Dietary fatty acids and risk for Alzheimer’s disease, dementia, and mild cognitive impairment: A prospective cohort meta-analysis
Abstract
The association between dietary fatty acid intake and Alzheimer's disease (AD), dementia, and mild cognitive impairment (MCI) risk is inconsistent. This meta-analysis examined the effect of dietary fatty acid intake in prospective cohort studies including patients with AD, dementia, and MCI. PubMed, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP Database were systematically searched through September 2020. The random-effects model was used to combine the highest and lowest categories of multivariable adjusted relative risk (RR). Prospective cohort studies that included associations between dietary fatty acid intake and the risk for AD, dementia, or MCI were included. Fourteen studies were included, comprising 54 177 participants: 1696 patients with AD, 1118 patients with dementia, and 2889 with MCI. The pooled RR showed a significant association only between ω-3 polyunsaturated fatty acid (PUFA) intake and MCI risk (RR, 0.86; 95% CI, 0.75-0.98), with no heterogeneity between studies (I 2 = 0%). The intake of total fatty acids, saturated fatty acids (SFAs), cholesterol, monounsaturated fatty acids (MUFAs), PUFAs, ω-3 PUFAs, ω-6 PUFAs, docosahexaenoic acids (DHAs), and eicosapentaenoic acids (EPAs) was not significantly associated with AD risk. The intake of total fatty acids, SFAs, MUFAs, PUFAs, and ω-3 PUFAs was not significantly associated with dementia risk. This meta-analysis provided evidence that ω-3 PUFA intake may be negatively associated with MCI risk.
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Maintaining cardiovascular health, eating a balanced diet rich in antioxidants, and exercising frequently can lower the incidence of AD.
“Conversely, maintaining cardiovascular health, eating a balanced diet rich in antioxidants, and exercising frequently can all lower the incidence of AD [55,58].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [58]
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Non-Genetic Risk Factors of Alzheimer's Disease: An Updated Umbrella Review
He, S.-Y., Su, W.-M., Wen, X.-J., Lu, S.-J., Cao, B., Yan, B., & Chen, Y.-P. (2024) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2024.100 · Cited by 12 · see citing works
Research Progress of Lipid Metabolism-Mediated Neuroinflammation in Alzheimer’s Disease
Shen, Y., Wang, X., Liu, X., Wang, G., Hou, X., & Zhou, X. (2025) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-025-01648-9 · Cited by 10 · see citing works
“Furthermore, a large-scale meta-analysis reveals that a higher intake of n-3 PUFAs is associated with a 14% reduced in the risk of mild cognitive impairment (MCI)(Zhu et al. 2021).”
Şimşek, H., & Uçar, A. (2024) · Clinical Nutrition Open Science · doi:10.1016/j.nutos.2024.05.012 · Cited by 10 · see citing works
Norgren, J., Sindi, S., Sandebring-Matton, A., Ngandu, T., Kivipelto, M., & Kåreholt, I. (2023) · Current Developments in Nutrition · doi:10.1016/j.cdnut.2023.100096 · Cited by 9 · see citing works
The role of nutrition in the prevention of cognitive decline
Charbit, J., Vidal, J., & Hanon, O. (2023) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000001002 · Cited by 9 · see citing works
Brikou, D., Dimopoulou, M.-A., Drouka, A., Ntanasi, E., Mamalaki, E., Gu, Y., Scarmeas, N., & Yannakoulia, M. (2024) · Journal of Nutrition · doi:10.1016/j.tjnut.2024.05.025 · Cited by 8 · see citing works
Huan, S., Liu, M., Liu, Z., Gao, J., & Yin, G. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-230422 · Cited by 8 · see citing works
Association between dietary fat intake and long-term risk of dementia: a prospective cohort study
Wu, M., Huang, L., Huang, Y.-H., Shen, J., Chen, H., Wang, B., Zong, G., Guasch‐Ferré, M., Rong, S., Liu, X., et al. (2025) · American Journal of Clinical Nutrition · doi:10.1016/j.ajcnut.2025.09.028 · Cited by 6 · see citing works
Li, Y., Liu, X., Zhuang, P., Zhang, L., Wu, Y., Wu, S., Zhang, Y., & Jiao, J. (2024) · The journal of nutrition health & aging · doi:10.1016/j.jnha.2024.100176 · Cited by 6 · see citing works
“A recent meta-analysis revealed that higher dietary n-3 PUFAintakewasrelatedtolowerriskofmildcognitiveimpairment(MCI) [5].”
Khatun, P., Li, X., Xiao-xi, Z., Zhai, J., Ullah, A., Bo, Y., & Lyu, Q. (2025) · Nutrition Reviews · doi:10.1093/nutrit/nuaf167 · Cited by 5 · see citing works
Yi, F., Gao, Y., Liu, X., Ying, Y., Xie, Q., You, Y., Zha, Q., Luo, C., Ni, M., Wang, Q., et al. (2024) · Neurological Sciences · doi:10.1007/s10072-024-07539-z · Cited by 5 · see citing works
Exploring differences in circulating metabolites of females and males with Alzheimer’s disease
Serafini, S., Angiolillo, A., Ferretti, G., Viviani, G., Matrone, C., & Costanzo, A. D. (2025) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x251340513 · Cited by 4 · see citing works
“57 The sex-specific differences in GLA levels in the present study could point to potential sex-specific mechanisms in AD pathology or progression and may inform future studies on targeted nutritional interventions or therapeutic approaches that consider the balance of omega-3 and omega-6 fatty…”
Nutrition senolytics - illusion or reality for cognitive ageing?
Chen, X., Brodaty, H., & O’Leary, F. (2021) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000796 · Cited by 4 · see citing works
Anti‐Neuroinflammation Activity of Essential Oils and Fatty Acids
Jin, Z., Song, Y., Abdelmoaty, A. A. A., Lin, F., Li, J., & Chen, X. (2026) · Food Science & Nutrition · doi:10.1002/fsn3.71422 · Cited by 3 · see citing works
“…in Alzheimer's disease and amyotrophic lateral sclerosis have not found a protective association for general omega-6 intake, and a high dietary omega-6 to omega-3 ratio is widely considered a risk factor for heightened neuroinflammation (Miyake et al. 2010; Zhu et al. 2021; Fitzgerald et al. 2014).”
Chen, H., Yang, Q., Yu, F., Shen, Y., Hong, X., Yang, M., Yin, R., Shen, Y., Fan, J., & Fan, Z. (2024) · Technology and Health Care · doi:10.3233/thc-240671 · Cited by 3 · see citing works
“…rich in unsaturated fatty acids (UFA), such as the “Mediterranean diet”, are believed to effectively reduce the risk of cognitive impairment and become the only diet recommended by the WHO in 2019 Risk Reduction of Cognitive Decline and Dementia guidelines to prevent cognitive impairment [9,10,11].”
Reducing excess dietary saturated fat intake to improve cognition in vascular dementia
Blake, S. M., Harding, T., Blake, C. P., & Borman, P. L. (2022) · GSC Advanced Research and Reviews · doi:10.30574/gscarr.2022.12.2.0220 · Cited by 3 · see citing works
Shi, J., Ni, L., Yu, S., Gao, X., & Qin, X. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1729885 · Cited by 2 · see citing works
“ALA can also inactivate extracellular regulatory protein kinase (ERK) and nuclear factor-κ B (NF-κ B), by inhibiting the corresponding pathways, to alleviate A β -induced neuroinflammation and pathological injury to the brain tissues (Zhu et al., 2021).”
Li, M., Li, C., He, M., Chen, L., & Wang, Q. (2025) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2025.118675 · Cited by 2 · see citing works
Wei, X., Tan, Y., Ke, C., Cao, Y., Xie, Z., Yuan, L., Pan, J., & Zhang, W. (2022) · Medicine · doi:10.1097/md.0000000000032093 · Cited by 1 · see citing works
“The typical pathological changes of AD are neuroinflammatory plaques, neurogenic fiber tangles, neuronal loss and gliosis.[4] Modern medical treatment of AD is mostly symptomatic with cholinesterase inhibitors such as donepezil and carbalatine.”
BackgroundMiller, V., Smith, E. E., Schulze, K. M., Desai, D., Ho, V., Dummer, T., Tardif, J., Lear, S. A., Poirier, P., Mir, H. R., et al. (2025) · EClinicalMedicine · doi:10.1016/j.eclinm.2025.103333 · Cited by 1 · see citing works
“14 .”
Ye, H., Liu, H., Li, Y., Huang, Y., Yao, J., Ao, Y., Liu, X., Lin, X., Song, X., Zhuang, P., et al. (2025) · Food Frontiers · doi:10.1002/fft2.70042 · Cited by 1 · see citing works
Gomes‐Bispo, A., Cardoso, C. L., Afonso, C., Lourenço, H. M., Pedro, S., Moniz, P., & Bandarra, N. M. (2026) · Marine Drugs · doi:10.3390/md24060197 · Cited by 1 · see citing works
Dietary Recommendations for Managing Dementia
Mashhadi, F., Roudi, F., Aminalroaya, R., Pouryazdanpanah, M., Khorasanchi, Z., & RahbariNezahd, P. (2024) · Nutritional neurosciences · doi:10.1007/978-981-97-4117-5_14 · Cited by 1 · see citing works
Kirk, M., Canfell, O. J., Pirbaglou, M., Chowdhury, F., Smith, M., Reid, R., Hitchcock, A. D., Baudin, J., Chang, B., Knight, H., et al. (2025) · medRxiv · doi:10.1101/2025.10.09.25337399 · Cited by 1 · see citing works
“…and minerals (e.g., B vitamins 15–18 , vitamin E 16,18,19 , vitamin C 16 , vitamin D 16 , folic acid 16 , magnesium 20 , omega-3 famy acids 21–23 , nitrate/nitrite 24 , (poly)phenols 25–28 ), macronutrients (e.g., protein 29 , fibre 30 , glucose 31,32 , fat 33,34 ) and single foods (e.g., fish…”
Advancing age, nutraceuticals, and neuroprotection
Woźniak, L. A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95735-9.00001-2
Functional Aspects of Polyunsaturated Fatty Acids as Nutraceuticals
Şimşek, H., & Uçar, A. (2025) · Springer eBooks · doi:10.1007/978-981-97-9723-3_8
Khairunnisa, S., Maruyama, K., Miyazaki, S., Saito, I., Tomooka, K., Tanigawa, T., Eguchi, E., Shiba, T., Kooka, A., Fujimura, K., et al. (2025) · Dietetics · doi:10.3390/dietetics4040043
“The associations between dietary fatty acid intake and cognitive performance (assessed using neuropsychological assessments) have been inconsistent [17].”
Intake of Dietary Fats and Links and Associations with Cognitive Function
Bodenrader, A., & Bigornia, S. (2025) · Springer eBooks · doi:10.1007/978-3-031-32047-7_156-1
Thompson, T., Shin, A. C., Decourt, B., Wang, Y., Vigil, B. Z., Solodukhina, A. A., Ranasinghe, S., Young, R. S., Hegde, V. K., & Moustaïd‐Moussa, N. (2026) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1673533
The role of diet in the risk of Alzheimer’s disease
Grant, W. B. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-33841-0.00031-2
O’Donoghue, C., Long-Smith, C. M., Janas, H., Clarke, G. A., Timmons, S., Grabrucker, S., & Nolan, Y. M. (2026) · Nutrition and Health · doi:10.1177/02601060261420675
Metabolic syndrome, cognitive impairments, the role of nutrition
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Can Nutrition Modulate the Progression of Alzheimer’s Disease? A Narrative Review
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Oparaugo, G., & Gaur, R. (2026) · Cureus · doi:10.7759/cureus.108502
“Similarly, Zhu et al. demonstrated that omega-3 fatty acids have a protective effect against cognitive impairment [37].”
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“7,8 A chronic diet leads to major metabolic disruptions in a”
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Dietary factors and cognitive aging: Mapping epidemiological evidence and the role of gut microbiota
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- Authors
- Zhu, R.-Z., Chen, M.-Q., Zhang, Z.-W., Wu, T.-Y., & Zhao, W.-H.
- Affiliations
- Bengbu Medical College (CN)
- Venue
- Nutrition
- Publisher
- Elsevier BV
- Published
- 2021-10
- Volume
- 90
- Pages
- 111355
- ISSN
- 0899-9007 (ISSN-L)
- OpenAlex
- W3164464105
- Cited by
- 61
- References
- 61
- Citations by year
- 2026: 14 · 2025: 15 · 2024: 13 · 2023: 10 · 2022: 8 · 2021: 1
- FWCI
- 1.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bengbu Medical College
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Keywords
- dietary fatty acids, Alzheimer's disease, dementia, mild cognitive impairment, omega-3 polyunsaturated fatty acids, saturated fatty acids, monounsaturated fatty acids, docosahexaenoic acid, eicosapentaenoic acid, omega-6 fatty acids, cholesterol, cognitive risk
- MeSH terms
- Alzheimer Disease, Fatty Acids, Humans, Prospective Studies, Cohort Studies, Fatty Acids, Omega-3, Cognitive Dysfunction
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