2026 年 12 巻 p. 3-5
Recent advances in dementia research have substantially improved our understanding of its pathogenesis, prevention, and treatment. While disease-modifying therapies, such as anti-amyloid-β monoclonal antibodies, have ushered in a new era in Alzheimer’s disease management, increasing attention has been directed toward dementia prevention strategies. Accumulating evidence suggests that lifestyle-related diseases, particularly vascular risk factors, play a critical role in cognitive decline and dementia development. This review discusses the relationship between vascular health and dementia prevention, with a focus on nutritional interventions and brain-targeted supplements, especially omega-3 polyunsaturated fatty acids, as adjunctive strategies for neuroprotection.
Dementia represents a major global public health challenge, with prevalence expected to rise dramatically in aging societies1). In parallel with progress in disease-modifying therapies for Alzheimer’s disease, preventive approaches targeting modifiable risk factors have gained increasing importance. Lifestyle-related diseases, including hypertension, diabetes mellitus, dyslipidemia, and smoking, have been consistently associated with an elevated risk of cognitive impairment and dementia2,3). Recent epidemiological and interventional studies have highlighted the contribution of vascular dysfunction to neurodegeneration, reinforcing the concept of “vascular cognitive impairment”4). Accordingly, comprehensive management of vascular risk factors, combined with nutritional optimization, has emerged as a promising strategy for maintaining brain health and preventing dementia.
An expanding body of evidence has identified several modifiable risk factors for dementia, particularly during midlife. These include smoking, excessive alcohol consumption, hypertension, diabetes mellitus, and elevated low-density lipoprotein cholesterol levels1,5). Collectively, these vascular risk factors are estimated to account for approximately one-third of preventable dementia factors1). Importantly, these factors directly affect cerebral vasculature through endothelial dysfunction, arterial stiffness, and atherosclerosis, ultimately impairing cerebral perfusion and promoting neuroinflammation4). Therefore, dementia prevention strategies focusing on vascular health represent an urgent and clinically relevant priority.
In recent years, numerous dietary supplements have been reported to influence vascular health and metabolic regulation, thereby indirectly contributing to neuroprotection. Nutrients such as omega-3 polyunsaturated fatty acids, vitamin E, and β-carotene have been associated with anti-atherosclerotic and antioxidant effects6,7). Furthermore, dietary patterns emphasizing legumes, coffee, tea, mushrooms, moderate alcohol consumption, omega-3 fatty acids, and vitamin B12 have been recommended for cardiovascular disease prevention8,9). However, when considering supplements for brain protection, it is essential to balance their potential benefits against associated risks and limitations, particularly in the context of long-term use.
Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), primarily derived from fish, as well as α-linolenic acid (ALA) from plant sources (Fig. 1). These fatty acids are essential components of cell membrane phospholipids and play crucial roles in modulating triglyceride synthesis, very-low-density lipoprotein production, blood pressure regulation, insulin signaling, and inflammatory pathways6,10). Omega-3 PUFAs also exhibit anti-arrhythmic properties and have been widely investigated for their cardiovascular protective effects11). In addition, experimental studies using animal models have provided mechanistic insights into the cerebrovascular protective effects of ω-3 PUFAs. In rodent models of chronic cerebral hypoperfusion that induce white matter lesions, ω-3 PUFA-enriched diets have been shown to preserve cerebrovascular integrity, partly through attenuation of pericyte degeneration and stabilization of the neurovascular unit12).
Omega-3 polyunsaturated fatty acids include plant-derived α-linolenic acid and fish-derived EPA and DHA.
A meta-analysis encompassing 16 studies and 422,786 participants demonstrated that EPA and DHA intake was associated with significant improvements in cardiovascular outcomes11). This advisory summarizes large randomized controlled trials of ω-3 PUFA supplementation, typically administering ~0.8–1.0 g/day of EPA + DHA (up to 1.8 g/day EPA) for 1–6 years in fish-oil formulations. The studies mainly targeted adults with established cardiovascular disease or high cardiovascular risk rather than the general population. These meta-analyses have further suggested modest but consistent blood pressure–lowering effects of EPA and DHA supplementation11). Additionally, a pooled analysis integrated 19 prospective cohort and nested case–control studies assessing ω-3 fatty acid exposure using circulating and tissue biomarkers that reflect habitual dietary intake rather than assigned supplementation. Long-term exposure to EPA, DHA, and α-linolenic acid (ALA) was evaluated in generally healthy, free-living adults without prior coronary heart disease across diverse populations. This analysis reported that higher circulating or adipose tissue levels of EPA and DHA were associated with reduced risks of fatal cardiovascular disease and myocardial infarction13). Similarly, a multicenter, double-blind, placebo-controlled randomized trial assigned post-myocardial infarction patients to receive low-dose ω-3 fatty acids for 40 months. Participants aged 60–80 years consumed margarine formulations providing ~400 mg/day EPA-DHA and/or 2 g/day ALA, targeting secondary prevention in patients receiving contemporary cardiovascular therapy. The dietary intake of ALA has been associated with a trend toward reduced cardiovascular risk in post–myocardial infarction patients14).
Our own clinical observations have shown that cancer patients with silent cerebral infarctions exhibited significantly lower circulating EPA levels, suggesting that insufficient ω-3 status may contribute to subclinical cerebrovascular pathology15).
3. Limitations and controversiesDespite these promising findings, the efficacy of fish-derived ω-3 supplements for primary prevention of cardiovascular disease remains controversial. A Cochrane systematic review concluded that EPA and DHA supplementation had little or no effect on all-cause mortality or cardiovascular outcomes in well-treated patients16). Plant-derived ω-3 fatty acids consumed through whole foods may slightly reduce cardiovascular and arrhythmia risk, although the level of evidence remains limited11,13). At present, ω-3 supplementation is generally recommended for secondary prevention in patients with established cardiovascular dysfunction; however, careful consideration of formulation, dosage, and patient selection is required11). Further high-quality randomized controlled trials are needed to clarify the role of ω-3 fatty acids in dementia prevention and long-term cognitive outcomes17).
4. Implications for dementia preventionGiven the strong link between vascular health and cognitive function, comprehensive management of lifestyle-related diseases represents a cornerstone of dementia prevention1,4). Nutritional supplementation, particularly ω-3 fatty acids, may serve as an adjunctive tool within a broader preventive framework that includes blood pressure control, glycemic management, lipid regulation, and lifestyle modification17). However, supplements should not be regarded as substitutes for evidence-based medical therapy or healthy dietary patterns.
On the other hand, ω-3 fatty acid treatment may contribute to the prevention of amyloid-related imaging abnormalities (ARIA) in disease-modifying therapies for Alzheimer’s disease. Clinically, ω-3 supplementation has been shown to be safe and well tolerated and to attenuate the annual decline in diffusion tensor imaging-derived fractional anisotropy, particularly in APOE4 carriers18). Given that a lower burden of white matter lesions is associated with a reduced incidence of ARIA-hemorrhage (ARIA-H) in APOE4 carriers, ω-3 supplementation may potentially represent a promising strategy for mitigating ARIA risk through preservation of white matter integrity19).
Management of lifestyle-related diseases aimed at maintaining vascular health forms the foundation of neuroprotection and dementia prevention. Omega-3 fatty acids may offer supportive benefits as part of a multifaceted preventive strategy. Nevertheless, further robust clinical evidence is required to determine their optimal use, long-term safety, and direct effects on cognitive decline and dementia risk.
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The author reports no disclosures.
