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Vitamin E bei Alzheimer‐Demenz und leichter kognitiver Beeinträchtigung

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Referencias

References to studies included in this review

Dysken 2014 {published data only}

Dysken MW, Guarino PD, Vertrees JE, Asthana S, Sano M, Llorente M, et al. Vitamin E and memantine in Alzheimer's disease: clinical trial methods and baseline data. Alzheimer's & Dementia: the Journal of the Alzheimer's Association 2014;10(1):36‐44. CENTRAL
Dysken MW, Sano M, Asthana S, Vertrees JE, Pallaki M, Llorente M, et al. Effect of vitamin E and memantine on functional decline in Alzheimer. JAMA 2014;311(11):1161. CENTRAL
Dysken MW, Sano M, Asthana S, Vertrees JE, Pallaki M, Llorente M, et al. 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. CENTRAL

Lloret 2009 {published data only (unpublished sought but not used)}

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(1):143‐9. CENTRAL

Petersen 2005 {published data only}

Petersen R, Grundman R, Thomas R, Thal L. Donepezil and vitamin E as treatments for mild cognitive impairment. NeuroBiology of Aging 2004;25(S2):20. CENTRAL
Petersen RC, Thomas RG, Grundman M, Bennett D, Doody R, Ferris S, et al. for the Alzheimer's Disease Cooperative Study Group. Vitamin E and donepezil for the treatment of mild cognitive impairment. New England Journal of Medicine 2005;352(23):2379‐88. CENTRAL

Sano 1996 {published data only}

Sano M, Ernesto C, Klauber MR, Schafer K, Woodbury P, Thomas R, et al. and members of the Alzheimer's Disease Cooperative Study. Rationale and design of a multicenter study of selegiline and a‐tocopherol in the treatment of Alzheimer's disease using novel clinical outcomes. Alzheimer Disease and Associated Disorders 1996;10(3):132‐40. CENTRAL
Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, et al. Effects of selegiline and alpha‐tocopherol on cognitive and functional outcome measures in moderately impaired patients with Alzheimer's disease. Neurology 1997;48(3):A377‐8. CENTRAL
Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, et al. for the members of the Alzheimer's Disease Cooperative Study. A controlled trial of selegiline, alpha‐tocopherol, or both as treatment for Alzheimer's disease. New England Journal of Medicine 1997;336(17):1216‐22. CENTRAL
Sano M, Growdon J, Klauber M, Ernesto C, Schafer P, Woodbury P, et al. Expanding the severity range of patients in clinical trials for Alzheimer's disease: a multicentre clinical trial of selegiline and a‐tocopherol. Neurology 1996;45 Suppl 4:289. CENTRAL

References to studies excluded from this review

Alavi 2013 {published data only}

Alavi Naeini AM, Elmadfa I, Djazayeri A, Barekatain M, Aghayeghazvini MR, Jalali M, et al. Effect of vitamin E and C supplementation on elderly with mild cognitive impairment (MCI) in Isfahan, Iran. Annals of Nutrition & Metabolism 2013:1145. CENTRAL

Alavi 2014 {published data only}

Alavi Naeini AM, Elmadfa I, Djazayery A, Barekatain M, Aghaye Ghazvini MR, Djalali M, et al. The effect of antioxidant vitamins E and C on cognitive performance of the elderly with mild cognitive impairment in Isfahan, Iran: a double‐blind, randomized, placebo‐controlled trial. European Journal of Nutrition 2014;53(5):1255‐62. CENTRAL

Alzoubi 2012 {published data only}

Alzoubi KH, Khabour OF, Abu Rashid B, Damaj IM, Salah HA. The neuroprotective effect of vitamin E on chronic sleep deprivation‐induced memory impairment: the role of oxidative stress. Behavioural Brain Research 2012;226(1):205‐10. CENTRAL

Anand 2011 {published data only}

Anand VPR, Kumar BJ, Varghese JM, Das SK. Supplementation of vitamin E improves cognitive status and oxidative stress in type 2 diabetes mellitus. International Research Journal of Pharmacy 2011;2(11):169‐72. CENTRAL

Anonymous 2014 {published data only}

Anonymous. High dose vitamin E may slow Alzheimer's decline. Harvard Men's Health Watch 2014;18(8):8. CENTRAL

Apostolova 2013 {published data only}

Apostolova LG, Babakchanian S, Hwang KS, Green AE, Zlatev D, Chou Y‐Y, et al. Ventricular enlargement and its clinical correlates in the imaging. Alzheimer Disease and Associated Disorders 2013;27(2):174‐81. CENTRAL

Arlt 2012 {published data only}

Arlt S, Muller‐Thomsen T, Beisiegel U, Kontush A. Effect of one‐year vitamin C‐ and E‐supplementation on cerebrospinal fluid oxidation parameters and clinical course in Alzheimer's disease. Neurochemical Research 2012;37(12):2706‐14. CENTRAL

Biesalski 2010 {published data only}

Biesalski HK, Grune T, Tinz J, Zollner I, Blumberg JB. Reexamination of a meta‐analysis of the effect of antioxidant supplementation on mortality and health in randomized trials. Nutrients 2010;2(9):929‐49. CENTRAL

Bittner 2009 {published data only}

Bittner DM. Combination therapy of acetylcholinesterase inhibitor and vitamin E in Alzheimer disease. Journal of Clinical Psychopharmacology 2009;29(5):511‐3. CENTRAL

Brewer 2010 {published data only}

Brewer GJ. Why vitamin E therapy fails for treatment of Alzheimer's disease. Journal of Alzheimer's Disease 2010;19(1):27‐30. CENTRAL

Carlsson 2002 {published data only}

Carlsson CM, Papcke‐Benson K, Carnes M, McBride PE, Stein JH. Health‐related quality of life and long‐term therapy with pravastatin and tocopherol (vitamin E) in older adults. Drugs and Aging 2002;19(10):793‐805. CENTRAL

Chan 2008‐2009 {published data only}

Chan A, Paskavitz J, Remington R, Rasmussen S, Shea TB. Efficacy of a vitamin/nutriceutical formulation for early‐stage Alzheimer's disease: a 1‐year, open‐label pilot study with an 16‐month caregiver extension. American Journal of Alzheimer's Disease & Other Dementias 2008‐2009;23(6):571‐85. CENTRAL

Chan 2010 {published data only}

Chan A, Remington R, Kotyla E, Lepore A, Zemianek J, Shea TB. A vitamin/nutriceutical formulation improves memory and cognitive performance in community‐dwelling adults without dementia. Journal of Nutrition, Health & Aging 2010;14(3):224‐30. CENTRAL

Chapman 2014 {published data only}

Chapman J. Vitamin E and Alzheimer's disease. Australian Journal of Pharmacy 2014;95(1126):92‐3. CENTRAL

Clarke 2003 {published data only}

Clarke R, Harrison G, Richards S, Vital Trial Collaborative Group. Effects of vitamins and aspirin on markers of platelet activation, oxidative stress and homocysteine in people at high risk of dementia. Journal of Internal Medicine 2003;245:67‐75. CENTRAL
Jacoby RJ. A pilot study for the VITAL trial (Vitamins and Aspirin for the treatment of Dementia). National Research Register2002. CENTRAL

Corbett 2014 {published data only}

Corbett A, Ballard C. The value of vitamin E as a treatment for Alzheimer's disease remains unproven despite functional improvement, due to a lack of established effect on cognition or other outcomes from RCTs. Evidence‐based Medicine 2014;19(4):140. CENTRAL

Cornelli 2010 {published data only}

Cornelli U. Treatment of Alzheimer's disease with a cholinesterase inhibitor combined with antioxidants. Neuro‐degenerative Diseases 2010;7(1‐3):193‐202. CENTRAL

de Oliveira 2012 {published data only}

de Oliveira BF, Veloso CA, Nogueira‐Machado JA, de Moraes EN, dos Santos RR, Cintra MTG, et al. Ascorbic acid, alpha‐tocopherol, and betacarotene reduce oxidative stress and proinflammatory cytokines in mononuclear cells of Alzheimer's disease patients. Nutritional Neuroscience 2012;15(6):244‐51. CENTRAL

Dunham 2013 {published data only}

Dunham A, Johnson EJ. Fruits, vegetables, and their components and mild cognitive impairment. Food Reviews International 2013;29(4):409‐40. CENTRAL

Dysken 2009 {published data only}

Dysken MW, Kirk LN, Kuskowski M. Changes in vitamin E prescribing for Alzheimer patients. American Journal of Geriatric Psychiatry 2009;17(7):621‐4. CENTRAL

Evans 2014 {published data only}

Evans DA, Morris MC, Rajan KB. Vitamin E, memantine, and Alzheimer disease. JAMA 2014;311(1):29‐30. CENTRAL

Galasko 2012 {published data only}

Galasko DR, Peskind E, Clark CM, Quinn JF, Ringman JM, Jicha GA, et al. Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. Archives of Neurology 2012;69(7):836‐41. CENTRAL

Geldmacher 2011 {published data only}

Geldmacher DS, Fritsch T, McClendon MJ, Landreth G. A randomized pilot clinical trial of the safety of pioglitazone in treatment of patients with Alzheimer disease. Archives of Neurology 2011;68(1):45‐50. CENTRAL

Gopalan 2014 {published data only}

Gopalan Y, Shuaib IL, Magosso E, Ansari MA, Abu BMR, Wong JW, et al. Clinical investigation of the protective effects of palm vitamin E tocotrienols on brain white matter. Stroke 2014;45(5):1422‐8. CENTRAL

Grodstein 2013 {published data only}

Grodstein F, O'Brien J, Kang JH, Dushkes R, Cook NR, Okereke O, et al. Long‐term multivitamin supplementation and cognitive function in men: a randomized trial. Annals of Internal Medicine 2013;159(12):806‐14. CENTRAL

Guan 2012 {published data only}

Guan JZ, Guan WP, Maeda T, Makino N. Effect of vitamin E administration on the elevated oxygen stress and the telomeric and subtelomeric status in Alzheimer's disease. Gerontology 2012;58(1):62‐9. CENTRAL

Gutierrez 2009 {published data only}

Gutierrez AD, de Serna DG, Robinson I, Schade DS. The response of gamma vitamin E to varying dosages of alpha vitamin E plus vitamin C. Metabolism: Clinical and Experimental 2009;58(4):469‐78. CENTRAL

Han 2011 {published data only}

Han SH, Li H, Liu LT. Therapeutic efficacy assessment of Chinese medicine on mild cognitive impairment [in Chinese]. Zhongguo Zhong xi yi jie he za zhi [Chinese Journal of Integrated Traditional and Western Medicine] 2011;31(5):608‐17. CENTRAL

Hermann 2014 {published data only}

Hermann DM. Vitamin E delays Alzheimer disease progression only slightly [in German]. MMW Fortschritte der Medizin 2014;156(11):36. CENTRAL

Jae 2006 {published data only}

Jae HK, Cook N, Manson J, Buring JE, Grodstein F. A randomized trial of vitamin E supplementation and cognitive function in women. Archives of Internal Medicine 2006;166(22):2462‐8. CENTRAL

Joshi 2012 {published data only}

Joshi YB, Pratico D. Vitamin E in aging, dementia, and Alzheimer's disease. Biofactors 2012;38(2):90‐7. CENTRAL

Jyvakorpi 2012 {published data only}

Jyvakorpi S, Puranen T, Suominen MH. Quality of life, cognition and physical functioning between higher and lower intakes of nutrients of home‐dwelling older AD patients. Clinical Nutrition, Supplement 2012:275. CENTRAL

Kamat 2008 {published data only}

Kamat CD, Gadal S, Mhatre M, Williamson KS, Pye QN, Hensley K. Antioxidants in central nervous system diseases: preclinical promise and translational challenges. Journal of Alzheimer's Disease 2008;15(3):473‐93. CENTRAL

Kesse‐Guyot 2011a {published data only}

Kesse‐Guyot E, Amieva H, Castetbon K, Henegar A, Ferry M, Jeandel C, et al. Adherence to nutritional recommendations and subsequent cognitive performance: findings from the prospective Supplementation with Antioxidant Vitamins and Minerals 2 (SU.VI.MAX 2) study. American Journal of Clinical Nutrition 2011;93(1):200‐10. CENTRAL

Kesse‐Guyot 2011b {published data only}

Kesse‐Guyot E, Fezeu L, Jeandel C, Ferry M, Andreeva V, Amieva H, et al. French adults' cognitive performance after daily supplementation with antioxidant vitamins and minerals at nutritional doses: a post hoc analysis of the Supplementation in Vitamins and Mineral Antioxidants (SU.VI.MAX) trial. American Journal of Clinical Nutrition 2011;94(3):892‐9. CENTRAL

Kryscio 2013a {published data only}

Kryscio RJ, Abner EL, Schmitt FA, Goodman PJ, Mendiondo M, Caban‐Holt A, et al. A randomized controlled Alzheimer's disease prevention trial's evolution. Journal of Nutrition, Health & Aging 2013;17(1):72‐5. CENTRAL

Kryscio 2013b {published data only}

Kryscio R, Abner E, Caban‐Holt A, Mathews M, Schmitt F. Baseline memory problems associate with clinical impairments eight years later: centralized follow‐up in the preadvise trial. Journal of Nutrition, Health & Aging 2013:782‐3. CENTRAL

Lee 2010 {published data only}

Lee HP, Zhu X, Casadesus G, Castellani RJ, Nunomura A, Smith MA, et al. Antioxidant approaches for the treatment of Alzheimer's disease. Expert Review of Neurotherapeutics 2010;10(7):1201‐8. CENTRAL

Lehtisalo 2013 {published data only}

Lehtisalo J, Lindstrom J, Ngandu T, Laatikainen T, Soininen H, Strandberg T, et al. Diet and cognition: baseline associations in the Finnish geriatric intervention study to prevent cognitive impairment and disability (FINGER). Alzheimer's & Dementia 2013:P604‐5. CENTRAL

Lehtisalo 2014 {published data only}

Lehtisalo J, Lindstrom J, Ngandu T, Honninen T, Laatikainen T, Strandberg T, et al. Feasibility of dietary intervention among individuals with elevated risk of dementia: 1st‐year results from the Finnish geriatric intervention study to prevent cognitive impairment and disability (finger). Alzheimer's & Dementia 2014:P166‐7. CENTRAL

Lewis 2014 {published data only}

Lewis JE, Melillo AB, Tiozzo E, Chen L, Leonard S, Howell M, et al. A double‐blind, randomized clinical trial of dietary supplementation on cognitive and immune functioning in healthy older adults. BMC Complementary and Alternative Medicine 2014;14:43. CENTRAL

Li 2015 {published data only}

Li Y, Liu S, Man Y, Li N, Zhou Y. Effects of vitamins E and C combined with β‐carotene on cognitive function in the elderly. Experimental and Therapeutic Medicine 2015;9(4):1489‐93. CENTRAL

Lott 2011 {published data only}

Lott IT, Doran E, Nguyen VQ, Tournay A, Head E, Gillen DL. Down syndrome and dementia: a randomized, controlled trial of antioxidant supplementation. American Journal of Medical Genetics, Part A 2011;155(8):1939‐48. CENTRAL

Lu 2009 {published data only}

Lu P, Edland S, Teng E, Tingus K, Petersen R, Cummings J, et al. Donepezil delays progression to AD in MCI subjects with depressive symptoms. Neurology 2009;72(24):2115‐21. CENTRAL

MacPherson 2012 {published data only}

MacPherson H, Ellis KA, Sali A, Pipingas A. Memory improvements in elderly women following 16 weeks treatment with a combined multivitamin, mineral and herbal supplement. A randomized controlled trial. Psychopharmacology 2012;220(2):351‐65. CENTRAL

Mecocci 2012 {published data only}

Mecocci P, Polidori MC. Antioxidant clinical trials in mild cognitive impairment and Alzheimer's disease. Biochimica et Biophysica Acta ‐ Molecular Basis of Disease 2012;1822(5):631‐8. CENTRAL

Mishra 2012 {published data only}

Mishra V, Mishra M, Kashaw V, Kashaw S. A survey on nutritional and other natural therapies for Alzheimer's disease. Alzheimer's & Dementia 2012:P404. CENTRAL

Morris 2012a {published data only}

Morris MC. Nutritional determinants of cognitive aging and dementia. Proceedings of the Nutrition Society 2012;71(1):1‐13. CENTRAL

Morris 2012b {published data only}

Morris MC. Symposium 1: vitamins and cognitive development and performance. Proceedings of the Nutrition Society 2012, (1):1‐13. CENTRAL

Muss 2015 {published data only}

Muss C, Mosgoeller W, Endler T. Neuroprotective impact of a vitamin trace element composition ‐ a randomized, double blind, placebo controlled clinical trial with healthy volunteers. Neuroendocrinology Letters 2015;36(1):31‐40. CENTRAL

Naeini 2014 {published data only}

Naeini AM, Elmadfa I, Djazayery A, Barekatain M, Ghazvini MR, Djalali M, et al. The effect of antioxidant vitamins E and C on cognitive performance of the elderly with mild cognitive impairment in Isfahan, Iran: a double‐blind, randomized, placebo‐controlled trial. European Journal of Nutrition 2014;53(5):1255‐62. CENTRAL

Onofrj 2002 {published data only}

Onofrj M, Thomas A, Luciano AL, Iacono D, Di Rollo A, D'Andreamatteo G, et al. Donepezil versus vitamin E in Alzheimer's disease: part 2: mild versus moderate‐severe Alzheimer's disease. Clinical Neuropharmacology 2002;25:207‐15. CENTRAL

Pavlik 2009 {published data only}

Pavlik VN, Doody RS, Rountree SD, Darby EJ. Vitamin E use is associated with improved survival in an Alzheimer's disease cohort. Dementia & Geriatric Cognitive Disorders 2009;28(6):536‐40. CENTRAL

Péneau 2011 {published data only}

Péneau S, Galan P, Jeandel C, Ferry M, Andreeva V, Hercberg S, et al. Fruit and vegetable intake and cognitive function in the SU.VI.MAX 2 prospective study. American Journal of Clinical Nutrition 2011;94(5):1295‐303. CENTRAL

Podea 2012 {published data only}

Podea D, Mila C. Therapeutically strategies and outcome in mild cognitive impairment. European Psychiatry 2012;27:1. CENTRAL

Polidori 2012 {published data only}

Polidori MC, De Spirt S, Stahl W, Pientka L. Conflict of evidence: carotenoids and other micronutrients in the prevention and treatment of cognitive impairment [Review]. BioFactors (Oxford, England) 2012;38(2):167‐71. CENTRAL

Pribis 2012 {published data only}

Pribis P, Bailey RN, Russell AA, Kilsby MA, Hernandez M, Craig WJ, et al. Effects of walnut consumption on cognitive performance in young adults. British Journal of Nutrition 2012;107(9):1393‐401. CENTRAL

Remington 2009 {published data only}

Remington R, Chan A, Paskavitz J, Shea TB. Efficacy of a vitamin/nutriceutical formulation for moderate‐stage to later‐stage Alzheimer's disease: a placebo‐controlled pilot study. American Journal of Alzheimer's Disease and Other Dementias 2009;24(1):27‐33. CENTRAL

Remington 2015 {published data only}

Remington R, Bechtel C, Larsen D, Samar A, Doshanjh L, Fishman P, et al. A phase II randomized clinical trial of a nutritional formulation for cognition and mood in Alzheimer's disease. Journal of Alzheimer's Disease 2015;45(2):395‐405. CENTRAL

Rijpma 2014a {published data only}

Rijpma A, Meulenbroek O, Van Hees AM, Sijben JW, Scheltens P, Olde Rikkert MG. Effects of a medical food on plasma micronutrient and fatty acid levels in mild to moderate Alzheimer's disease. Clinical Nutrition (Edinburgh, Scotland) 2014:S193. CENTRAL

Rijpma 2014b {published data only}

Rijpma A, Meulenbroek O, Olde Rikkert MG. Cholinesterase inhibitors and add‐on nutritional supplements in Alzheimer's disease: a systematic review of randomized controlled trials. Ageing Research Reviews 2014;16:105‐12. CENTRAL

Satalich 2014 {published data only}

Satalich TA, Shankle WR, Alexander GE, Batchelder WH. Markov models detect vitamin E and donepezil treatment effects in ADCS MCI trial. Alzheimer's & Dementia 2014:P776. CENTRAL

Schmitt 2009 {published data only}

Schmitt FA, Kryscio RJ, Xu L, Mendiondo M, Caban‐Holt A, Abner E, et al. Effects of repeated screening and potential impact on AD prevention trial design: the antioxidant AD prevention (PREADVISE) trial. Alzheimer's and Dementia 2009;5 Suppl 1(4):258. CENTRAL

Schneider 2009 {published data only}

Schneider LS, Raman R, Schmitt FA, Doody RS, Insel P, Clark CM, et al. Characteristics and performance of a modified version of the ADCS‐CGIC CIBIC+ for mild cognitive impairment clinical trials. Alzheimer Disease & Associated Disorders 2009;23(3):260‐7. CENTRAL

Shea 2013 {published data only}

Shea T, Remington R, Bechtel C, Sammar AM, Larsen D, Lortie JJ, et al. A nutritional formulation for cognitive performance and mood in Alzheimer's disease and mild cognitive impairment: a phase II multisite randomized trial with an open‐label extension. Alzheimer's & Dementia 2013:P658‐9. CENTRAL

Srour 2013 {published data only}

Srour M, Alavi Naeini AM, Elmadfa I. Status of serum 25 (OH)‐vitamin d in elderly Iranian subjects after one year supplementation with vitamin E and C. Annals of Nutrition & Metabolism 2013:1506. CENTRAL

Stough 2012 {published data only}

Stough C, Downey L, Silber B, Lloyd J, Kure C, Wesnes K, et al. The effects of 90‐day supplementation with the omega‐3 essential fatty acid docosahexaenoic acid (DHA) on cognitive function and visual acuity in a healthy aging population. Neurobiology of Aging 2012;33(4):e1‐3. CENTRAL

Suominen 2013 {published data only}

Suominen MH, Puranen TM, Eloniemi‐Sulkava U, Jyvakorpi SK, Siljamaki‐Ojansuu U, Kautiainen H, et al. Effectiveness of a tailored nutrition intervention on nutrient intake and quality of life of aged persons with Alzheimer disease living at home with their spouses. A randomized, controlled trial. European Geriatric Medicine 2013:S96. CENTRAL

Takahashi 2009 {published data only}

Takahashi T, Murata T, Kosaka H, Wada Y, Yoneda M. Effect of vitamin E treatment on progressive cognitive impairment in a patient with adult‐onset ataxia: a case report. Progress in Neuro‐Psychopharmacology & Biological Psychiatry 2009;33(1):150‐2. CENTRAL

Usoro 2010 {published data only}

Usoro OB, Mousa SA. Vitamin E forms in Alzheimer's disease: a review of controversial and clinical experiences. Critical Reviews in Food Science & Nutrition 2010;50(5):414‐9. CENTRAL

Vinyoles‐Bargallo 2010 {published data only}

Vinyoles‐Bargallo E. During the first year of treatment, donepezil delays the incidence of Alzheimer's disease in patients with cognitive deterioration. Vitamin E is not efficient. FMC Formacion Medica Continuada en Atencion Primaria 2010;12(10):715. CENTRAL

von Arnim 2013 {published data only}

von Arnim CA, Dismar S, Ott‐Renzer CS, Noeth N, Ludolph AC, Biesalski HK. Micronutrients supplementation and nutritional status in cognitively impaired elderly persons: a two‐month open label pilot study. Nutrition Journal 2013;12(1):148. CENTRAL

Whitehair 2010 {published data only}

Whitehair DC, Sherzai A, Emond J, Raman R, Aisen PS, Petersen RC, et al. Influence of apolipoprotein e 4 on rates of cognitive and functional decline in mild cognitive impairment. Alzheimer's and Dementia 2010;6(5):412‐9. CENTRAL

Zanotta 2014 {published data only}

Zanotta D, Puricelli S, Bonoldi G. Cognitive effects of a dietary supplement made from extract of Bacopa monnieri, astaxanthin, phosphatidylserine, and vitamin E in subjects with mild cognitive impairment: a noncomparative, exploratory clinical study. Neuropsychiatric Disease and Treatment 2014;10:225‐30. CENTRAL

Gopal 2005 {published data only}

Gopal V. A pilot study of effect of vitamin E on cognition and measures of activities of daily living in patients with moderately severe Alzheimer's disease. National Research Register2005. CENTRAL

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References to other published versions of this review

Farina 2012

Farina N, Isaac MGEKN, Clark AR, Rusted J, Tabet N. Vitamin E for Alzheimer's dementia and mild cognitive impairment. Cochrane Database of Systematic Reviews 2012, Issue 11. [DOI: 10.1002/14651858.CD002854.pub3]

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Characteristics of studies

Characteristics of included studies [ordered by study ID]

Dysken 2014

Methods

Design: multicentre, randomised, double‐blind, placebo‐controlled trial

Duration: 6 months to 4 years

Participants

Diagnosis (including criteria used): possible or probable AD (NINCDS‐ADRDA)

Number of participants: 613 total randomised (completers: 140 in vitamin E group, 140 in placebo group, 142 in memantine group, 139 in the vitamin E + memantine group)

Age: 53 to 96 years, mean age 78.8 years

Gender: 97% men

Cognitive status (e.g. MMSE): 21

Ethnicity: 86% white

Inclusion criteria: diagnosis of possible or probable AD (NINCDS‐ADRDA); presence of a carer (friend or relative); informed consent; MMSE 12 to 26; administration of maintenance dosage of acetylcholinesterase inhibitors for at least 4 weeks; agreement not to take vitamin E/memantine outside the study.

Exclusion criteria: non‐Alzheimer's primary dementia; current major depression, delirium, alcohol or psychoactive substance abuse or dependency; schizophrenia, or delusional disorder as defined by DSM‐IV; presence of any uncontrolled systemic illness that would interfere with participation in the study or life expectancy of < 1 year; pregnant or intention to become pregnant; enrolment in another interventional clinical trial; current prescription with more than one acetylcholinesterase inhibitor; current prescription for warfarin; use of vitamin E supplements in the past 2 weeks; use of memantine in the past 4 weeks or known intolerance; estimated creatinine clearance < 5 mL/minute; use of amantadine in the past 2 weeks.

Interventions

Treatment 1: vitamin E (2000 IU total daily dose divided into 2 doses)

Treatment 2: memantine (20 mg/day)

Treatment 3: vitamin E + memantine

Treatment 4: placebo

Outcomes

ADCS‐ADL (months 0, 6, 12, 18, 24, 30, 36, 42, 48)

MMSE (months 0, 6, 12, 18, 24, 30, 36, 42, 48)

ADAS‐Cog (months 0, 6, 12, 18, 24, 30, 36, 42, 48)

DS (months 0, 6, 12, 18, 24, 30, 36, 42, 48)

NPI (months 0, 6, 12, 18, 24, 30, 36, 42, 48)

Caregiver Activity Survey (months 0, 6, 12, 18, 24, 30, 36, 42, 48)

Adverse events

Notes

On average, carers reported that vitamin E was taken on 65% of the days.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Participants randomised centrally using "...a random permuted block design of randomly varying sizes between 4 and 12."

Allocation concealment (selection bias)

Low risk

"…participants were randomized centrally into one of the four treatment groups…"

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

"The patient, caregivers, and all site investigators were blinded to the treatment assignment." Participants received "matching placebos for vitamin E were hard‐gelatin, liquid‐filled capsules containing soybean oil." The authors did not describe whether blinding was successful.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

"The patient, caregivers, and all site investigators were blinded to the treatment assignment." The authors did not describe how blinding was maintained and whether it was successful.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Incomplete outcome data was comparable between the vitamin E group and placebo group (12 participants excluded in each due to a lack of follow‐up data).

Selective reporting (reporting bias)

Low risk

Study protocol was published, which included the primary and secondary outcomes as included in the main paper.

Other bias

Low risk

No other sources of bias noted.

Lloret 2009

Methods

Design: randomised, placebo‐controlled, double‐blind study

Duration: 6 months

Participants

Country: Spain

Number of centres: 1

Diagnosis: probable AD according to NINCDS‐ADRDA

Number of participants: 57 participants total randomised (completers: 19 in vitamin E group, 14 in placebo group), 18 healthy controls

Age: not described

Gender: not described

Ethnicity: not described

Cognitive status: severity of participants based on the Geriatric Dementia Scale ‐ mild (n = 25), moderate (n = 26) and severe (n = 6)

Inclusion criteria: not described

Exclusion criteria: people taking antioxidant supplements or any medication other than cholinesterase inhibitors

Interventions

Treatment 1: vitamin E 800 IU/day

Treatment 2: placebo daily

Outcomes

Clock Drawing Test (months 0 and 6)

BDS (months 0 and 6)

MMSE (months 0 and 6)

Blood total glutathione levels and oxidised glutathione (months 0 and 6)

Plasma malondialdehyde (months 0 and 6)

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"Randomization was performed using a randomized list of numbers."

Allocation concealment (selection bias)

Unclear risk

No reference made to how allocation concealment was ensured.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Study described as 'double blind' but authors did not describe how blinding was maintained and whether it was successful. It is unclear whether the placebo was identical in appearance to the vitamin E treatment.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Study described as 'double blind' but authors did not describe how blinding was maintained and whether it was successful.

Incomplete outcome data (attrition bias)
All outcomes

High risk

24/57 AD participants did not complete the research. "Of the patients who finished the study, 14 had been treated with placebo and 19 with vitamin E." The reasons for participant dropout were not described.

Selective reporting (reporting bias)

Unclear risk

Outcomes reported, though the level of detail lacking. For example, means and SDs not described.

Other bias

Low risk

No evidence of other bias.

Petersen 2005

Methods

Design: randomised, placebo‐controlled, double‐blind study

Duration: 36 months

Participants

Country: US and Canada

Number of centres: 69

Diagnosis: amnestic type of MCI

Number of participants: 769 total randomised (ITT: 257 in vitamin E group, 259 in placebo group, 253 in donepezil group)

Gender: 46% women

Age: 55 to 90 years, mean 73 years

Cognitive status: MMSE 24 to 30, mean MMSE 27.3

Inclusion criteria: amnestic MCI of a degenerative nature, impaired memory, a Logical Memory delayed‐recall score approximately 1.5 to 2 SD below an education adjusted‐norm, a CDR of 0.5, MMSE score 24 to 30, and 55 to 90 years of age. adequate vision and hearing for neuropsychological testing, normal vitamin B12 and thyroid function studies and non‐reactive RPR. ECG normal or no clinical significant abnormalities. Study informant available.

Exclusion criteria: significant cerebral vascular disease, modified Hachinski > 4; Hamilton Depression Rating Scale > 12; central nervous system infarct, infection or focal lesions of clinical significance on CT or MRI scan. Medical diseases or psychiatric disorders that could interfere with study participation. Pregnant, lactating or of child‐bearing potential; taking vitamin supplements, other supplements or multivitamin. Restriction on concomitant medication usage, including those with significant cholinergic or anticholinergic effects or potential adverse effects on cognition.

Interventions

Treatment 1: vitamin E group (2000 IU total daily dose divided into 2 doses, placebo donepezil and a multivitamin daily)

Treatment 2: donepezil group (donepezil 10 mg, placebo vitamin E and a multivitamin daily)

Treatment 3: placebo group (placebo vitamin E, placebo donepezil and a multivitamin daily)

Note: the initial dose of vitamin E was 1000 IU/day, and the dose was increased to 2000 IU (1000 IU twice daily) after 6 weeks. The multivitamin contained vitamin E 15 IU

Outcomes

Time to possible or probable development of AD

MMSE (months 0, 6, 12, 18, 24, 30, 36)

ADAS‐Cog (months 0, 6, 12, 18, 24, 30, 36)

Global CDR (months 0, 6, 12, 18, 24, 30, 36)

ADCS Mild Cognitive Impairment Activities of Daily Living Scale (months 0, 6, 12, 18, 24, 30, 36)

GDS (months 0, 6, 12, 18, 24, 30, 36)

Neuropsychological battery including; New York University paragraph‐recall test, the Symbol Digit Modalities Test, the category‐fluency test, a number‐cancellation test, the Boston Naming Test, the digits‐backward test, the Clock Drawing Test, and a maze‐tracing task (months 0, 6, 12, 18, 24, 30, 36)

Adverse events

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Participants randomly assigned to treatment groups. The authors used "…an adaptive allocation scheme for the treatment assignment, with the MMSE score, age, and APOE e4 status as balancing covariates."

Allocation concealment (selection bias)

Unclear risk

No reference made to the method in which allocation concealment was ensured.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Study described as 'double blind' but authors did not describe how blinding was maintained and whether it was successful. Unclear whether the placebo was identical in appearance to the vitamin E treatment.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Study described as 'double blind' but authors did not describe how blinding was maintained and whether it was successful.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

"The primary analysis was conducted according to the intention‐to‐treat principle." During the double‐blind phase, 72 participants discontinued in the vitamin E group, and 66 in placebo group. Sensitivity analyses suggested no impact of dropouts on the results regarding vitamin E and placebo groups. 76 participants in the vitamin E group and 73 in the placebo group developed AD and switched to open label donepezil. It is not clear how subsequent data from these participants was handled.

Selective reporting (reporting bias)

Low risk

All outcomes reported in accordance with the methods section.

Other bias

Low risk

No evidence of other bias.

Sano 1996

Methods

Design: randomised, placebo‐controlled, double‐blind study

Duration: 24 months

Participants

Country: US

Multicentre: 23 sites

Diagnosis: probable AD according to NINCDS‐ADRDA

Number of participants: 341 total randomised (completers: 85 in vitamin E group, 84 in placebo group, 87 in selegiline group, 85 in selegiline + vitamin E group)

Gender: 65% women

Age: mean 73 years

Ethnicity: not described

Cognitive status: mean MMSE 12.6

Inclusion criteria: diagnosis of probable AD, aged ≥ 45 years, fluent in English or Spanish, CDR score 2, modified Hachinski score 4, supervised by a responsible carer.

Exclusion criteria: other central nervous system or psychiatric diagnosis; achieving end point on any primary outcome measure at time of entry; participation in any other investigational drug study or treatment with a psychoactive medication within 2 months of initiation of this trial; treatment with antiparkinsonian medications; recent initiated treatment for a non‐psychiatric condition with an agent to have psychoactive properties (e.g. beta‐blockers, calcium channel blockers). Entry permitted if medication and dose had been stable for 3 months prior to entry into the protocol; antilipaemic drugs specifically contradicted with selegiline (i.e. cholestyramine or colestipol) within 2 weeks of enrolment; some narcotics: demerol has been reported to interact with selegiline; ancillary vitamin E (alpha tocopherol) other than the 30 IU to 32 IU included in a standard multivitamin.

Interventions

Treatment 1: placebo

Treatment 2: vitamin E (2000 IU total daily dose divided into 2 doses)

Treatment 3: selegiline (10 mg total daily dose divided into 2 doses)

Treatment 4: vitamin E (2000 IU total daily dose divided into 2 doses) + selegiline (10 mg total daily dose divided into 2 doses)

Outcomes

Delay in any of 4 end points: death; institutionalisation; severity of dementia; loss of ADL

ADAS‐Cog (1 month after enrolment and at 3‐month intervals)

MMSE (1 month after enrolment and at 3‐month intervals)

BDS (1 month after enrolment and at 3‐month intervals)

DS (1 month after enrolment and at 3‐month intervals)

BRSD (1 month after enrolment and at 3‐month intervals)

Adverse events

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Participants were "...randomly assigned (after stratification according to center with the use of a permuted‐block procedure)..." to receive vitamin E or placebo.

Allocation concealment (selection bias)

Unclear risk

Method in which allocation concealment was ensured was not reported.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Study described as 'double blind' but authors did not describe how blinding was maintained and whether it was successful. Unclear whether the placebo and vitamin E treatment capsules were visually identical.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Study described as 'double blind' but authors did not describe how blinding was maintained and whether it was successful.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Attrition was only able to be reported up until the point a participant reached 1 of the primary end points of the study. Loss to follow‐up was defined as those who did not reach an end point and did not complete the study: 6/84 for the placebo group and 8/85 for the vitamin E group. The reasons for withdrawal were not described in each treatment group.

Selective reporting (reporting bias)

Unclear risk

All outcome measures were reported as per the protocol paper. No SDs reported for change scores.

Other bias

Low risk

No evidence of other bias.

AD: Alzheimer's dementia; ADAS‐Cog: Alzheimer's Disease Assessment Scale ‐ Cognitive subsection; ADCS: Alzheimer's Disease Cooperative Study; ADL: activities of daily living; APoE: apolipoprotein E; BDS: Blessed Dementia Scale; BRSD: Behavior Rating Scale for Dementia; CDR: Clinical Dementia Rating; CT: computer tomography; DS: Dependence Scale; DSM‐IV: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; ECG: electrocardiography; GDS: Global Deterioration Scale; ITT: intention to treat; MCI: mild cognitive impairment; MMSE: Mini‐Mental State Examination; MRI: magnetic resonance imaging; n: number of participants; NINCDS‐ADRDA: National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association; NPI: Neuropsychiatric Inventory; RPR: rapid plasmin reagin; SD: standard deviation.

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Alavi 2013

Not suitable placebo

Alavi 2014

Control group did not receive a suitable placebo.

Alzoubi 2012

Sample population did not have a diagnosis of MCI or AD.

Anand 2011

Sample population did not have a diagnosis of MCI or AD.

Anonymous 2014

Newsletter

Apostolova 2013

Not an RCT

Arlt 2012

Not an RCT

Biesalski 2010

Review

Bittner 2009

Retrospective design

Brewer 2010

Review

Carlsson 2002

Sample population did not have a diagnosis of MCI or AD.

Chan 2008‐2009

Used a nutriceutical formulation and there was no placebo.

Chan 2010

Used a nutriceutical formulation. Placebo was just inert ingredients.

Chapman 2014

Editorial

Clarke 2003

Vitamin E was used in conjunction with vitamin C.
It examined the association of cognitive impairment with platelet activation and reactive oxygen species and total homocysteine levels.

Corbett 2014

Commentary

Cornelli 2010

Used a nutriceutical formulation, not vitamin E separately.

de Oliveira 2012

In vitro study

Dunham 2013

Review

Dysken 2009

No vitamin E intervention, just a questionnaire

Evans 2014

Editorial

Galasko 2012

Not suitable placebo

Geldmacher 2011

Pioglitazone was the primary intervention. Placebo was administered alongside vitamin E.

Gopalan 2014

Sample population did not have a diagnosis of MCI or AD.

Grodstein 2013

Sample population did not have a diagnosis of MCI or AD.

Guan 2012

No relevant outcome measures

Gutierrez 2009

Sample population did not have a diagnosis of MCI or AD.

Han 2011

Review

Hermann 2014

Newsletter

Jae 2006

Vitamin E intervention given to healthy older women.

Joshi 2012

Review

Jyvakorpi 2012

Not an RCT

Kamat 2008

Literature review about antioxidants

Kesse‐Guyot 2011a

Sample population did not have a diagnosis of MCI or AD.

Kesse‐Guyot 2011b

Sample population did not have a diagnosis of MCI or AD.

Kryscio 2013a

Sample population did not have a diagnosis of MCI or AD.

Kryscio 2013b

Sample population did not have a diagnosis of MCI or AD.

Lee 2010

Literature review about antioxidants

Lehtisalo 2013

No vitamin E intervention group

Lehtisalo 2014

No vitamin E intervention group

Lewis 2014

Sample population did not have a diagnosis of MCI or AD.

Li 2015

No placebo group

Lott 2011

Sample population had a diagnosis of Down's syndrome and dementia.

Lu 2009

Focus of intervention was towards depressed vs non‐depressed MCI population.

MacPherson 2012

Sample population did not have a diagnosis of MCI or AD.

Mecocci 2012

Review

Mishra 2012

Survey

Morris 2012a

Review

Morris 2012b

Review

Muss 2015

Sample population did not have a diagnosis of MCI or AD.

Naeini 2014

No co‐administration of other compounds to controls

Onofrj 2002

Vitamin E compared to donepezil not placebo.

Pavlik 2009

Retrospective in nature. No controls or placebo group

Podea 2012

Not an RCT

Polidori 2012

Review

Pribis 2012

Did not use vitamin E as an intervention.

Péneau 2011

Not a randomised double‐blinded study; investigated the intake of fruits and vegetables.

Remington 2009

Used a nutriceutical formulation and the placebo was inert.

Remington 2015

Used a nutriceutical formulation.

Rijpma 2014a

Systematic review

Rijpma 2014b

Used a nutriceutical formulation.

Satalich 2014

Secondary analysis (modelling) of intervention data

Schmitt 2009

Used a healthy population.

Schneider 2009

Same data as Petersen 2005

Shea 2013

Used a nutriceutical formulation, not vitamin E separately.

Srour 2013

Vitamin C taken by treatment arm but not controls, no relevant outcomes.

Stough 2012

Sample population did not have a diagnosis of MCI or AD.

Suominen 2013

Vitamin E not administered

Takahashi 2009

Case study, no placebo and no controls

Usoro 2010

Review

Vinyoles‐Bargallo 2010

Not an original paper, just a personal comment

von Arnim 2013

Vitamin E not administered

Whitehair 2010

Same data as Petersen 2005

Zanotta 2014

Not an RCT

AD: Alzheimer's dementia; MCI: mild cognitive impairment; RCT: randomised controlled trial.

Characteristics of ongoing studies [ordered by year of study]

Gopal 2005

Trial name or title

Effects of Vitamin E on Cognition and Measures of Activities of Daily Living in Patients with Moderately Severe Alzheimer's Disease

Methods

Unknown

Participants

People with moderately severe Alzheimer's disease

Interventions

Vitamin E 500 mg twice daily with cholinesterase inhibitors

Outcomes

Changes in cognition and activities of daily living

Starting date

1 November 2002

Contact information

Dr Vishnu Gopal; Argyll House, 9 Williamson Road, Nether Edge, Sheffield S11 9AR; tel: (+44) 114 2718656; email: [email protected]

Notes

Study topic and author searched online, no evidence of trial or published data. Author no longer at contact address, emailed for an update but no response.

Data and analyses

Open in table viewer
Comparison 1. Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Alzheimer's Disease Assessment Scale ‐ Cognitive subscale (ADAS‐Cog) (least square (LS) mean change from baseline at 6 to 48 months): completers Show forest plot

1

272

Mean Difference (IV, Random, 95% CI)

‐1.81 [‐3.75, 0.13]

Analysis 1.1

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 1 Alzheimer's Disease Assessment Scale ‐ Cognitive subscale (ADAS‐Cog) (least square (LS) mean change from baseline at 6 to 48 months): completers.

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 1 Alzheimer's Disease Assessment Scale ‐ Cognitive subscale (ADAS‐Cog) (least square (LS) mean change from baseline at 6 to 48 months): completers.

2 Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS‐ADL) (LS mean change from baseline at 6 to 48 months): completers Show forest plot

1

280

Mean Difference (IV, Fixed, 95% CI)

3.15 [0.07, 6.23]

Analysis 1.2

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 2 Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS‐ADL) (LS mean change from baseline at 6 to 48 months): completers.

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 2 Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS‐ADL) (LS mean change from baseline at 6 to 48 months): completers.

3 Deaths (number of deaths over 48 months) Show forest plot

1

304

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.52, 1.34]

Analysis 1.3

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 3 Deaths (number of deaths over 48 months).

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 3 Deaths (number of deaths over 48 months).

4 Serious adverse events (number of participants reporting ≥ 1 serious adverse event over 48 months) Show forest plot

1

304

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.71, 1.05]

Analysis 1.4

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 4 Serious adverse events (number of participants reporting ≥ 1 serious adverse event over 48 months).

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 4 Serious adverse events (number of participants reporting ≥ 1 serious adverse event over 48 months).

5 Neuropsychiatric Inventory (NPI) (LS mean change from baseline at 6 to 48 months): completers Show forest plot

1

280

Mean Difference (IV, Fixed, 95% CI)

‐1.47 [‐4.26, 1.32]

Analysis 1.5

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 5 Neuropsychiatric Inventory (NPI) (LS mean change from baseline at 6 to 48 months): completers.

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 5 Neuropsychiatric Inventory (NPI) (LS mean change from baseline at 6 to 48 months): completers.

6 Mini‐Mental State Examination (MMSE) (LS mean change from baseline at 6 to 48 months): completers Show forest plot

1

273

Mean Difference (IV, Fixed, 95% CI)

0.19 [‐0.72, 1.10]

Analysis 1.6

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 6 Mini‐Mental State Examination (MMSE) (LS mean change from baseline at 6 to 48 months): completers.

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 6 Mini‐Mental State Examination (MMSE) (LS mean change from baseline at 6 to 48 months): completers.

7 Adverse events (number of participants reporting ≥ 1 adverse event over 48 months) Show forest plot

1

304

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.85, 1.23]

Analysis 1.7

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 7 Adverse events (number of participants reporting ≥ 1 adverse event over 48 months).

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 7 Adverse events (number of participants reporting ≥ 1 adverse event over 48 months).

Open in table viewer
Comparison 2. Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with mild cognitive impairment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Progression to Alzheimer's disease (AD) (number of people progressing to AD by 36 months) Show forest plot

1

516

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.79, 1.35]

Analysis 2.1

Comparison 2 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with mild cognitive impairment, Outcome 1 Progression to Alzheimer's disease (AD) (number of people progressing to AD by 36 months).

Comparison 2 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with mild cognitive impairment, Outcome 1 Progression to Alzheimer's disease (AD) (number of people progressing to AD by 36 months).

2 Deaths (number of deaths over 36 months) Show forest plot

1

516

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.30, 3.44]

Analysis 2.2

Comparison 2 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with mild cognitive impairment, Outcome 2 Deaths (number of deaths over 36 months).

Comparison 2 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with mild cognitive impairment, Outcome 2 Deaths (number of deaths over 36 months).

Study flow diagram for study for the search April 2016.
Figuras y tablas -
Figure 1

Study flow diagram for study for the search April 2016.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figuras y tablas -
Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figuras y tablas -
Figure 3

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 1 Alzheimer's Disease Assessment Scale ‐ Cognitive subscale (ADAS‐Cog) (least square (LS) mean change from baseline at 6 to 48 months): completers.
Figuras y tablas -
Analysis 1.1

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 1 Alzheimer's Disease Assessment Scale ‐ Cognitive subscale (ADAS‐Cog) (least square (LS) mean change from baseline at 6 to 48 months): completers.

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 2 Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS‐ADL) (LS mean change from baseline at 6 to 48 months): completers.
Figuras y tablas -
Analysis 1.2

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 2 Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS‐ADL) (LS mean change from baseline at 6 to 48 months): completers.

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 3 Deaths (number of deaths over 48 months).
Figuras y tablas -
Analysis 1.3

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 3 Deaths (number of deaths over 48 months).

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 4 Serious adverse events (number of participants reporting ≥ 1 serious adverse event over 48 months).
Figuras y tablas -
Analysis 1.4

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 4 Serious adverse events (number of participants reporting ≥ 1 serious adverse event over 48 months).

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 5 Neuropsychiatric Inventory (NPI) (LS mean change from baseline at 6 to 48 months): completers.
Figuras y tablas -
Analysis 1.5

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 5 Neuropsychiatric Inventory (NPI) (LS mean change from baseline at 6 to 48 months): completers.

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 6 Mini‐Mental State Examination (MMSE) (LS mean change from baseline at 6 to 48 months): completers.
Figuras y tablas -
Analysis 1.6

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 6 Mini‐Mental State Examination (MMSE) (LS mean change from baseline at 6 to 48 months): completers.

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 7 Adverse events (number of participants reporting ≥ 1 adverse event over 48 months).
Figuras y tablas -
Analysis 1.7

Comparison 1 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease, Outcome 7 Adverse events (number of participants reporting ≥ 1 adverse event over 48 months).

Comparison 2 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with mild cognitive impairment, Outcome 1 Progression to Alzheimer's disease (AD) (number of people progressing to AD by 36 months).
Figuras y tablas -
Analysis 2.1

Comparison 2 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with mild cognitive impairment, Outcome 1 Progression to Alzheimer's disease (AD) (number of people progressing to AD by 36 months).

Comparison 2 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with mild cognitive impairment, Outcome 2 Deaths (number of deaths over 36 months).
Figuras y tablas -
Analysis 2.2

Comparison 2 Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with mild cognitive impairment, Outcome 2 Deaths (number of deaths over 36 months).

Summary of findings for the main comparison. Vitamin E (capsules 2000 IU/day in two divided doses) compared to placebo for people with Alzheimer's disease

Vitamin E (capsules 2000 IU/day in 2 divided doses) compared to placebo for people with Alzheimer's disease

Patient or population: people with Alzheimer's disease

Settings: multicentre, US

Intervention: vitamin E (capsules 2000 IU/day in 2 divided doses)

Comparison: placebo

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Placebo

Vitamin E (capsules 2000 IU/day in 2 divided doses)

Cognitive function
LS mean change from baseline using the ADAS‐Cog

Scale from: 0 to 70

Follow‐up: 6 to 48 months

The LS mean change from baseline in cognitive function in placebo group was 7.78

The LS mean change from baseline in cognitive function in the intervention group was 1.81 lower
(3.75 lower to 0.13 higher)

272
(1 study)

⊕⊕⊕⊝
Moderate1

Higher scores represent worse cognitive function.

A 4‐point difference in ADAS‐cog has been considered the MCID.

Adverse events

Number of participants reporting ≥ 1 serious adverse event

Follow‐up: 6 to 48 months

625 per 1000

538 per 1000
(444 to 656)

RR 0.86
(0.71 to 1.05)

304
(1 study)

⊕⊕⊕⊝
Moderate1

Deaths

Number of deaths

Follow‐up: 6 to 48 months

204 per 1000

171 per 1000
(106 to 273)

RR 0.84
(0.52 to 1.34)

304
(1 study)

⊕⊕⊕⊝
Moderate1

Activities of daily living
LS mean change from baseline using the ADCS‐ADL

Scale from: 0 to 78

Follow‐up: 6 to 48 months

The LS mean change from baseline in activities of daily living in the placebo group was ‐16.96

The LS mean change from baseline in activities of daily living in the intervention group was 3.15 higher
(0.07 to 6.23 higher)

280
(1 study)

⊕⊕⊕⊝
Moderate1

Higher scores represent better activities of daily living.

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

ADAS‐Cog: Alzheimer Disease Assessment Scale ‐ Cognitive Subscale; ADCS‐ADL: Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory;CI: confidence interval; LS: least square; MCID: minimum clinically important difference; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1Quality downgraded one level due to imprecision. Evidence from a single study of modest size. This is supported by dichotomous data not reaching the optimal information size criterion (assuming α of 0.05, and β of 0.2) (Guyatt 2011).

Figuras y tablas -
Summary of findings for the main comparison. Vitamin E (capsules 2000 IU/day in two divided doses) compared to placebo for people with Alzheimer's disease
Summary of findings 2. Vitamin E (capsules 2000 IU/day in two divided doses) compared to placebo for people with mild cognitive impairment

Vitamin E (capsules 2000 IU/day in 2 divided doses) compared to placebo for people with mild cognitive impairment

Patient or population: people with mild cognitive impairment
Settings: US and Canada
Intervention: vitamin E (capsules 2000 IU/day in 2 divided doses)
Comparison: placeb

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Placebo

Vitamin E (capsules 2000 IU/day in 2 divided doses)

Progression to Alzheimer's disease

Number of people progressing to AD

Follow‐up: 36 months

284 per 1000

293 per 1000
(224 to 383)

RR 1.03
(0.79 to 1.35)

516
(1 study)

⊕⊕⊕⊝
Moderate1

Cognitive function

Mean change from baseline of ADAS‐Cog

Scale from: 0 to 70

Follow‐up: 36 months

Not possible to extract data for analysis.

Not possible to extract data for analysis.

Unable to evaluate quality of evidence.

Uncertainty about how missing data were handled. Study reports no significant difference between intervention and control groups.

Adverse events

Number of participants reporting ≥ 1 serious adverse event.

Follow‐up: 36 months

Not possible to extract data for analysis.

516
(1 study)

Unable to evaluate quality of evidence.

Overall adverse event rates not reported.

Death

Number of deaths over 36 months

Follow‐up: 36 months

19 per 1000

19 per 1000
(6 to 66)

RR 1.01
(0.3 to 3.44)

516
(1 study)

⊕⊕⊕⊝
Moderate1

Activities of daily living

Mean change from baseline using the ADCS
Mild Cognitive Impairment Activities of Daily Living

Scale from: 0 to 53

Follow‐up: 36 months

Not possible to extract data for analysis.

Not possible to extract data for analysis.

Unable to evaluate quality of evidence.

Uncertainty about how missing data were handled. Study reports no significant difference between intervention and control groups.

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

ADAS‐Cog: Alzheimer Disease Assessment Scale ‐ Cognitive Subscale; ADCS‐ADL: Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory;CI: confidence interval; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1Quality downgraded one level due to imprecision. Evidence from a single study of modest size. This was supported by dichotomous data not reaching the optimal information size criterion (assuming α of 0.05, and β of 0.2) (Guyatt 2011).

Figuras y tablas -
Summary of findings 2. Vitamin E (capsules 2000 IU/day in two divided doses) compared to placebo for people with mild cognitive impairment
Comparison 1. Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Alzheimer's Disease Assessment Scale ‐ Cognitive subscale (ADAS‐Cog) (least square (LS) mean change from baseline at 6 to 48 months): completers Show forest plot

1

272

Mean Difference (IV, Random, 95% CI)

‐1.81 [‐3.75, 0.13]

2 Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS‐ADL) (LS mean change from baseline at 6 to 48 months): completers Show forest plot

1

280

Mean Difference (IV, Fixed, 95% CI)

3.15 [0.07, 6.23]

3 Deaths (number of deaths over 48 months) Show forest plot

1

304

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.52, 1.34]

4 Serious adverse events (number of participants reporting ≥ 1 serious adverse event over 48 months) Show forest plot

1

304

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.71, 1.05]

5 Neuropsychiatric Inventory (NPI) (LS mean change from baseline at 6 to 48 months): completers Show forest plot

1

280

Mean Difference (IV, Fixed, 95% CI)

‐1.47 [‐4.26, 1.32]

6 Mini‐Mental State Examination (MMSE) (LS mean change from baseline at 6 to 48 months): completers Show forest plot

1

273

Mean Difference (IV, Fixed, 95% CI)

0.19 [‐0.72, 1.10]

7 Adverse events (number of participants reporting ≥ 1 adverse event over 48 months) Show forest plot

1

304

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.85, 1.23]

Figuras y tablas -
Comparison 1. Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with Alzheimer's disease
Comparison 2. Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with mild cognitive impairment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Progression to Alzheimer's disease (AD) (number of people progressing to AD by 36 months) Show forest plot

1

516

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.79, 1.35]

2 Deaths (number of deaths over 36 months) Show forest plot

1

516

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.30, 3.44]

Figuras y tablas -
Comparison 2. Vitamin E (capsules 2000 IU/day in two divided doses) versus placebo in people with mild cognitive impairment