PLASMA PHOSPHOLIPIDS AND INCIDENT MILD COGNITIVE IMPAIRMENT/DEMENTIA IN THE ARIC NEUROCOGNITIVE STUDY (ARIC-NCS)

Mapstone et al. demonstrated a set of 10 phospholipids in plasma predicted conversion from control to either amnestic MCI or dementia within 2-3 years with a robust Area Under Curve (AUC) of 0.96. The objective of this study is to evaluate the ability of these 10 phospholipids to predict incident MCI and/or dementia in a subset of ARIC study participants [1]. We applied a targeted metabolomics method (i.e., the Biocrates Absolute-IDQ P180 kits, Life Science AG, Innsbruck, Austria) to measure 188 metabolites in plasma samples of 221 participants collected both at the Atherosclerosis Risk in Community (ARIC) MRI visit (2004-2006) and the ARIC Neurocognitive Study (ARIC-NCS, 2012-2014). We correlated the baseline concentrations of these 10 phospholipids with incident MCI and/or dementia at the ARIC NCS using multinomial logistic regression. Among the 221 participants who were cognitively normal at the ARIC MRI visit (mean age 71 years, 66% women), 77 developed MCI and 18 dementia at the ARIC NCS with a follow up of 5.8-9.6 years (mean 7.3 years). Higher concentration of lyso PC a C18:2 was significantly associated with a higher incident of MCI (OR 1.50, 95% CI: 1.01-2.23), but not higher in incident dementia. The association remained significantly after adjusting age, race, sex, & APOE (OR 1.49, 95% CI: 1.00: 2.23) or after adjusting additional clinical variables (OR 1.66, 95% CI: 1.04: 2.64). Addition of all these phospholipids simultaneously to a model containing clinical variables led to minimal improvements in the C-statistic (from 0.698 to 0.729). Even though our study demonstrated the baseline association of lyso PC a C18:2 with incident MCI, the association of these phospholipids with incident MCI and dementia were relatively weak, and prediction of MCI and/or dementia did not improve on clinical variables. Reference: [1] Mapstone M, Cheema AK, Fiandaca MS, Zhong X, Mhyre TR, MacArthur LH, Hall WJ, Fisher SG, Peterson DR, Haley JM, Nazar MD, Rich SA, Berlau DJ, Peltz CB, Tan MT, Kawas CH, Federoff HJ. Plasma phospholipids identify antecedent memory impairment in older adults. Nature Medicine. 2014;20(4):415-8.