Higher Serum DHA and Slower Cognitive Decline in Patients with Alzheimer’s Disease: Two-Year Follow-Up
Tóm tắt
Omega-3 polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been associated with slower rates of cognitive decline. We investigated the association between omega-3 PUFAs and cognitive function in patients with Alzheimer’s disease (AD) receiving acetylcholinesterase inhibitors (AChEIs). This was a prospective cohort study using registered data. Patients with AD receiving AChEIs were recruited from 1 May 2016 to 30 April 2019 and were followed up for two years. Their daily diet record and blood concentration of omega-3 PUFAs were analyzed. Multiple linear and binary logistic regression was used to determine the factors associated with cognitive decline (continuous and dichotomized cognitive change). In the research, 129 patients with AD were identified with a mean age of 76.5 ± 6.6. Patients with AD with lower baseline omega-3 PUFAs levels were associated with a higher risk of cognitive decline than those with higher levels (odds ratio [OR] = 1.067, 95% confidence interval [CI]: 1.012, 1.125; p = 0.016) after adjustment. Patients with AD with a lower baseline DHA (OR = 1.131, 95% CI: 1.020, 1.254; p = 0.020), but not EPA, were associated with a higher risk of cognitive decline. We found that higher Mini-Nutritional Assessment scores (beta = −0.383, 95% CI = −0.182–−0.048, p = 0.001) and total fat (beta = −0.248, 95% CI = −0.067–−0.003, p = 0.031) were independently associated with slow cognitive decline in patients with AD receiving AChEIs. The baseline blood levels of omega-3 PUFAs were associated with cognitive decline in patients with AD receiving AChEIs. Future randomized controlled trials are needed to clarify whether this association is causal.
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Tài liệu tham khảo
Livingston, 2020, Dementia prevention, intervention, and care: 2020 report of the Lancet Commission, Lancet, 396, 413, 10.1016/S0140-6736(20)30367-6
Fink, H.A., Hemmy, L.S., Linskens, E.J., Silverman, P.C., MacDonald, R., McCarten, J.R., Talley, K.M.C., Desai, P.J., Forte, M.L., and Miller, M.A. (2020). Diagnosis and Treatment of Clinical Alzheimer’s-Type Dementia: A Systematic Review [Internet], Agency for Healthcare Research and Quality (US). Apr. Report;.
Simonetto, M., Infante, M., Sacco, R.L., Rundek, T., and Della-Morte, D. (2019). A Novel Anti-Inflammatory Role of Omega-3 PUFAs in Prevention and Treatment of Atherosclerosis and Vascular Cognitive Impairment and Dementia. Nutrients, 11.
Dyall, 2015, Long-chain omega-3 fatty acids and the brain: A review of the independent and shared effects of EPA, DPA and DHA, Front. Aging Neurosci., 7, 52, 10.3389/fnagi.2015.00052
Thomas, 2015, Omega-3 Fatty Acids in Early Prevention of Inflammatory Neurodegenerative Disease: A Focus on Alzheimer’s Disease, Biomed. Res. Int., 2015, 172801, 10.1155/2015/172801
Arellanes, 2020, Brain delivery of supplemental docosahexaenoic acid (DHA): A randomized placebo-controlled clinical trial, EBioMedicine, 59, 102883, 10.1016/j.ebiom.2020.102883
Albanese, 2009, Dietary fish and meat intake and dementia in Latin America, China, and India: A 10/66 Dementia Research Group population-based study, Am. J. Clin. Nutr., 90, 392, 10.3945/ajcn.2009.27580
Huang, 2005, Benefits of fatty fish on dementia risk are stronger for those without APOE epsilon4, Neurology, 65, 1409, 10.1212/01.wnl.0000183148.34197.2e
Melo van Lent, D., Egert, S., Wolfsgruber, S., Kleineidam, L., Weinhold, L., Wagner-Thelen, H., Maier, W., Jessen, F., Ramirez, A., and Schmid, M. (2021). Eicosapentaenoic Acid Is Associated with Decreased Incidence of Alzheimer’s Dementia in the Oldest Old. Nutrients, 13.
Thomas, 2020, Blood polyunsaturated omega-3 fatty acids, brain atrophy, cognitive decline, and dementia risk, Alzheimers Dement., 17, 407, 10.1002/alz.12195
Teunissen, 2018, Circulating metabolites and general cognitive ability and dementia: Evidence from 11 cohort studies, Alzheimers Dement., 14, 707, 10.1016/j.jalz.2017.11.012
Lin, 2022, Omega-3 fatty acids and blood-based biomarkers in Alzheimer’s disease and mild cognitive impairment: A randomized placebo-controlled trial, Brain Behav. Immun., 99, 289, 10.1016/j.bbi.2021.10.014
Shinto, 2014, A randomized placebo-controlled pilot trial of omega-3 fatty acids and alpha lipoic acid in Alzheimer’s disease, J. Alzheimers Dis., 38, 111, 10.3233/JAD-130722
Quinn, 2010, Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: A randomized trial, JAMA, 304, 1903, 10.1001/jama.2010.1510
Cederholm, 2006, Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: A randomized double-blind trial, Arch. Neurol., 63, 1402, 10.1001/archneur.63.10.1402
Kelley, 2012, Similarities and differences between the effects of EPA and DHA on markers of atherosclerosis in human subjects, Proc. Nutr. Soc., 71, 322, 10.1017/S0029665112000080
Su, 2009, Biological mechanism of antidepressant effect of omega-3 fatty acids: How does fish oil act as a ’mind-body interface’?, Neurosignals, 17, 144, 10.1159/000198167
Schaefer, 2006, Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: The Framingham Heart Study, Arch. Neurol., 63, 1545, 10.1001/archneur.63.11.1545
Lin, 2012, A meta-analytic review of polyunsaturated fatty acid compositions in dementia, J. Clin. Psychiatry, 73, 1245, 10.4088/JCP.11r07546
Folstein, 1975, “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician, J. Psychiatr Res., 12, 189, 10.1016/0022-3956(75)90026-6
Morris, 1993, The Clinical Dementia Rating (CDR): Current version and scoring rules, Neurology, 43, 2412, 10.1212/WNL.43.11.2412-a
Pasupuleti, 2022, Green sample pre-treatment technique coupled with UHPLC-MS/MS for the rapid biomonitoring of dietary poly-unsaturated (omega) fatty acids to predict health risks, Chemosphere, 291, 132685, 10.1016/j.chemosphere.2021.132685
Vellas, 1999, The Mini Nutritional Assessment (MNA) and its use in grading the nutritional state of elderly patients, Nutrition, 15, 116, 10.1016/S0899-9007(98)00171-3
Ammann, 2017, Erythrocyte omega-3 fatty acids are inversely associated with incident dementia: Secondary analyses of longitudinal data from the Women’s Health Initiative Memory Study (WHIMS), Prostaglandins Leukot Essent Fat. Acids, 121, 68, 10.1016/j.plefa.2017.06.006
Kroger, 2009, Omega-3 fatty acids and risk of dementia: The Canadian Study of Health and Aging, Am. J. Clin. Nutr., 90, 184, 10.3945/ajcn.2008.26987
Chiu, 2008, The effects of omega-3 fatty acids monotherapy in Alzheimer’s disease and mild cognitive impairment: A preliminary randomized double-blind placebo-controlled study, Prog. Neuropsychopharmacol. Biol. Psychiatry, 32, 1538, 10.1016/j.pnpbp.2008.05.015
Zhang, 2016, Intakes of fish and polyunsaturated fatty acids and mild-to-severe cognitive impairment risks: A dose-response meta-analysis of 21 cohort studies, Am. J. Clin. Nutr., 103, 330, 10.3945/ajcn.115.124081
Dubois, 2016, Preclinical Alzheimer’s disease: Definition, natural history, and diagnostic criteria, Alzheimers Dement., 12, 292, 10.1016/j.jalz.2016.02.002
Fujita, 2001, Docosahexaenoic acid improves long-term potentiation attenuated by phospholipase A(2) inhibitor in rat hippocampal slices, Br. J. Pharmacol., 132, 1417, 10.1038/sj.bjp.0703970
Fabelo, 2010, Lipid alterations in lipid rafts from Alzheimer’s disease human brain cortex, J. Alzheimers Dis., 19, 489, 10.3233/JAD-2010-1242
Hooper, 2018, The Relationship of Omega 3 Polyunsaturated Fatty Acids in Red Blood Cell Membranes with Cognitive Function and Brain Structure: A Review Focussed on Alzheimer’s Disease, J. Prev. Alzheimers Dis., 5, 78
Leng, 2021, Neuroinflammation and microglial activation in Alzheimer disease: Where do we go from here?, Nat. Rev. Neurol., 17, 157, 10.1038/s41582-020-00435-y
Xia, 1998, Immunohistochemical study of the beta-chemokine receptors CCR3 and CCR5 and their ligands in normal and Alzheimer’s disease brains, Am. J. Pathol., 153, 31, 10.1016/S0002-9440(10)65542-3
Hjorth, 2013, Omega-3 fatty acids enhance phagocytosis of Alzheimer’s disease-related amyloid-β42 by human microglia and decrease inflammatory markers, J Alzheimers Dis, 35, 697, 10.3233/JAD-130131
Wang, 2016, APOE epsilon4 and the associations of seafood and long-chain omega-3 fatty acids with cognitive decline, Neurology, 86, 2063, 10.1212/WNL.0000000000002719
Huang, 2015, Effect of vitamin B-12 and n-3 polyunsaturated fatty acids on plasma homocysteine, ferritin, C-reaction protein, and other cardiovascular risk factors: A randomized controlled trial, Asia Pac. J. Clin. Nutr., 24, 403