Three Year Pre-analytical and Intra-individual Stability of Plasma Nutrient Biomarkers in Older Adults at Risk for Dementia: Effects of Sex, apoE Genotype and Cognition

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Objectives: Nutrient biomarkers (NBs) are objective indicators of diet quality and health status reflecting the nourishing liquor readily available to support the metabolic needs of the brain. Prior to more significant investment and broad deployment in medicine and public health the pre-analytical and intra-individual reproducibility over time to refine the design and interpretation of future studies. We quantified annual NBs over 3-years to estimate pre-analytical and intraindividual stability for future use to establish nutritional requirements for brain health. Methods: Blood samples from the NIA-Layton Aging & Alzheimer's Disease Research Center's Nutrition and Brain Aging Study (NBAS) participants were collected annually over 3-years. Blood plasma minerals, amino acids, hydro-and-liposoluble micronutrients, lipids, and 1-carbon pathway metabolites were quantified using a variety of analytical methods, including inductively coupled mass spectrometry. Coefficients of variation (CV) on replicates and intraclass correlation coefficients (ICC) were calculated for each NB to document intra-individual performance characteristics in a NBAS cohort (n=315) and subset (n=144), stratified by sex, apoE genotype (e4 carriers or not), and CDR of 0 or 0.5. Results: Analytical cohort mean baseline age was 85.6 (±8.3, 57-101 years) and mean MMSE was 28.3 (±1.8) with all participants having a Clinical Dementia Rating Scale score of 0.5 or less. Seventy-three percent were female, 19% carried an apoEe4 allele, and 15% had mild cognitive impairment (i.e., CDR of 0.5). Pre-analytical CVs ranged from 0.9-55.0% and the ICC from 0-0.87 (25%-tile/median/75 %-tile; 0.41/0.54/0.66). Twenty-four percent had ICC< 0.40, 76% had ICC > 0.40. Minerals, such as iron, lithium, iodine, cobalt, mercury, titanium and strontium had ICC categories different by sex while molybdenum, vanadium, iron, lithium, chromium, zinc, among others had ICC categories different by apoE. Conclusions: Intraindividual NB variation ranges widely in older adults. The majority have fair to good 3-year stability (ICC³0.40). NB stability may be sex, apoE genotype and cognitive status dependent in older adults at risk of dementia.