical progression. In MCI, a profile with high theobromine and HDL and low triglycerides and a second profile with high plasma SAM and low cholesterol were associated with risk of dementia. Conclusion and Implications: High HDL was most consistently associated with clinical progression. Moreover, different nutritional biomarker profiles for SCD and MCI showed promising associations with clinical progression. Future dietary (intervention) studies could use nutritional biomarker profiles to select patients, taking into account the disease stage.
AB - Objectives: Nutritional insufficiencies have been associated with cognitive impairment. Understanding whether nutritional biomarker levels are associated with clinical progression could help to design dietary intervention trials. This longitudinal study examined a panel of nutritional biomarkers in relation to clinical progression in patients with subjective cognitive decline (SCD) or mild cognitive impairment (MCI). Design, setting and participants: We included 299 patients without dementia (n = 149 SCD; age 61 ± 10 years, female 44%, n = 150 MCI; age 66 ± 8 years, female 38%). Median (interquartile range) follow-up was 3 (2-5) years. Methods: We measured 28 nutritional biomarkers in blood and 5 in cerebrospinal fluid (CSF), associated with 3 Alzheimer's disease pathologic processes: vascular change (lipids), synaptic dysfunction (homocysteine-related metabolites), and oxidative stress (minerals and vitamins). Nutritional biomarker associations with clinical progression to MCI/dementia and cognitive decline based on the Mini-Mental State Examination score were evaluated using Cox proportional hazard models and linear mixed models. We used partial least squares Cox models (PLS-Cox) to examine nutritional biomarker profiles associated with clinical progression. Results: In the total group, high high-density lipoprotein (HDL) levels were associated with clinical progression and cognitive decline. In SCD, high folate and low bilirubin levels were associated with cognitive decline. In MCI, low CSF S-adenosylmethionine (SAM) and high theobromine were associated with clinical progression to dementia and high HDL, cholesterol, iron, and 1,25(OH)2 vitamin D were associated with cognitive decline. PLS-Cox showed 1 profile for SCD, characterized by high betaine and folate and low zinc associated with clinical progression. In MCI, a profile with high theobromine and HDL and low triglycerides and a second profile with high plasma SAM and low cholesterol were associated with risk of dementia. Conclusion and Implications: High HDL was most consistently associated with clinical progression. Moreover, different nutritional biomarker profiles for SCD and MCI showed promising associations with clinical progression. Future dietary (intervention) studies could use nutritional biomarker profiles to select patients, taking into account the disease stage.
KW - Clinical progression
KW - Cognitive decline
KW - Mild cognitive impairment
KW - Nutrients
KW - Nutritional biomarker
KW - Nutritional biomarker profiles
KW - Subjective cognitive decline
UR - http://www.scopus.com/inward/record.url?scp=85078467995&partnerID=8YFLogxK
U2 - 10.1016/j.jamda.2019.12.009
DO - 10.1016/j.jamda.2019.12.009
M3 - Article
C2 - 32001171
AN - SCOPUS:85078467995
SN - 1525-8610
VL - 21
SP - 1513.e1-1513.e17
JO - Journal of the American Medical Directors Association
JF - Journal of the American Medical Directors Association
IS - 10
ER -