A recent JAMA Network Open study assesses the role of ω-3 polyunsaturated fatty acids (PUFAs) in reducing white matter lesion (WML) accumulation and neuronal integrity degeneration in older adults. What is WML accumulation? Cerebral WML accumulation is associated with an increased risk of cognitive decline and Alzheimer’s Disease (AD). The pathophysiological mechanisms involved in this association include the reduced regenerative capacity of oligodendrocytes, cerebral hypoperfusion, blood-brain barrier degeneration, and endothelial cell activation.
Although periventricular WMLs may suggest microglial activation, the deeper subcortical tissue WMLs may be more indicative of progressive myelin loss, astrogliosis, and axonal degeneration. Reduced WML burden has been associated with diet-derived bioactive lipids, such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and ω-3 PUFAs. The ω-3 PUFAs may act as lipophilic inflammation-resolving metabolite synthesis substrates, thereby shifting metabolism and cell signaling towards a reduced inflammatory state.
Previous studies have demonstrated the ability of ω-3 PUFAs to reduce the expression of endothelial and immune cell surface protein CD54, which can increase blood-brain barrier permeability and microglial cytokine release. Meta-analyses of clinical trials have shown that plasma ω-3 levels can be directly related to up to 25% of WML variations. Furthermore, higher levels of ω-3 PUFAs have been associated with a 4.