• The Interconnection Between Fatty Acids and Neuroplasticity: Implications for the Prevention of Cognitive Decline
  • Arvin nazari,1 Mahsa Rafieipour,2 Mohammad Mahdi Elahiyan,3,* Parnian Behjati,4
    1. Laboratory Sciences, Zanjan University of Medical Sciences, Zanjan, Iran
    2. College Of Science, Faculty Of Biotechnology, University Of Tehran, Tehran, Iran
    3. Student Research Committee, School of Allied Medical Sciences, Iran University of medical sciences, Tehran, Iran
    4. nutrition, graduated from Varastegan University, Mashhad, Iran


  • Introduction: Cognitive decline, particularly in aging populations, poses a significant public health challenge. Neuroplasticity—the brain's intrinsic capacity to adapt and reorganize—is increasingly recognized as a crucial determinant of cognitive health. Among the biological factors influencing neuroplasticity, fatty acids, especially polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have emerged as critical modulators of brain structure and function. This review examines the relationship between dietary and endogenous fatty acids and their role in enhancing neuroplasticity and preventing cognitive deterioration.
  • Methods: This narrative review synthesizes findings from 15 systematic and narrative reviews selected via Google Scholar and PubMed using keywords such as neuroplasticity, cognitive decline, fatty acids, Alzheimer’s disease, aging, DHA, inflammation, and synaptic function. The literature spans from 1995 to 2025, with emphasis placed on studies elucidating molecular mechanisms, neuroimaging findings, and interventional trials. Key databases included PubMed and ScienceDirect, with articles prioritizing experimental, clinical, and epidemiological research.
  • Results: The analysis reveals consistent evidence that long-chain omega-3 fatty acids, particularly DHA, support synaptic fluidity, neurogenesis, and anti-inflammatory processes central to cognitive resilience. DHA and EPA modulate membrane phospholipids, enhance synaptic signaling, and reduce the production of pro-inflammatory cytokines. SCFAs like butyrate and propionate, derived from gut microbiota, further influence neuroplastic pathways via the gut-brain axis. Additionally, MCFAs promote mitochondrial efficiency and autophagy, particularly in neurodegenerative settings. Conversely, deficits in fatty acid availability or metabolism—exacerbated by APOE4 genotype—are linked to impaired plasticity and accelerated cognitive decline.
  • Conclusion: Fatty acids, through both direct neuronal modulation and systemic metabolic pathways, play a pivotal role in sustaining neuroplasticity and protecting against cognitive impairment. Optimizing fatty acid intake, particularly DHA and EPA, may constitute a preventive strategy against age-related neurodegeneration and dementia. Future research should focus on personalized interventions considering genetic predispositions (e.g., APOE4 carriers) and gut microbiota composition to enhance therapeutic efficacy.
  • Keywords: Fatty Acids, Neuroplasticity, Cognition