Recent Advances in the Role of Vitamins in the Prevention and Treatment of Alzheimer’s Disease: A Literature Review

Bazza Sohail, Abdul Wasay Nafe, Robina Malik

Abstract


Main objective of this review is critically evaluate the use of vitamins in the safety measure as well as treatments of Alzheimer’s disease (AD) using recent findings of research on both humans and animals. The authors combed through the fundamental literature on association of vitamins (fat-soluble vitamins, water-soluble vitamins and some quasi vitamins) with prevention/treatment of AD to create this narrative review. An online search was conducted in Science Direct, Google Scholar, EBSCO & PubMed, a manual search via catalogues and scientific journals for review the literature regarding the relationship between vitamins and AD and to comprehend the potential mechanisms that may clarify such a relationship. After evaluating the titles and abstracts of the preliminary 500 articles, 350 were chosen. After reading the full texts and accomplishing a supplemental search on "Related citations" and the references of the chosen articles, a total of 282 references were found. The two most frequently mentioned ways that vitamins may affect cognitive function in AD are (1) by influences on a particular plasma amino acid called homocysteine (Hcy) for B vitamins (B6, B9 & B12), and (2) through antioxidant effects, decreasing the free radicals’ contents which can impairment human cells, for vitamins B2, C, D, E, as well as ß-carotene. These theories concerning potential mechanisms are mostly based on preclinical research and findings of links between dementia or cognitive decline and elevated Hcy levels or elevated markers of oxidative stress. The results from current studies show an effectiveness and safety of vitamin supplementation to avert mild cognitive impairment (MCI) as well as the initial phases of AD will likely rely on firstly which metabolic pathways are affected, secondly which vitamins are lacking and could correct the pertinent metabolic flaw, and thirdly, the modulating effect of nutrient-nutrient and nutrient-genotype interaction. Further emphasis on an accurate dietary strategy is needed to recognize the complete prospective of vitamin therapy in avoiding dementia and cognitive function as well as to avoid causing devastation.


Full Text:

PDF

References


Dey A, Bhattacharya R, Mukherjee A, Pandey DK. Natural products against Alzheimer's disease: Pharmaco-therapeutics and biotechnological interventions. Biotechnology Advances, (2017); 35: 178-216.

Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Molecular Medicine, (2016); 8(6): 595-608.

Agostinho P, Cunha RA, Oliveira C. Neuroinflammation, oxidative stress and the pathogenesis of Alzheimer’s disease. Current Pharmaceutical Design, (2010); 16(25): 2766-2778.

Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Fore-casting the global burden of Alzheimer’s disease. Alzheimer’s Dementia, (2007); 3: 186-191.

Alzheimer’s Disease International. World Alzheimer Report. The Global Economic Impact of Dementia. 2015. https://www.alz.co.uk/research/world-report-2015

Hurd MD, Martorell P, Delavande A, Mullen KJ, Langa KM. Monetary costs of dementia in the United States. The New England Journal of Medicine, (2013); 368: 1326-1334.

Di Carlo A, Baldereschi M, Amaducci L, Lepore V, Bracco L, Maggi S, Bonaiuto S, Perissinotto E, Scarlato G, Farchi G, Inzitari D. Incidence of dementia, Alzheimer's disease, and vascular dementia in Italy. The Italian Longitudinal Study on Aging (ILSA): Jounal of the American Geriatrics Society, (2002); 50: 41-48.

De-Paula VJ, Radanovic M, Diniz BS, Forlenza OV. Alzheimer's disease. Subcell. Biochemstry, (2012); 65: 329-352.

Pivi1 GAK, Vieira NMdeA, da Ponte, JB, de Moraes DSC, Bertolucci PHF. Nutritional management for Alzheimer’s disease in all stages: mild, moderate, and severe. Nutrire, (2017); 42:1.

Cauwenberghe CV, Broeckhoven CV, Sleegers K. The genetic landscape of Alzheimer disease: clinical implications and perspectives. Genetics in Medicine, (2016); 18(5): 421-430.

Jiang Y, Gao H, Turdu G. 2017. Traditional Chinese medicinal herbs as potential AChE inhibitors for anti-Alzheimer’s disease: A review. Bioorganic Chemistry, (2017); 75: 50-61.

Colizzi C. The protective effects of polyphenols on Alzheimer’s disease: A systematic review. Alzheimer’s & Dementia: Translational Research and Clinical Interventions, (2019);5:184-196.

Abate G, Marziano M, Rungratanawanich W, Memo M, Uberti D. Nutrition and ageing: focusing on Alzheimer’s disease. Oxidative Medicine and Cell Longivty, (2017); Article ID 7039816, 10 pages.

Hu N, Yu J, Tan L, Wang Y, Sun L, Tan L. Nutrition and the risk of Alzheimer’s disease. BioMed Research International, (2013); 1-12.

Bhatti AB, Usman M, Ali F, Satti SA. Vitamin supplementation as an adjuvant treatment for Alzheimer’s disease. Journal of Clinical and Diagnostic Research, (2016); 10(8): OE07-OE11.

Ono K, Yamada M. Vitamin A and Alzheimer’s disease. Geriatrics & Gerontology International, (2012); 12(2): 180-188.

Przybelski RJ, Binkley NC. Is vitamin D important for preserving cognition? A positive correlation of serum 25-hydroxyvitamin D concentration with cognitive function.

Archives of Biochemistry and Biophysics, (2007); 460(2):202-205.

Farina N, Isaac MG, Clark AR, Rusted J, Tabet N. Vitamin E for Alzheimer’s dementia and mild cognitive impairment. Cochrane Database of Systematic Review. 2012; 11.

Osiezagha K, Ali S, Freeman C, Barker N C, Jabeen S, Maitra S, Olagbemiro Y, Richie W, Bailey RK. Thiamine deficiency and delirium. Innov Clin Neurosci. 2013; 10(4):26-32. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659035/pdf/icns_10_4_26.pdf

Pawlak R, Lester SE, Babatunde T. The prevalence of cobalamin deficiency among vegetarians assessed by serum vitamin B12: a review of literature. European Journal of Clinical Nutrition, (2014); 68(5):541-548.

da Silva SL, Vellas B, Elemans S, Luchsinger J, Kamphuis P, Yaffe K, Sijben J, Groenendijk M, Stijnen T. Plasma nutrient status of patients with Al¬zheimer’s disease: systematic review and meta-analysis. Alzheimer’s

Demensia, (2014); 10: 485-502.

Lee H-P, Casadesus G, Zhu X, Lee H-g, Perry G, Smith MA, Gustaw-Rothenberg K, Lerner A. All-trans retinoic acid as a novel therapeutic strategy for Alzheimer’s disease. Expert Review of Neurotherapeutics, (2009); 9: 1615-1621.

Moneim AE. Oxidant/antioxidant imbalance and the risk of Alzheimer’s disease. Current Alzheimer Re¬search, (2015); 12: 335-349.

Green KN, Steffan JS, Martinez-Coria H, Sun X, Schreiber SS, Thompson LM, LaFerla FM. Nicotinamide restores cognition in Alzheimer’s disease transgenic mice via a mechanism involving sirtuin inhibition and selective reduction of Thr231-phosphotau.

Journal of Neurosciences, (2008); 28: 11500-11510.

Kennedy DO. B vitamins and the brain: mechanisms, dose and efficacy– A review. Nutrients, (2016); 8:68.

Sánchez-Hernández D, Anderson GH, Poon AN, Pannia E, Cho CE, Huot PSP, Kubant R. Maternal fat-soluble vitamins, brain development, and regulation of feeding behavior: an overview of research. Nutrition Research, (2016); 36(10): 1045-1054.

Khillan JS. Vitamin A/retinol and maintenance of pluripotency of stem cells. Nutrients, (2014); 6:1209-1222.

Hira H, Saleem U, Anwar F, Sohail MF, Raza Z, Ahmad B. β-carotene: A natural compound improves cognitive impairment and oxidative stress in a mouse model of streptozotocin-induced Alzheimer’s disease. Biomolecules, (2019); 9(9): 441.

Ono K, Yamada M. Vitamin A and Alzheimer’s disease. Geriatrics & Gerontology International, 2012; 12(2): 180-188.

Takasaki J, Ono K, Yoshiike Y, Hirohata M, Ikeda T, Morinaga A, Takashima A, Yamada M. Vitamin A has antioligomerization effects on amyloid-𝛽 in vitro. Journal of Alzheimer’s Disease, (2011); 27(2): 271-280.

Johnson EJ, Vishwanathan R, Johnson MA, Hausman DB, Davey A, Scott TM, Green RC, Miller LS, Gearing M, Woodard J, Nelson PT, Chung H-Y, Schalch W, Wittwer J, Poon LW. Relationship between serum and brain carotenoids, 𝛼-tocopherol, and retinol concentrations and cognitive performance in the oldest old from the Georgia centenarian study. Journal of Aging Reserch, (2013). http://dx.doi.org/10.1155/2013/951786

Feart C, Letenneur L, Helmer C, Samieri C, Schalch W, Etheve S, Delcourt C, Dartigues J-F, Barberger-Gateau P. Plasma carotenoids are inversely associated with dementia risk in an elderly French cohort. Journals of Gerontology: Medical Sciences, (2016); 71(5): 683-688.

Wang Y, Chung SJ, McCullough ML, Song WO, Fernandez ML, Koo S, Chun OK. Dietary carotenoids are associated with cardiovascular disease risk biomarkers mediated by serum carotenoid concentrations. Journal of Nutrition, (2014); 144:1067-1074.

Heidari-Beni M, Rafie N, Golpour-Hamedani S, Derakhshande-Rishehri S-M. The role of nutrition in the prevention and treatment of Alzheimer’s disease. E-Book: Alzheimer’s Disease & Treatment. 2018; MedDocs Publishers LLC, Online edition: http://meddocsonline.org/.

Goodman AB, Pardee AB. Evidence for defective retinoid transport and function in late onset Alzheimer’s disease. The Proceedings of the National Academy of Sciences, USA, (2003); 100: 2901-2905.

Kirchmeyer M, Koufany M, Sebillaud S, Netter P, Jouzeau J-Y, Bianchi A. All-trans retinoic acid suppresses interleukin-6 expression in interleukin-1-stimulated synovial fibroblasts by inhibition of ERK1/2 pathway independently of RAR activation. Arthritis Research & Therapy, (2008); 10:R141.

Kaur C, Sivakumar V, Dheen ST, Ling EA. Insulin-like growth factor I and II expression and modulation in amoeboid microglial cells by lipopolysaccharide and retinoic acid. Neurosciences, (2006);138:1233-1244.

Behairi N, Belkhelfa M, Rafa H, Labsi M, Deghbar N, Bouzid N, Mesbah-Amroun H, Touil-Boukoffa C. All-trans retinoic acid (ATRA) prevents lipopolysaccharide-induced neuroinflammation, amyloidogenesis and memory impairment in aged rats. Journal of Neuroimmunology, (2016); 300:21-29.

Takamura R, Watamura N, Nikkuni M, Ohshima T. All-trans retinoic acid improved impaired proliferation of neural stem cells and suppressed microglial activation in the hippocampus in an Alzheimer’s mouse model. Journal of Neurosciences Reseach, (2017); 95:897-906.

Priyanka SH, Syam Das S, Thushara AJ, Rauf AA, Indira M. All trans retinoic acid attenuates markers of neuroinflammation in rat brain by modulation of SIRT1 and NF-κB. Neurochemical Research, (2018); 43:1791-180.

Das, BC, Dasgupta S, Ray SK. Potential therapeutic roles of retinoids for prevention of neuroinflammation and neurodegeneration in Alzheimer’s disease. Neural Regeneration Research, (2019); 14(11): 1880-1892.

Szutowicz A, Bielarczyk H, Jankowska-Kulawy A, Ronowska A, Pawełczyk T. Retinoic acid as a therapeutic option in Alzheimer’s disease: a focus on cholinergic restoration. Expert Review Neurotherapy, (2015); 15:239-249.

Kawahara K, Suenobu M, Ohtsuka H, Kuniyasu A, Sugimoto Y, Nakagomi M, Fukasawa H, Shudo K, Nakayama H. Cooperative therapeutic action of retinoic acid receptor and retinoid x receptor agonists in a mouse model of Alzheimer’s disease. Journal of Alzheimers Disease, (2014); 42:587-605.

Nourhashemi F, Hooper C, Cantet C, Féart C, Gennero I, Payoux P, Salabert AS, Guyonnet S, Barreto P-D-S, Vellas B. Cross-sectional associations of plasma vitamin D with cerebral β-amyloid in older adults at risk of dementia. Alzheimer's Research Therapy, (2018); 10:43.

Przybelski RJ, Binkley NC. Is vitamin D important for preserving cognition? A positive correlation of serum 25- hydroxyvitamin D concentration with cognitive function. Archives of Biochemistry & Biophysics, (2007); 460 (2):202-205.

Sommer I, Griebler U, Kien C, Auer S, Klerings I, Hammer R, Holzer P, Gartlehner G. Vitamin D deficiency as a risk factor for dementia: a systematic review and meta-analysis. BMC Geriatrics, (2017); 17:16.

Littlejohns TJ, Kos K, Henley WE, Kuźma E, Llewellyn DJ. Vitamin D and dementia. Journal of Prevention Alzheimer’s Disease, (2016); 3(1): 43-52.

Holick MF. Vitamin D deficiency. New England Journal of Medicine, (2007); 357:266-81.

Balion C, Griffith LE, Strifler L, Henderson M, Patterson C, Heckman G, Llewellyn DJ, Raina P. Vitamin D, cognition, and dementia: a systematic review and meta-analysis. Neurology, (2012); 79(13):1397-1405.

Annweiler C, Llewellyn DJ, Beauchet O. Low serum vitamin D concentrations in Alzheimer’s disease: a systematic review and meta-analysis. Journal of Alzheimers Disease, (2013); 33(3):659-74.

Annweiler C, Annweiler T, Bartha R, Herrmann FR, Camicioli R, Beauchet O. Vitamin D and white matter abnormalities in older adults: a cross-sectional neuroimaging study. European Journal of Neurology, (2014); 21(12):1436-e95.

Shen L, Ji H-F. Vitamin D deficiency is associated with increased risk of Alzheimer’s disease and dementia: evidence from meta-analysis. Nutrition Journal, (2015); 14: 76.

Barnard K, Colon-Emeric C. Extraskeletal effects of vitamin D in older adults: cardiovascular disease, mortality, mood, and cognition. American Journal of Geriatric Pharmacotherapy, (2010); 8(1):4-33.

Llewellyn DJ, Lang IA, Langa KM, Muniz-Terrera G, Phillips CL, Cherubini A, Ferrucci L, Melzer D. Vitamin D and risk of cognitive decline in elderly persons. Archives of International Medicine, (2010); 170:1135-1141.

Slinin Y, Paudel ML, Taylor BC, Fink HA, Ishani A, Canales MT, Yaffe K, Barrett-Connor E, Orwoll ES, Shikany JM, Leblanc ES, Cauley JA, Ensrud KE. 25-Hydroxyvitamin D levels and cognitive performance and decline in elderly men. Neurology, (2010); 74:33-41.

Wilson VK, Houston DK, Kilpatrick L, Lovato J, Yaffe K, Cauley JA, Harris TB, Simonsick EM, Ayonayon HN, Kritchevsky SB, Sink KM. Relationship between 25-hydroxyvitamin D and cognitive function in older adults: the health, aging and body composition study. Journal of the American Geriatric Society, (2014); 62:636-641.

Toffanello ED, Coin A, Perissinotto E, Zambon S, Sarti S, Veronese N, De Rui M, Bolzetta F, Corti M-C, Crepaldi G, Manzato E, Sergi G. Vitamin D deficiency predicts cognitive decline in older men and women: The Progetto Veneto Anziani (Pro.V.A.) Study. Neurology, (2014); 83(24):2292-2298.

Perna L, Mons U, Kliegel M, Brenner H. Serum 25-hydroxyvitamin D and cognitive decline: a longitudinal study among non-demented older adults. Dementia and Geriatric Cognitive Disorders, (2014); 38:254-263.

Breitling LP, Perna L, Müller H, Raum E, Kliegel M, Brenner H. Vitamin D and cognitive functioning in the elderly population in Germany. Experimental Gerontology, (2012); 47:122-127.

Granic A, Hill TR, Kirkwood TBL, Davies K, Collerton J, Martin-Ruiz C, von Zglinicki T, Saxby BK, Wesnes KA, Collertonf D, Mathers JC, Jagger C. Serum 25-hydroxyvitamin D and cognitive decline in the very old: the Newcastle 85+ Study. European Journal of Neurology, (2015); 22:106-115.

Przybelski R, Agrawal S, Krueger D, Engelke JA, Walbrun F, Binkley N. Rapid correction of low vitamin D status in nursing home residents. Osteoporos International, 2008; 19:1621-1628.

Stein MS, Scherer SC, Ladd KS, Harrison LC. A randomized controlled trial of high-dose vitamin D2 followed by intranasal insulin in Alzheimer’s disease. Journal of Alzheimer’s Disease, (2011); 26: 47-84.

Annweiler C, Fantino B, Gautier J, Beaudenon M, Thiery S, Beauchet O. Cognitive effects of vitamin D supplementation in older outpatients visiting a memory clinic: a pre-post study. Journal of American Geriatric Society, (2012); 60:793-795.

Rossom RC, Espeland MA, Manson JE, Dysken MW, Johnson KC, Lane DS, LeBlanc ES, Lederle FA, Masaki KH, Margolis KL. Calcium and vitamin D supplementation and cognitive impairment in the women’s health initiative. Journal of American Geriatric Society, (2012); 60:2197-2205.

Annweiler C, Rolland Y, Schott AM, Blain H, Vellas B, Beauchet O. Serum vitamin D deficiency as a predictor of incident non-Alzheimer dementias: a 7-year longitudinal study. Dementia and Geriatric Cognitive Disorders, (2011); 32:273-278.

Afzal S, Bojesen SE, Nordestgaard BG. Reduced 25-hydroxyvitamin D and risk of Alzheimer’s disease and vascular dementia. Alzheimer’s Dementia, (2014); 10:296-302.

Littlejohns TJ, Henley WE, Lang IA, Annweiler C, Beauchet O, Chaves PHM, Fried L, Kestenbaum BR, Kuller LH, Langa KM, Lopez OL, Kos K, Soni M, Llewellyn DJ. Vitamin D and the risk of dementia and Alzheimer disease. Neurology, (2014); 83: 920-928.

Knekt P, Sääksjärvi K, Järvinen R, Marniemi J, Männistö S, Kanerva N, Heliövaara M. Serum 25-hydroxyvitamin D concentration and risk of dementia. Epidemiology, (2014); 25:799-804.

Karakis I, Pase M P, Beiser A, Booth SL, Jacques PF, Rogers G, DeCarli C, Vasan RS, Wang TJ, Himali JJ, Annweiler C, Seshadri S. Association of serum vitamin D with the risk of incident dementia and subclinical indices of brain aging: the framingham heart study. Journal of Alzheimer’s Disease, (2016); 51: 451-461.

Feart C, Helmer C, Merle B, Herrmann FR, Annweiler C, Dartigues J-F. Associations of lower vitamin D concentrations with cognitive decline and long-term risk of dementia and Alzheimer’s disease in older adults. Alzheimer’s Dementia, (2017); 13: 1207-1216.

Licher S, de Bruijn R, Wolters FJ, Zillikens MC, Ikram MA, Ikram MK. Vitamin D and the risk of dementia: the Rotterdam study. Journal of Alzheimer’s Disease, (2017); 60: 989-997.

Chen H, Xue W, Li J, Fu K, Shi H, Zhang B, Teng W, Tian L. 25-hydroxyvitamin D levels and the risk of dementia and Alzheimer’s disease: A dose–response meta-analysis. Front Aging Neuroscience, (2018); 10:368.

Olsson E, Byberg L, Karlstrom B, Cederholm T, Melhus H, Sjogren P, Kilander L. Vitamin D is not associated with incident dementia or cognitive impairment: an 18-y follow-up study in community-living old men. American Journal of Clinical Nutrition, (2017); 105: 936-943.

Gezen-Ak D, Dursun E, Ertan T, Hanagasi H, Gurvit H, Emre M, Eker E, Ozturk M, Engin F, Yilmazer S. Association between vitamin D receptor gene polymorphism and Alzheimer’s disease. The Tohoku Journal of Experimental Medicine, (2007); 212: 275-282.

Kuningas M, Mooijaart SP, Jolles J, Slagboom PE, Westendorp RG, van Heemst D. VDR gene variants associate with cognitive function and depressive symptoms in old age. Neurobiology of Aging, (2009); 30: 466-473.

Lehmann DJ, Refsum H, Warden DR, Medway C, Wilcock GK, Smith AD. The vitamin D receptor gene is associated with Alzheimer’s disease. Neuroscience Letters, (2011); 504: 79-82.

Laczmanski L, Jakubik M, Bednarek-Tupikowska G, Rymaszewska J, Sloka N, Lwow F. Vitamin D receptor gene polymorphisms in Alzheimer’s disease patients. Experimental Gerontology, (2015); 69: 142-147.

Wang L, Hara K, Van Baaren JM, Price JC, Beecham GW, Gallins PJ, Whitehead PL, Wang G, Lu C, Slifer MA, Zuchner S, Martin ER, Mash D, Haines JL, PericakVance MA, Gilbert JR. Vitamin D receptor and Alzheimer’s disease: A genetic and functional study. Neurobiology of Aging, (2012); 33: 1844 e1841-1849.

Beydoun MA, Ding EL, Beydoun HA, Tanaka T, Ferrucci L, Zonderman AB. Vitamin D receptor and megalin gene polymorphisms and their associations with longitudinal cognitive change in US adults. American Journal of Clinical Nutrition, (2012); 95: 163-178.

Galli F, Azzi A, Birringer M, Cook-Mills JM, Eggersdorfer M, Frank J, Cruciani G, Lorkowski S, Ozer NK. Vitamin E: Emerging aspects and new directions. Free Radical Biology and Medicine, (2017); 102:16-36.

Shahidi F, de Camargo AC. Tocopherols and tocotrienols in common and emerging dietary sources: Occurrence, applications, and health benefits. International Journal of Molecular Science, (2016); 17:1745.

Jiang Q. Natural forms of vitamin E: Metabolism, antioxidant, and anti-inflammatory activities and their role in disease prevention and therapy. Radical Biology and Medicine, (2014); 72: 76-90.

Ulatowski LM, Manor D. Vitamin E and neurodegeneration. Neurobiology of Disease, (2015); 84: 78-83.

Ulatowski L, Manor D. Vitamin E trafficking in neurologic health and disease. Annual Review of Nutrition, (2013); 33: 87-103.

Ulatowski L, Dreussi C, Noy N, Barnholtz-Sloan J, Klein E, Manor D. Expression of the -tocopherol transfer protein gene is regulated by oxidative stress and common single-nucleotide polymorphisms. Radical Biology and Medicine, (2012); 53: 2318-2326.

Reiter E, Jiang Q, Christen S. Anti-inflammatory properties of - and γ-tocopherol. Molecular Aspects of Medicine, (2007); 28(5-6): 668-691.

Lloret A, Esteve D, Monllor P, Cervera-Ferri A, Lloret A. The Effectiveness of vitamin E treatment in Alzheimer’s disease. International Journal of Molecular Science, (2019); 20: 879.

Lee CY, Man-FanWan J. Vitamin E supplementation improves cell-mediated immunity and oxidative stress of Asian men and women. Journal of Nutrition, (2000); 130: 2932-2937.

De la Fuente M, Hernanz A, Guayerbas N, Victor VM, Arnalich F. Vitamin E ingestion improves several immune functions in elderly men and women. Free Radical Researsh, (2008); 42: 272-280.

Jiang Z, Yin X, Jiang Q. Natural forms of vitamin E and 130-carboxychromanol, a long-chain vitamin E metabolite, inhibit leukotriene generation from stimulated neutrophils by blocking calcium influx and suppressing 5-lipoxygenase activity, respectively. Journal of Immunology, (2011); 186: 1173-1179.

Lopes da Silva S, Vellas B, Elemans S, Luchsinger J, Kamphuis P, Yaffe K, Sijben J, Groenendijk M, Stijnen T. Plasma nutrient status of patients with Alzheimer’s disease: Systematic review and meta-analysis. Alzheimer’s Dementia, (2014); 10: 485-502.

de Wilde MC, Vellas B, Girault E, Yavuz AC, Sijben JW. Lower brain and blood nutrient status in Alzheimer’s disease: Results from meta-analyses. Alzheimer’s Dementia, (2017); 3: 416-431.

Dong Y , Chen X, Liu Y, Shu Y , Chen T, Xu L, Li M, Guan X. Do low-serum vitamin E levels increase the risk of Alzheimer disease in older people? Evidence from a meta-analysis of case-control studies. International Journal of Geriatric Psychiatry, (2018); 33: e257-e263.

Liu G, Zhao Y, Jin S, Hu Y, Wang T, Tian R, Han Z, Xu D, Jiang Q. Circulating vitamin E levels and Alzheimer’s disease: A Mendelian randomization study. Neurobiology of Aging. (2018); 72: e1-e189.

Zandi PP, Anthony JC, Khachaturian AS, Stone SV, Gustafson D, Tschanz JT, Norton MC, Welsh-Bohmer KA, Breitner JC. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: The Cache County Study. Archives of Neurology, (2004); 61: 82-88.

Devore EE, F. Grodstein, F. J. A. van Rooij, Stampfer MJ, Witteman JC, Breteler MM. Dietary antioxidants and long-term risk of dementia. Archives of Neurology, (2010); 67(7): 819-825.

Basambombo LL, Carmichael PH, Côté S, Laurin D. Use of vitamin E and C supplements for the prevention of cognitive decline. Annals of Pharmacotherapy, (2017); 51: 118-124.

Gray SL, Anderson ML, Crane PK, Breitner JC, McCormick W, Bowen JD, Teri L, Larson E. Antioxidant vitamin supplement use and risk of dementia or Alzheimer’s disease in older adults. Journal of American Geriatric Society, (2008); 56: 291-295.

Masaki KH, Losonczy KG, Izmirlian G, Foley DJ, Ross GW, Petrovitch H, Havlik R, White LR. Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology, (2000); 54: 1265-1272.

Luchsinger JA, Tang MX, Shea S, Mayeux R. Antioxidant vitamin intake and risk of Alzheimer disease. Archives of Neurology, (2003); 60(2): 203-208.

Petersen RC, Thomas RG, Grundman M, Bennett D, Doody R, Ferris S, Galasko D, Jin S, Kaye J, Levey A, Pfeiffer E, Sano M, van Dyck CH, Thal LJ. Vitamin E and donepezil for the treatment of mild cognitive impairment. New England Journal of Medicine, (2005); 352: 2379-2388.

Kang JH, Cook N, Manson J, Buring JE, Grodstein F. A randomized trial of vitamin E supplementation and cognitive function in women. Archives of International Medicine, (2006); 166: 2462-2468.

Lloret A, Badía MC, Mora NJ, Pallardó FV, Alonso MD, Viña J. Vitamin E paradox in Alzheimer’s disease: It does not prevent loss of cognition and may even be detrimental. Journal of Alzheimer’s Disease, (2009); 17: 143-149.

Dysken MW, Sano M, Asthana S, Vertrees JE, Pallaki M, Llorente M, Love S, Schellenberg GD, McCarten JR, Malphurs J, Prieto S, Chen P, Loreck DJ, Trapp G, Bakshi RS, Mintzer JE, Heidebrink JL, Vidal-Cardona A, Arroyo LM, Cruz AR, Zachariah S, Kowall NW, Chopra MP, Craft S, Thielke S, Turvey CL, Woodman C, Monnell KA, Gordon K, Tomaska J, Segal Y, Peduzzi PN, Guarino PD. Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial. JAMA, (2014); 311(1): 33-44.

Kryscio RJ, Abner EL, Caban-Holt A, Lovell M, Goodman P, Darke AK, Yee M, Crowley J, Schmitt FA. Association of antioxidant supplement use and dementia in the prevention of Alzheimer’s disease by vitamin E and selenium trial (PREADViSE). JAMA Neurology, (2017); 74: 567-573.

Ibrahima NF, Yanagisawa D, Durani LW, Hamezah HS, Damanhuri HA, Ngah WZW, Tsuji M, Kiuchi Y, Ono K, Tooyama I. Tocotrienol-rich fraction modulates amyloid pathology and improves cognitive function in A_PP/PS1 mice. Journal of Alzheimer’s Disease, (2017); 55: 597-612.

Dong S, Huang X, Zhen J, Van Halm-Lutterodt N, Wang J, Zhou C, Yuan L. Dietary vitamin E status dictates oxidative stress outcomes by modulating effects of fish oil supplementation in Alzheimer’s disease model APPswe/PS1dE9 mice. Molecular Neurobiology, (2018); 55: 9204-9209.

Ferland G. Vitamin K and brain function. Seminars in Thrombosis and Hemostasis, (2013); 39: 849-855.

Ferland G, Doucet I, Mainville D. Phylloquinone and menaquinone-4 tissue distribution at different life stages in male and female spraguedawley rats fed different VK levels since weaning or subjected to a 40% calorie restriction since adulthood. Nutrients, (2016); 8:141.

Ohsaki Y, Shirakawa H, Hiwatashi K, Furukawa Y, Mizutani T, Komai M. Vitamin K suppresses lipopolysaccharide-induced inflammation in the rat. Bioscience, Biotechnology and Biochemistry, (2006); 70: 926-632.

Ohsaki Y, Shirakawa H, Miura A, Giriwono PE, Sato S, Ohashi A, Iribe M, Goto T, Komai M. Vitamin K suppresses the lipopolysaccharide-induced expression of inflammatory cytokines in cultured macrophage-like cells via the inhibition of the activation of nuclear factor κB through the repression of IKKα/β phosphorylation. Journal of Nutrition and Biochemistry, (2010); 21:1120-1126.

Carrié I, Bélanger E, Portoukalian J, Rochford J, Ferland G. Lifelong lowphylloquinone intake is associated with cognitive impairments in old rats. Journal of Nutrition, (2011); 141:1495-1501.

Sato Y, Honda Y, Hayashida N, Iwamoto J, Kanoko T, Satoh K. Vitamin K deficiency and osteopenia in elderly women with Alzheimer’s disease. The Archives of Physical Medicine and Rehabilitation, 2005; 86: 576-581.

Presse N, Belleville S, Gaudreau P, Greenwood CE, Kergoat MJ, Morais JA, Payette H, Shatenstein B, Ferland G. Vitamin K status and cognitive function in healthy older adults. Neurobiology of Aging, (2013); 34(12): 2777-2783.

van den Heuvel EGHM, van Schoor NM, Vermeer CRML, Zwijsen MH, Comijs HC. Vitamin K status is not associated with cognitive decline in middle aged adults. Journal of Nutrition Health and Aging, (2015); 19: 908-912.

Chouet J, Ferland G, Féart C, Rolland Y, Presse N, Boucher K, Barberger-Gateau P, Beauchet O, Annweiler C. Dietary vitamin K intake is associated with cognition and behaviour among geriatric patients: the CLIP study. Nutrients, (2015); 7: 6739-6750.

Soutif-Veillon A, Ferland G, Rolland Y, Presse N, Boucher K, Féart C, Annweiler C. Increased dietary vitamin K intake is associated with less severe subjective memory complaint among older adults. Maturitas, (2016); 93:131-136.

Kiely A, Ferland G, Ouliass B, O’Toole PW, Purtill H, O’Connor EM. Vitamin K status and inflammation are associated with cognition in older Irish adults. Nutritional Neuroscience, (2020); 23(8): 591-599.

Van Gorp RH, Schurgers LJ. New insights into the pros and cons of the clinical use of vitamin K antagonists (VKAs) versus direct oral anticoagulants (DOACs). Nutrients, (2015); 7: 9538-9557.

Alisi L, Cao R, De Angelis C, Cafolla A, Caramia F, Cartocci G, Librando A, Fiorelli M. The relationships between vitamin K and cognition: A review of current evidence. Frontiers in Neurology, (2019); 10: 239.

Ferland G, Doucet I, Mainville D. Phylloquinone and menaquinone-4 tissue distribution at different life stages in male and female spraguedawley rats fed different VK levels since weaning or subjected to a 40% calorie restriction since adulthood. Nutrients, (2016); 8:141.

Brangier A, Celle S, Roche F, Beauchet O, Ferland G, Annweiler C. Use of vitamin K antagonists and brain morphological changes in older adults: an exposed/unexposed voxel-based morphometric study. Dementia and Geriatric Cognitive Disorders, (2018); 45:18-26.

Cafolla A, Gentili A, Cafolla C, Perez V, Baldacci E, Pasqualetti D, Demasi B, Curini R. Plasma vitamin K1 levels in Italian patients receiving oral anticoagulant therapy for mechanical heart prosthesis: a case-control study. American Journal of Cardiovascuular Drugs, (2016); 16:267-274.

Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther MG, Palareti G. Pharmacology and management of the vitamin K antagonists: American college of chest physicians evidence- based clinical practice guidelines (8th edition). Chest, (2008); 133(6): 160S-198S.

Scheltens P, Blennow K, Breteler MM, de Strooper B, Frisoni GB, Salloway S, Van der Flier WM. Alzheimer’s disease. Lancet, (2016); 388: 505-517.

Morris MC, Schneider JA, Tangney CC. Thoughts on B-vitamins and dementia. Journal of Alzheimer’s Disease, (2006); 9(4):429-433.

Smith AD, Smith SM, de Jager CA,Whitbread P, Johnston C, Agacinski G, Oulhaj A, Bradley KM, Jacoby R, Refsum H. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One, (2010); 5: e12244.

Oulhaj A, Jernerén F, Refsum H, Smith AD, de Jager CA. Omega-3 fatty acid status enhances the prevention of cognitive decline by B vitamins in mild cognitive impairment. Journal of Alzheimer’s Disease, (2016); 50:547-557.

Khosravi-Largani M, Pourvali-Talatappeha P, Roustaa AM, Karimi-Kivia M, Noroozia E, Mahjooba A, Asaadib Y, Shahmohammadia A, Sadeghia S, Shakeria S, Ghiyasvanda K, Tavakoli-Yaraki M. A review on potential roles of vitamins in incidence, progression, and improvement of multiple sclerosis. eNeurologicalScience, (2018); 10: 37-44.

Vauzour D, Camprubi-Robles M, Miquel-Kergoat S, Andres-Lacueva C, Bánáti D, Barberger-Gateau P, Bowman GL, Caberlotto L, Clarke R, Hogervorst E, Kiliaan AJ, Lucca U, Manach C, Minihane A-M, Mitchell ES, Perneczky R, Perry H, Roussel A-M, Schuermans J, Sijben J, Spencer JPE, Thuret S, van de Rest O, Vandewoude M, Wesnes K, Williams RJ, Williams RSB, Ramirez M. Nutrition for the ageing brain: Towards evidence for an optimal diet. Ageing Research Reviews, (2017); 35: 222-240.

Obeid R, Herrmann W. Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. FEBS Letters, (2006); 580: 2994-3005.

O’Leary F, Allman-Farinelli M, Samman S. Vitamin B12 status, cognitive decline and dementia: a systematic review of prospective cohort studies. British Journal of Nutrition, (2012); 108: 1948-1961.

Ford AH, Almeida OP. Effect of homocysteine lowering treatment on cognitive function: a systematic review and meta-analysis of randomized controlled trials. Journal of Alzheimer’s Disease, (2012); 29: 133-149.

Malouf R, Areosa Sastre A. Vitamin B12 for cognition. Cochrane Database Systematic Reviews, (2003); 3: CD004326.

Malouf R, Grimley Evans J. Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people. Cochrane Database Systematic Reviews, (2008); 4: CD004514.

Durga J, van Boxtel MP, Schouten EG, Kok FJ, Jolles J, Katan MB, Verhoef P. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomized, double blind, controlled trial. Lancet, (2007); 369(9557): 208-216.

Calderón-Ospina CA, Nava-Mesa MO. B vitamins in the nervous system: Current knowledge of the biochemical modes of action and synergies of thiamine, pyridoxine, and cobalamin. CNS Neuroscience Therapy, (2020); 26: 5-13.

da Silva SL, Vellas B, Elemans S, Luchsinger J, Kamphuis P, Yaffe K, Sijbena J, Groenendijka M, Stijnenf T. Plasma nutrient status of patients with Al¬zheimer’s disease: systematic review and meta-analysis. Alzheimer’s Dementia, (2014); 10: 485-502.

Ulstein I, Bøhmer T. Normal vitamin levels and nutritional indices in Alzheimer’s disease patients with mild cognitive impairment or dementia with normal body mass indexes. Journal of Alzheimer’s Disease, (2017); 55: 717-725.

Froese DS, Fowler B, Baumgartner MR. Vitamin B12, folate and the methionine remethylation cycle-biochemistry, pathways and regulation. Journal of Inherited Metabolic Disese, (2019); 42: 673-685.

Green R, Allen LH, Bjørke-Monsen A-L, Brito A, Gueant J-L, Miller JW, Molloy AM, Nexo E, Stabler S, Toh BH, Ueland PM, Yajnik C. Vitamin B12 deficiency. Nature Reviews Disease Primers, (2017); 3:17040.

Moore EM, Ames D, Mander AG, Carne RP, Brodaty H, Woodward MC, Boundy K, Ellis KA, Bush AI, Faux NG, Martins RN, Masters CL, Rowe CC, Szoeke C, Watters DA. Among vitamin B12 deficient older people, high folate levels are associated with worse cognitive function: combined data from three cohorts. Journal of Alzheimer’s Disease, (2014); 39: 661-668.

Grarup N, Sulem P, Sandholt CH, Thorleifsson G, Ahluwalia TS, Steinthorsdottir V, Bjarnason H, Gudbjartsson DF, Magnusson OT, Sparsø T, Albrechtsen A, Kong A, Masson G, Tian G, Cao H, Nie C, Kristiansen K, Husemoen LL, Thuesen B, Li Y, Nielsen R, Linneberg A, Olafsson I, Eyjolfsson GI, Jørgensen T, Wang J, Hansen T, Thorsteinsdottir U, Stefánsson K, Pedersen O. Genetic architecture of vitamin B12 and folate levels uncovered applying deeply sequenced large datasets. Plos Genetics, (2013); 9:e1003530.

Larsson SC, Traylor M, Malik R, Dichgans M, Burgess S, Markus HS. Modifiable pathways in Alzheimer’s disease: Mendelian randomization analysis. BMJ, (2017); 359: j5375.

Taliun SAG. Genetic determinants of low vitamin B12 levels in Alzheimer’s disease risk. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, (2019); 11: 430-434.

Ikram MA, Vrooman HA, Vernooij MW, den Heijer T, Hofman A, Niessen WJ, Breteler MM. Brain tissue volumes in relation to cognitive function and risk of dementia. Neurobiology of Aging, (2010); 31:378-386.

Gallucci M, Spagnolo P, Arico M, Grossi E. Predictors of response to cholinesterase inhibitors treatment of Alzheimer’s disease: date mining from the TREDEM registry. Journal of Alzheimer’s Disease, (2016); 50: 969-979.

Gibson GE, Hirsch JA, Fonzetti P, Jordan BD, Cirio RT, Elder J. Vitamin B1 (thiamine) and dementia. Annals of the New York Academy of Sciences, (2016); 1367: 21-30.

Pan X, Gong N, Zhao J, Yu Z, Gu F, Chen J, Sun X, Zhao L, Yu M, Xu Z, Dong W, Qin Y, Fei G, Zhong C, Xu TL. Powerful beneficial effects of benfotiamine on cognitive impairment and beta-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice. Brain, (2010); 133:1342-1351.

Pan X, Fei G, Lu J, Jin L, Pan S, Chen Z, Wang C, Sang S, Liu H, Hu W, Zhang H, Wang H, Wang, Tan Q, Qin Y, Zhang Q, Xie X, Ji Y, Cui D, Gu X, Xu J, Yu Y, Zhong C. Measurement of blood thiamine metabolites for Alzheimer’s disease diagnosis. EBioMedicine, (2016); 3:155-162.

Pan X, Sang S, Fei G, Jin L, Liu H, Wang Z, Wang H, Zhong C. Enhanced activities of blood thiamine diphosphatase and monophosphatase in Alzheimer’s disease. PLoS One, (2017);12:e0167273.

Liu, D., Zunji, K. and Jia, L. Thiamine deficiency and neurodegeneration: the interplay among oxidative stress, endoplasmic reticulum stress, and autophagy. Pharmacology and Nutritional Sciences Faculty Publications, (2017); 91.

Saedisomeolia A, Ashoori M. Riboflavin in human health: a review of current evidences. Advances in Food and Nutrition Research, (2018); 83: 57-81.

Kim H, Kim G, Jang W, Kim SY, Chang N. Association between intake of B vitamins and cognitive function in elderly Koreans with cognitive impairment. Nutrition Journal, (2014); 13:118.

Araki A, Yoshimura Y, Sakurai T, Umegaki H, Kamada C, Iimuro S, Ohashi, Y, Ito H. Low intakes of carotene, vitamin B2, pantothenate and calcium predict cognitive decline among elderly patients with diabetes mellitus: the Japanese elderly diabetes intervention trial. Geriatric Gerontology International, (2017); 17: 1168-1175.

Tao L, Liu K, Chen S, Yu H, An Y, Wang Y, Zhang X, Wang Y, Qin Z, Xiao R. Dietary intake of riboflavin and unsaturated fatty acid can improve the multi-domain cognitive function in middle-aged and elderly populations: A 2-year prospective cohort study. Frontiers in Aging Neuroscience, (2019); 11: 226.

Zhao R, Wang H, Qiao C, Zhao K. Vitamin B2 blocks development of Alzheimer’s disease in APP/PS1 transgenic mice via anti-oxidative mechanism. Tropical Jounal of Pharmacological Research, (2018); 17(6): 1049-1054.

Cui X, Chopp M, Zacharek A, Roberts C, Buller B, Ion M, Chen J. Niacin treatment of stroke increases synaptic plasticity and axon growth in rats. Stroke, (2010); 41:2044-2049.

Morris MC, Evans DA, Bienias JL, Scherr PA, Tangney CC, Hebert LE, Bennett DA, Wilson RS, Aggarwal N. Dietary niacin and the risk of incident Alzheimer’s disease and of cognitive decline. Journal of Neurology and Neurosurgery Psychiatry, (2004); 75:1093-1099.

Kerr JS, Adriaanse BA, Greig NH, Mattson MP, Cader MZ, Bohr VA, Fang EF. Mitophagy and Alzheimer’s disease: Cellular and molecular mechanisms. Trends in Neurosciences, (2017); 40: 151-166.

Wang X, Hu X, Yang Y, Takata T, Sakurai T. Nicotinamide mononucleotide protects against β-amyloid oligomer-induced cognitive impairment and neuronal death. Brain Research, (2016); 1643, 1-9.

Kim EJ, Yang SJ. Nicotinamide reduces amyloid precursor protein and presenilin 1 in brain tissues of amyloid beta-tail vein injected mice. Clinical Nutrition Research, (2017); 6: 130-135.

Jesko H, Wencel P, Strosznajder RP, Strosznajder JB. Sirtuins and their roles in brain aging and neurodegenerative disorders. Neurochemical Research, (2017); 42: 876-890.

Rizzi L, Roriz-Cruz M. Sirtuin 1 and Alzheimer’s disease: An up-to-date review. Neuropeptides, (2018); 71: 54-60.

Leonardi R, Zhang YM, Rock CO, Jackowski S. Coenzyme A. Back in action. Progress in Lipid Research, (2005); 44(2e3): 125e53.

Lee J-H, Ahn S-Y, Lee HA, Won KS, Chang HW, Oh JS, Kim HW. Dietary intake of pantothenic acid is associated with cerebral amyloid burden in patients with cognitive impairment. Food and Nutrition Research, (2018); 62: 1415.

Sato K. Why is vitamin B6 effective in alleviating the symptoms of autism? Medical Hypotheses, (2018);115:103-106.

Zhuo J-M, Wang H, Praticò D. Is hyperhomocysteinemia an Alzheimer’s disease (AD) risk factor, an AD marker or neither? Trends in Pharmacological Sciences, (2011); 32(9): 562-571.

Moretti R, Caruso P. The Controversial role of homocysteine in neurology: From labs to clinical practice. International Journal of Molecular Science, (2019); 20(1): 231.

Tinelli C, Pino AD, Ficulle E, Marcelli S, Feligioni M. Hyperhomocysteinemia as a risk factor and potential nutraceutical target for certain pathologies. Frontiers in Nutrition, (2019); 6: 49.

Miller JW, Green R, Mungas DM, Reed BR, Jagus WJ. Homocysteine, vitamin B6, and vascular disease in AD patients. Neurology, (2002); 58(10).

Tong L. Structure and function of biotin-dependent carboxylases. Cellular and Molecular Life Sciences, (2013); 70(5):863-891.

McCarty MF, DiNicolantonio JJ. Neuroprotective potential of high-dose biotin. Medical Hypotheses, (2017); 109:145-149.

Palmeri A, Ricciarelli R, Gulisano W, Rivera D, Rebosio C, Calcagno E, Tropea MR, Conti S, Das U, Roy S, Pronzato MA, Arancio O, Fedele E , Puzzo D. Amyloid-β peptide is needed for cGMP-induced long-term potentiation and memory. Journal of Neurosciences, (2017) ; 37(29): 6926-6937.

Gonos ES, Kapetanou M, Sereikaite J, Bartosz G, Naparło K, Grzesik M, Sadowska-Bartosz I. Origin and pathophysiology of protein carbonylation, nitration and chlorination in age-related brain diseases and aging. Aging, (2018); 10: 868-901.

Kang WB, Chen YJ, Lu DY, Yan JZ. Folic acid contributes to peripheral nerve injury repair by promoting Schwann cell proliferation, migration, and secretion of nerve growth factor. Neural Regeneration Research, (2019); 14(1):132-139.

Chen, H., Liu, S., Ji, L., Wu, T., Ji, Y., Zhou, Y., Zheng, M., Zhang, M., Xu, W. and Huang, G. Folic Acid supplementation mitigates Alzheimer’s disease by reducing inflammation: A randomized controlled trial. Mediators of Inflammation, (2016); Article ID 5912146, 10 pages http://dx.doi.org/10.1155/2016/5912146

Morris MC, Evans DA, Bienias JL, Tangney CC, Hebert LE, Scherr PA, Schneider JA. Dietary folate and vitamin B12 intake and cognitive decline among community-dwelling older persons. Archives of Neurology, (2005); 62(4):641-645.

Ma F, Wu T, Zhao J, Song A, Liu H, Xu W, Huang G. Folic acid supplementation improves cognitive function by reducing the levels of peripheral inflammatory cytokines in elderly Chinese subjects with MCI. Scientific Reports, (2016); 6: 37487.

Hankey GJ, Ford AH, Yi Q, Eikelboom JW, Lees KR, Chen C, Xavier D, Navarro JC, Ranawaka UK, Uddin W, Ricci S, Gommans J, Schmidt R, Almeida OP, van Bockxmeer FM. VITATOPS trial study group. Effect of B vitamins and lowering homocysteine on cognitive impairment in patients with previous stroke or transient ischemic attack: a prespecified secondary analysis of a randomized, placebo-controlled trial and meta-analysis. Stroke, (2013); 44: 2232-2239.

Li MM, Yu JT, Wang HF, Jiang T, Wang J, Meng XF, Tan CC, Wang C, Tan L. Efficacy of vitamins B supplementation on mild cognitive impairment and Alzheimer's disease: a systematic review and meta-analysis. Current Alzheimer Research, (2014);11(9):844-52.

Love S, Miners JS. Cerebrovascular disease in ageing and Alzheimer’s disease. Acta Neuropathology, (2016); 131:645-658.

Kruman II, Kumaravel TS, Lohani A, Pedersen WA, Cutler RG, Kruman Y, Haughey N, Lee J, Evans M, Mattson MP. Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer’s disease. Journal of Neuroscience, (2002); 22:1752-1762.

Corradaa MM, Kawasa CH, Hallfrischc J, Mullerd D, Brookmeyer R. Reduced risk of Alzheimer’s disease with high folate intake: The Baltimore longitudinal study of aging. Alzheimers Dementia, (2005); 1(1): 11-18.

Almeida CC, Brentani HP, Forlenza OV, Diniz BS. Serum folic acid is reduced in patients with Alzheimer’s disease. Revista de Psiquiatria Clínica, (2012); 39(3): 90-93.

Harrison FE, Bowman GL, Polidori MC. Ascorbic acid and the brain: rationale for the use against cognitive decline. Nutrients, (2014); 6:1752-1781.

Monacelli F, Acquarone E, Giannotti C, Borghi R, Nencioni A. Vitamin C, aging and Alzheimer’s disease. Nutrients, (2017); 9: 670.

Murakami K., Murata N, Ozawa Y, Kinoshita N, Irie K, Shirasawa T, Shimizu T. Vitamin C restores behavioral deficits and amyloid-β-oligomerization without affecting plaque formation in a mouse model of Alzheimer’s disease. Journal of Alzheimer’s Disease, (2011); 26(1): 7-18.

Luchsinger JA, Tang M-X, Shea S, Mayeux R. Antioxidant vitamin intake and risk of Alzheimer’s disease. Archives of Neurology, (2003); 60(2): 203-208.

Zandi PP, Anthony JC, Khachaturian AS, Stone SV, Gustafson D, Tschanz JT, Norton MC, Welsh-Bohmer KA, Breitner JC. Reduced risk of Alzheimer’s disease in users of antioxidant vitamin supplements: The cache county study. Archives of Neurology, (2004); 61: 82-88.

Harrison FE. A critical review of vitamin C for the prevention of age-related cognitive decline and Alzheimer’s disease. Journal of Alzheimer’s Disase, (2012); 29(4): 711-726.

Choudhry F, Howlett DR, Richardson JC, Francis PT, Williams RJ. Pro-oxidant diet enhances beta/gamma secretase-mediated APP processing in APP/PS1 transgenic mice. Neurobiology of Aging, (2012); 33: 960-968.

Covarrubias-Pinto A, Acuna AI, Beltran FA, Torres-Diaz L, Castro MA. Old things new view: Ascorbic acid protects the brain in neurodegenerative disorders. International Journal of Molecular Science, (2015); 16: 28194-28217.

Rohl C, Armbrust E, Herbst E, Jess A, Gulden M, Maser E, Rimbach G, Bosch-Saadatmandi C. Mechanisms involved in the modulation of astroglial resistance to oxidative stress induced by activated microglia: Antioxidative systems, peroxide elimination, radical generation, lipid peroxidation. Neurotoxicity Research, (2010); 17: 317-331.

Lam V, Hackett M, Takechi R. Antioxidants and dementia risk: Consideration through a cerebrovascular perspective. Nutrients, (2016); 8(12): 828.

Quinn J, Suh J, Moore MM, Kaye J, Frei B. Antioxidants in Alzheimer’s disease-vitamin C delivery to a demanding brain. Journal of Alzheimer’s Disease, (2003); 5: 309-313.

Devore EE, Kang JH, Stampfer MJ, Grodstein F. The association of antioxidants and cognition in the nurses’ health study. American Journal of Epidemiology, (2013); 177: 33-41.

Fillenbaum GG, Kuchibhatla MN, Hanlon JT, Artz MB, Pieper CF, Schmader KE, Dysken MW, Gray SL. Dementia and Alzheimer’s disease in community-dwelling elders taking vitamin C and/or vitamin E. Annals of Pharmacotherapy, (2005); 39: 2009-2014.

Emir UE, Raatz S, McPherson S, Hodges JS, Torkelson C, Tawfik P, White T, Terpstra M. Noninvasive quantification of ascorbate and glutathione concentration in the elderly human brain. NMR Biomedicine, (2011); 24: 888-894.

González HF, Visentin S. Micronutrients and neurodevelopment: An update. Archivos Argentinos de Pediatria, (2016); 114(6):570-575.

Tayebati SK, Amenta F. Choline-containing phospholipids: relevance to brain functional pathways. Clinical Chemistry and Laboratory Medicine, (2013); 51:513-521.

Shea, T.B. Choline and phosphatidylcholine may maintain cognitive performance by multiple mechanisms. American Journal of Clinical Nutrition, (2019); 110(6):1268-1269.

Pohanka, M. Alpha7 nicotinic acetylcholine receptor is a target in pharmacology and toxicology. International Journal of Molecular Science, (2012); 13(2): 2219-2238.

Tremblay ME, Stevens B, Sierra A, Wake H, Bessis A, Nimmerjahn A. The role of microglia in the healthy brain. Journal of Neuroscience, (2011); 31(45): 16064-16069.

Jin JL, Fang M, Zhao YX, Liu XY. Roles of sigma-1 receptors in Alzheimer's disease. Int J Clin Exp Med. 2015; 8(4): 4808-4820. PMCID: PMC4484039

Matsumura A, Suzuki S, Iwahara N, Hisahara S, Kawamata J, Suzuki H, Yamauchi A, Takata K, Kitamura Y, Shimohama, S. Temporal changes of CD68 and α7 nicotinic acetylcholine receptor expression in microglia in Alzheimer’s disease-like mouse models. Journal of Alzheimer's Disease, (2015); 44(2): 409-423.

Brailoiu E, Chakraborty S, Brailoiu GC, Zhao P, Barr JL, Ilies MA, Unterwald EM, Abood ME. Taylor, C.W. Choline is an intracellular messenger linking extracellular stimuli to IP3-evoked Ca(2+) signals through sigma-1 receptors. Cell Reports, (2019); 26(2): 330-337 e4.

Hall AA, Herrera Y, Ajmo CTJr, Cuevas J, Pennypacker KR. Sigma receptors suppress multiple aspects of microglial activation. Glia, (2009); 57(7): 744-754.

US Standing Committee on the Scientific Evaluation. US standing committee on the scientific evaluation of dietary reference intakes and its panel on folate, other B vitamins, and choline dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline, (1998); Washingdon, DC: The National Academies Collection.

Velazquez R, Ferreira E, Knowles S, Fux C, Rodin A, Winslow W, Oddo S. Lifelong choline supplementation ameliorates Alzheimer’s disease pathology and associated cognitive deficits by attenuating microglia activation. Aging Cell, (2019); 18:e13037.

Caudill MA, Strupp BJ, Muscalu L, Nevins JEH, Canfield RL. Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: A randomized, double-blind, controlled feeding study. FASEB Journal, (2018); 32(4):2172-2180.

Secades JJ. Citicoline in the treatment of cognitive impairment. Journal of Neurology and Experimental Neuroscience, (2019); 5(1): 14-26.

McGlade E, Agoston AM, DiMuzio J, Kizaki M, Nakazaki E, Kamiya T, Yurgelun-Todd D. The effect of citicoline supplementation on motor speed and attention in adolescent males. Journal of Attention Disorders, (2019); 23(2):121-134.

Bruce SE, Werner KB, Preston BF, Baker LM. Improvements in concentration, working memory and sustained attention following consumption of a natural citicoline-caffeine beverage. International Journal of Food Science and Nutrition, (2014); 65: 1003-1007.

De Jesus M.M.M. Cognitive improvement in mild to moderate Alzheimer’s dementia after treatment with the acetylcholine precursor choline alfoscerate: A multicenter, double-blind, randomized, placebo-controlled trial. Clinical Therapy, (2003); 25(1):178-193.

Amenta F, Parnetti L, Gallai V, Wallin A. Treatment of cognitive dysfunction associated with Alzheimer’s disease with cholinergic precursors. Ineffective treatments or inappropriate approaches? Mechanisms of Ageing and Development, (2001); 122(16):2025-2040.

Scapicchio PL. Revisiting choline alphoscerate profile: a new, perspective, role in dementia? International Journal of Neuroscience, (2013); 123(7): 444-449.

Higgins JP, Flicker L. Lecithin for dementia and cognitive impairment. Cochrane Database of Systematic Reviews, (2003); (3):CD001015.

Chheri, DR. Myo-Inositol and Its Derivatives: Their emerging role in the treatment of human diseases. Frontiers in Pharmacology, (2019); 10: 1172.

Siger M, Schuff N, Zhu X, Miller BL, Weiner MW. Regional myo-inositol concentration in mild cognitive impairment using 1H magnetic resonance spectroscopic imaging. Alzheimer Disease and Associated Disorders, (2009); 23(1): 57-62.

Lee D, Lee W-S, Lim S, Kim YK, Jung H-Y, Das S, Lee J, Luo W, Kim K-T, Chung S-K. A guanidine-appended scylloinositol derivative AAD-66 enhances brain delivery and ameliorates Alzheimer’s phenotypes. Scientific Repotrts, (2017); 7(1):14125.

Fenili D, Weng Y-Q , Aubert I, Nitz M , McLaurin J. Sodium/myo-Inositol Transporters: Substrate Transport Requirements and Regional Brain Expression in the TgCRND8 Mouse Model of Amyloid Pathology. PLoS ONE, (2011); 6(8): e24032.

Lyketsos C, Abushakra S, Liang E, Hernandez R, Tariot P, Porsteinsson A, Wagg J. Effects of oral ELND005 (Scylloinositol) on neuropsychiatric symptoms in a 78-week phase 2 study in mild/ moderate Alzheimer’s disease (AD): potential role of Myo-inositol reduction. Alzheimer's & Dementia: Journal of the Alzheimer's Association, (2012); 8(4S): S771-S772.

Liang E, Tariot P, Abushakra S, Porsteinsson A, Hernandez R, Crans G, Narayanan S, Arnold D, Wagg J. Effects of oral ELND005 (Scylloinositol) on brain Scyllo-inositol and Myo-inositol levels: spectroscopy results from a phase 2 study in mild-tomoderate Alzheimer’s disease. Alzheimer's & Dementia: Journal of the Alzheimer's Association, (2012); 8(4S): S783-S784.

Ribas GS, Vargas CR, Wajner M. L-carnitine supplementation as a potential antioxidant therapy for inherited neurometabolic disorders. Gene, (2014); 533: 469-76.

Flanagan JL, Simmons PA, Vehige J, Willcox MDP, Garrett Q. Review role of carnitine in disease. Nutrition & Metabolism (Lond), (2010); 7:30.

Liu J, Head E, Gharib AM, Yuan W, Ingersoll RT, Hagen TM, Cotman CW, Ames BN. Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid. Proceedings of the National Academy of Sciences of the USA, (2002); 99: 2356-2361.

Pettegrew JW, Klunk WE, Panchalingam K, Kanfer JN, McClure RJ. Clinical and neurochemical effects of acetyl-L-carnitine in Alzheimer's disease. Neurobiology of Aging, (1995); 16: 1-4.

Hudson S, Tabet N. Acetyl-L-carnitine for dementia. Cochrane Database of Systematic Reviws, (2003); (2):CD003158.

Cristofano A, Sapere N, Marca GL, Angiolillo A, Vitale M, Corbi G, Scapagnini G, Intrieri M, Russo C, Corso G, Costanzo AD. Serum levels of acyl-carnitines along the continuum from normal to Alzheimer's dementia. PLoS One, (2016); 11(5): e0155694.

Onofrj M, Ciccocioppo F, Varanese S, di Muzio A, Calvani M, Chiechio S, Osio M, Thomas A. Acetyl-L-carnitine: from a biological curiosity to a drug for the peripheral nervous system and beyond. Expert Review of Neurotherapy, (2013); 13: 925-936.

Thal LJ, Calvani M, Amato A, Carta A. A 1-year controlled trial of acetyl-l-carnitine in early-onset AD. Neurology, (2000); 55: 805-810.

Montgomery SA, Thal LJ, Amrein R. Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease. International Clinical Psychopharmacology, (2003); 18: 61-71.

Yang YS, Choi H, Lee CN, Kim YB, Kwak YT. A multicenter, randomized, double blind, placebo-controlled clinical trial for efficacy of acetyl-L-carnitine in patients with dementia associated with cerebrovascular disease. Dementia and Neurocognitive Disorders, (2018); 17(1):1-10.

Fenech M. Vitamins associated with brain aging, mild cognitive impairment, and Alzheimer disease: biomarkers, epidemiological and experimental evidence, plausible mechanisms, and knowledge gaps. Advances in Nutrition, (2017); 8:958-970.

Kennedy DO. B vitamins and the brain: mechanisms, dose and efficacy– a review. Nutrients, (2016); 8:68.

Araújo JR, Martel F, Borges N, Araújo JM, Keating E. Folates and aging: Role in mild cognitive impairment, dementia and depression. Ageing Research Reviews, (2015); 22: 9-19.

Fuso A, Seminara L, Cavallaro RA, D'Anselmi F, Scarpa S. S-adenosylmethionine / homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production. Molecular and Cellular Neuroscience, (2005); 28(1):195-204.

Porter K, Hoey L, Hughes CF, Ward M, McNulty H. Causes, consequences and public health implications of low B-vitamin status in ageing. Nutrients, (2016); 8(11): 725.

Serot J-M, Barbe´ F, Arning E, Bottiglieri T, Franck P, Montagne P, Nicolas J-P. Homocysteine and methylmalonic acid concentrations in cerebrospinal fluid: relation with age and Alzheimer’s disease. Joural of Neurology and Neurosurgey Psychiatry, 2005; 76:1585-1587.

Herrmann W, Schorr H, Bodis M, Knapp JP, Müller A, Stein G, Geisel J. Role of homocysteine, cystathionine and methylmalonic acid measurement for diagnosis of vitamin deficiency in high-aged subjects. European

Journal of Clinical Investigation, (2000); 30:1083-1089.

Maynard S, Fang EF, Scheibye-Knudsen M, Croteau DL, Bohr VA. DNA damage, DNA repair, aging, and neurodegeneration. Cold Spring Harbor Perspectives in Medicine, (2015); 5: a025130.

Madabhushi R, Pan L, Tsai L-H. DNA damage and its links to neurodegeneration. Neuron, (2014); 83(2): 266-282.

Gruz-Gibelli E, Chessel N, Allioux C, Marin P, Piotton F, Leuba G, Herrmann FR, Savioz A. The vitamin A derivative all-trans retinoic acid repairs amyloid-𝛽-induced double-strand breaks in neural cells and in the murine neocortex. Neural Plasticity, (2016); Article ID 3707406, 11 pages.

Kim GH, Kim JE, Rhie SJ Yoon S. The Role of oxidative stress in neurodegenerative diseases. Experimental Neurobiology, (2015); 24(4):325-340.

Reddy PV, Perry G, Cooke MS, Sayre LM, Smith MA. Mechanisms of DNA Damage and Repair in Alzheimer Disease. In: Madame Curie Bioscience Database [Internet]. Austin (TX): Landes Bioscience, (2000-2013).

Sajjad N, Wani A, Hassan S, Ali R, Hamid R, Akbar S , Ganai BA, Bhat EA. Interplay of antioxidants in Alzheimer’s disease. Jounal of Translational Science, (2019); 5: 1-11.

Wimalawansa SJ. Vitamin D deficiency: Effects on oxidative stress, epigenetics, gene regulation, and aging. Biology (Basel), (2019); 8: 30.

Surjana D, Halliday GM, Damian DL. Role of nicotinamide in DNA damage, mutagenesis, and DNA repair. Journal of Nucleic Acids, (2010); 2010: Article No.157591.

Ladeira C, Carolino E, Gomes MC, Brito M. Role of macronutrients and micronutrients in DNA damage: Results from a food frequency questionnaire. Nutrition and Metabolic Insights, (2017); 1-8.

Karapiperi K, Gousis C, Papaioannidou P. The role of vitamin B12 in DNA modulation mechanisms. Front. Pharmacol. Conference Abstract: 8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET (2010). Held on 01-05 Oct. 2010 at Porto Palace Hotel, Thessaloniki, Greece. doi: 10.3389/conf.fphar.2010.60.00140

Zhao Y, Zhao B. Oxidative stress and the pathogenesis of Alzheimer's disease. Oxid Med Cell Longevity, (2013); 2013:316523.

Wang X, Wang W, Li L, Perry G, Lee HG, Zhu X. Oxidative stress and mitochondrial dysfunction in Alzheimer's disease. Biochimica et Biophysica Acta (2014); 1842(8):1240-1247.

Berridge MJ. Vitamin D deficiency accelerates ageing and age-related diseases: a novel hypothesis. Journal of Physiology, (2017); 595(22): 6825-6836.

Scaini G, Rezin GT, Carvalho AF, Streck EL, Berk M, Quevedo J. Mitochondrial dysfunction in bipolar disorder: Evidence, pathophysiology and translational implications. Neuroscience and Biobehavioral Reviews, (2016); 68: 694-713.

Depeint F, Bruce WR, Shangari N, Mehta R, O’Brien PJ. Mitochondrial function and toxicity: Role of the B vitamin family on mitochondrial energy metabolism. Chemico-Biological Interactions, (2006); 163: 94-112.

Janssen JJE, Grefte S, Keijer J and de Boer VCJ. Mito-Nuclear Communication by Mitochondrial Metabolites and Its Regulation by B-Vitamins. Frontiers in Physiology, (2019);10:78.

Hamilton JA, Hillard CJ, Spector AA, Watkins PA. Brain uptake and utilization of fatty acids, lipids and lipoproteins: application to neurological disorders. Journal of Molecular Neuroscience, (2007); 33, 2-11.

Mosconi L, Murray J, Davies M, Williams S, Pirraglia E, Spector N, Tsui WH, Li Y, Butler T, Osorio RS, Glodzik L, Vallabhajosula S, McHugh P, Marmar CR, de Leon MJ. Nutrient intake and brain biomarkers of Alzheimer’s disease in at-risk cognitively normal individuals: a cross-sectional neuroimaging pilot study. BMJ Open, (2014); 4: e004850.

Lloret A, Esteve D, Monllor P, Cervera-Ferri A, Lloret A. The Effectiveness of vitamin E treatment in Alzheimer’s disease. International Journal of Molecular Science, (2019); 20: 879.

Langelier B, Linard A, Bordat C, Lavialle M, Heberden C. Long chain-polyunsaturated fatty acids modulate membrane phospholipids composition and protein localization in lipid rafts of neural stem cell cultures. Journal of Cellular Biochemistry, (2010); 15: 1356-1364.

Schaefer EJ, Bongard V, Beiser AS, Lamon-Fava S, Robins SJ, Au R, Tucker KL, Kyle DJ, Wilson PW, Wolf PA. Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer’s disease: the Framingham Heart Study. Archives of Neurology, (2006); 63.

Hassouneh LKM. Effects of vitamin E on the synthesis of phospholipids and brain functions in old rats. Neurophysiology, (2018); 50(3): 166-172.

Shearer MJ, Newman P. Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis. Journal of Lipid Research, (2014); 55: 345-362.

Crivello NA, Casseus SL, Peterson JW, Smith DE, Booth SL. Age- and brain-region-specific effects of dietary vitamin K on myelin sulfatides. Journal of Nutrition and Biochemistry, (2010); 21(11): 1083-1088.

Aggarwal S, Yurlova L, Simons M. Central nervous system myelin: structure, synthesis and assembly. Tends in Cell Biology, (2011); 21(10): 585-592.

Ismail N, Kureishy N, Church SJ, Scholefield M, Unwin RD, Xu J, Patassini S, Cooper GJS. Vitamin B5 (D-pantothenic acid) localizes in myelinated structures of the rat brain: Potential role for cerebral vitamin B5 stores in local myelin homeostasis.Biochemical and Biophysical Research Communications, 2020; 522(1): 220-225.

Briani C, Dalla Torre C, Citton V, Manara R, Pompanin S, Binotto G, Adami F. Cobalamin deficiency: clinical picture and radiological findings. Nutrients, (2013); 5(11):4521-39.

Heffernan C, Jain MR, Liu T, Kim H, Barretto K, Li H, Maurel P. Nectin-like 4 complexes with choline transporter-like protein-1 and regulates schwann cell choline homeostasis and lipid biogenesis in vitro. Journal of Biological Chemisty, 2017; 292(11):4484-4498.

Blusztajn JK, Slack BE, Mellott TJ. Neuroprotective actions of dietary choline. Nutrients, (2017); 9(8): 815.

McEnery MW, Siegel RE. Encyclopedia of the neurological sciences. 2. Academic press; Oxford. Neurotransmitter receptors, (2014): 552-564.

Kandimalla R, Reddy PH. Therapeutics of neurotransmitters in Alzheimer’s disease. Journal of Alzheimers Disease, (2017); 57(4): 1049-1069.

Anjum I, Jaffery SS, Fayyaz M, Samoo Z, Anjum S. The Role of vitamin D in brain health: A mini literature review. Cureus, (2018); 10(7): e2960.

Banerjee A, Khemka VK, Ganguly A, Roy D, Ganguly U, Chakrabarti S. Vitamin D and Alzheimer’s disease: Neurocognition to therapeutics. International Journal of Alzheimer’s Disease, (2015); 2015, Article ID 192747, 11 pages.

Plaitakis A, Kalef-Ezra E, Kotzamani D, Zaganas I, Spanaki C. The glutamate dehydrogenase pathway and its roles in cell and tissue biology in health and disease. Biology, (2017); 6(11).

Best J, Nijhout HF, Samaranayake S, Hashemi P, Reed M. A mathematical model for histamine synthesis, release, and control in varicosities. Theoretical Biology and Medical Modelling, (2017); 14:24.

Mahmood L. The metabolic processes of folic acid and vitamin B12 deficiency. Journal of Health and Research Reviews, (2014); 1(1): 5-9. doi: 10.4103/2394-2010.143318

Nicolia V, Fuso A, Cavallaro RA, Luzio AD, Scarpa S. B vitamin deficiency promotes tau phosphorylation through regulation of GSK3β and PP2A. Journal of Alzheimer’s Disease, (2010); 19: 895-907.

Gong CX, Lidsky T, Wegiel J, Zuck L, Grundke-Iqbal I, Iqbal K. Phosphorylation of microtubule-associated protein tau is regulated by protein phosphatase 2A in mammalian brain. Implications for neurofibrillary degeneration in Alzheimer’s disease. Journal of Biological Chemistry, (2000); 275: 5535-5544.

Briones TL, Darwish H. Decrease in age-related tau hyperphosphorylation and cognitive improvement following vitamin D supplementation are associated with modulation of brain energy metabolism and redox state. Neuroscience, (2014); 262:143-155.

McLaurin J, Golomb R, Jurewicz A, Antel JP, Fraser PE. Inositol stereoisomers stabilize an oligomeric aggregate of Alzheimer amyloid beta peptide and inhibit a beta-induced toxicity. Journal of Biological Chemistry, (2000); 275(24):18495-18502.

Tanaka K, Takenaka S and Yoshida K. Scyllo-Inositol, a therapeutic agent for Alzheimer’s disease. Austin Journal of Clinical Neurology, (2015); 2(4): 1040-9154.




DOI: http://dx.doi.org/10.62940/als.v9i3.1468

Refbacks

  • There are currently no refbacks.