Volume 3, Issue 1, June 2019, Page: 7-21
Review of Alzheimer’s Disease: Treatments and New Pharmacological Strategies
Ara Santos Pérez, Department of Pharmacy, Universidad Europea de Madrid, Madrid, Spain
Received: Apr. 26, 2019;       Accepted: May 23, 2019;       Published: Jun. 13, 2019
DOI: 10.11648/j.pst.20190301.12      View  43      Downloads  19
Abstract
Alzheimer's disease belongs to a group of pathologies called dementias, being this one the most common type. It is a neurodegenerative disease that causes a progressive and disabling impairment of cognitive functions, including memory, comprehension, language, attention, reasoning and judgment. Until now there is no cure, although there are treatments available that can improve the symptoms. In this paper we describe the disease, its classification and prognosis, as well as its physio pathological mechanism and the different diagnostic techniques currently being used. In addition, we perform an analysis of different therapies both pharmacological and non-pharmacological, focusing on conventional drugs marketed so far, making a comparison between them, as well as those strategies or therapeutic targets that are being researched, different phases of clinical trials which project different perspectives towards the future. For this, we carry out a bibliographic review of the most updated scientific literature, analyzing the most relevant information about this disease. Unfortunately, in the last years there have not been relevant bibliography or studies done. Finally, as a practical contribution to complement and conclude this study, we collect the dispensing data of several pharmacy offices, in order to approximate the data obtained through the bibliographic analysis with the treatments that are currently used in the Spanish population. The data found coincide with the daily practice at the pharmacy: the population gets older and the most used drug is Donepezil.
Keywords
Alzheimer’s Disease, Dementia, Pharmacological and Non-pharmacological Therapies, Dispensing Data
To cite this article
Ara Santos Pérez, Review of Alzheimer’s Disease: Treatments and New Pharmacological Strategies, Pharmaceutical Science and Technology. Vol. 3, No. 1, 2019, pp. 7-21. doi: 10.11648/j.pst.20190301.12
Copyright
Copyright © 2019 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Reference
[1]
Kumar A, Tsao JW, Sanidad MDE. Enfermedad de Alzheimer. StatPearls [Internet]. StatPearls Publishing; 2016 May 4 [cited 2018 May 24]; 1–416. Available from: http://cofsegovia.portalfarma.com/Documentos/Portada/108 - Alzheimer.pdf.
[2]
Sanidad MDE. Guía de práctica clínica sobre la atención integral a las personas con enfermedad de Alzheimer y otras demencias Guía de práctica clínica sobre la atención integral a las personas con enfermedad de Alzheimer y otras demencias. 2011. 1-416 p.
[3]
Kumar A, Tsao JW. Alzheimer Disease [Internet]. StatPearls. StatPearls Publishing; 2018 [cited 2018 May 24]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29763097.
[4]
Freire M. ENFERMEDADES DEL SISTEMA NERVIOSO A TRAVÉS DE LAS PREPARACIONES HISTOLÓGICAS Y DIBUJOS DE RAMÓN Y CAJAL. 2015.
[5]
Altuna-Azkargorta M, Mendioroz-Iriarte M. Biomarcadores sanguíneos en la enfermedad de Alzheimer. Neurología [Internet]. 2018 May [cited 2018 May 24]; Available from: http://linkinghub.elsevier.com/retrieve/pii/S0213485318300914.
[6]
Khan TK. An Algorithm for Preclinical Diagnosis of Alzheimer’s Disease. Front Neurosci [Internet]. Frontiers Media SA; 2018 [cited 2018 May 24]; 12: 275. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29760644.
[7]
Velazquez R, Ferreira E, Tran A, Turner EC, Belfiore R, Branca C, et al. Acute tau knockdown in the hippocampus of adult mice causes learning and memory deficits. Aging Cell [Internet]. Wiley/Blackwell (10.1111); 2018 May 10 [cited 2018 May 24]; e12775. Available from: http://doi.wiley.com/10.1111/acel.12775.
[8]
Quinn JP, Corbett NJ, Kellett KAB, Hooper NM. Tau Proteolysis in the Pathogenesis of Tauopathies: Neurotoxic Fragments and Novel Biomarkers. J Alzheimers Dis [Internet]. IOS Press; 2018 [cited 2018 May 24]; 63 (1): 13–33. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29630551.
[9]
Marsh J, Alifragis P. Synaptic dysfunction in Alzheimer’s disease: the effects of amyloid beta on synaptic vesicle dynamics as a novel target for therapeutic intervention. Neural Regen Res [Internet]. Medknow Publications and Media Pvt. Ltd.; 2018 Apr [cited 2018 May 24]; 13 (4): 616–23. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29722304.
[10]
Suidan GL, Singh PK, Patel-Hett S, Chen Z-L, Volfson D, Yamamoto-Imoto H, et al. Abnormal clotting of the intrinsic/contact pathway in Alzheimer disease patients is related to cognitive ability. Blood Adv [Internet]. 2018 May 8 [cited 2018 May 24]; 2 (9): 954–63. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29700007.
[11]
Baldeiras I, Santana I, Leitão MJ, Gens H, Pascoal R, Tábuas-Pereira M, et al. Addition of the Aβ42/40 ratio to the cerebrospinal fluid biomarker profile increases the predictive value for underlying Alzheimer’s disease dementia in mild cognitive impairment. Alzheimers Res Ther [Internet]. BioMed Central; 2018 Mar 20 [cited 2018 May 24]; 10 (1): 33. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29558986.
[12]
Shimizu S, Hirose D, Hatanaka H, Takenoshita N, Kaneko Y, Ogawa Y, et al. Role of Neuroimaging as a Biomarker for Neurodegenerative Diseases. Front Neurol [Internet]. Frontiers Media SA; 2018 [cited 2018 May 24]; 9: 265. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29720959.
[13]
Bateman RJ, Xiong C, Benzinger TLS, Fagan AM, Goate A, Fox NC, et al. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med [Internet]. NIH Public Access; 2012 Aug 30 [cited 2018 May 24]; 367 (9): 795–804. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22784036.
[14]
Taehan Sin’gyŏngkwa Hakhoe Y, 대한 신경과 학회 DL, Hahn S. Journal of the Korean Neurological Association. J Korean Neurol Assoc [Internet]. 1997 Apr 1 [cited 2018 May 24]; 15 (2): 300–8. Available from: https://www.koreamed.org/SearchBasic.php?RID=0031JKNA/1997.15.2.300&DT=1.
[15]
Prescott JW, Guidon A, Doraiswamy PM, Roy Choudhury K, Liu C, Petrella JR, et al. The Alzheimer structural connectome: changes in cortical network topology with increased amyloid plaque burden. Radiology [Internet]. Radiological Society of North America; 2014 Oct [cited 2018 May 24]; 273 (1): 175–84. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24865310.
[16]
Hommet C, Mondon K, Camus V, Ribeiro MJ, Beaufils E, Arlicot N, et al. Neuroinflammation and β amyloid deposition in Alzheimer’s disease: in vivo quantification with molecular imaging. Dement Geriatr Cogn Disord [Internet]. Karger Publishers; 2014 [cited 2018 May 24]; 37 (1–2): 1–18. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24107621.
[17]
Johnson KA, Sperling RA, Gidicsin CM, Carmasin JS, Maye JE, Coleman RE, et al. Florbetapir (F18-AV-45) PET to assess amyloid burden in Alzheimer’s disease dementia, mild cognitive impairment, and normal aging. Alzheimers Dement [Internet]. NIH Public Access; 2013 Oct [cited 2018 May 24]; 9 (5 Suppl): S72-83. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23375563.
[18]
Sohn D, Shpanskaya K, Lucas JE, Petrella JR, Saykin AJ, Tanzi RE, et al. Sex Differences in Cognitive Decline in Subjects with High Likelihood of Mild Cognitive Impairment due to Alzheimer’s disease. Sci Rep [Internet]. Nature Publishing Group; 2018 May 10 [cited 2018 May 24]; 8 (1): 7490. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29748598.
[19]
Mosca A, Sperduti S, Pop V, Ciavardelli D, Granzotto A, Punzi M, et al. Influence of APOE and RNF219 on Behavioral and Cognitive Features of Female Patients Affected by Mild Cognitive Impairment or Alzheimer’s Disease. Front Aging Neurosci [Internet]. Frontiers Media SA; 2018 [cited 2018 May 24]; 10: 92. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29755337.
[20]
Zhong G, Wang Y, Zhang Y, Guo JJ, Zhao Y. Smoking is associated with an increased risk of dementia: a meta-analysis of prospective cohort studies with investigation of potential effect modifiers. PLoS One [Internet]. Public Library of Science; 2015 [cited 2018 May 24]; 10 (3): e0118333. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25763939.
[21]
Iadecola C, Yaffe K, Biller J, Bratzke LC, Faraci FM, Gorelick PB, et al. Impact of Hypertension on Cognitive Function: A Scientific Statement From the American Heart Association. Hypertens (Dallas, Tex 1979) [Internet]. NIH Public Access; 2016 [cited 2018 May 24]; 68 (6): e67–94. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27977393.
[22]
Blake DT, Terry A V, Plagenhoef M, Constantinidis C, Liu R. Potential for intermittent stimulation of nucleus basalis of Meynert to impact treatment of alzheimer’s disease. Commun Integr Biol [Internet]. Taylor & Francis; 2017 [cited 2018 May 24]; 10 (5–6): e1389359. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29260798.
[23]
Tratamiento NO Farmacológico - Fundación Azheimer España [Internet]. [cited 2018 May 24]. Available from: http://www.alzfae.org/fundacion/150/tratamiento-no-farmacologico.
[24]
Fernandez E, Bergado Rosado JA, Rodriguez Perez D, Salazar Santana S, Torres Aguilar M, Bringas ML. Effectiveness of a Computer-Based Training Program of Attention and Memory in Patients with Acquired Brain Damage. Behav Sci (Basel, Switzerland) [Internet]. Multidisciplinary Digital Publishing Institute (MDPI); 2017 Dec 30 [cited 2018 May 24]; 8 (1). Available from: http://www.ncbi.nlm.nih.gov/pubmed/29301194.
[25]
Tárraga L, Boada M, Modinos G, Espinosa A, Diego S, Morera A, et al. A randomised pilot study to assess the efficacy of an interactive, multimedia tool of cognitive stimulation in Alzheimer’s disease. J Neurol Neurosurg Psychiatry [Internet]. BMJ Publishing Group; 2006 Oct [cited 2018 May 24]; 77 (10): 1116–21. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16820420.
[26]
Groot C, Hooghiemstra AM, Raijmakers PGHM, van Berckel BNM, Scheltens P, Scherder EJA, et al. The effect of physical activity on cognitive function in patients with dementia: A meta-analysis of randomized control trials. Ageing Res Rev [Internet]. Elsevier; 2016 Jan 1 [cited 2018 May 24]; 25: 13–23. Available from: https://www.sciencedirect.com/science/article/pii/S1568163715300349?via%3Dihub.
[27]
Tratamiento farmacológico actual de la enfermedad de Alzheimer | kNOWAlzheimer [Internet]. [cited 2018 May 24]. Available from: https://knowalzheimer.com/profesionales/tratamiento-farmacologico-actual-de-la-enfermedad-de-alzheimer/.
[28]
Ministerio de Sanidad SS e IAE de M y PS. Donepezilo - Ficha técnica [Internet]. 2016. p. 1–9. Available from: https://www.aemps.gob.es/cima/pdfs/es/ft/75250/75250_ft.pd.
[29]
Ministerio de Sanidad SS e IAE de M y PS. Ficha técnica: Rivatigmina Kern Pharma [Internet]. 2016. p. 1–16. Available from: https://www.aemps.gob.es/cima/pdfs/es/ft/77243/77243_ft.pdf.
[30]
Ministerio de Sanidad SS e IAE de M y PS. Ficha técnica de Reminyl (galantamina) [Internet]. Ministerio de Sanidad, Política Social e Igualdad. 2013. p. 1–14. Available from: https://www.aemps.gob.es/cima/pdfs/es/ft/66652/FT_66652.pdf.
[31]
Ministerio de Sanidad SS e IAE de M y PS. Ficha técnica: Memantina Alter [Internet]. 2016. p. 1–8. Available from: https://www.aemps.gob.es/cima/pdfs/es/ft/77746/77746_ft.pdf.
[32]
Knight R, Khondoker M, Magill N, Stewart R, Landau S. A Systematic Review and Meta-Analysis of the Effectiveness of Acetylcholinesterase Inhibitors and Memantine in Treating the Cognitive Symptoms of Dementia. Dement Geriatr Cogn Disord [Internet]. Karger Publishers; 2018 May 7 [cited 2018 May 24]; 45 (3–4): 131–51. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29734182.
[33]
Mezeiova E, Korabecny J, Sepsova V, Hrabinova M, Jost P, Muckova L, et al. Development of 2-Methoxyhuprine as Novel Lead for Alzheimer’s Disease Therapy. Molecules [Internet]. Multidisciplinary Digital Publishing Institute; 2017 Jul 28 [cited 2018 May 24]; 22 (8): 1265. Available from: http://www.mdpi.com/1420-3049/22/8/1265.
[34]
Ma Y, Ji J, Li G, Yang S, Pan S. Effects of donepezil on cognitive functions and the expression level of β-amyloid in peripheral blood of patients with Alzheimer’s disease. Exp Ther Med [Internet]. Spandidos Publications; 2018 Feb [cited 2018 May 24]; 15 (2): 1875–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29434777.
[35]
Furiya Y, Tomiyama T, Izumi T, Ohba N, Ueno S. Rivastigmine Improves Appetite by Increasing the Plasma Acyl/Des-Acyl Ghrelin Ratio and Cortisol in Alzheimer Disease. Dement Geriatr Cogn Dis Extra [Internet]. Karger Publishers; 2018 [cited 2018 May 24]; 8 (1): 77–84. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29706984.
[36]
Meng Q, Wang A, Hua H, Jiang Y, Wang Y, Mu H, et al. Intranasal delivery of Huperzine A to the brain using lactoferrin-conjugated N-trimethylated chitosan surface-modified PLGA nanoparticles for treatment of Alzheimer’s disease. Int J Nanomedicine [Internet]. Dove Press; 2018 [cited 2018 May 24]; 13: 705–18. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29440896.
[37]
Tao L-X, Huang X-T, Chen Y-T, Tang X-C, Zhang H-Y. Acetylcholinesterase-independent protective effects of huperzine A against iron overload-induced oxidative damage and aberrant iron metabolism signaling in rat cortical neurons. Acta Pharmacol Sin [Internet]. Nature Publishing Group; 2016 Nov [cited 2018 May 24]; 37 (11): 1391–400. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27498774.
[38]
Korabecny J, Andrs M, Nepovimova E, Dolezal R, Babkova K, Horova A, et al. 7-Methoxytacrine-p-Anisidine Hybrids as Novel Dual Binding Site Acetylcholinesterase Inhibitors for Alzheimer’s Disease Treatment. Molecules [Internet]. Multidisciplinary Digital Publishing Institute; 2015 Dec 10 [cited 2018 May 24]; 20 (12): 22084–101. Available from: http://www.mdpi.com/1420-3049/20/12/19836.
[39]
Gazova Z, Soukup O, Sepsova V, Siposova K, Drtinova L, Jost P, et al. Multi-target-directed therapeutic potential of 7-methoxytacrine-adamantylamine heterodimers in the Alzheimer’s disease treatment. Biochim Biophys Acta - Mol Basis Dis [Internet]. Elsevier; 2017 Feb 1 [cited 2018 May 24]; 1863 (2): 607–19. Available from: https://www.sciencedirect.com/science/article/pii/S0925443916303027?via%3Dihub.
[40]
Misik J, Korabecny J, Nepovimova E, Cabelova P, Kassa J. The effects of novel 7-MEOTA-donepezil like hybrids and N-alkylated tacrine analogues in the treatment of quinuclidinyl benzilate-induced behavioural deficits in rats performing the multiple T-maze test. Biomed Pap [Internet]. Biomedical Papers; 2015 Feb 10 [cited 2018 May 24]; 159 (4): 547–53. Available from: http://biomed.papers.upol.cz/doi/10.5507/bp.2015.006.html.
[41]
Akilo OD, Kumar P, Choonara YE, Pradeep P, du Toit LC, Pillay V. Hypothesis: apo-lactoferrin-Galantamine Proteo-alkaloid Conjugate for Alzheimer’s disease Intervention. J Cell Mol Med [Internet]. Wiley-Blackwell; 2018 Mar [cited 2018 May 24]; 22 (3): 1957–63. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29377514.
[42]
Wisniewski T, Drummond E. Developing therapeutic vaccines against Alzheimer’s disease. Expert Rev Vaccines [Internet]. NIH Public Access; 2016 [cited 2018 May 24]; 15 (3): 401–15. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26577574.
[43]
Heiner F, Feistel B, Wink M. Sideritis scardica extracts inhibit aggregation and toxicity of amyloid-β in Caenorhabditis elegans used as a model for Alzheimer’s disease. PeerJ [Internet]. PeerJ, Inc; 2018 [cited 2018 May 24]; 6: e4683. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29736334.
[44]
Zhou J, Peng W, Xu M, Li W, Liu Z. The effectiveness and safety of acupuncture for patients with Alzheimer disease: a systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore) [Internet]. Wolters Kluwer Health; 2015 Jun [cited 2018 May 24]; 94 (22): e933. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26039131.
[45]
Gardener S, Gu Y, Rainey-Smith SR, Keogh JB, Clifton PM, Mathieson SL, et al. Adherence to a Mediterranean diet and Alzheimer’s disease risk in an Australian population. Transl Psychiatry [Internet]. Nature Publishing Group; 2012 Oct 2 [cited 2018 May 24]; 2 (10): e164. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23032941.
[46]
Shen L, Ji H-F. Vitamin D deficiency is associated with increased risk of Alzheimer’s disease and dementia: evidence from meta-analysis. Nutr J [Internet]. BioMed Central; 2015 Aug 1 [cited 2018 May 24]; 14: 76. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26231781.
[47]
Basurto-Islas G, Blanchard J, Tung YC, Fernandez JR, Voronkov M, Stock M, et al. Therapeutic benefits of a component of coffee in a rat model of Alzheimer’s disease. Neurobiol Aging [Internet]. NIH Public Access; 2014 Dec [cited 2018 May 24]; 35 (12): 2701–12. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25034344.
[48]
Kwok MK, Leung GM, Schooling CM. Habitual coffee consumption and risk of type 2 diabetes, ischemic heart disease, depression and Alzheimer’s disease: a Mendelian randomization study. Sci Rep [Internet]. Nature Publishing Group; 2016 [cited 2018 May 24]; 6: 36500. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27845333.
[49]
Taqi MM, Bazov I, Watanabe H, Sheedy D, Harper C, Alkass K, et al. Prodynorphin CpG-SNPs associated with alcohol dependence: elevated methylation in the brain of human alcoholics. Addict Biol [Internet]. NIH Public Access; 2011 Jul [cited 2018 May 24]; 16 (3): 499–509. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21521424.
[50]
Kell DB. Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases. BMC Med Genomics [Internet]. BioMed Central; 2009 Jan 8 [cited 2018 May 24]; 2: 2. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19133145.
[51]
Greenan C, Murphy L, Yu L-M, Kehoe PG, Coulthard E, Bath P, et al. A randomised controlled trial of calcium channel blockade (CCB) with Amlodipine For the treatment oF subcortical ischaEmic vasCular demenTia (AFFECT): study protocol. Trials [Internet]. BioMed Central; 2016 [cited 2018 May 24]; 17 (1): 324. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27430267.
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