TY - JOUR
T1 - Specific Nutritional Biomarker Profiles in Mild Cognitive Impairment and Subjective Cognitive Decline Are Associated With Clinical Progression: 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, J. rgen
AU - van Wijk, Nick
AU - van den Heuvel, Ellen G. H. M.
AU - Mohajeri, M. Hasan
AU - Teunissen, Charlotte E.
AU - Kester, Maartje I.
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 - Nutrients
KW - clinical progression
KW - cognitive decline
KW - mild cognitive impairment
KW - nutritional biomarker
KW - nutritional biomarker profiles
KW - subjective cognitive decline
UR - http://www.scopus.com/inward/record.url?scp=85078467995&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jamda.2019.12.009
DO - https://doi.org/10.1016/j.jamda.2019.12.009
M3 - Article
C2 - 32001171
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 -