Wetenschappelijk onderzoek over de behandeling van Alzheimer

Het protocol voor de behandeling de ziekte van Alzheimer is op basis van wetenschappelijke publicaties ontwikkeld. Hierbij is gebruik gemaakt van de National Library of Medicine (PubMed). Daar waar mogelijk werden studies die opgezet zijn volgens het “placebo controlled cross-over” principe gebruikt. Andere vormen die vaak werden gebruik zijn reviews en epidemiologisch onderzoek. Publicaties uit bladen als The Lancet, The New England Journal of Medicine hadden de voorkeur

National Library of Medicine (PubMed)

Causes

    Supplements

    Algemeen

    1. Wollen KA. Altern Med Rev. 2010 Sep;15(3):223-44. Alzheimer’s disease: the pros and cons of pharmaceutical, nutritional, botanical, and stimulatory therapies, with a discussion of treatment strategies from the perspective of patients and practitioners
      Alzheimer’s disease (AD) is characterized by dysfunctional intracellular and extracellular biochemical processes that result in neuron death. This article summarizes hypotheses regarding cell dysfunction in AD and discusses the effectiveness of, and problems with, different therapies. Pharmaceutical therapies discussed include cholinesterase inhibitors, memantine, antihypertensive drugs, anti-inflammatory drugs, secretase inhibitors, insulin resistance drugs, etanercept, brain-derived neurotrophic factor, and immunization. Nutritional and botanical therapies included are huperzine A, polyphenols, Ginkgo, Panax ginseng, Withania somnifera, phosphatidylserine, alpha-lipoic acid, omega-3 fatty acids, acetyl L-carnitine, coenzyme Q10, various vitamins and minerals, and melatonin. Stimulatory therapies discussed are physical exercise, cognitive training, music, and socialization. Finally, treatment strategies are discussed in light of the benefits and drawbacks of different therapeutic approaches. It is concluded that potential risks of both approved and non-approved therapies should be weighed against the potential benefits and certain consequences of disease progression. Approaches that target several dysfunctions simultaneously and that emphasize nutritional, botanical, and stimulatory therapies may offer the most benefit at this time.
    [Article]
  1. Suchy J, Chan A, Shea TB. Nutr Res. 2009 Jan;29(1):70-4. Dietary supplementation with a combination of alpha-lipoic acid, acetyl-L-carnitine, glycerophosphocoline, docosahexaenoic acid, and phosphatidylserine reduces oxidative damage to murine brain and improves cognitive performance
    Alzheimer disease has a complex etiology composed of nutritional and genetic risk factors and predispositions. Moreover, genetic risk factors for cognitive decline may remain latent pending age-related decline in nutrition, suggesting the potential importance of early nutritional intervention, including preventative approaches. We hypothesized that a combination of multiple nutritional additives may be able to provide neuroprotection. We demonstrate herein that dietary supplementation with a mixture of ALA, ALCAR, GPC, DHA, and PS reduced reactive oxygen species in normal mice by 57% and prevented the increase in reactive oxygen species normally observed in mice lacking murine ApoE when maintained on a vitamin-free, iron-enriched, oxidative-challenge diet. We further demonstrate that supplementation with these agents prevented the marked cognitive decline otherwise observed in normal mice maintained on this challenge diet. These findings add to the growing body of research indicating that key dietary supplementation may delay the progression of age-related cognitive decline.[Abstract]
  2. Kidd PM. Altern Med Rev. 2005 Dec;10(4):268-93. Neurodegeneration from mitochondrial insufficiency: nutrients, stem cells, growth factors, and prospects for brain rebuilding using integrative management
    Degenerative brain disorders (neurodegeneration) can be frustrating for both conventional and alternative practitioners. A more comprehensive, integrative approach is urgently needed. One emerging focus for intervention is brain energetics. Specifically, mitochondrial insufficiency contributes to the etiopathology of many such disorders. Electron leakages inherent to mitochondrial energetics generate reactive oxygen free radical species that may place the ultimate limit on lifespan. Exogenous toxins, such as mercury and other environmental contaminants, exacerbate mitochondrial electron leakage, hastening their demise and that of their host cells. Studies of the brain in Alzheimer’s and other dementias, Down syndrome, stroke, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s disease, Friedreich’s ataxia, aging, and constitutive disorders demonstrate impairments of the mitochondrial citric acid cycle and oxidative phosphorylation (OXPHOS) enzymes. Imaging or metabolic assays frequently reveal energetic insufficiency and depleted energy reserve in brain tissue in situ. Orthomolecular nutrients involved in mitochondrial metabolism provide clinical benefit. Among these are the essential minerals and the B vitamin group; vitamins E and K; and the antioxidant and energetic cofactors alpha-lipoic acid (ALA), ubiquinone (coenzyme Q10; CoQ10), and nicotinamide adenine dinucleotide, reduced (NADH). Recent advances in the area of stem cells and growth factors encourage optimism regarding brain regeneration. The trophic nutrients acetyl L-carnitine (ALCAR), glycerophosphocholine (GPC), and phosphatidylserine (PS) provide mitochondrial support and conserve growth factor receptors; all three improved cognition in double-blind trials. The omega-3 fatty acid docosahexaenoic acid (DHA) is enzymatically combined with GPC and PS to form membrane phospholipids for nerve cell expansion. Practical recommendations are presented for integrating these safe and well-tolerated orthomolecular nutrients into a comprehensive dietary supplementation program for brain vitality and productive lifespan.[Abstract]
  3. Kelley BJ, Knopman DS. Neurologist. 2008 Sep;14(5):299-306. Alternative medicine and Alzheimer disease
    Although many of these compounds have been associated with interesting basic science, none has shown clear clinical benefit to date. Data available for some, such as Ginkgo biloba, curcumin, and huperzine A, suggest that further evaluation is warranted. Familiarity with this literature will allow clinicians to provide meaningful recommendations to patients who wish to use these agents.[Article]
  4. Wollen KA. Altern Med Rev. 2010 Sep;15(3):223-44. Alzheimer’s disease: the pros and cons of pharmaceutical, nutritional, botanical, and stimulatory therapies, with a discussion of treatment strategies from the perspective of patients and practitioners
    Approaches that target several dysfunctions simultaneously and that emphasize nutritional, botanical, and stimulatory therapies may offer the most benefit at this time.[Article]
  5. Galantamine

      RCT
    1. Keller C, Kadir A, Forsberg A, Porras O, Nordberg A. J Alzheimers Dis. 2011;24(1):109-23. Long-term effects of galantamine treatment on brain functional activities as measured by PET in Alzheimer’s disease patients
      The effects of galantamine (16 to 24 mg/day) treatment on brain functional activities (blood flow and glucose metabolism) were examined in 18 patients with mild Alzheimer’s disease (AD) in relation to brain acetylcholinesterase (AChE) activity and nicotinic receptors and cognitive function. Our results ultimately suggest that treatment with galantamine has a long-term positive effect on brain perfusion and rCMRglc and stabilizes cognition.[Abstract]
    2. Gavrilova SI, Kolykhanov IV, Kalyn IaB, Selezneva ND. Zh Nevrol Psikhiatr Im S S Korsakova. 2009;109(7):57-61 Galantamine (reminyl) in the treatment of severe Alzheimer’s disease
      Twenty-five patients with Alzheimer’s disease (AD) in moderate-severe and severe stages received galantamine in dosage 8 mg daily during the 1st month with the following increasing to 16 mg daily. Six patients received 24 mg per day from the 3rd month. The total duration of therapy was 26 weeks. The therapeutic effects of reminyl and its good tolerability allow to recommend this drug for treatment of severe stages of AD. [Abstract]
    3. Erkinjuntti T, Gauthier S, Bullock R, Kurz A, Hammond G, Schwalen S, Zhu Y, Brashear R. J Psychopharmacol. 2008 Sep;22(7):761-8. Galantamine treatment in Alzheimer’s disease with cerebrovascular disease: responder analyses from a randomized, controlled trial (GAL-INT-6)
      Significantly higher responder rates were observed with galantamine for behaviour (64.9% versus 56.6%; P = 0.024), and numerically favourable responder rates were seen with galantamine for activities of daily living. Treatment-emergent adverse events were generally related with the gastrointestinal system (nausea 20% versus 10%; vomiting 12% versus 5%; galantamine and placebo groups, respectively). Three deaths occurred during double-blind treatment: 2 of 188 subjects receiving galantamine, and 1 of 97 subjects receiving placebo. These findings are consistent with a broad range of cognitive, functional and behavioural benefits with galantamine across the spectrum of AD and AD with CVD.[Abstract]
    4. Suh GH, Jung HY, Lee CU, Choi S; Korean Galantamine Study Group J Korean Med Sci. 2008 Feb;23(1):10-7. Economic and clinical benefits of galantamine in the treatment of mild to moderate Alzheimer’s disease in a Korean population: a 52-week prospective study
      Galantamine had a beneficial effect not only to slow functional decline in patients with mild to moderate AD, but also to save a substantial amount of costs, closely related to reduction in caregiver burden and decrease in caregiver time.[Article]
    5. Rockwood K, Fay S, Jarrett P, Asp E. Neurology. 2007 Apr 3;68(14):1116-21. Effect of galantamine on verbal repetition in AD: a secondary analysis of the VISTA trial
      Reduction of verbal repetition is a common goal of Alzheimer disease treatment. After 4 months, patients treated with galantamine were more likely to experience a reduction of verbal repetition than those treated with placebo. Diminution of verbal repetition was associated with other improvements, suggesting it might be a clinical marker of a positive treatment response.[Abstract]
    6. Rockwood K, Fay S, Song X, MacKnight C, Gorman M; Video-Imaging Synthesis of Treating Alzheimer’s Disease (VISTA) Investigators. CMAJ. 2006 Apr 11;174(8):1099-105. Attainment of treatment goals by people with Alzheimer’s disease receiving galantamine: a randomized controlled trial
      Clinicians, but not patients and caregivers, observed a significantly greater improvement in goal attainment among patients with mild to moderate Alzheimer’s disease who were taking galantamine than among those who were taking placebo.[Article]
    7. Ancoli-Israel S, Amatniek J, Ascher S, Sadik K, Ramaswamy K. Alzheimer Dis Assoc Disord. 2005 Oct-Dec;19(4):240-5. Effects of galantamine versus donepezil on sleep in patients with mild to moderate Alzheimer disease and their caregivers: a double-blind, head-to-head, randomized pilot study
      This pilot study was the first to compare the effects of these drugs on sleep in patients or caregivers. Both drugs were safe and well tolerated. Neither galantamine nor donepezil negatively affected sleep; however, on every measure, there were suggestions of slightly more benefit associated with galantamine treatment. Although these results are suggestive of a differential effect of the drugs on sleep, further research is needed to confirm the clinical significance.[Abstract]
    8. Koontz J, Baskys A. Am J Alzheimers Dis Other Demen. 2005 Sep-Oct;20(5):295-302. Effects of galantamine on working memory and global functioning in patients with mild cognitive impairment: a double-blind placebo-controlled study
      There was a significant improvement in scores on the Functional Activities Questionnaire, which is a measure of global functioning. There were also improvements in the galantamine group on two of six measures in the Cambridge Automated Neuropsychiatric Test Assessment Battery and in immediate free recall on the California Verbal Learning Test.[Abstract]
    9. Suh GH, Yeon Jung H, Uk Lee C, Hoon Oh B, Nam Bae J, Jung HY, Ju YS, Kil Yeon B, Park J, Hong I, Choi S, Ho Lee J; Korean Galantamine Study Group Clin Ther. 2004 Oct;26(10):1608-18. A prospective, double-blind, community-controlled comparison of three doses of galantamine in the treatment of mild to moderate Alzheimer’s disease in a Korean population
      In this prospective, multicenter, double-blind, community-controlled, comparative study, patients with mild to moderate AD were randomized to receive galantamine 8, 16, or 24 mg/d; patients were evaluated at baseline (week 0) and after 4, 8, and 16 weeks of treatment. A 4-week dose-titration schedule was used in the 16-and 24-mg/d groups. This study found that galantamine effected significant benefits on the cognitive, functional, and behavioral symptoms of mild to moderate AD in this population of Korean patients. The tolerability results suggest that galantamine is well tolerated in these patients.[Abstract]
    10. Orgogozo JM, Small GW, Hammond G, Van Baelen B, Schwalen S. Curr Med Res Opin. 2004 Nov;20(11):1815-20. Effects of galantamine in patients with mild Alzheimer’s disease
      Pooled data from four randomised trials of patients with mild AD indicate that patients who received galantamine 24 mg/day for 6 months improved cognition more often than those who received placebo and that a higher proportion receiving galantamine were globally improved. This suggests that patients with mild AD benefit from galantamine treatment.[Abstract]
    11. Lyketsos CG, Reichman WE, Kershaw P, Zhu Y. Am J Geriatr Psychiatry. 2004 Sep-Oct;12(5):473-82. Long-term outcomes of galantamine treatment in patients with Alzheimer disease
      Patients completing two double-blind, placebo-controlled trials (N=699) were escalated to a 24-mg dose (12 mg bid) of galantamine during a period of 2 weeks and treated for 12 months beyond the initial 6.5-month, double-blind period (total treatment duration: 18.5 months). Patients taking galantamine continuously throughout the double-blind and open-label studies (N=288) showed sustained cognitive benefits on ADAS-Cog/11 scores at 18.5 months. Results of this open-label extension support the findings from previous galantamine studies and demonstrate the safety and tolerability of galantamine for up to 18.5 months[Abstract]
    12. Raskind MA, Peskind ER, Truyen L, Kershaw P, Damaraju CV. Arch Neurol. 2004 Feb;61(2):252-6. The cognitive benefits of galantamine are sustained for at least 36 months: a long-term extension trial
      Cognitive decline over 36 months of continuous galantamine treatment was substantially less than the predicted cognitive decline of untreated patients with mild to moderate dementia. Thus, the cognitive benefits of galantamine seemed to be sustained for at least 36 months. These findings suggest that galantamine slows the clinical progression of AD.[Article]
    13. Kadir A, Darreh-Shori T, Almkvist O, Wall A, Grut M, Strandberg B, Ringheim A, B Eriksson, Blomquist G, Långström B, Nordberg A. Neurobiol Aging. 2008 Aug;29(8):1204-17. PET imaging of the in vivo brain acetylcholinesterase activity and nicotine binding in galantamine-treated patients with AD
      In conclusion, galantamine caused sustained AChE inhibition for up to 12 months. At the individual level, the in vivo cortical AChE inhibition and (11)C-nicotine binding were associated with changes in the attention domain of cognition rather than episodic memory.[Abstract]
    14. Blesa R, Davidson M, Kurz A, Reichman W, van Baelen B, Schwalen S. Dement Geriatr Cogn Disord. 2003;15(2):79-87. Galantamine provides sustained benefits in patients with ‘advanced moderate’ Alzheimer’s disease for at least 12 months
      In conclusion, galantamine offered sustained efficacy to patients with ‘advanced moderate’ AD, confirming the benefits seen in published studies of patients with mild-to-moderate AD. This drug has potential for broader use in clinical practice.[Abstract]
    15. COCHRANE
    16. Birks J. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD005593. Cholinesterase inhibitors for Alzheimer’s disease
      Since the introduction of the first cholinesterase inhibitor (ChEI) in 1997, most clinicians and probably most patients would consider the cholinergic drugs, donepezil, galantamine and rivastigmine, to be the first line pharmacotherapy for mild to moderate Alzheimer’s disease.The drugs have slightly different pharmacological properties, but they all work by inhibiting the breakdown of acetylcholine, an important neurotransmitter associated with memory, by blocking the enzyme acetylcholinesterase. The three cholinesterase inhibitors are efficacious for mild to moderate Alzheimer’s disease. It is not possible to identify those who will respond to treatment prior to treatment.[Abstract]
    17. Loy C, Schneider L. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD001747. Galantamine for Alzheimer’s disease and mild cognitive impairment
      Galantamine’s effect on more severely impaired subjects has not yet been assessed. Nevertheless, this review shows consistent positive effects for galantamine for trials of three to six months’ duration. Although there was not a statistically significant dose-response effect, doses above 8 mg/d were, for the most part, consistently statistically significant. Galantamine’s safety profile in AD is similar to that of other cholinesterase inhibitors with respect to cholinergically mediated gastrointestinal symptoms.[Abstract]
    18. REVIEW
    19. Razay G, Wilcock GK. Expert Rev Neurother. 2008 Jan;8(1):9-17. Galantamine in Alzheimer’s disease
      Galantamine is a cholinesterase inhibitor with a dual mechanism of action. It is a reversible inhibitor of acetylcholine esterase and enhances the intrinsic action of acetylcholine on nicotinic receptors, leading to increased cholinergic neurotransmission in the CNS. Galantamine has a large volume clearance, low plasma protein binding and a high bioavailability. Short-term, double-blind, placebo-controlled studies have shown that treatment with galantamine produces small improvements on cognitive tests and global measures of change in selected patients with mild to moderately severe Alzheimer’s disease. A dose of 16-24 mg/day appears to be the most efficacious, and is the licensed maintenance dose range in most territories. The magnitude of the treatment effect is similar to that of other cholinesterase inhibitors. Adverse events experienced by patients treated with galantamine are usually mild, gastrointestinal and may improve with dose reduction.[Abstract]
    20. Scott LJ, Goa KL. Drugs. 2000 Nov;60(5):1095-122. Galantamine: a review of its use in Alzheimer’s disease
      Currently, acetylcholinesterase (AChE) inhibitors are the most promising class of drugs for the treatment of Alzheimer’s disease (AD). Galantamine is a reversible, competitive, tertiary alkaloid AChE inhibitor. The drug is selective for AChE rather than butyrylcholinesterase. In addition to inhibition of AChE galantamine interacts allosterically with nicotinic acetylcholine receptors to potentiate the action of agonists at these receptors. Recipients of galantamine 16 or 24 mg/day achieved significant improvements in cognitive and global symptoms relative to placebo recipients in large (n = 285 to 978 patients with mild to moderate AD) well-designed trials of 3 to 6 months’ duration. Galantamine also improved activities of daily living in these patients and significantly reduced the requirement for caregiver assistance with activities of daily living. Moreover, galantamine recipients achieved significantly better outcomes on behavioural symptoms than placebo recipients. In a long term study (12 months), galantamine 24 mg/day slowed the progression of symptoms of the disease and maintained cognitive function and activities of daily living in patients with mild to moderate AD. Galantamine was generally well tolerated with the majority of adverse events being mild to moderate in intensity and transient. Predictably, adverse events were cholinergic in nature and generally related to the gastrointestinal system.[Abstract]

    Huperzine

      RCT
    1. Zhang Z, Wang X, Chen Q, Shu L, Wang J, Shan G. Zhonghua Yi Xue Za Zhi. 2002 Jul 25;82(14):941-4. Clinical efficacy and safety of huperzine Alpha in treatment of mild to moderate Alzheimer disease, a placebo-controlled, double-blind, randomized trial
      A safe and effective medicine, huperzine Alpha remarkably improves the cognition, behavior, ADL,and mood of AD patients.[Abstract]
    2. Xu SS, Cai ZY, Qu ZW, Yang RM, Cai YL, Wang GQ, Su XQ, Zhong XS, Cheng RY, Xu WA, Li JX, Feng B. Zhongguo Yao Li Xue Bao. 1999 Jun;20(6):486-90. Huperzine-A in capsules and tablets for treating patients with Alzheimer disease
      There is equal efficacy and safety between Hup in capsule and tablet for treating patients with AD, and Hup can reduce the pathological changes of the oxygen free radicals in the plasma and erythrocytes of patients with AD.[Abstract]
    3. Xu SS, Gao ZX, Weng Z, Du ZM, Xu WA, Yang JS, Zhang ML, Tong ZH, Fang YS, Chai XS, et al. Zhongguo Yao Li Xue Bao. 1995 Sep;16(5):391-5. Efficacy of tablet huperzine-A on memory, cognition, and behavior in Alzheimer’s disease
      Hup is a promising drug for symptomatic treatment of Alzheimer’s disease.[Abstract]
    4. COCHRANE
    5. Li J, Wu HM, Zhou RL, Liu GJ, Dong BR. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD005592. Huperzine A for Alzheimer’s disease
      From the available evidence, Huperzine A seems to have some beneficial effects on improvement of general cognitive function, global clinical status, behavioral disturbance and functional performance, with no obvious serious adverse events for patients with AD.[Abstract]
    6. REVIEW
    7. Ha GT, Wong RK, Zhang Y. Chem Biodivers. 2011 Jul;8(7):1189-204. doi: 10.1002/cbdv.201000269. Huperzine a as potential treatment of Alzheimer’s disease: an assessment on chemistry, pharmacology, and clinical studies
      The MMSE scores indicated cognitive enhancement at 0.4?mg. Promising data suggested that huperzine A is well tolerated at doses up to 0.4?mg for 24 weeks. Therefore, huperzine A seems to be a potential treatment option for AD.[Abstract]
    8. Little JT, Walsh S, Aisen PS. Expert Opin Investig Drugs. 2008 Feb;17(2):209-15. An update on huperzine A as a treatment for Alzheimer’s disease
      Huperzine A is a natural cholinesterase inhibitor derived from the Chinese herb Huperzia serrata. There is evidence that huperzine A may compare favorably in symptomatic efficacy to cholinesterase inhibitors in use. In addition, huperzine A has antioxidant and neuroprotective properties that suggest that it may be useful as a disease-modifying treatment for Alzheimer’s disease (AD).[Abstract]
    9. Pilotaz F, Masson P. Ann Pharm Fr. 1999 Sep;57(5):363-73. Huperzine a: an acetylcholinesterase inhibitor with high pharmacological potential
      Huperzine A is an alkaloid isolated from a chinese club-moss. The molecule is a potent and selective inhibitor of acetylcholinesterase. Several pharmacological and clinical studies showed that huperzine A improves the mnesic capacity and cognitive functions. Huperzine A was also found to be a neuroprotective agent. This molecule which possesses a high pharmacological potential is under clinical evaluation for the palliative treatment of Alzheimer’s disease. In addition, its use in the pretreatment of poisoning by organophosphorous nerve agents could be another indication.[Abstract]
    10. Li WM, Kan KK, Carlier PR, Pang YP, Han YF. Curr Alzheimer Res. 2007 Sep;4(4):386-96. East meets West in the search for Alzheimer’s therapeutics – novel dimeric inhibitors from tacrine and huperzine A
      Alzheimer’s disease (AD) is linked to cholinergic deficiency and the overactivation of glutamate receptors. The acetylcholinesterase (AChE) inhibition treatment approach has produced the most encouraging results in clinical practice, and memantine, a moderate antagonist of N-methyl-D-aspartate (NMDA) receptors, has been approved for treating AD. The novel dimers, derived from tacrine and the fragment of huperzine A (HA’), have been demonstrated to be potent and selective reversible inhibitors of AChE.[Abstract]
    11. Wang R, Yan H, Tang XC. Acta Pharmacol Sin. 2006 Jan;27(1):1-26. Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine
      The phase IV clinical trials in China have demonstrated that HupA significantly improved memory deficits in elderly people with benign senescent forgetfulness, and patients with Alzheimer disease and vascular dementia, with minimal peripheral cholinergic side effects and no unexpected toxicity. HupA can also be used as a protective agent against organophosphate intoxication.[Abstract]
    12. Haviv H, Wong DM, Silman I, Sussman JL. Curr Top Med Chem. 2007;7(4):375-87. Bivalent ligands derived from Huperzine A as acetylcholinesterase inhibitors
      The naturally occurring alkaloid Huperzine A (HupA) is an acetylcholinesterase (AChE) inhibitor that has been used for centuries as a Chinese folk medicine in the context of its source plant Huperzia Serrata. The potency and relative safety of HupA rendered it a promising drug for the ameliorative treatment of Alzheimer’s disease (AD) vis-à-vis the “cholinergic hypothesis” that attributes the cognitive decrements associated with AD to acetylcholine deficiency in the brain. However, recent evidence supports a neuroprotective role for HupA, suggesting that it could act as more than a mere palliative.[Abstract]
    13. Wang R, Tang XC. Neurosignals. 2005;14(1-2):71-82. Neuroprotective effects of huperzine A. A natural cholinesterase inhibitor for the treatment of Alzheimer’s disease
      Huperzine A (HupA), isolated from Chinese herb Huperzia serrata, is a potent, highly specific and reversible inhibitor of acetylcholinesterase. It has been found to reverse or attenuate cognitive deficits in a broad range of animal models. Clinical trials in China have demonstrated that HupA significantly relieves memory deficits in aged subjects, patients with benign senescent forgetfulness, Alzheimer’s disease (AD) and vascular dementia (VD), with minimal peripheral cholinergic side effects compared with other AChEIs in use.[Article]
    14. Zangara A. Pharmacol Biochem Behav. 2003 Jun;75(3):675-86. The psychopharmacology of huperzine A: an alkaloid with cognitive enhancin
      Huperzine A (HupA), extracted from a club moss (Huperzia serrata), is a sesquiterpene alkaloid and a powerful and reversible inhibitor of acetylcholinesterase (AChE). It has been used in China for centuries for the treatment of swelling, fever and blood disorders. It has demonstrated both memory enhancement in animal and clinical trials and neuroprotective effects. Recently it has undergone double-blind, placebo-controlled clinical trials in patients with Alzheimer’s disease (AD), with significant improvements both to cognitive function and the quality of life.[Abstract]
    15. Bai DL, Tang XC, He XC. Curr Med Chem. 2000 Mar;7(3):355-74. Huperzine A, a potential therapeutic agent for treatment of Alzheimer’s disease
      HupA is a potent, reversible and selective inhibitor of AChE with a rapid absorption and penetration into the brain in animal tests. It exhibits memory-enhancing activities in animal and clinical trials. Compared to tacrine and donepezil, HupA possesses a longer duration of action and higher therapeutic index, and the peripheral cholinergic side effects are minimal at therapeutic doses. Recently, it has been reported that HupA could reduce neuronal cell death caused by glutamate. The dual bio-activities of HupA would further enhance its value and potentiality as the therapeutic agent for Alzheimer s disease.[Abstract]

    Acetyl-L-carnitine

      RCT
    1. Carta A, Calvani M. Ann N Y Acad Sci. 1991;640:228-32. Acetyl-L-carnitine: a drug able to slow the progress of Alzheimer’s disease?
      ALC has a variety of pharmacologic properties that exhibit restorative or even protective actions against aging processes and neurodegeneration. A review of a series of controlled clinical studies suggests that ALC may also slow the natural course of AD.[Abstract]
    2. Brooks JO 3rd, Yesavage JA, Carta A, Bravi D. Int Psychogeriatr. 1998 Jun;10(2):193-203. Acetyl L-carnitine slows decline in younger patients with Alzheimer’s disease: a reanalysis of a double-blind, placebo-controlled study using the trilinear approach
      ALC slows the progression of Alzheimer’s disease in younger subjects, and the use of the trilinear approach to estimate the average rate of change may prove valuable in pharmacological trials.[Abstract]
    3. Pettegrew JW, Klunk WE, Panchalingam K, Kanfer JN, McClure RJ. Neurobiol Aging. 1995 Jan-Feb;16(1):1-4. Clinical and neurochemical effects of acetyl-L-carnitine in Alzheimer’s disease
      Compared to AD patients on placebo, acetyl-L-carnitine-treated patients showed significantly less deterioration in their Mini-Mental Status and Alzheimer’s Disease Assessment Scale test scores. Furthermore, the decrease in phosphomonoester levels observed in both the acetyl-L-carnitine and placebo AD groups at entry was normalized in the acetyl-L-carnitine-treated but not in the placebo-treated patients. Similar normalization of high-energy phosphate levels was observed in the acetyl-L-carnitine-treated but not in the placebo-treated patients. This is the first direct in vivo demonstration of a beneficial effect of a drug on both clinical and CNS neurochemical parameters in AD.[Abstract]
    4. Palacios HH, Yendluri BB, Parvathaneni K, Shadlinski VB, Obrenovich ME, Leszek J, Gokhman D, G?siorowski K, Bragin V, Aliev G. CNS Neurol Disord Drug Targets. 2011 Mar;10(2):149-62. Mitochondrion-specific antioxidants as drug treatments for Alzheimer disease
      Neuronal mitochondria are especially vulnerable to oxidative stress due to their role in energy supply and use, causing a cascade of debilitating factors such as the production of giant and/or vulnerable young mitochondrion who’s DNA has been compromised. Therefore, mitochondria specific antioxidants such as acetyl-L-carnitine and R-alphalipoic acid seem to be potential treatments for AD. They target the factors that damage mitochondria and reverse its effect, thus eliminating the imbalance seen in energy production and amyloid beta oxidation and making these antioxidants very powerful alternate strategies for the treatment of AD.[Abstract]
    5. Remington R, Chan A, Paskavitz J, Shea TB. Am J Alzheimers Dis Other Demen. 2009 Feb-Mar;24(1):27-33 Efficacy of a vitamin/nutriceutical formulation for moderate-stage to later-stage Alzheimer’s disease: a placebo-controlled pilot stud
      Recent studies demonstrated efficacy of a vitamin/ nutriceutical formulation (folate, vitamin B12, alpha-tocopherol, S-adenosyl methionine, N-acetyl cysteine, and acetyl-L-carnitine) for mild to moderate Alzheimer’s disease. This formulation holds promise for delaying the decline in cognition, mood, and daily function that accompanies the progression of Alzheimer’s disease, and may be particularly useful as a supplement for pharmacological approaches during later stages of this disorder.[Abstract]
    6. Passeri M, Cucinotta D, Bonati PA, Iannuccelli M, Parnetti L, Senin U. Int J Clin Pharmacol Res. 1990;10(1-2):75-9. Acetyl-L-carnitine in the treatment of mildly demented elderly patients
      It was possible to affirm that the acetyl-L-carnitine treated patients showed statistically significant improvement in the behavioural scales, in the memory tests, in the attention barrage test and in the Verbal Fluency test. These satisfactory results confirm the therapeutic importance of acetyl-L-carnitine in the treatment of elderly patients with mental impairment, which could be related principally to acetylcholine defects.[Abstract]
    7. Rai G, Wright G, Scott L, Beston B, Rest J, Exton-Smith AN. Curr Med Res Opin. 1990;11(10):638-47. Double-blind, placebo controlled study of acetyl-l-carnitine in patients with Alzheimer’s dementia
      The results suggest that acetyl-l-carnitine may have a beneficial effect on some clinical features of Alzheimer-type dementia, particularly those related to short-term memory.[Abstract]
    8. Sano M, Bell K, Cote L, Dooneief G, Lawton A, Legler L, Marder K, Naini A, Stern Y, Mayeux R. Arch Neurol. 1992 Nov;49(11):1137-41. Double-blind parallel design pilot study of acetyl levocarnitine in patients with Alzheimer’s disease
      These results suggest that acetyl levocarnitine may retard the deterioration in some cognitive areas in patients with Alzheimer’s disease and stress the need for a larger study of this drug.[Abstract]
    9. Spagnoli A, Lucca U, Menasce G, Bandera L, Cizza G, Forloni G, Tettamanti M, Frattura L, Tiraboschi P, Comelli M, et al. Neurology. 1991 Nov;41(11):1726-32. Long-term acetyl-L-carnitine treatment in Alzheimer’s disease
      Adjusting for initial scores with analysis of covariance, the treated group showed better scores on all outcome measures, reaching statistical significance for the Blessed Dementia Scale, logical intelligence, verbal critical abilities, long-term verbal memory, and selective attention. The analysis for patients with good treatment compliance showed a greater drug benefit than for the overall sample.[Abstract]
    10. REVIEW
    11. Ames BN, Liu J. Ann N Y Acad Sci. 2004 Nov;1033:108-16. Delaying the mitochondrial decay of aging with acetylcarnitine
      A recent meta-analysis of 21 double-blind clinical trials of ALC in the treatment of mild cognitive impairment and mild Alzheimer’s disease showed significant efficacy vs. placebo.[Abstract]
    12. Liu J, Atamna H, Kuratsune H, Ames BN. Ann N Y Acad Sci. 2002 Apr;959:133-66. Delaying brain mitochondrial decay and aging with mitochondrial antioxidants and metabolites
      Mitochondria decay with age due to the oxidation of lipids, proteins, RNA, and DNA. Some of this decay can be reversed in aged animals by feeding them the mitochondrial metabolites acetylcarnitine and lipoic acid.[Abstract]
    13. Pettegrew JW, Levine J, McClure RJ. Mol Psychiatry. 2000 Nov;5(6):616-32. Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties: relevance for its mode of action in Alzheimer’s disease and geriatric depression
      ALCAR is reported in double-blind controlled studies to have beneficial effects in major depressive disorders and Alzheimer’s disease (AD), both of which are highly prevalent in the geriatric population.[Abstract]
    14. CLINICAL TRIAL
    15. Bianchetti A, Rozzini R, Trabucchi M. Curr Med Res Opin. 2003;19(4):350-3. Effects of acetyl-L-carnitine in Alzheimer’s disease patients unresponsive to acetylcholinesterase inhibitors
      The response rate, which was 38% after AChE-I treatment, increased to 50% after the addition of ALC, indicating that the combination of these two drugs may be a useful therapeutic option in AD patients.[Abstract]

    Ginkgo-Biloba

      RCT
    1. Mix JA, Crews WD Jr. Hum Psychopharmacol. 2002 Aug;17(6):267-77. A double-blind, placebo-controlled, randomized trial of Ginkgo biloba extract EGb 761 in a sample of cognitively intact older adults: neuropsychological findings
      Overall, the results from both objective, standardized, neuropsychological tests and a subjective, follow-up self-report questionnaire provided complementary evidence of the potential efficacy of Ginkgo biloba EGb 761 in enhancing certain neuropsychological/memory processes of cognitively intact older adults, 60 years of age and over.[Abstract]
    2. Yancheva S, Ihl R, Nikolova G, Panayotov P, Schlaefke S, Hoerr R; GINDON Study Group. Aging Ment Health. 2009 Mar;13(2):183-90. Ginkgo biloba extract EGb 761(R), donepezil or both combined in the treatment of Alzheimer’s disease with neuropsychiatric features: a randomised, double-blind, exploratory trial
      These exploratory findings helped to develop three hypotheses that will have to be proven in further studies: (1) there is no significant difference in the efficiency between EGb 761(R) and donepezil, (2) a combination therapy will be superior to a mono-therapy with one of both substances and (3) there will be less side effects under a combination therapy than under mono-therapy with donepezil.[Abstract]
    3. Napryeyenko O, Sonnik G, Tartakovsky I. J Neurol Sci. 2009 Aug 15;283(1-2):224-9. Efficacy and tolerability of Ginkgo biloba extract EGb 761 by type of dementia: analyses of a randomised controlled trial
      Significant drug-placebo differences were found for all secondary outcome variables with no major differences between AD and VaD subgroups.[Abstract]
    4. Scripnikov A, Khomenko A, Napryeyenko O; GINDEM-NP Study Group. Wien Med Wochenschr. 2007;157(13-14):295-300. Effects of Ginkgo biloba extract EGb 761 on neuropsychiatric symptoms of dementia: findings from a randomised controlled trial
      EGb 761 was significantly superior to placebo with respect to the primary (SKT test battery) and all secondary outcome variables.[Abstract]
    5. Napryeyenko O, Borzenko I; GINDEM-NP Study Group. Arzneimittelforschung. 2007;57(1):4-11. Ginkgo biloba special extract in dementia with neuropsychiatric features. A randomised, placebo-controlled, double-blind clinical trial
      The data add further evidence on the safety and efficacy of EGb 761 in the treatment of cognitive and non-cognitive symptoms of dementia.[Abstract]
    6. Mazza M, Capuano A, Bria P, Mazza S. Eur J Neurol. 2006 Sep;13(9):981-5. Ginkgo biloba and donepezil: a comparison in the treatment of Alzheimer’s dementia in a randomized placebo-controlled double-blind study
      Our study suggests that there is no evidence of relevant differences in the efficacy of EGb 761 and donepezil in the treatment of mild to moderate Alzheimer’s dementia, so the use of both substances can be justified. In addition, this study contributes to establish the efficacy and tolerability of the Ginkgo biloba special extract E.S. in the dementia of the Alzheimer type with special respect to moderately severe stages.[Abstract]
    7. Kanowski S, Hoerr R. Pharmacopsychiatry. 2003 Nov;36(6):297-303. Ginkgo biloba extract EGb 761 in dementia: intent-to-treat analyses of a 24-week, multi-center, double-blind, placebo-controlled, randomized trial
      In 1996, Kanowski et al. reported about the beneficial effects of ginkgo biloba special extract EGb 761 (240 mg/day) in outpatients with pre-senile and senile primary degenerative dementia of the Alzheimer type (DAT) and multi-infarct dementia (MID) of mild to moderate severity. The results of this ITT analysis substantiate the outcomes previously obtained with a responder analysis of the per-protocol population and confirm that EGb 761 improves cognitive function in a clinically relevant manner in patients suffering from dementia. The therapeutic effect is in line with the outcome of another EGb 761 study conducted in the U.S.[Abstract]
    8. Kanowski S, Herrmann WM, Stephan K, Wierich W, Hörr R. Pharmacopsychiatry. 1996 Mar;29(2):47-56. Proof of efficacy of the ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia
      Thus, the clinical efficacy of the ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type and multi-infarct dementia was confirmed. The investigational drug was found to be well tolerated.[Abstract]
    9. COCHRANE
    10. Birks J, Grimley EV, Van Dongen M. Cochrane Database Syst Rev. 2002;(4):CD003120. Ginkgo biloba for cognitive impairment and dementia
      Overall there is promising evidence of improvement in cognition and function associated with Ginkgo.[Abstract]
    11. REVIEW
    12. Kaschel R. Hum Psychopharmacol. 2009 Jul;24(5):345-70. Ginkgo biloba: specificity of neuropsychological improvement–a selective review in search of differential effects
      There is consistent evidence that chronic administration improves selective attention, some executive processes and long-term memory for verbal and non-verbal material.[Abstract]
    13. Janssen IM, Sturtz S, Skipka G, Zentner A, Velasco Garrido M, Busse R. Wien Med Wochenschr. 2010 Dec;160(21-22):539-46. Ginkgo biloba in Alzheimer’s disease: a systematic review
      Cognition and accompanying psychopathological symptoms show an indication of a benefit. A harm of Ginkgo is not evident..[Abstract]
    14. Weinmann S, Roll S, Schwarzbach C, Vauth C, Willich SN. BMC Geriatr. 2010 Mar 17;10:14. Effects of Ginkgo biloba in dementia: systematic review and meta-analysis
      Ginkgo biloba appears more effective than placebo. Effect sizes were moderate, while clinical relevance is, similar to other dementia drugs, difficult to determine.[Article]
    15. OTHER
    16. Stackman RW, Eckenstein F, Frei B, Kulhanek D, Nowlin J, Quinn JF. Exp Neurol. 2003 Nov;184(1):510-20. Prevention of age-related spatial memory deficits in a transgenic mouse model of Alzheimer’s disease by chronic Ginkgo biloba treatment
      These data indicate that chronic Ginkgo biloba treatment can block an age-dependent decline in spatial cognition without altering Abeta levels and without suppressing protein oxidation in a transgenic mouse model of AD.[Abstract]

    Blauwe bessen

      REVIEW
    1. Lau FC, Shukitt-Hale B, Joseph JA. Neurobiol Aging. 2005 Dec;26 Suppl 1:128-32. Epub 2005 Sep 27. The beneficial effects of fruit polyphenols on brain aging
      Research from our laboratory has shown that nutritional antioxidants, such as the polyphenols found in blueberries, can reverse age-related declines in neuronal signal transduction as well as cognitive and motor deficits. Furthermore, we have shown that short-term blueberry (BB) supplementation increases hippocampal plasticity.[Abstract]
    2. Joseph JA, Shukitt-Hale B, Lau FC. Ann N Y Acad Sci. 2007 Apr;1100:470-85. Fruit polyphenols and their effects on neuronal signaling and behavior in senescence
      Research suggests that the polyphenolic compounds found in fruits, such as blueberries, may exert their beneficial effects by altering stress signaling and neuronal communication, suggesting that interventions may exert protection against age-related deficits in cognitive and motor function.[Abstract]
    3. Shukitt-Hale B, Lau FC, Joseph JA. J Agric Food Chem. 2008 Feb 13;56(3):636-41. Berry fruit supplementation and the aging brain
      Research suggests that the polyphenolic compounds found in berry fruits, such as blueberries and strawberries, may exert their beneficial effects either through their ability to lower oxidative stress and inflammation or directly by altering the signaling involved in neuronal communication, calcium buffering ability, neuroprotective stress shock proteins, plasticity, and stress signaling pathways. These interventions, in turn, may exert protection against age-related deficits in cognitive and motor function.[Abstract]
    4. Williams RJ, Spencer JP. Free Radic Biol Med. 2012 Jan 1;52(1):35-45. doi: 10.1016/j.freeradbiomed.2011.09.010. Flavonoids, cognition, and dementia: actions, mechanisms, and potential therapeutic utility for Alzheimer disease
      Together, these processes act to maintain the number and quality of synaptic connections in key brain regions and thus flavonoids have the potential to prevent the progression of neurodegenerative pathologies and to promote cognitive performance.[Abstract]
    5. Balk E, Chung M, Raman G, Tatsioni A, Chew P, Ip S, DeVine D, Lau J. Evid Rep Technol Assess (Full Rep). 2006 Apr;(134):1-161. B vitamins and berries and age-related neurodegenerative disorders
      Berry extracts may protect against the deleterious effects of compounds associated with AD.[Article]

    Kurkuma

      REVIEW
    1. Hamaguchi T, Ono K, Yamada M. CNS Neurosci Ther. 2010 Oct;16(5):285-97. doi: 10.1111/j.1755-5949.2010.00147.x. REVIEW: Curcumin and Alzheimer’s disease
      These findings suggest that curcumin might be one of the most promising compounds for the development of AD therapies. At present, four clinical trials concerning the effects of curcumin on AD has been conducted. Two of them that were performed in China and USA have been reported no significant differences in changes in cognitive function between placebo and curcumin groups, and no results have been reported from two other clinical studies.[Abstract]
    2. Li Y, Wang P. Zhongguo Zhong Yao Za Zhi. 2009 Dec;34(24):3173-5. Neuroprotective effects of curcumin
      Recent evidence suggests that curcumin has activities with potential for neuroprotective efficacy, including anti-inflammatory, antioxidant, and antiprotein-aggregate activities. In the current review, we provide the newly evidence for the potential role of curcumin in the neuroprotective effects of neurodegenerative diseases like Alzheimer’s disease (AD).[Abstract]
    3. Ono K, Naiki H, Yamada M. Curr Pharm Des. 2006;12(33):4357-75. The development of preventives and therapeutics for Alzheimer’s disease that inhibit the formation of beta-amyloid fibrils (fAbeta), as well as destabilize preformed fAbeta
      Neuritic plaques composed mainly of amyloid beta-protein (Abeta) in the brain are an early and invariant neuropathological feature of Alzheimer’s disease (AD). Recently, various compounds such as curcumin, nicotine and wine-related polyphenols have been reported to inhibit the formation, extension of fAbeta, as well as destabilize preformed fAbeta at pH 7.5 at 37 degrees C in vitro. In cell culture experiments, destabilized fAbeta were suggested to be less toxic than intact fAbeta. In transgenic mice model study, some coumpounds such as curcumin and nicotine have also been reported to reduce plaque burden in vivo.[Abstract]
    4. Calcul L, Zhang B, Jinwal UK, Dickey CA, Baker BJ. Future Med Chem. 2012 Sep;4(13):1751-61. doi: 10.4155/fmc.12.124. Natural products as a rich source of tau-targeting drugs for Alzheimer’s disease
      Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common form of dementia, affecting more than 5.4 million people in the USA. Although the cause of AD is not well understood, the cholinergic, amyloid and tau hypotheses were proposed to explain its development. Drug discovery for AD based on the cholinergic and amyloid theories have not been effective. In this article we summarize tau-based natural products as AD therapeutics from a variety of biological sources, including the anti-amyloid agent curcumin, isolated from turmeric, the microtubule stabilizer paclitaxel, from the Pacific Yew Taxus brevifolia, and the Streptomyces-derived Hsp90 inhibitor, geldanamycin. The overlooked approach of clearing tau aggregation will most likely be the next objective for AD drug discovery.[Article]

    Druivenpittenextract

      REVIEW
    1. Shi J, Yu J, Pohorly JE, Kakuda Y. J Med Food. 2003 Winter;6(4):291-9. Polyphenolics in grape seeds-biochemistry and functionality
      Polyphenols in grape seeds are mainly flavonoids, including gallic acid, the monomeric flavan-3-ols catechin, epicatechin, gallocatechin, epigallocatechin, and epicatechin 3-O-gallate, and procyanidin dimers, trimers, and more highly polymerized procyanidins. Grape seed extract is known as a powerful antioxidant that protects the body from premature aging, disease, and decay. Grape seeds contains mainly phenols such as proanthocyanidins (oligomeric proanthocyanidins). Scientific studies have shown that the antioxidant power of proanthocyanidins is 20 times greater than vitamin E and 50 times greater than vitamin C.[Abstract]
    2. OTHER
    3. Wang J, Santa-Maria I, Ho L, Ksiezak-Reding H, Ono K, Teplow DB, Pasinetti GM. J Alzheimers Dis. 2010;22(2):653-61. Grape derived polyphenols attenuate tau neuropathology in a mouse model of Alzheimer’s disease
      Moreover, oral administration of GSPE significantly attenuated the development of AD type tau neuropathology in the brain of TMHT mouse model of AD through mechanisms associated with attenuation of extracellular signal-receptor kinase 1/2 signaling in the brain.[Abstract]
    4. Wang J, Ho L, Zhao W, Ono K, Rosensweig C, Chen L, Humala N, Teplow DB, Pasinetti GM. J Neurosci. 2008 Jun 18;28(25):6388-92. Grape-derived polyphenolics prevent Abeta oligomerization and attenuate cognitive deterioration in a mouse model of Alzheimer’s disease
      Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive impairments in memory and cognition. When orally administered to Tg2576 mice, this polyphenolic preparation significantly attenuates AD-type cognitive deterioration coincidentally with reduced HMW soluble oligomeric Abeta in the brain. Our study suggests that grape seed-derived polyphenolics may be useful agents to prevent or treat AD.[Article]
    5. Ho L, Chen LH, Wang J, Zhao W, Talcott ST, Ono K, Teplow D, Humala N, Cheng A, Percival SS, Ferruzzi M, Janle E, Dickstein DL, Pasinetti GM. J Alzheimers Dis. 2009;16(1):59-72. Heterogeneity in red wine polyphenolic contents differentially influences Alzheimer’s disease-type neuropathology and cognitive deterioration
      We recently found that moderate consumption of two unrelated red wines generate from different grape species, a Cabernet Sauvignon and a muscadine wine that are characterized by distinct component composition of polyphenolic compounds, significantly attenuated the development of Alzheimer’s disease (AD)-type brain pathology and memory deterioration in a transgenic AD mouse model. Results from these studies suggest the possibility of developing a “combination” of dietary polyphenolic compounds for AD prevention and/or therapy by modulating multiple Abeta-related mechanisms. [Article]
    6. Wang YJ, Thomas P, Zhong JH, Bi FF, Kosaraju S, Pollard A, Fenech M, Zhou XF. Neurotox Res. 2009 Jan;15(1):3-14. Consumption of grape seed extract prevents amyloid-beta deposition and attenuates inflammation in brain of an Alzheimer’s disease mouse
      Conclusively, polyphenol-rich GSE prevents the Abeta deposition and attenuates the inflammation in the brain of a transgenic mouse model, and this thus is promising in delaying development of AD. [Abstract]

    Alfa-Liponzuur

      REVIEW
    1. Maczurek A, Hager K, Kenklies M, Sharman M, Martins R, Engel J, Carlson DA, Münch G. Adv Drug Deliv Rev. 2008 Oct-Nov;60(13-14):1463-70. Lipoic acid as an anti-inflammatory and neuroprotective treatment for Alzheimer’s disease
      Data from cell culture and animal models suggest that LA could be combined with nutraceuticals such as curcumin, (-)-epigallocatechin gallate (from green tea) and docosahexaenoic acid (from fish oil) to synergistically decrease oxidative stress, inflammation, Abeta levels and Abeta plaque load and thus provide a combined benefit in the treatment of AD.[Abstract]
    2. Holmquist L, Stuchbury G, Berbaum K, Muscat S, Young S, Hager K, Engel J, Münch G. Pharmacol Ther. 2007 Jan;113(1):154-64. Lipoic acid as a novel treatment for Alzheimer’s disease and related dementias
      In this review, the properties of LA are explored with particular emphasis on how this agent, particularly the R-alpha-enantiomer, may be effective to treat AD and related dementias.[Abstract]
    3. CLINICAL TRIAL
    4. Hager K, Kenklies M, McAfoose J, Engel J, Münch G. J Neural Transm Suppl. 2007;(72):189-93. Alpha-lipoic acid as a new treatment option for Alzheimer’s disease–a 48 months follow-up analysis
      Despite the fact that this study was not double-blinded, placebo-controlled and randomized, our data suggest that treatment with alpha-lipoic acid might be a successful ‘neuroprotective’ therapy option for AD.[Abstract]

    Glycerophosphorylcholine (GPC)

      RCT
    1. Parnetti L, Abate G, Bartorelli L, Cucinotta D, Cuzzupoli M, Maggioni M, Villardita C, Senin U. Drugs Aging. 1993 Mar-Apr;3(2):159-64. Multicentre study of l-alpha-glyceryl-phosphorylcholine vs ST200 among patients with probable senile dementia of Alzheimer’s type
      The results showed significant improvements in most neuropsychological parameters in the alpha GPC recipients. Improvements also occurred in the ST200 recipients but to a lesser extent. Tolerability was good in both groups. These positive findings require replication in larger, double-blind, longitudinal studies coupling clinical and biological determinations.[Abstract]
    2. De Jesus Moreno Moreno M. Clin Ther. 2003 Jan;25(1):178-93. Cognitive improvement in mild to moderate Alzheimer’s dementia after treatment with the acetylcholine precursor choline alfoscerate: a multicenter, double-blind, randomized, placebo-controlled trial
      The results of this study suggest the clinical usefulness and tolerability of CA in the treatment of the cognitive symptoms of dementia disorders of the Alzheimer type.[Abstract]
    3. REVIEW
    4. Tayebati SK, Amenta F. Clin Chem Lab Med. 2013 Mar 1;51(3):513-21. doi: 10.1515/cclm-2012-0559. Choline-containing phospholipids: relevance to brain functional pathways
      Based on the results of the controlled clinical trials available, we suggest that due to the lack of novel therapeutic strategies, safe compounds developed a long time ago such as effective CCPLs could have still a place in pharmacotherapy.[Article]

    Phosphatidylserine

      RCT
    1. Heiss WD, Kessler J, Slansky I, Mielke R, Szelies B, Herholz K. Ann N Y Acad Sci. 1993 Sep 24;695:327-31. Activation PET as an instrument to determine therapeutic efficacy in Alzheimer’s disease
      After the treatment period the group with cognitive training + phosphatidylserine showed a significant glucose enhancement during the stimulation tasks in various brain regions, and an improvement in cognitive functioning compared to the other groups. The group with cognitive training + pyritinol had better stimulation effect as that of the social support group indicating that a combination of cognitive training + pharmacological intervention was superior than that of cognitive training alone.[Abstract]

    CoQ10

      ANIMAL
    1. Dumont M, Kipiani K, Yu F, Wille E, Katz M, Calingasan NY, Gouras GK, Lin MT, Beal MF. J Alzheimers Dis. 2011;27(1):211-23. doi: 10.3233/JAD-2011-110209. Coenzyme Q10 decreases amyloid pathology and improves behavior in a transgenic mouse model of Alzheimer’s disease
      Our results show decreased pathology and improved behavior in transgenic AD mice treated with the naturally occurring antioxidant compound CoQ10. CoQ10 is well tolerated in humans and may be promising for therapeutic trials in AD.[Article]

    EPA/DHA

      RCT
    1. Yurko-Mauro K, McCarthy D, Rom D, Nelson EB, Ryan AS, Blackwell A, Salem N Jr, Stedman M; MIDAS Investigators Alzheimers Dement. 2010 Nov;6(6):456-64. Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline
      Twenty-four week supplementation with 900 mg/d DHA improved learning and memory function in ARCD and is a beneficial supplement that supports cognitive health with aging.[Abstract]
    2. OTHER
    3. Akbar M, Calderon F, Wen Z, Kim HY. Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):10858-63. Docosahexaenoic acid: a positive modulator of Akt signaling in neuronal survival
      Docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid highly enriched in neuronal membranes, promotes neuronal survival by facilitating membrane translocation/activation of Akt through its capacity to increase phosphatidylserine (PS), the major acidic phospholipid in cell membranes.[Article]

    Pyritinol

      RCT
    1. Fischhof PK, Saletu B, Rüther E, Litschauer G, Möslinger-Gehmayr R, Herrmann WM. Neuropsychobiology. 1992;26(1-2):65-70. Therapeutic efficacy of pyritinol in patients with senile dementia of the Alzheimer type (SDAT) and multi-infarct dementia (MID)
      Based on the results of this trial, it can be accepted that the therapeutic effect of pyritinol is superior to placebo in patients with mild to moderate dementia of both degenerative and vascular etiology.[Abstract]
    2. Knezevic S, Mubrin Z, Risberg J, Vucinic G, Spilich G, Gubarev N, Wannenmacher W. Int Clin Psychopharmacol. 1989 Jan;4(1):25-38. Pyritinol treatment of SDAT patients: evaluation by psychiatric and neurological examination, psychometric testing and rCBF measurements
      The results of the study showed that pyritinol was associated with a significant improvement in cognitive performance.[Abstract]

    Aged garlic extract

      REVIEW
    1. Ray B, Chauhan NB, Lahiri DK. Curr Med Chem. 2011;18(22):3306-13. The “aged garlic extract:” (AGE) and one of its active ingredients S-allyl-L-cysteine (SAC) as potential preventive and therapeutic agents for Alzheimer’s disease (AD)
      Thus, based on the reported positive preliminary results reviewed herein, further research is required to develop the full potential of AGE and/or SAC into an effective preventative strategy for AD.[Abstract]

    Fuzhisan

      CRT
    1. Bi M, Tong S, Zhang Z, Ma Q, Zhang S, Luo Z, Zhang Y, Li X, Wang D. Neurosci Lett. 2011 Aug 21;501(1):35-4 Changes in cerebral glucose metabolism in patients with mild-to-moderate Alzheimer’s disease: a pilot study with the Chinese herbal medicine fuzhisan
      These results suggest that FZS treatment may have a positive effect on cognition, behavioral functions, and rCMRglc in mild-to-moderate AD patients.[Abstract]

    Salvia officinalis

      CRT
    1. Akhondzadeh S, Noroozian M, Mohammadi M, Ohadinia S, Jamshidi AH, Khani M. J Clin Pharm Ther. 2003 Feb;28(1):53-9. Salvia officinalis extract in the treatment of patients with mild to moderate Alzheimer’s disease: a double blind, randomized and placebo-controlled trial
      The results of this study indicate the efficacy of S. officinalis extract in the management of mild to moderate Alzheimer’s disease. Moreover, S. officinalis may well reduce agitation of patients but this needs to be confirmed.[Abstract]

    CDP Choline

    1. Fioravanti M, Yanagi M. Cochrane Database Syst Rev. 2004;(2):CD000269. Cytidinediphosphocholine (CDP choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly
      There is some evidence that CDP Choline has a positive effect on memory and behaviour in at least the short/medium term. The evidence of benefit from global impression is stronger, but is still limited by the duration of the studies. Further research with CDP-choline should focus on longer term studies in subjects who have been diagnosed with currently accepted standardised criteria, especially vascular dementia.[Abstract]

    2. .[Abstract]

    Nutrition

      META
    1. Singh B1, Parsaik AK2, Mielke MM3, Erwin PJ4, Knopman DS2, Petersen RC5, Roberts RO5. J Alzheimers Dis. 2014 Jan 1;39(2):271-82. doi: 10.3233/JAD-130830. Association of mediterranean diet with mild cognitive impairment and Alzheimer’s disease: a systematic review and meta-analysis
      Conclusions: While the overall number of studies is small, pooled results suggest that a higher adherence to the MeDi is associated with a reduced risk of developing MCI and AD, and a reduced risk of progressing from MCI to AD.[Abstract]
    2. REVIEW
    3. Lourida I, Soni M, Thompson-Coon J, Purandare N, Lang IA, Ukoumunne OC, Llewellyn DJ. Epidemiology. 2013 Jul;24(4):479-89. doi: 10.1097/EDE.0b013e3182944410. Mediterranean diet, cognitive function, and dementia: a systematic review
      Published studies suggest that greater adherence to Mediterranean diet is associated with slower cognitive decline and lower risk of developing Alzheimer disease. Further studies would be useful to clarify the association with mild cognitive impairment and vascular dementia. Long-term randomized controlled trials promoting a Mediterranean diet may help establish whether improved adherence helps to prevent or delay the onset of Alzheimer disease and dementia.[Abstract]
    4. Solfrizzi V1, Panza F2. J Alzheimers Dis. 2014 Jan 1;39(2):283-6. doi: 10.3233/JAD-130831. Mediterranean diet and cognitive decline. A lesson from the whole-diet approach: what challenges lie ahead?
      The findings from prospective studies and very recent systematic reviews and meta-analyses suggested that adherence to the MeDi fulfilling the whole-diet approach may affect not only the risk of Alzheimer’s disease, but also of predementia syndromes and their progression to overt dementia.[Abstract]
    5. Joseph J, Cole G, Head E, Ingram D. J Neurosci. 2009 Oct 14;29(41):12795-801. Nutrition, brain aging, and neurodegeneration
      Recent studies suggest that consumption of diets rich in antioxidants and anti-inflammatory components such as those found in fruits, nuts, vegetables, and spices, or even reduced caloric intake, may lower age-related cognitive declines and the risk of developing neurodegenerative disease.[Article]
    6. Lau FC, Shukitt-Hale B, Joseph JA. Subcell Biochem. 2007;42:299-318. Nutritional intervention in brain aging: reducing the effects of inflammation and oxidative stress
      Epidemiological studies have shown that consumption of diets rich in antioxidant and anti-inflammatory agents, such as those found in fruits and vegetables, may lower the risk of developing age-related neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. Research from our laboratory suggests that dietary supplementation with fruit or vegetable extracts can decrease the age-enhanced vulnerability to oxidative stress and inflammation. Additional research suggests that the polyphenolic compounds found in fruits such as blueberries may exert their beneficial effects through signal transduction and neuronal communication.[Abstract]

    7. .[Abstract]