Research Paper Volume 13, Issue 18 pp 22078—22091

The relationship between plasma free fatty acids, cognitive function and structural integrity of the brain in middle-aged healthy humans

Markus Herrmann1, , Sebastian Simstich1, , Günter Fauler1, , Edith Hofer2,3, , Eva Fritz-Petrin1, , Wolfgang Herrmann4, , Reinhold Schmidt2, ,

  • 1 Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
  • 2 Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria
  • 3 Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria
  • 4 Medical School, Saarland University, Homburg/Saar, Germany

Received: July 5, 2021       Accepted: September 7, 2021       Published: September 23, 2021
How to Cite

Copyright: © 2021 Herrmann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Background: The cerebral composition of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) is believed to influence cognitive function and structural damage of the aging brain. However, existing data is inconsistent.

Materials and Methods: This retrospective study explored the association between free plasma PUFA concentrations, cognitive function and brain structure atrophy in a well-characterized community-dwelling cohort of elderly individuals without stroke and dementia. Ten different fatty acids were analyzed in stored plasma samples from 391 non-demented elderly individuals by gas chromatography mass spectrometry. Neuropsychiatric tests capturing memory, executive function and visuopractical skills were performed in all participants. Brain atrophy was assessed by MRI in a subset of 167 individuals.

Results: Higher plasma concentrations of free ω-6 PUFAs (p = 0.042), and, in particular, linoleic acid (p = 0.01), were significantly associated with lower executive function. No significant association existed between ω-3 PUFA concentrations and cognitive functioning. The volume of the frontal lobes was inversely associated with ω-6 PUFAs, whereas ω-3 PUFAs were positively related with temporal lobe volumes. All associations did not withstand correction for multiple comparisons.

Conclusions: Our study suggests subtle effects of PUFA imbalances on cognition and brain structure. Yet the observed associations are weak and unlikely to be of clinical relevance. The brain regions that seem to be most sensitive to imbalances of ω-3 and ω-6 PUFAs are the frontal and temporal lobes.


FA: Fatty acids; PUFAs: Polyunsaturated fatty acids; EPA: Eicosapentaenoic acid; DHA: Docosahexaenoic acid; LA: Linoleic acid; GLA: Gamma linolenic acid; AA: Arachidonic acid; MUFAs: Monounsaturated fatty acids; BBB: Blood Brain Barrier; u-FFAs: unbound free fatty acids; t-FFAs: total free fatty acids; Aβ: amyloid beta; MMSE: Mini Mental State Examination; ASPS: Austrian Stroke Prevention Study; ASPS-Fam: Austrian Stroke Prevention Family Study; GC-MS: Gas Chromatography-Mass Spectrometry; MTBE: Methyl tert-butyl ether; IS: Internal Standard; DIPEA: Diisopropylethylamine; PFBBr: Pentafluorobenzyl bromide; NCI: negative chemical ionization; SIM: Single Ion Monitoring; MRI: Magnetic Resonance Imaging; WMH: White Matter Hyperintensities; PSMD: Peak width of the Skeletonized Mean Diffusivity; STD: standard deviation; IQR: Inter Quartile Range; β: regression coefficient; SE: Standard Error of the regression coefficient; p: p-values; FDR: False Discovery Rate; NPD1: Neuroprotectin D1; BDNF: Brain-derived Neurotrophic Factor.