ORAL NUTRITIONAL FORMULATIONS |
Lauque et al. (2004)2626. Lauque S, Arnaud-Battandier F, Gillette S, Plaze JM, Andrieu S, Cantet C, et al. Improvement of weight and fat-free mass with oral nutritional supplementation in patients with Alzheimer's disease at risk of malnutrition: A prospective randomized study. J Am Geriatr Soc. 2004;52(10):1702-7. https://doi.org/10.1111/j.1532-5415.2004.52464.x https://doi.org/https://doi.org/10.1111/...
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39 subjects (78.8+5.4 years old, proportion of individuals by gender not described)
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Diagnosis of AD by NINCDS/ADRDA criteria
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MMSE=15.2±8.2
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IG: Usual nutritional care+hypercaloric oral nutritional supplement enriched with proteins, vitamins and minerals, offering an additional 300 to 500 kcal per day.
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CG: usual nutritional care.
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Obs.: CG patients who received oral supplementation during the study were not excluded, but prescriptions were recorded.
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Period of intervention: 3 months.
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MMSE |
There was no significant difference between groups in the change in MMSE scores after 3 and 6 months of intervention compared to the baseline. |
Planas et al. (2004)2727. Planas M, Conde M, Audivert S, Pérez-Portabella C, Burgos R, Chacón P, et al. Micronutrient supplementation in mild Alzheimer disease patients. Clin Nutr. 2004;23(2):265-72. https://doi.org/10.1016/s0261-5614(03)00106-7 https://doi.org/https://doi.org/10.1016/...
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IG: ONS hypercaloric and hyperproteic, 2 times daily.
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Composition: 500 kcal, 45% carbohydrates, 25% lipids, 30% protein, additional nutrients: 38 mg of α-tocopherol, 250 mg of vitamin C, 1.5 ìg of B12, 200 ìg of folate, 10 mg of Zn, 1,500 ìg of Cu, 3 mg Mn, 15% WheyProtein, 3.5 g arginine.
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CG: placebo isocaloric, 2 times daily with the same distribution of macronutrients.
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Composition: 5 mg of α-tocopherol, 30 mg of vitamin C, 0.38 μg of B12, 52 μg of folate, 5 mg of Zn, 500 μg of Cu, 1.25 mg of Mn, 0% of WheyProtein, 0 g of arginine.
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MEC and Set |
There was no significant difference between groups in the change in MMSE scores after 3 and 6 months of intervention compared to the baseline. |
Salas-Salvadó et al. (2005)2828. Salas-Salvadó J, Torres M, Planas M, Altimir S, Pagan C, Gonzalez ME, et al. Effect of oral administration of a whole formula diet on nutritional and cognitive status in patients with Alzheimer's disease. Clin Nutr. 2005;24(3):390-7. https://doi.org/10.1016/j.clnu.2004.12.006 https://doi.org/https://doi.org/10.1016/...
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IG: Complete dietary formula, semi-solid or liquid, based on frozen-dried foods (Vegenat®-med), replacing breakfast, lunch and supper+dietary guidelines.
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CG: dietary guidelines similar to IG.
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GDS scale and Pfeiffer test |
No statistically significant difference was found between the groups in the change in Mini-cog and Set scores after 6 months of treatment. |
Scheltens et al. (2010)2929. Scheltens P, Kamphuis PJ, Verhey FR, Olde Rikkert MG, Wurtman RJ, Wilkinson D, et al. Efficacy of a medical food in mild Alzheimer’s disease: A randomized controlled trial. Alzheimers Dement. 2010;6(1):1-10.e1. https://doi.org/10.1016/j.jalz.2009.10.003 https://doi.org/https://doi.org/10.1016/...
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RCT, parallel, double-blind, placebo-controlled
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Holland, Germany, Belgium, United Kingdom and United States.
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12 weeks with possible 12-week extension
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24 weeks
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IG: Bottle of Souvenaid®, once a day (300 mg of EPA+1,200 mg of DHA+106 mg of phospholipids+400 mg of choline+625 mg of uridine monophosphate+40 mg of vitamin E+80 mg of vitamin C+60 mcg of selenium+3 mg of vitamin B12+1 mg of vitamin B6+400 mg of folic acid)
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CG: isocaloric placebo.
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WMS-r, ADAS-cog and MMSE |
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Significant difference was found between groups on the percentual of cognitive decline evaluated with WMS-r immediate recall. No statistically significant difference was observed for the remaining outcomes.
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Changes on WMS-r immediate recall test after 12 weeks (p=0.021)
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IG: Decline=19%; No change=41%; improvement=40%
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CG: Decline=45%; No change=15%; Improvement=40%
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De Sousa et al. (2012)3030. De Sousa OL, Amaral TF. Three-week nutritional supplementation effect on long-term nutritional status of patients with mild Alzheimer disease. Alzheimer Dis Assoc Disord. 2012;26(2):119-23. https://doi.org/10.1097/wad.0b013e31822c5bb3 https://doi.org/https://doi.org/10.1097/...
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IG: ONS, providing 400 kcal, 42.8 g of carbohydrates, 17.4 g of lipids and 18 g of proteins per day+standard dietary advice.
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IG: standard dietary advice.
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Period of intervention: 21 days.
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MMSE and CLOX-1 |
There was no significant difference between the groups in the MMSE and CLOX-1 scores. Differences in scores relative to the baseline were not computed in both tests. |
Scheltens et al. (2012)3131. Scheltens P, Twisk JWR, Blesa R, Scarpini E, Von Arnim CAF, Bongers A, et al. Efficacy of souvenaid in mild Alzheimer's disease: Results from a randomized, controlled trial. J Alzheimers Dis. 2012;31(1):225-36. https://doi.org/10.3233/jad-2012-121189 https://doi.org/https://doi.org/10.3233/...
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RCT, parallel, double-blind, placebo-controlled
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Netherlands, Germany, Belgium, Spain, Italy, and France
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24 weeks
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IG: Bottle of Souvenaid®, once a day (300 mg of EPA+1,200 mg of DHA+106 mg of phospholipids+400 mg of choline+625 mg of uridine monophosphate+40 mg of vitamin E+80 mg of vitamin C+60 mcg of selenium+3 mg of vitamin B12+1 mg of vitamin B6+400 mg of folic acid).
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CG: isocaloric placebo.
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NTB (z-score): memory function, executive function and total score. |
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A significant difference was found between the groups in the memory domain of the NTB scale and a trend to effect on the total NTB composition score after 24 weeks of treatment. No difference was found on the executive function.
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NTB memory domain - Z-score (p=0.023)
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IG: baseline=-0.021+0.812
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12 weeks=0.089±0.381
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24 weeks=0.202±0.395
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CG: baseline=0.078+0.884
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12 weeks=0.143±0.429
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24 weeks=0.111±0.463
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NTB total compositions - Z-score (p=0.053)
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IG: baseline=0.029+0.695
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12 weeks=0.03±0.284
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24 weeks=0.120±0.278
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CG: baseline=0.115+0.719
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12 weeks=0.075±0.262
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24 weeks=0.035±0.28
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Shah et al. (2013)3232. Shah RC, Kamphuis PJ, Leurgans S, Swinkels SH, Sadowsky CH, Bongers A. The S-Connect study: results from a randomized, controlled trial of souvenaid in mild-to-moderate Alzheimer’s disease. Alzheimers Res Ther. 2013;5(6):59. https://doi.org/10.1186/alzrt224 https://doi.org/https://doi.org/10.1186/...
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IG: Bottle of Souvenaid®, once a day (300 mg of EPA+1,200 mg of DHA+106 mg of phospholipids+400 mg of choline+625 mg of uridine monophosphate+40 mg of vitamin E+80 mg of vitamin C+60 mcg of selenium+3 mg of vitamin B12+1 mg of vitamin B6+400 mg of folic acid)
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CG: isocaloric placebo.
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ADAS-cog, CDR-SOB and cognitive test battery |
No significant difference was found between the groups in the rates of change of all cognitive outcomes after 24weeks of treatment. |
Soininen et al. (2017)33
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RCT, parallel, double-blind, placebo-controlled
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Finland, Germany, Netherlands And Sweden
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24 months
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311 subjects (71.9±6.6 years old, 50% men).
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Diagnosis of prodromal Alzheimer disease according to the IWG-1 classification and NIA-AA criteria
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MMSE≥24
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IG: Bottle of Souvenaid®, once a day (300 mg of EPA+1,200 mg of DHA+106 mg of phospholipids+400 mg of choline+625 mg of uridine monophosphate+40 mg of vitamin E+80 mg of vitamin C+60 mcg of selenium+3 mg of vitamin B12+1 mg of vitamin B6+400 mg of folic acid)
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CG: isocaloric placebo.
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- NTB composite score
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- NTB total score, memory function and executive function
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- CDR-SOB
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- Progressiontodementia (DSM-IV and NINCDS-ADRDA
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- Brain volumes (MRI)
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There was no significant difference between the groups in changing the NTB score in relation to the baseline, the primary outcome of the study.
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There was a difference for CDR-SOB, hippocampal volume and ventricular volume, the latter assessed by MRI.
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Changes on CDR-SOB after 24 months (p=0.005)
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IG: 0.56+1.32
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CG: 1.12+1.72
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Changes on hippocampal volume after 24 month (p=0.005)
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IG: -0.30+0.27
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CG: -0.43+0.33
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Changes on ventricular volume after 24 months (p=0.046)
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IG: 5.96+4.66
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CG: 7.80+5.53
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OMEGA-3 FATTY ACIDS ISOLATED OR IN ASSOCIATION WITH OTHER NUTRIENTS |
Yehuda et al. (1996)3434. Yehuda S, Rabinovtz S, Carasso RL, Mostofsky DI. Essential fatty acids preparation (SR-3) improves Alzheimer’s patients quality of life. Intern J Neurosci. 1996;87(3-4):141-9. https://doi.org/10.3109/00207459609070833 https://doi.org/https://doi.org/10.3109/...
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IG: 1 mL of SR-3 formulation (0.25 mL mixture of a-linolenic and
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linoleic acids in ratio of 1:4.5; 0.73 mL of mineral oil; and 0.02 mL α-tocopherol), twice a day.
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CG: 1 mL of placebo (mineral oil+α-tocopherol), twice a day.
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12-item questionnaire, completed by caregivers, including areas of spatial orientation; cooperation; humor; appetite; organization; short-term memory; long-term memory; sleep disorders; alertness during the day; hallucinations; capacity for expression; and bladder control. |
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For all items of the questionnaire, the percentages of improvement in the IG were higher, however the level of statistical significance of this finding was not presented.
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Regarding the evaluation of the effects of the intervention by the caregivers, a greater number of reports of improvement in the conditions of the patients was found in the IG (p<0.001).
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IG: 0 reported worsening, 11 observed no difference, and 49 reported improvement.
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CG: 5 reported worsening, 30 did not observe any difference, and 5 reported improvement.
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Obs.: blinded caregivers.
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Freud-Levi et al. (2006)3535. Freund-Levi Y, Eriksdotter-Jönhagen M, Cederholm T, Basun H, Faxén-Irving G, Garlind A, et al. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Arch Neurol. 2006;63(10):1402-8. https://doi.org/10.1001/archneur.63.10.1402 https://doi.org/https://doi.org/10.1001/...
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IG: omega-3 in capsules, 4,000 mg per day (1,700 mg of DHA+600 mg of EPA), added with 16 mg of vitamin E.
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CG: Corn oil in capsules, 4,000 mg per day, added with 16 mg of vitamin E.
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6 months of placebo-controlled intervention, followed by 6 months with omega-3 supplementation for both groups (4,000 mg per day).
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MMSE, ADAS-cog, CDR and CDR-SOB. |
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There was no significant difference between the groups after 6 months and 12 months in the MMSE, ADAS-cog, CDR and CDR-SOB.
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In subgroups with mild AD (MMSE >27 points) (n=32), IG individuals showed a smaller decline in MMSE in the first 6 months compared to the control group. In the other cognitive tests, the difference was not statistically significant.
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Subgroup with mild AD:
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MMSE (p=0.02)
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IG: baseline=28.4, 95%CI 28.1-28.7
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6 months=27.9, 95%CI 27.1-28.7
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12 months=27.3, 95%CI 26.1-28.4
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GC: Baseline=28.5, 95%CI 28.2-28.9
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6 months=26.0, 95%CI 24.2-27.8
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12 months=25.4, 95%CI 23.3-27.5
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Rate of decline in MMSE at 6 months (p=0.01)
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IG: -0.5 points
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CG: -2.6 points
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GC decline in the MMSE in the two periods (0-6 months and 6-12months)
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0-6 months= -2.6 points (p<0.001)
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6-12 months= -0.83 points (p=0.23)
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Quinn et al. (2010)3636. Quinn JF, Raman R, Thomas RG, Yurko-Mauro K, Nelson EB, van Dyck C, et al. Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. JAMA. 2010;304(17):1903-11. https://doi.org/10.1001/jama.2010.1510 https://doi.org/https://doi.org/10.1001/...
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IG: DHA derived from algae in capsules, 2,000 mg per day (45‒55% of the DHA weight).
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CG: placebo (corn or soybean oil).
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ADAS-cog, MMSE, CDR-SOB. |
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No significant difference was found between the groups in the rates of change of the ADAS-cog, CDR-SOB and MMSE scores after 18 months of treatment.
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In the analysis of subgroups with and without the APOE ε4 allele in the APOE å4 negative group, subjects receiving DHA supplementation (n=61) had a significantly lower decline in ADAS-cog and MMSE compared to those receiving placebo (n=48), whereas in the other outcomes the differences were not statistically significant.
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In the APOE ε4 positive group, there was no significant difference between the groups in any outcome evaluated.
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Subgroup APOE ε4 negative:
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Changing in ADAS-cog after 18 months (p=0.03)
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IG: 6.23 points,95%CI 4.08‒8.38
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CG: 10.11 points, 95%CI 7.12‒13.1
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Changing in MMSE after 18 months (p=0.03)
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GI: -3.36 points, 95%CI 2.16‒4.56
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GC: -5.12 points; 95%CI 3.70‒6.54
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Shinto et al. (2014)3737. Shinto L, Quinn J, Montine T, Dodge HH, Woodward W, Baldauf-Wagner S, et al. A randomized placebo-controlled pilot trial of omega-3 fatty acids and alpha lipoic acid in Alzheimer's disease. J Alzheimers Dis. 2014;38(1):111-20. https://doi.org/10.3233/JAD-130722 https://doi.org/https://doi.org/10.3233/...
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IG-1: omega-3 in capsules, 3,000 mg per day (675 mg of DHA+975 mg of EPA)+placebo from ALA.
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IG-2: omega-3 in capsules, 3,000 mg per day (675 mg of DHA+975 mg of EPA)+ALA in tablets, 600 mg per day.
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CG: Placebo of omega-3+placebo from ALA.
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MMSE and ADAS-cog |
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In the comparison with the CG, after 12 months of intervention only the IG-2 presented smaller cognitive decline evaluated by the MMSE.
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There was no statistically significant difference in the decline assessed by the ADAS-CGI in the IG-1 vs. CG and IG-2 vs. CG.
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MMSE
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IG-1: -4.3+1.3 points (p=0.80)
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IG-2: -1.0+0.7 points (p<0.01)
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CG: -4.6+1.4 points
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MICRONUTRIENTS ISOLATED OR IN ASSOCIATION |
Sano et al. (1997)3838. Sano M, Ernesto C, Thomas RG, Klauber MR, Shafer K, Grundman M, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. N Engl J Med. 1997;336(17):1216-22. https://doi.org/10.1056/nejm199704243361704 https://doi.org/https://doi.org/10.1056/...
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IG-1: 10 mg of Selegiline+2,000 IU of α-tocopherol per day.
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IG-2: Selegiline placebo+2,000 IU of α-tocopherol per day.
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IG-3: Placebo of α-tocopherol+10 mg of Selegiline per day.
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CG: Selegiline placebo+α-tocopherol placebo.
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ADAS-cog and MMSE |
There was no significative difference among the groups in both outcomes. |
Sun et al. (2007)3939. Sun Y, Lu CJ, Chien KL, Chen ST, Che RC. Efficacy of multivitamin supplementation containing vitamins B6 and B12 and folic acid as adjunctive treatment with cholinesterase inhibitor in Alzheimer’s disease: a 26-week, randomized, double-blind, placebo-controlled study in Taiwanese patients. Clin Ther. 2007;29(10):2204-14. https://doi.org/10.1016/j.clinthera.2007.10.012 https://doi.org/https://doi.org/10.1016/...
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IG: Methylcobalamin, 0.5 mg, once a day+multivitamin supplement once a day (1 mg of folic acid, 5 mg of pyridoxine hydrochloride, 60 mg of iron carbonate, 10 mg of nicotinamide, 250 mg of calcium carbonate, 2 mg of riboflavin, 3 mg monohydrate thiamine, 1 mg calcium pantothenate, 100 µg ascorbic acid, 100 µg iodine, 150 µg copper, 3 µg B12, 4,000 IU vitamin A, 400 IU vitamin D3).
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CG: placebo.
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ADAS-Cog/11, MMSE and CASI |
There was no significative difference among the groups in all outcomes. |
Kessler et al. (2008)4040. Kessler H, Bayer TA, Bach D, Schneider-Axmann T, Supprian T, Herrmann W, et al. Intake of copper has no effect on cognition in patients with mild Alzheimer’s disease: a pilot phase 2 clinical trial. J Neural Transm (Vienna). 2008;115(8):1181-7. https://doi.org/10.1007/s00702-008-0080-1 https://doi.org/https://doi.org/10.1007/...
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ADAS-cog and MMSE |
There was no significant difference between the groups in the analysis of time x treatment interaction for both ADAS-cog and MMSE. |
Aisen et al. (2008)4141. Aisen PS, Schneider LS, Sano M, Diaz-Arrastia R, van Dyck CH, Weiner MF, et al. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA. 2008;300(15):1774-83. https://doi.org/10.1001/jama.300.15.1774 https://doi.org/https://doi.org/10.1001/...
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ADAS-cog, MMSE, CDR-SOB |
There was no significant difference between groups in the rate of decline of ADAS-cog, MMSE, CDR-SOB during treatment. |
Lloret et al. (2009)4242. Lloret A, Badía M, Mora NJ, Pallardó FV, Alonso M, Viña J. Vitamin E paradox in Alzheimer’s disease: it does not prevent loss of cognition and may even be detrimental. J Alzheimers Dis. 2009;17(1):143-9. https://doi.org/10.3233/jad-2009-1033 https://doi.org/https://doi.org/10.3233/...
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75 subjects (mean age and proportion of individuals by gender not described).
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Diagnosis of AD by the NINCDS-ADRDA criteria
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Individuals at different stages of the disease (mild, moderate and severe dementia)
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MMSE, CLOX-1 and Blessed-Dementia Scale, |
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There was no significant difference between IG and CG in the analyzed outcomes.
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In analysis of IG subgroups with respondents (RP) and non-respondents (NRP) patients*, when comparing both, NRP showed a decline in MMSE (p<0.05). When comparing subgroups with placebo, NRP also declined (p<0.05).
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*NRP=showed no decline in serious levels of oxidized glutathione after treatment.
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*RP=showed a decline of oxidized glutathione after treatment.
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Note: Results presented graphically. Values not reported by the authors.
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Remington et al. (2009)4343. 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. Am J Alzheimers Dis Other Demen. 2009;24(1):27-33. https://doi.org/10.1177/1533317508325094 https://doi.org/https://doi.org/10.1177/...
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IG: Nutraceutical Formulation, 2 tablets per day (400 ìg of folic acid, 6 ìg of vitamin B12, 30 IU of α-Tocopherol, 400 mg of S-Adenosyl-Methionine, 600 mg of N-Acetyl-Cysteine, 500 mg of Acetyl-L-Carnitine).
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CG: placebo.
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DRS-2 and CLOX-1 |
There was no significant difference between the groups in the comparison of the total DRS-2 and CLOX-1 scores after treatment. |
Galasko et al. (2012)4444. 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. Arch Neurol. 2012;69(7):836-41. https://doi.org/10.1001/archneurol.2012.85 https://doi.org/https://doi.org/10.1001/...
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MMSE |
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Dysken et al. (2014)4545. 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. 10.1001/jama.2013.282834 https://doi.org/10.1001/jama.2013.282834...
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613 subjects (78.8+7.1 years old, 97% men)
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Diagnosis of Possible or Probable AD by the NINCDS-ADRDA criteria
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MMSE=12‒26
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IG-1: 2,000 IU α-Tocopherol+20 mg memantine per day.
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IG-2: 2,000 IU α-Tocopherol per day+memantine placebo.
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IG-3: 20 mg of memantine per day+α-Tocopherol placebo.
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IG-3: 20 mg de Memantina por dia+placebo de á-Tocoferol.
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CG: placebo of α-Tocopherol+placebo of Memantine.
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ADAS-cog and MMSE |
There were no significant differences between the groups in the MMSE and ADAS-cog scores. |
Nolan et al. (2015)4646. Nolan JM, Loskutova E, Howard A, Mulcahy R, Moran R, Stack J, et al. The impact of supplemental macular carotenoids in Alzheimer’s disease: a randomized clinical trial. J Alzheimers Dis. 2015;44(4):1157-69. https://doi.org/10.3233/jad-142265 https://doi.org/https://doi.org/10.3233/...
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62 subjects (78.0+7.2 years old, 50% men)
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Diagnosis of mild to moderate AD defined as MMSE score between 14 and 24 with documented difficulty in other cognitive domains
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Two branches of the study: individuals with AD and individuals without AD (age-matched controls). Both received intervention or placebo.
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IG: Supplement Macushield® - (10 mg of meso-zeaxanthin+10 mg of lutein+2 mg of zeaxanthin per day).
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CG: placebo.
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MMSE |
There was no statistically significant difference in MMSE after 6 months of treatment in the two branches of the study (individuals with AD and individuals without AD). |
Remington et al. (2015)4747. Remington R, Bechtelb C, Larsenc D, Samard A, Doshanjhf L, Fishman P, et al. A phase ii randomized clinical trial of a nutritional formulation for cognition and mood in Alzheimer’s disease. J Alzheimers Dis. 2015;45(2):395-405. https://doi.org/10.3233/jad-142499 https://doi.org/https://doi.org/10.3233/...
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141 subjects (77.8+8.4 years old, proportion of individuals by gender not described)
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Previous diagnosis of AD, diagnostic criterion not described
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MMSE=22.2+5.1
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IG: Nutraceutical Formulation, 2 tablets per day (400 ìg of folic acid, 6 ìg of vitamin B12, 30 IU of α-Tocopherol, 400 mg of S-Adenosyl-Methionine, 600 mg of N-Acetyl-Cysteine, 500 mg of Acetyl-L-Carnitine).
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CG: placebo.
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Treatment period: 3 or 6 months.
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CLOX-1 and DRS-AEMSS |
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390/5,000
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After 3 months, only the IG showed a statistically significant increase in the CLOX-1 scores (p=0.0002; 95%CI 0.8727‒2.6273) and DRS-AEMSS (p<0.0001; 95%CI 1.2363‒3.2283) compared to the baseline.
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Results presented graphically as mean+SD of the change in scores in each group. Mean IG and CG scores at baseline and at 3 months were not reported by the authors.
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GINSENG |
Lee et al. (2008)4848. Lee ST, Chu K, Sim JY, Heo JH, Kim M. Panax ginseng enhances cognitive performance in Alzheimer disease. Alzheimer Dis Assoc Disord. 2008;22(3):222-6. https://doi.org/10.1097/WAD.0b013e31816c92e6 https://doi.org/https://doi.org/10.1097/...
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IG: conventional treatment+4.5 g White Korean powder Ginseng a day.
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Obs.: in addition, 9 patients were treated with 9.0 g of Ginseng (GI-2) a day to evaluate any possible effect of dose-response.
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CG: only conservative and supportive treatment.
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Period of intervention: 12 weeks.
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ADAS-cog and MMSE |
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In comparison with control, the groups treated with Ginseng presented improvement in the cognitive performance (ADAS-cog and MMSE) during 12 weeks of treatment, being eliminated 12 weeks after its discontinuation.
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There was no difference in the effect of both Ginseng dosages on the cognitive performance (comparison IG vs. IG-2).
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MMSE (change of score)
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- After 4 weeks of treatment (p=0.033)
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IG: 1.0+2.4
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CG: -0.58+2.4
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- After 12 weeks of treatment (p=0.009)
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IG: 1.8+2.8
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CG: -0.03+3.1
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- 12 weeks after discontinuation (p=0.673)
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IG: 0.56+3.6
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CG: 0.88+2.5
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ADAS-cog (change of score)
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- After 4 weeks of treatment (p=0.012)
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IG: -4.2+4.1
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CG: 1.1+3.9
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- After 12 weeks of treatment (p=0.029)
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IG: -3.3+5.3
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CG: -0.45+6.0
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- 12 weeks after discontinuation (p=0.407)
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IG: -0.26+4.6
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CG: -1.4+3.8
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Heo et al. (2012)4949. Heo JH, Lee ST, Chu K, Oh MJ, Park HJ, Shim JY, et al. Heat-processed ginseng enhances the cognitive function in patients with moderately severe Alzheimer's disease. Nutr Neurosci. 2012;15(6):278-82. https://doi.org/10.1179/1476830512y.0000000027 https://doi.org/https://doi.org/10.1179/...
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GI-1: 1.5 g de SG-135 a day.
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GI-2: 3.0 g de SG-135 a day.
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GI-3: 4.5 g de SG-135 a day
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CG: only conservative and supportive treatment.
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ADAS-cog and MMSE |
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Subjects from GI-3 presented improvement in the scores ADAS-cog and MMSE in 12 weeks and 24 weeks in comparison with the Baseline. The other groups did not show any difference in any of the periods.
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ADAS-cog: GI-3
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Baseline=41.3+17.0
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12 weeks=27.4+ 22.2 (p=0.028)
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24 weeks=28.5+23.3 (p=0.028)
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MMSE: GI-3
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Baseline=14.6+6.8
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12 weeks=20.8+ 7.2 (p=0.027)
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24 weeks=17.0+8.2 (p=0.045)
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PHYTOCHEMICALS |
Baumet al. (2008)5050. Baum L, Lam CW, Cheung SK, Kwok T, Lui V, Tsoh J, et al. Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. J Clin Psychopharmacol. 2008;28(1):110-3. https://doi.org/10.1097/jcp.0b013e318160862c https://doi.org/https://doi.org/10.1097/...
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IG-1: Turmeric supplement, 4 g a day, tablets or powder.
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IG-2: Turmeric supplement, 1 g a day, tablets or powder+3 g of placebo powder a day.
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CG:4 g placebo powder a day.
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MMSE |
There was no significative difference among the groups in changes of MMSE score after 6 months. |
Ringman et al. (2012)5151. Ringman JM, Frautschy SA, Teng E, Begum AN, Bardens J, Beigi M, et al. Oral curcumin for Alzheimer’s disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study. Alzheimers Res Ther. 2012;4(5):43. https://doi.org/10.1186/alzrt146 https://doi.org/https://doi.org/10.1186/...
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GI-1; 2 g per day of Curcumin C3 Complex*.
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GI-2: 4 g per day of Curcumin C3 Complex.
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CG: placebo
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*Curcumin C3 Complex - formula with 95% Curcuminoids (70-80% Curcumin, 15-25% demetoxicurcumin and 2.5-6.5% Bis-demetoxicurcumin).
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ADAS-cog, MMSE. |
There was no significant difference between groups in the changes presented in all cognitive parameters after 24 weeks of treatment. |
Farokhnia et al. (2014)5252. Farokhnia M, Shafiee Sabet M, Iranpour N, Gougol A, Yekehtaz H, Alimardani R, et al. Comparing the efficacy and safety of Crocus sativus L. with memantine in patients with moderate to severe Alzheimer's disease: A double-blind randomized clinical trial. Hum Psychopharmacol. 2014;29(4):351-9. https://doi.org/10.1002/hup.2412 https://doi.org/https://doi.org/10.1002/...
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IG-1: 10 mg Memantin a day in the first month and 20 mg a day the rest of the period.
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IG-2: 15 mg per day of dry safflower extract (Crocus Sativus L.) the first month and 30 mg a day the rest of the period.
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MMSE and SCIRS |
There was no difference among the groups in the changes of scores of MMSE and SCIR after 12 months of treatment. |
Gleason et al. (2015)5353. Gleason CE, Fischer BL, Dowling NM, Setchell KD, Atwood CS, Carlsson CM, et al. Cognitive effects of soy isoflavones in patients with Alzheimer's disease. J Alzheimers Dis. 2015;47(4):1009-19. https://doi.org/10.3233/jad-142958 https://doi.org/https://doi.org/10.3233/...
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MMSE and Battery of Neuropsychological Tests. |
There was no difference among the groups in the MMSE and tests of verbal memory, executive function, executive function and language, visual memory and visuomotor function after 6 months of treatment. |
Turner et al. (2015)5454. Turner RS, Thomas RG, Craft S, van Dyck CH, Mintzer J, Reynolds BA, et al. A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. Neurology. 2015;85(16):1383-91. https://doi.org/10.1212/WNL.0000000000002035 https://doi.org/https://doi.org/10.1212/...
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IG: staggered daily doses of Resveratrol
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- Weeks 1 to 13: 500 mg
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- Weeks 14 to 26: 1,000 mg
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- Weeks 27 to 39:
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- Weeks 40 to 52: 2,000 mg
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CG: placebo.
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CDR-SOB, ADAS-cog, and MMSE |
There was no significative difference among the groups in the scores of CDR-SOB, ADAS-cog, and MMSE (data not provided by the authors). |
COCCONUT OIL |
Chan et al. (2017)5555. Chan SC, Esther GE, Yip HL, Sugathan S, Chin PS. Effect of cold pressed coconut oil on cognition and behavior among patients with Alzheimer's disease - A pilot intervention study. Natl J Physiol Pharm Pharmacol. 2017;7(12):1432-5. https://doi.org/10.5455/njppp.2017.0829311082017 https://doi.org/https://doi.org/10.5455/...
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IG: coconut oil.
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- Week 1 and 2: 30 mL per day
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- Week 3 to 24: 60 mL per day
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CG: placebo of water with coconut essence.
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- Weeks 1 and 2: 30 mL per day
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- Weeks 3 to 24: 60 mL per day
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MMSE and CLOX-1 |
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MMSE:
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In both IG and CG, no significant changes were observed in relation to the baseline after 24 weeks.
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CLOX-1:
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- IG: there was no significant difference in relation to the baseline (values not shown).
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- GC: -0.78571 (p=0.035; 95%CI 1.50824- -0.06319)
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PROBIOTIC |
Akbari et al. (2016)5656. Akbari E, Asemi Z, Kakhaki RD, Bahmani F, Kouchaki E, Tamtaji OR, et al. Effect of probiotic supplementation on cognitive function and metabolic status in Alzheimer's disease: a randomized, double-blind and controlled trial. Front Aging Neurosci. 2016;10(8):256. https://doi.org/10.3389/fnagi.2016.00256 https://doi.org/https://doi.org/10.3389/...
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IG: 200 mL per day of probiotic milk containing Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, and Lactobacillus fermentum (2×109 CFU/g for each).
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CG: 200 mL per day of milk.
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MMSE |
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INOSITOL |
Barak et al. (1996)5757. Barak Y, Levine J, Glasman A, Elizur A, Belmaker RH. Inositol treatment of alzheimer’s disease. a double blind, cross-over placebo controlled trial. Prog Neuropsychopharmacol Biol Psychiatr. 1996;20(4):729-35. https://doi.org/10.1016/0278-5846(96)00043-7 https://doi.org/https://doi.org/10.1016/...
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RCT, cross-over, double-blind, placebo-controlled
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Israel
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8 weeks (4 weeks of cross-over)
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CAMCOG |
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