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<p>Research suggests varying effects of fatty acids on cognitive function and brain structure in neurocognitive disorders, but inconsistent findings call for further investigation and advanced neuroimaging techniques. This study investigated the relationship between serum fatty acid levels (omega-3 PUFAs, omega-6 PUFAs, omega-6:omega-3 ratio, MUFAs, and SFAs) and temporal lobe volume in cognitively normal (CN) individuals, those with mild cognitive impairment (MCI), and those with Alzheimer’s disease (AD). The results indicated that, as expected, there was a significant difference in temporal lobe volumes (<i>p</i> &lt; 0.001), with the AD group showing more pronounced reductions in volume compared to both the CN and MCI groups. Unexpectedly, higher plasma omega-3 PUFA levels were associated with reduced temporal lobe volume (<i>β</i> = − 0.31, <i>p</i> = 0.021), and a lower omega-6:omega-3 ratio was also associated with diminished temporal lobe volume (<i>β</i> = 0.26, <i>p</i> = 0.039), both observed only in the AD group, after adjustment for age, gender, education, and APOE ε4 allele status as potential confounders. No significant associations were observed for any lipids with temporal lobe volumes in the CN or MCI groups. Interestingly, the only significant association observed between fatty acids and cognitive function was in the CN group, where higher MUFAs and SFAs were both associated with worse cognitive scores. In short, higher omega-3 PUFA levels and a lower omega-6:omega-3 ratio were associated with reduced temporal lobe volume in Alzheimer’s patients not using fatty acid supplements. Notably, this observational cross-sectional study cannot establish causality and should be interpreted cautiously, as the findings may be influenced by residual confounding, non-fasting sampling, potential reverse causality, lack of detailed dietary and longitudinal data, and methodological constraints including limited lipid characterization and region-specific morphometric analysis. Further research is needed to confirm these findings and investigate potential mechanisms.</p>

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Higher Total Omega-3 PUFA Levels and a Lower Omega-6:Omega-3 Ratio Are Associated with Lower Temporal Lobe Volume in Alzheimer’s Disease

  • 期刊论文

  • 发表日期：

    2026年1月1日

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  • M. Emam,
  • Sara Albadri,
  • Amna Mohamed Ahmed,
  • Iman M. Mirza,
  • Halah Abdulrahman Hafiz,
  • Mozdalifah Elnaeem,
  • Yasser Alzamil,
  • Malik Bader Alazzam

摘要

Research suggests varying effects of fatty acids on cognitive function and brain structure in neurocognitive disorders, but inconsistent findings call for further investigation and advanced neuroimaging techniques. This study investigated the relationship between serum fatty acid levels (omega-3 PUFAs, omega-6 PUFAs, omega-6:omega-3 ratio, MUFAs, and SFAs) and temporal lobe volume in cognitively normal (CN) individuals, those with mild cognitive impairment (MCI), and those with Alzheimer’s disease (AD). The results indicated that, as expected, there was a significant difference in temporal lobe volumes (p < 0.001), with the AD group showing more pronounced reductions in volume compared to both the CN and MCI groups. Unexpectedly, higher plasma omega-3 PUFA levels were associated with reduced temporal lobe volume (β = − 0.31, p = 0.021), and a lower omega-6:omega-3 ratio was also associated with diminished temporal lobe volume (β = 0.26, p = 0.039), both observed only in the AD group, after adjustment for age, gender, education, and APOE ε4 allele status as potential confounders. No significant associations were observed for any lipids with temporal lobe volumes in the CN or MCI groups. Interestingly, the only significant association observed between fatty acids and cognitive function was in the CN group, where higher MUFAs and SFAs were both associated with worse cognitive scores. In short, higher omega-3 PUFA levels and a lower omega-6:omega-3 ratio were associated with reduced temporal lobe volume in Alzheimer’s patients not using fatty acid supplements. Notably, this observational cross-sectional study cannot establish causality and should be interpreted cautiously, as the findings may be influenced by residual confounding, non-fasting sampling, potential reverse causality, lack of detailed dietary and longitudinal data, and methodological constraints including limited lipid characterization and region-specific morphometric analysis. Further research is needed to confirm these findings and investigate potential mechanisms.