A three-molecular-window approach for H-1 NMR spectroscopy of serum is presented to obtain specific molecular data on lipoproteins, Various low-molecular-weight metabolites, and individual lipid molecules together with their degree of (poly)(un)saturation. The multiple data were analysed with self-organising maps, illustrating the strength of the approach as a holistic metabonomics framework in solely data-driven metabolic phenotyping. We studied 180 serum samples of which 30% were related to mild cognitive impairment (MCI), a neuropsychological diagnosis with severely increased risk for Alzheimer's disease (AD). The results underline the association between MCI and the metabolic syndrome (MetS). Additionally, the low relative amount of omega-3 fatty acids appears more indicative of MCI than low serum omega-3 OF polyunsaturated fatty acid concentration as such. The analyses also feature the role of elevated glycoproteins in the risk for AD, Supporting the view that coexistence of inflammation and the MetS forms a high risk condition for cognitive decline. (C) 2008 Elsevier Inc. All rights reserved.