Associations of Plasma Lipid Correlation Network Profiles with Global Cognition in Cognitively Normal Older Adults — The Association Specialists
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Associations of Plasma Lipid Correlation Network Profiles with Global Cognition in Cognitively Normal Older Adults (22014)

Maria Kadyrov 1 2 3 , Luke Whiley 1 4 , Kirk I Erickson 5 , Elaine Holmes 1 2 3 , Belinda Brown 2 6 7
  1. Australian National Phenome Centre, Health Futures Institute, Murdoch University, Perth, WA, Australia
  2. Centre for Healthy Ageing, Murdoch University, Perth, WA, Australia
  3. Centre for Computational and Systems Medicine, Health Futures Institute, Murdoch University, Murdoch, Perth, WA, Australia
  4. Perron Institute for Neurological and Translation Science, Nedlands, WA, Australia
  5. Neuroscience Institute, AdventHealth Research Institute, Orlando, Florida, United States of America
  6. Discipline of Exercise Science, Murdoch University, Perth, WA, Australia
  7. School of Medical Science, Sarich Neuroscience Research Institute, Edith Cowan University, Nedlands, WA, Australia

Objectives: Cognitive decline is a common phenomenon associated with ageing and has been linked to disruptions in lipid metabolism. Lipidomics, the comprehensive analysis of all lipids, is a useful tool for investigating cognitive decline due to the ability of lipidomics to provide a “snapshot” of current physiological state of an individual. This study aimed to use a lipidomics approach to investigate the associations between plasma lipids and global cognition in cognitively normal older adults.

 

Methods: Mass spectrometry based targeted lipid profiling of 926 plasma lipids from 94 participants (aged 60-80, 54% female, MMSE > 26) was performed. Participants underwent neuropsychological assessments, and from this data a composite score for global cognition was generated. Weight Gene Co-Expression Network Analysis was performed to identify lipid clusters that co-vary, suggesting similar functions and involvement in common metabolic pathways. Pearson correlation analysis between each cluster and global cognition was performed.

 

Key Findings: From the 11 lipid clusters, one was significantly correlated (r = 0.37, FDR p = 0.03) with global cognition. This cluster contained 44 phospholipid species, of which 75% were plasmalogens, a subclass of lipids that are highly enriched in neuronal membranes. Plasmalogens are increasingly recognised for their potential role in neuroprotection as they have been shown to suppress amyloid and tau accumulation, promote neurogenesis and reduce inflammation.

 

Conclusion: Our study has demonstrated that plasmalogen lipid species are positively associated with global cognition in cognitively normal older adults, highlighting a possible target for future healthy cognitive ageing interventions.