Nutrition and prevention of Alzheimer's dementia

Arun Swaminathan, Gregory A Jicha, Arun Swaminathan, Gregory A Jicha

Abstract

A nutritional approach to prevent, slow, or halt the progression of disease is a promising strategy that has been widely investigated. Much epidemiologic data suggests that nutritional intake may influence the development and progression of Alzheimer's dementia (AD). Modifiable, environmental causes of AD include potential metabolic derangements caused by dietary insufficiency and or excess that may be corrected by nutritional supplementation and or dietary modification. Many nutritional supplements contain a myriad of health promoting constituents (anti-oxidants, vitamins, trace minerals, flavonoids, lipids, …etc.) that may have novel mechanisms of action affecting cellular health and regeneration, the aging process itself, or may specifically disrupt pathogenic pathways in the development of AD. Nutritional modifications have the advantage of being cost effective, easy to implement, socially acceptable and generally safe and devoid of significant adverse events in most cases. Many nutritional interventions have been studied and continue to be evaluated in hopes of finding a successful agent, combination of agents, or dietary modifications that can be used for the prevention and or treatment of AD. The current review focuses on several key nutritional compounds and dietary modifications that have been studied in humans, and further discusses the rationale underlying their potential utility for the prevention and treatment of AD.

Keywords: Alzheimer; clinical trial; nutrition; prevention; treatment.

Figures

FIGURE 1
FIGURE 1
Diagram of multiple influences of dietary constituents on cellular pathways and process linked to neurodegeneration in AD. Antioxidants, trace minerals, flavonoids, metabolic substrates and modulators, vitamins, and omega-3 fatty acids, among others, have all been shown to downregulate the many pathological processes linked to the development of AD, including aging, amyloid deposition, neurofibrillary degeneration, synapse loss, inflammation, metabolic compromise, loss of vascular integrity, and neuronal injury and loss. Note: specific dietary factors may have more than one potential mechanism of action on the pathogenic processes contributing to neurodegeneration in AD. Links between pathological processes implicated in the development of AD may not be linear, but rather additive and are shown in a circular fashion without implication for specific linkages or temporal associations between such processes.

References

    1. Aggarwal B. B. (2010). Targeting inflammation-induced obesity and metabolic diseases by curcumin and other nutraceuticals. Annu. Rev. Nutr. 30 173–199. 10.1146/annurev.nutr.012809.104755
    1. Aisen P. S., Schneider L. S., Sano M., Diaz-Arrastia R., van Dyck C. H., Weiner M. F., et al. (2008). High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA 300 1774–1783. 10.1001/jama.300.15.1774
    1. Anekonda T. S. (2006). Resveratrol – a boon for treating Alzheimer’s disease? Brain Res. Rev. 52 316–326. 10.1016/j.brainresrev.2006.04.004
    1. Anekonda T. S., Reddy P. H. (2006). Neuronal protection by sirtuins in Alzheimer’s disease. J. Neurochem. 96 305–313. 10.1111/j.1471-4159.2005.03492.x
    1. Baum L., Lam C. W., Cheung S. K., Kwok T., Lui V., Tsoh J., et al. (2008). Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. J. Clin. Psychopharmacol. 28 110–113. 10.1097/jcp.0b013e318160862c
    1. Baur J. A., Pearson K. J., Price N. L., Jamieson H. A., Lerin C., Kalra A., et al. (2006). Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444 337–342. 10.1038/nature05354
    1. Bhagavan H. N., Chopra R. K. (2006). Coenzyme Q10: absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic. Res. 40 445–453. 10.1080/10715760600617843
    1. Bharadwaj P. R., Bates K. A., Porter T., Teimouri E., Perry G., Steele J. W., et al. (2013). Latrepirdine: molecular mechanisms underlying potential therapeutic roles in Alzheimer’s and other neurodegenerative diseases. Transl. Psychiatry 3:e332. 10.1038/tp.2013.97
    1. Bowman G. L. (2012). Ascorbic acid, cognitive function, and Alzheimer’s disease: a current review and future direction. Biofactors 38 114–122. 10.1002/biof.1002
    1. Brookmeyer R., Johnson E., Ziegler-Graham K., Arrighi H. M. (2007). Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement. 3 186–191. 10.1016/j.jalz.2007.04.381
    1. Cardoso B. R., Cominetti C., Cozzolino S. M. (2013). Importance and management of micronutrient deficiencies in patients with Alzheimer’s disease. Clin. Interv. Aging 8 531–542. 10.2147/CIA.S27983
    1. Cordain L., Eaton S. B., Sebastian A., Mann N., Lindeberg S., Watkins B. A., et al. (2005). Origins and evolution of the Western diet: health implications for the 21st century. Am. J. Clin. Nutr. 81 341–354
    1. Craft S., Cholerton B., Baker L. D. (2013). Insulin and Alzheimer’s disease: untangling the web. J. Alzheimers Dis. 33(Suppl. 1), S263–S275. 10.3233/JAD-2012-129042
    1. Cunnane S., Nugent S., Roy M., Courchesne-Loyer A., Croteau E., Tremblay S., et al. (2011). Brain fuel metabolism, aging, and Alzheimer’s disease. Nutrition 27 3–20. 10.1016/j.nut.2010.07.021
    1. Dangour A. D., Whitehouse P. J., Rafferty K., Mitchell S. A., Smith L., Hawkesworth S., et al. (2010). B-vitamins and fatty acids in the prevention and treatment of Alzheimer’s disease and dementia: a systematic review. J. Alzheimers Dis. 22 205–224. 10.3233/JAD-2010-090940
    1. Daviglus M. L., Bell C. C., Berrettini W., Bowen P. E., Connolly E. S., Jr., Cox N. J., et al. (2010). NIH state-of-the-science conference statement: preventing Alzheimer’s disease and cognitive decline. NIH Consens. State Sci. Statements 27 1–30
    1. Daviglus M. L., Plassman B. L., Pirzada A., Bell C. C., Bowen P. E., Burke J. R., et al. (2011). Risk factors and preventive interventions for Alzheimer disease: state of the science. Arch. Neurol. 68 1185–1190. 10.1001/archneurol.2011.100
    1. de la Monte S. M., Tong M. (2014). Brain metabolic dysfunction at the core of Alzheimer’s disease. Biochem. Pharmacol. 88 548–559. 10.1016/j.bcp.2013.12.012
    1. DeDea L. (2012). Can coconut oil replace caprylidene for Alzheimer disease? JAAPA 25:19. 10.1097/01720610-201208000-00002
    1. DeKosky S. T., Williamson J. D., Fitzpatrick A. L., Kronmal R. A., Ives D. G., Saxton J. A., et al. (2008). Ginkgo biloba for prevention of dementia: a randomized controlled trial. JAMA 300 2253–2262. 10.1001/jama.2008.683
    1. Doody R. S. (2009). Dimebon as a potential therapy for Alzheimer’s disease. CNS Spectr. 14(8Suppl. 7), 14–16; discussion 16–18
    1. Douaud G., Refsum H., de Jager C. A., Jacoby R., Nichols T. E., Smith S. M., et al. (2013). Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment. Proc. Natl. Acad. Sci. U.S.A. 110 9523–9528. 10.1073/pnas.1301816110
    1. Dysken M. W., Sano M., Asthana S., Vertrees J. E., Pallaki M., Llorente M., et al. (2014). Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial. JAMA 311 33–44. 10.1001/jama.2013.282834
    1. Fang L., Gou S., Liu X., Cao F., Cheng L. (2014). Design, synthesis and anti-Alzheimer properties of dimethylaminomethyl-substituted curcumin derivatives. Bioorg. Med. Chem. Lett. 24 40–43. 10.1016/j.bmcl.2013.12.011
    1. Feart C., Samieri C., Barberger-Gateau P. (2010). Mediterranean diet and cognitive function in older adults. Curr. Opin. Clin. Nutr. Metab. Care 13 14–18. 10.1097/MCO.0b013e3283331fe4
    1. Filipcik P., Cente M., Ferencik M., Hulin I., Novak M. (2006). The role of oxidative stress in the pathogenesis of Alzheimer’s disease. Bratisl. Lek. Listy 107 384–394. 10.4172/2161-0460.1000116
    1. Freund-Levi Y., Eriksdotter-Jönhagen M., Cederholm T., Basun H., Faxén-Irving G., Garlind A., et al. (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 1402–1408. 10.1001/archneur.63.10.1402
    1. Frisardi V., Solfrizzi V., Seripa D., Capurso C., Santamato A., Sancarlo D., et al. (2010). Metabolic-cognitive syndrome: a cross-talk between metabolic syndrome and Alzheimer’s disease. Ageing Res. Rev. 9 399–417. 10.1016/j.arr.2010.04.007
    1. Galasko D. R., Peskind E., Clark C. M., Quinn J. F., Ringman J. M., Jicha G. A., et al. (2012). Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. Arch. Neurol. 69 836–841. 10.1001/archneurol.2012.85
    1. Gillette-Guyonnet S., Secher M., Vellas B. (2013). Nutrition and neurodegeneration: epidemiological evidence and challenges for future research. Br. J. Clin. Pharmacol. 75 738–755. 10.1111/bcp.12058
    1. Gillette-Guyonnet S., Vellas B. (2008). Caloric restriction and brain function. Curr. Opin. Clin. Nutr. Metab. Care 11 686–692. 10.1097/MCO.0b013e328313968f
    1. Grundy S. M., Cleeman J. I., Daniels S. R., Donato K. A., Eckel R. H., Franklin B. A., et al. (2005). Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 112 2735–2752. 10.1161/CIRCULATIONAHA.105.169404
    1. Henderson S. T., Vogel J. L., Barr L. J., Garvin F., Jones J. J., Costantini L. C. (2009). Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled, multicenter trial. Nutr. Metab. (Lond.) 6:31. 10.1186/1743-7075-6-31
    1. Hidaka T., Fujii K., Funahashi I., Fukutomi N., Hosoe K. (2008). Safety assessment of coenzyme Q10 (CoQ10). Biofactors 32 199–208. 10.1002/biof.5520320124
    1. Hu N., Yu J. T., Tan L., Wang Y. L., Sun L., Tan L. (2013). Nutrition and the risk of Alzheimer’s disease. Biomed. Res. Int. 2013:524820. 10.1155/2013/524820
    1. Huang X. T., Qian Z. M., He X., Gong Q., Wu K. C., Jiang L. R., et al. (2014). Reducing iron in the brain: a novel pharmacologic mechanism of huperzine A in the treatment of Alzheimer’s disease. Neurobiol. Aging 35 1045–1054. 10.1016/j.neurobiolaging.2013.11.004
    1. Jicha G. A., Carr S. A. (2010). Conceptual evolution in Alzheimer’s disease: implications for understanding the clinical phenotype of progressive neurodegenerative disease. J. Alzheimers Dis. 19 253–272. 10.3233/JAD-2010-1237
    1. Jicha G. A., Markesbery W. R. (2010). Omega-3 fatty acids: potential role in the management of early Alzheimer’s disease. Clin. Interv. Aging 5 45–61. 10.2147/CIA.S5231
    1. Kamphuis P. J., Scheltens P. (2010). Can nutrients prevent or delay onset of Alzheimer’s disease? J. Alzheimers Dis. 20 765–775. 10.3233/JAD-2010-091558
    1. Kamphuis P. J., Verhey F. R., Olde Rikkert M. G., Twisk J. W., Swinkels S. H., Scheltens P. (2011). Efficacy of a medical food on cognition in Alzheimer’s disease: results from secondary analyses of a randomized, controlled trial. J. Nutr. Health Aging 15 720–724. 10.1007/s12603-011-0105-6
    1. Kashiwaya Y., Bergman C., Lee J. H., Wan R., King M. T., Mughal M. R., et al. (2013). A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer’s disease. Neurobiol. Aging 34 1530–1539. 10.1016/j.neurobiolaging.2012.11.023
    1. Knopman D. S., DeKosky S. T., Cummings J. L., Chui H., Corey-Bloom J., Relkin N., et al. (2001). Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 56 1143–1153. 10.1212/WNL.56.9.1143
    1. Kryscio R. J., Abner E. L., Schmitt F. A., Goodman P. J., Mendiondo M., Caban-Holt A., et al. (2013). A randomized controlled Alzheimer’s disease prevention trial’s evolution into an exposure trial: the PREADViSE Trial. J. Nutr. Health Aging 17 72–75. 10.1007/s12603-013-0004-0
    1. Lau F. C., Shukitt-Hale B., Joseph J. A. (2007). Nutritional intervention in brain aging: reducing the effects of inflammation and oxidative stress. Subcell. Biochem. 42 299–318. 10.1007/1-4020-5688-5_14
    1. Lopes da Silva S., Vellas B., Elemans S., Luchsinger J., Kamphuis P., Yaffe K., et al. (2014). Plasma nutrient status of patients with Alzheimer’s disease: systematic review and meta-analysis. Alzheimers Dement. 10 485–502. 10.1016/j.jalz.2013.05.1771
    1. Malaguarnera M., Ferri R., Bella R., Alagona G., Carnemolla A., Pennisi G. (2004). Homocysteine, vitamin B12 and folate in vascular dementia and in Alzheimer disease. Clin. Chem. Lab. Med. 42 1032–1035. 10.1515/CCLM.2004.208
    1. Masse I., Bordet R., Deplanque D., Al Khedr A., Richard F., Libersa C., et al. (2005). Lipid lowering agents are associated with a slower cognitive decline in Alzheimer’s disease. J. Neurol. Neurosurg. Psychiatry 76 1624–1629. 10.1136/jnnp.2005.063388
    1. Miller E. R., III, Pastor-Barriuso R., Dalal D., Riemersma R. A., Appel L. J., Guallar E. (2005). Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann. Intern. Med. 142 37–46. 10.7326/0003-4819-142-1-200501040-00110
    1. Monti M. C., Margarucci L., Tosco A., Riccio R., Casapullo A. (2011). New insights on the interaction mechanism between tau protein and oleocanthal, an extra-virgin olive-oil bioactive component. Food Funct. 2 423–428. 10.1039/c1fo10064e
    1. Morris M. S. (2002). Folate, homocysteine, and neurological function. Nutr. Clin. Care 5 124–132. 10.1046/j.1523-5408.2002.t01-1-00006.x
    1. Morris M. S. (2003). Homocysteine and Alzheimer’s disease. Lancet Neurol. 2 425–428. 10.1016/S1474-4422(03)00438-1
    1. Morris M. S. (2012). The role of B vitamins in preventing and treating cognitive impairment and decline. Adv. Nutr. 3 801–812. 10.3945/an.112.002535
    1. Nishida Y., Yokota T., Takahashi T., Uchihara T., Jishage K., Mizusawa H. (2006). Deletion of vitamin E enhances phenotype of Alzheimer disease model mouse. Biochem. Biophys. Res. Commun. 350 530–536. 10.1016/j.bbrc.2006.09.083
    1. Panza F., Frisardi V., Capurso C., Imbimbo B. P., Vendemiale G., Santamato A., et al. (2010). Metabolic syndrome and cognitive impairment: current epidemiology and possible underlying mechanisms. J. Alzheimers Dis. 21 691–724. 10.3233/JAD-2010-091669
    1. Pasinetti G. M., Eberstein J. A. (2008). Metabolic syndrome and the role of dietary lifestyles in Alzheimer’s disease. J. Neurochem. 106 1503–14. 10.1111/j.1471-4159.2008.05454.x
    1. Pervaiz S., Holme A. L. (2009). Resveratrol: its biologic targets and functional activity. Antioxid. Redox Signal. 11 2851–2897. 10.1089/ars.2008.2412
    1. Pocernich C. B., Lange M. L., Sultana R., Butterfield D. A. (2011). Nutritional approaches to modulate oxidative stress in Alzheimer’s disease. Curr. Alzheimer Res. 8 452–469. 10.2174/156720511796391908
    1. Quinn J. F., Raman R., Thomas R. G., Yurko-Mauro K., Nelson E. B., Van Dyck C., et al. (2010). Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. JAMA 304 1903–1911. 10.1001/jama.2010.1510
    1. Rafii M. S., Walsh S., Little J. T., Behan K., Reynolds B., Ward C., et al. (2011). A phase II trial of huperzine A in mild to moderate Alzheimer disease. Neurology 76 1389–1394. 10.1212/WNL.0b013e318216eb7b
    1. Rao A. V., Balachandran B. (2002). Role of oxidative stress and antioxidants in neurodegenerative diseases. Nutr. Neurosci. 5 291–309. 10.1080/1028415021000033767
    1. Reger M. A., Henderson S. T., Hale C., Cholerton B., Baker L. D., Watson G. S., et al. (2004). Effects of beta-hydroxybutyrate on cognition in memory-impaired adults. Neurobiol. Aging 25 311–314. 10.1016/S0197-4580(03)00087-3
    1. Ringman J. M., Cole G. M., Tend E., Badmaev V., Bardens J., Frautschy S., et al. (2008). “Oral curcumin for the treatment of mild-to-moderate Alzheimer’s disease: tolerability and clinical and biomarker efficacy results of a placebo-controlled 24-week study,” in Proceedings of the International Conference on Alzheimer’s Disease Chicago, IL
    1. Rockwood K. (2006). Epidemiological and clinical trials evidence about a preventive role for statins in Alzheimer’s disease. Acta Neurol. Scand. Suppl. 185 71–77. 10.1111/j.1600-0404.2006.00688.x
    1. Rubio-Perez J. M., Morillas-Ruiz J. M. (2012). A review: inflammatory process in Alzheimer’s disease, role of cytokines. ScientificWorldJournal 2012:756357. 10.1100/2012/756357
    1. Sano M., Bell K. L., Galasko D., Galvin J. E., Thomas R. G., van Dyck C. H., et al. (2011). A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease. Neurology 77 556–563. 10.1212/WNL.0b013e318228bf11
    1. Sano M., Ernesto C., Thomas R. G., Klauber M. R., Schafer K., Grundman M., et al. (1997). A controlled trial of selegiline, α-tocopherol, or both as treatment for Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. N. Engl. J. Med. 336 1216–1222. 10.1056/NEJM199704243361704
    1. Scarmeas N., Luchsinger J. A., Mayeux R., Stern Y. (2007). Mediterranean diet and Alzheimer disease mortality. Neurology 69 1084–1093. 10.1212/01.wnl.0000277320.50685.7c
    1. Scarmeas N., Stern Y., Tang M. X., Mayeux R., Luchsinger J. A. (2006). Mediterranean diet and risk for Alzheimer’s disease. Ann. Neurol. 59 912–921. 10.1002/ana.20854
    1. Seshadri S., Beiser A., Selhub J., Jacques P. F., Rosenberg I. H., D’Agostino R. B., et al. (2002). Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N. Engl. J. Med. 346 476–483. 10.1056/NEJMoa011613
    1. Shah R. (2013). The role of nutrition and diet in Alzheimer disease: a systematic review. J. Am. Med. Dir. Assoc. 14 398–402. 10.1016/j.jamda.2013.01.014
    1. Shah R. C., Kamphuis P. J., Leurgans S., Swinkels S. H., Sadowsky C. H., Bongers A., et al. (2013). The S-Connect study: results from a randomized, controlled trial of Souvenaid in mild-to-moderate Alzheimer’s disease. Alzheimers Res. Ther. 5:59. 10.1186/alzrt224
    1. Snitz B. E., O’Meara E. S., Carlson M. C., Arnold A. M., Ives D. G., Rapp S. R., et al. (2009). Ginkgo biloba for preventing cognitive decline in older adults: a randomized trial. JAMA 302 2663–2670. 10.1001/jama.2009.1913
    1. Sofi F., Macchi C., Abbate R., Gensini G. F., Casini A. (2010). Effectiveness of the Mediterranean diet: can it help delay or prevent Alzheimer’s disease? J. Alzheimers Dis. 20 795–801. 10.3233/JAD-2010-1418
    1. Solfrizzi V., Panza F., Frisardi V., Seripa D., Logroscino G., Imbimbo B. P., et al. (2011). Diet and Alzheimer’s disease risk factors or prevention: the current evidence. Expert Rev. Neurother. 11 677–708. 10.1586/ern.11.56
    1. Solfrizzi V., Scafato E., Capurso C., D’Introno A., Colacicco A. M., Frisardi V., et al. (2010). Metabolic syndrome and the risk of vascular dementia: the Italian Longitudinal Study on Ageing. J. Neurol. Neurosurg. Psychiatry 81 433–440. 10.1136/jnnp.2009.181743
    1. Tatton W. G. (1993). Selegiline can mediate neuronal rescue rather than neuronal protection. Mov. Disord. 8(Suppl. 1), S20–S30. 10.1002/mds.870080506
    1. Thaipisuttikul P., Galvin J. E. (2012). Use of medical foods and nutritional approaches in the treatment of Alzheimer’s disease. Clin. Pract. (Lond.) 9 199–209. 10.2217/cpr.12.3
    1. Tzourio C., Anderson C., Chapman N., Woodward M., Neal B., MacMahon S., et al. (2003). Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch. Intern. Med. 163 1069–1075. 10.1001/archinte.163.9.1069
    1. Wang Y., Yin H., Wang L., Shuboy A., Lou J., Han B., et al. (2013). Curcumin as a potential treatment for Alzheimer’s disease: a study of the effects of curcumin on hippocampal expression of glial fibrillary acidic protein. Am. J. Chin. Med. 41 59–70. 10.1142/S0192415X13500055
    1. Weih M., Wiltfang J., Kornhuber J. (2007). Non-pharmacologic prevention of Alzheimer’s disease: nutritional and life-style risk factors. J. Neural Transm. 114 1187–1197. 10.1007/s00702-007-0704-x
    1. Xiong S., Markesbery W. R., Shao C., Lovell M. A. (2007). Seleno-L-methionine protects against beta-amyloid and iron/hydrogen peroxide-mediated neuron death. Antioxid. Redox Signal. 9 457–467. 10.1089/ars.2006.1363
    1. Yang G., Wang Y., Tian J., Liu J.-P. (2013). Huperzine a for Alzheimer’s disease: a systematic review and meta-analysis of randomized clinical trials. PLoS ONE 8:e74916. 10.1371/journal.pone.0074916
    1. Yang X., Dai G., Li G., Yang E. S. (2010). Coenzyme Q10 reduces beta-amyloid plaque in an APP/PS1 transgenic mouse model of Alzheimer’s disease. J. Mol. Neurosci. 41 110–113. 10.1007/s12031-009-9297-1
    1. Yehuda S., Rabinovitz S., Mostofsky D. I. (2005). Essential fatty acids and the brain: from infancy to aging. Neurobiol. Aging 26(Suppl. 1), 98–102. 10.1016/j.neurobiolaging.2005.09.013
    1. Yurko-Mauro K., McCarthy D., Rom D., Nelson E. B., Ryan A. S., Blackwell A., et al. (2010). Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimers Dement. 6 456–464. 10.1016/j.jalz.2010.01.013
    1. Zhang J., Cao Q., Li S., Lu X., Zhao Y., Guan J. S., et al. (2013). 3-Hydroxybutyrate methyl ester as a potential drug against Alzheimer’s disease via mitochondria protection mechanism. Biomaterials 34 7552–7562. 10.1016/j.biomaterials.2013.06.043
    1. Zhang S., Rocourt C., Cheng W. H. (2010). Selenoproteins and the aging brain. Mech. Ageing Dev. 131 253–260. 10.1016/j.mad.2010.02.006
    1. Zilberter M., Ivanov A., Ziyatdinova S., Mukhtarov M., Malkov A., Alpár A., et al. (2013). Dietary energy substrates reverse early neuronal hyperactivity in a mouse model of Alzheimer’s disease. J. Neurochem. 125 157–171. 10.1111/jnc.12127

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever