18 |
Léon et al., 201318. León R, Garcia AG, Marco-Contelles J. Recent advances in the multitarget-directed ligands approach for the treatment of Alzheimer's disease. Med Res Rev. 2013;33(1):139-89. (England) |
Cholinesterase inhibitors; statins: lipid-modifying agents; antioxidants; chelating agents |
Clinical evidence |
Narrative review |
Unclear |
19 |
Konrath et al., 201319. Konrath EL, Passos Cdos S, Klein LC Jr, Henriques AT. Alkaloids as a source of potential anticholinesterase inhibitors for the treatment of Alzheimer's disease. J Pharm Pharmacol. 2013;65(12):1701-25. (Brazil) |
Cholinesterase inhibitors; alkaloids |
Not specific |
Narrative review |
High |
20 |
McGuinness et al., 201320. McGuinness B, O'Hare J, Craig D, et al. Cochrane review on 'Statins for the treatment of dementia'. Int J Geriatr Psychiatry. 2013;28(2):119-26. (Ireland) |
Statins: lipid-modifying agents |
Phase III clinical trial |
Systematic review (randomized with meta-analysis) |
Low |
21 |
Rubio-Perez and Morrilas-Ruiz, 201221. Rubio-Perez JM, Morillas-Ruiz JM. A review: inflammatory process in Alzheimer's disease, role of cytokines. ScientificWorldJournal. 2012;2012:756357. (Spain) |
Anti-inflammatory agents; cytokines |
Not specific |
Narrative review |
High |
22 |
Appleby et al., 201322. Appleby BS, Nacopoulos D, Milano N, Zhong K, Cummings JL. A review: treatment of Alzheimer's disease discovered in repurposed agents. Dement Geriatr Cogn Disord. 2013;35(1-2):1-22. (USA) |
Agents for treating diabetes mellitus; nicotinic receptor agonists; phosphodiesterase inhibitors |
Clinical evidence |
Narrative review |
Unclear |
25 |
Pettenati et al., 200325. Pettenati C, Annicchiarico R, Caltagirone C. Clinical pharmacology of anti-Alzheimer drugs. Fundam Clin Pharmacol. 2003;17(6):659-72. (Italy) |
Cholinesterase inhibitors; immunomodulators; anti-inflammatory agents; NMDA receptor antagonists; antioxidants; phospholipase A2 inhibitors; nootropic drugs without elucidated mechanism of action for Alzheimer's disease; hormone therapy agents; chelating agents |
Clinical evidence |
Narrative review |
Unclear |
26 |
Sun et al., 201252. Sun GY, He Y, Chuang DY, et al. Integrating cytosolic phospholipase A2 with oxidative/nitrosative signaling pathways in neurons: a novel therapeutic strategy for AD. Mol Neurobiol. 2012;46(1):85-95. (China) |
Cholinesterase inhibitors; muscarinic agonists; immunomodulators; anti-inflammatory agents; statins: lipid modifying agents; antioxidants; chelating agents; antihypertensive agents |
Clinical evidence |
Narrative review |
Unclear |
27 |
Yoo and Park, 201227. Yoo KY, Park SY. Terpenoids as potential anti-Alzheimer's disease therapeutics. Molecules. 2012;17(3):3524-38. (Korea) |
Terpenoids; antioxidants |
Not specific |
Narrative review |
High |
28 |
Dodel, 201328. Dodel R. [Towards a vaccine against Alzheimer's?]. Drug Res (Stuttg). 2013;63 Suppl 1:S18-20. (Germany) |
Immunomodulators |
Clinical evidence |
Narrative review |
Unclear |
29 |
Mikulka et al., 201429. Mikulca JA, Nguyen V, Gajdosik DA, et al. Potential novel targets for Alzheimer pharmacotherapy: II. Update on secretase inhibitors and related approaches. J Clin Pharm Ther. 2014;39(1):25-37. (USA) |
Immunomodulators; secretase inhibitors; Inhibitors or modulators of beta and gamma-secretase |
Phases I, II and III clinical trial |
Systematic review (with clinical trial) |
Low |
30 |
Shukla et al., 201230. Shukla V, Skuntz S, Pant HC. Deregulated Cdk5 activity is involved in inducing Alzheimer's disease. Arch Med Res. 2012;43(8):655-62. (USA) |
Immunomodulators; cyclin kinase-5 dependent modulators |
Not specific |
Narrative review |
High |
31 |
Doody et al., 201431. Doody RS, Thomas RG, Farlow M, et al. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease. N Engl J Med. 2014;370(4):311-21. (Germany) |
Immunomodulators |
Phase III clinical trial |
Randomized clinical trial (double blind) |
Low |
32 |
Salloway et al., 201432. Salloway S, Sperling R, Fox NC, et al. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's disease. N Engl J Med. 2014;370(4):322-33. (USA) |
Immunomodulators |
Phase III clinical trial |
Randomized clinical trial (double blind) |
Low |
33 |
Enciu and Popescu, 201333. Enciu AM, Popescu BO. Is there a causal link between inflammation and dementia? Biomed Res Int. 2013;2013:316495. (Romania) |
Anti-inflammatory agents |
Clinical evidence |
Narrative review |
Unclear |
34 |
Feng and Wang, 201234. Feng Y, Wang X. Antioxidant therapies for Alzheimer's disease. Oxid Med Cell Longev. 2012;2012:472932. (China) |
Anti-inflammatory agents; antioxidants; phospholipase A2 inhibitors |
Not specific |
Systematic review |
High risk of bias |
35 |
Wolfe, 201235. Wolfe MS. γ-Secretase inhibitors and modulators for Alzheimer's disease. J Neurochem. 2012;120 Suppl 1:89-98. (USA) |
Anti-inflammatory agents; Inhibitors or modulators of beta and gamma-secretase; chelating agents |
Clinical evidence |
Narrative review |
Unclear |
36 |
Ghosh et al., 201236. Ghosh AK, Brindisi M, Tang J. Developing β-secretase inhibitors for treatment of Alzheimer's disease. J Neurochem. 2012;120 Suppl 1:71-83. (USA) |
Inhibitors or modulators of beta and gamma-secretase |
Phase II clinical trial |
Narrative review |
Low |
37 |
Hopkins, 201137. Hopkins CR. ACS chemical neuroscience molecule spotlight on ELND006: another γ-secretase inhibitor fails in the clinic. ACS Chem Neurosci. 2011;2(6):279-80. (USA) |
Inhibitors or modulators of beta and gamma-secretase |
Phase III Clinical trial |
Short report |
Unclear |
38 |
Piccinni et al., 201338. Piccinni A, Origlia N, Veltri A, et al. Neurodegeneration, β-amyloid and mood disorders: state of the art and future perspectives. Int J Geriatr Psychiatry. 2013;28(7):661-71. (Italy) |
Inhibitors or modulators of beta and gamma-secretase |
Not specific |
Narrative review |
High |
39 |
Eschecerria et al., 201239. Echeverria V, Zeitlin R. Cotinine: a potential new therapeutic agent against Alzheimer's disease. CNS Neurosci Ther. 2012;18(7):517-23. (USA) |
Nicotinic receptor agonists |
Clinical evidence |
Narrative review |
Unclear |
40 |
Freiherr et al., 201340. Freiherr J, Hallschmid M, Frey WH 2nd , et al. Intranasal insulin as a treatment for Alzheimer's disease: a review of basic research and clinical evidence. CNS Drugs. 2013;27(7):505-14. (Germany) |
Agents for treating diabetes mellitus |
Clinical evidence |
Narrative review |
Unclear |
41 |
Morris and Burns, 201241. Morris JK, Burns JM. Insulin: an emerging treatment for Alzheimer's disease dementia? Curr Neurol Neurosci Rep. 2012;12(5):520-7. (USA) |
Agents for treating diabetes mellitus |
Clinical evidence |
Narrative review |
Unclear |
42 |
Xu et al., 201542. Xu S, Liu G, Bao X, et al. Rosiglitazone prevents amyloid-β oligomer-induced impairment of synapse formation and plasticity via increasing dendrite and spine mitochondrial number. J Alzheimers Dis. 2014;39(2):239-51. (China) |
Agents for treating diabetes mellitus |
In vitro, in laboratory |
Experimental study |
High |
43 |
Papadopoulos et al., 201343. Papadopoulos P, Rosa-Neto P, Rochford J, Hamel E. Pioglitazone improves reversal learning and exerts mixed cerebrovascular effects in a mouse model of Alzheimer's disease with combined amyloid-β and cerebrovascular pathology. PloS One. 2013;8(7):e68612. (Canada) |
Agents for treating diabetes mellitus |
In vivo, in laboratory |
Experimental study |
High |
44 |
Fukasawa et al., 201244. Fukasawa H, Nakagomi M, Yamagata N, et al. Tamibarotene: a candidate retinoid drug for Alzheimer's disease. Biol Pharm Bull. 2012;35(8):1206-12. (Japan) |
Retinoids |
In vivo, in laboratory |
Experimental study |
High |
45 |
Wong et al., 201345. Wong WB, Lin VW, Boudreau D, Devine EB. Statins in the prevention of dementia and Alzheimer's disease: a meta-analysis of observational studies and an assessment of confounding. Pharmacoepidemiol Drug Saf. 2013;22(4):345-58. (USA) |
Statins: lipid-modifying agents |
Not specific |
Systematic review (randomized with meta-analysis) |
Unclear |
46 |
Calcul et al., 201246. Calcul L, Zhang B, Jinwal UK, Dickey CA, Baker BJ. Natural products as a rich source of tau-targeting drugs for Alzheimer's disease. Future Med Chem. 2012;4(13):1751-61. (USA) |
Polyphenols |
Clinical evidence |
Narrative review |
Unclear |
47 |
García-Osta et al., 201247. García-Osta A, Cuadrado-Tejedor M, García-Barroso C, Oyarzábal J, Franco R. Phosphodiesterases as therapeutic targets for Alzheimer's disease. ACS Chem Neurosci. 2012;3(11):832-44. (Spain) |
Phosphodiesterase inhibitors |
Clinical evidence |
Narrative review |
Unclear |
48 |
Evans et al., 201448. Evans DA, Morris MC, Rajan KB. Vitamin E, memantine, and Alzheimer disease. JAMA. 2014;311(1):29-30. (USA) |
Antioxidants; NMDA receptor antagonists |
Phase III clinical trial |
Randomized controlled clinical trial |
Low |
49 |
Revett et al., 201349. Revett TJ, Baker GB, Jhamandas J, Kar S. Glutamate system, amyloid β peptides and tau protein: functional interrelationships and relevance to Alzheimer disease pathology. J Psychiatry Neurosci. 2013;38(1):6-23. (Canada) |
Antioxidants; NMDA receptor antagonists |
Not specific |
Narrative review |
High |
50 |
Kellermann et al., 201150. Kellermann AJ, Kloft C. Is there a risk of bleeding associated with standardized Ginkgo biloba extract therapy? A systematic review and meta-analysis. Pharmacotherapy. 2011;31(5):490-502. (Germany) |
Antioxidants |
Phase III clinical trial |
Systematic review (randomized with meta-analysis) |
Low |
51 |
Freund Levi et al., 201451. Freund Levi Y, Vedin I, Cederholm T, et al. Transfer of omega-3 fatty acids across the blood-brain barrier after dietary supplementation with a docosahexaenoic acid-rich omega-3 fatty acid preparation in patients with Alzheimer's disease: the OmegAD study. J Intern Med. 2014;275(4):428-36. (USA) |
Antioxidants |
Phase II clinical trial |
Randomized controlled clinical trial |
Low |
52 |
Sun et al., 201252. Sun GY, He Y, Chuang DY, et al. Integrating cytosolic phospholipase A2 with oxidative/nitrosative signaling pathways in neurons: a novel therapeutic strategy for AD. Mol Neurobiol. 2012;46(1):85-95. (USA) |
Phospholipase A2 inhibitors |
Not specific |
Narrative review |
High |
53 |
Koliaki et al., 201253. Koliaki CC, Messini C, Tsolaki M. Clinical efficacy of aniracetam, either as monotherapy or combined with cholinesterase inhibitors, in patients with cognitive impairment: a comparative open study. CNS Neurosci Ther. 2012;18(4):302-12. (Greece) |
Nootropic drugs without elucidated mechanism of action for Alzheimer's disease |
Phase III clinical trial |
Randomized controlled clinical trial |
Low |
54 |
Maki and Henderson, 201254. Maki PM, Henderson VW. Hormone therapy, dementia, and cognition: the Women's Health Initiative 10 years on. Climacteric. 2012;15(3):256-62. (USA) |
Hormone therapy agents |
Randomized clinical trial |
Narrative review |
Low |
55 |
Anekonda and Quinn, 201155. Anekonda TS, Quinn JF. Calcium channel blocking as a therapeutic strategy for Alzheimer's disease: the case for isradipine. Biochim Biophys Acta. 2011;1812(12):1584-90. (Canada) |
Antihypertensive agents |
Clinical trials |
Narrative review |
Low |
56 |
Valenzuela et al., 201256. Valenzuela M, Esler M, Ritchie K, Brodaty H. Antihypertensives for combating dementia? A perspective on candidate molecular mechanisms and population-based prevention. Transl Psychiatry. 2012;2:e107. (Australia) |
Antihypertensive agents |
Randomized controlled clinical trial |
Narrative review |
Low |