Alzheimer’s Disease: A Critical Review

Alzheimer’s Disease: A Critical Review

Abstract

Alzheimer’s illness is a neurological disorder that results in the loss of the cells of the brain and causes loss of memory as wells as the cognitive decline. The disease is classified as the principal cause of dementia, which accounts for 60 to 80 per hundred of death in the US[1]. In the year 2013, it was reported that over 6.8 million individuals in the US alone had been established to be suffering from dementia. Out of these, over 5 million have diagnosed with Alzheimer’s disease. This number is expected to double by 2015 if nothing much is done to prevent it. Its symptoms at the initial stage are always minded but get severe with time and are hard to detect at the first preventable stage[2].  The result of the study indicates the Alzheimer’s disease is not much related to any genetical history but rather other physical and psychological condition which could have affected the victim or the patient in the past. The study, however, finds out the clinical implication of this disease is often associated with the loss of memory. This can adversely impact an individual’s way of life and even death[3].  This report discusses the signs and symptoms, causes of the disorders a, diagnosis and management of the disease

Keywords: Alzheimer’s, dementia, neurological, cognitive and symbols, cognitive disease

                                                Introduction

Alzheimer’s illness is a permanent, advanced condition of the brain that gradually abolish the element of intellectual skills and memory, and finally, the ability of a person to undertake small responsibilities[4]. In most individuals with the condition, signs do seem first in their mid-60s. As such, as the real estimate does vary, most scientists recommend that over 5 million US citizens. It is common those above the age of 65 maybe be experiencing dementia as a result of Alzheimer’s sickness[5]. The diseases are currently ranked as the number six leading cause of Americans’ death, but new approximations show that the disorder may be the third just after the heart diseases and tumor as a foundation of demise for the elderly. Alzheimer’s is the maximum recognized case of the loss of memory condition amid elder[6]. Dementia, on the other hand, is the loss of intellectual operational, smart reasoning, remembers, and reasoning abilities. This interferes typically with an individual’s behavioral skills and an individual’s regular life and events[7]

                                                         Methods

The methodology of the study involves the analysis of the other sources which have been written on Alzheimer’s diseases[8]. It consists of the review of secondary sources on the information concerning the Alzheimer’s. The data from the different articles and healthcare journals will be coordinated to develop a proper understanding of these diseases, including the signs and symptoms, the clinical implication, pathophysiology, biochemistry, genetics, and the scientific analysis of Alzheimer’s diseases. However, the gap which exists in the study will be identified.

                                                             Results

From the research conducted on Alzheimer’s illness, I was able to develop a comprehensive indulgent of the condition. The result from the review of the healthcare journals and article does reveal that   Alzheimer’s diseases in the primary cause of Dementia, especially among elderly persons[9]. Researches have indicated that early detection of the disease is possible, but more studies are however required before these techniques can be used on a routine diagnosis of Alzheimer’s disease in everyday medical practices[10]. Neurosurgeons do not yet fully comprehend the actual cause of the illnesses in most individuals[11]. However, it is suggested that persons with early beginning Alzheimer’s hereditary kind of mutation might be the causes. Late-onset of the same conditions is through o be arising from a complex series of changes in the brain that has occurred from decades[12]. The actual cause problem may include a mixture of both inherited, environmentally related, and life aspects.

Discussion

                       Pathophysiology of Alzheimer’s Disease.

Neurosurgeons are continuing to undo the compound brain alterations that are coupled on the onset and the progression of this disorder. For individuals who have Alzheimer’s diseases, it usually appears that changes in the reason may commence either ten years.  in some it is more before the onset of memory loss and other related mental hitches that may arise[13]. During the preclinical stage of the disease, patients appear to be free from the symptoms. Still, other toxic changes do occur in the parts of the brain at this time[14]. It is unusual despite various toxic proteins forms amyloid plaques and the tau tangles in the entire brain. Once a health neuron stops being an operational, loose connection with other neurons, and at this point, dies. Many other complex changes do take place in the brain at this time[15].

Most of the damages initially appear to occur in the hippocampus and the entorhinal cortex, which is the part of the brain, which is critical in the formation of the much-needed retentions[16]. As new neurons tend to die, the other portions of the mind are at this point exaggerated and started shrinking. Towards the latter era of the illness, the damages in the brain are widespread, and the tissue of the brain does get fully shrink.

Biochemistry of Alzheimer’s Disease

Loss of memory is the first most sign of the conditions. This cognitive impairment connects to Alzheimer’s disease does occur almost at the same time when the patient is seen to be having a problem with other elements of the behavior. Most individuals with loss of memory do have a disorder termed as slight reasoning damage MCI. However, in MCI, persons tend to have additional recall difficulties than ordinary for their age. However, this problem does not always interfere with the element of daily life. Movement’s issues and problems with the sense of scent have also been associated with MCI. Older individuals with MCI are at more critical risk of emergent Alzheimer’s disorder[17].

Genetics of the Disease

Scientists have not established a precise genetic factor that straight bases the late-onset procedure of the sickness[18]. Though, one hereditary risk factor having a single process of the apolipoprotein E (APOE) gene proceeding DNA 19 does development an individual’s risk.  Having supplementary APOE ε4 alleles increases the risk of emerging Alzheimer’s[19]. A family‘s past of Alzheimer’s is not essential for a person to have the condition. However, study demonstrations that persons who have a parental or familial with Alzheimer’s are more probable to suffer the state compared who do not have a first-degree relation with a disease of Alzheimer’s. Persons who have got more than a single first-degree family member with Alzheimer’s are at even advanced risk. When sicknesses have a habit of running in families, also inheritance (genetics) and ecofriendly issues or both may be a contributing factor[20].

The significance of any of the listed factors in either cumulative or reducing the risk of emerging the condition may vary from an individual to another. The scientist is, in this way conducting more studies aimed at learning more about plaques, tangles, and other biological features if the disease. Developments in the brain imaging procedures do permit scientists to be able to see the growth and extension of the unusual amyloid and tau proteins in the brain and changes in the organization of the brain and its purpose[21].

4d.    Scientific Analysis of Alzheimer Disease

Neurosurgeons today are studying numerous means and gears to help in the determination of whether an individual is suffering memory problems, which might be related to thinkable Alzheimer’s dementia or feasible Alzheimer’s[22]. In doing so, they may;

• As the individuals and a member of the patient’s family or acquaintance inquiries about the general well-being of the person, use treatment and over the pawn medical, diet and other previous medical difficulties, the individual capacity to undertaking day-to-day duties and change in conduct or any character change
• Do a test of memory, the ability to solve problems, and language issues.
• Do scans of the brain such as figured tomography and attractive resonance imaging MRI to rule out of the symptoms.

 The Clinical Implication of Alzheimer’s Disease

Alzheimer’s disease is a rare highest significant complex illness, and it is unlike that somewhat one medication or mediation can effectively treat it. Presently, methods emphasis on serving in the maintenance of psychological purposes, achieve common symptoms, and deliberate end confident difficulties related to losses of memory. Neurosurgeons hope to come up with critical treatments that target precise hereditary and molecular devices so that the definite original cause of the condition be stopped[23].

 Unanswered Questions

Despite the extensive study that has been conducted on the various elements of Alzheimer’s disorder of the brain, there remain multiple forms of mysteries that still surround the understanding of the condition[24].  The lading mystery about the situation is based on the question, what will be a safe and effective method of treatment of this disease. Besides, the item of why are clinical trials of some highly promising drugs did fail to show positive results on the treatment of Alzheimer’s diseases[25].

                                                   Conclusion

Today, Alzheimer’s diseases are at the forefront of biomedical research[26]. Researchers are working on means of uncovering as many aspects of the disorders, and other dementias are possible to help come up with an improved understanding of the illness, which will be critical to the diagnose and treatment of the disease[27]. With much to knowledge still missing, the conditions continue to be one of the most dangerous, especially among the old adults in the USA[28]. Most of the disorder has been found out to be more prevalence to elder people[29]. Studies reveal most people above the age of 60 are the most affected[30].

Author: Dennis Adjepong, MD, MBA

Email address: Dennisadjepong@gmail.com

Efax: 1-804-409-409-1695

Mentor : Dr. Bilal Haider Malik

Email Address: Cardibilal88@gmail.com

References

1. Alzheimer’s A. 2015 Alzheimer’s disease, facts and figures. Alzheimer’s & dementia: the journal of the Alzheimer’s Association. 2015 Mar;11(3):332.
2. Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E, Cruchaga C, Sassi C, Kauwe JS, Younkin S, Hazrati L. TREM2 variants in Alzheimer’s disease. New England Journal of Medicine. 2013 Jan 10;368(2):117-27.
3. Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, Jacobs AH, Wyss-Coray T, Vitoria J, Ransohoff RM, Herrup K. Neuroinflammation in Alzheimer’s disease. The Lancet Neurology. 2015 Apr 1;14(4):388-405.
4. Birks JS, Evans JG. Rivastigmine for Alzheimer’s disease. Cochrane Database of Systematic Reviews. 2015(4).
5. Jonsson T, Stefansson H, Steinberg S, Jonsdottir I, Jonsson PV, Snaedal J, Bjornsson S, Huttenlocher J, Levey AI, Lah JJ, Rujescu D. Variant of TREM2 associated with the risk of Alzheimer’s disease. New England Journal of Medicine. 2013 Jan 10;368(2):107-16.
6. Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO molecular medicine. 2016 Jun 1;8(6):595-608.
7. Doody RS, Thomas RG, Farlow M, Iwatsubo T, Vellas B, Joffe S, Kieburtz K, Raman R, Sun X, Aisen PS, Siemers E. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease. New England Journal of Medicine. 2014 Jan 23;370(4):311-21.
8. Jack Jr CR, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, Shaw LM, Vemuri P, Wiste HJ, Weigand SD, Lesnick TG. Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. The Lancet Neurology. 2013 Feb 1;12(2):207-16.
9. Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, DeKosky ST, Gauthier S, Selkoe D, Bateman R, Cappa S. Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. The Lancet Neurology. 2014 Jun 1;13(6):614-29.
10. Lambert JC, Ibrahim-Verbaas CA, Harold D, Naj AC, Sims R, Bellenguez C, Jun G, DeStefano AL, Bis JC, Beecham GW, Grenier-Boley B. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nature genetics. 2013 Dec;45(12):1452.
11. Salloway S, Sperling R, Fox NC, Blennow K, Klunk W, Raskind M, Sabbagh M, Honig LS, Porsteinsson AP, Ferris S, Reichert M. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. New England Journal of Medicine. 2014 Jan 23;370(4):322-33.
12. Alzheimer’s Association. 2016 Alzheimer’s disease facts and figures. Alzheimer’s & Dementia. 2016 Apr 1;12(4):459-509.
13. Norton S, Matthews FE, Barnes DE, Yaffe K, Brayne C. Potential for primary prevention of Alzheimer’s disease: an analysis of population-based data. The Lancet Neurology. 2014 Aug 1;13(8):788-94.
14. Sevigny J, Chiao P, Bussière T, Weinreb PH, Williams L, Maier M, Dunstan R, Salloway S, Chen T, Ling Y, O’Gorman J. The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. Nature. 2016 Sep;537(7618):50.
15. Bettens K, Sleegers K, Van Broeckhoven C. Genetic insights into Alzheimer’s disease. The Lancet Neurology. 2013 Jan 1;12(1):92-104.
16. Birks JS, Harvey RJ. Donepezil for dementia due to Alzheimer’s disease. Cochrane Database of systematic reviews. 2018(6).
17. Kumar A, Singh A. A review on Alzheimer’s disease pathophysiology and its management: an update. Pharmacological reports. 2015 Apr 1;67(2):195-203.
18. Alzheimer’s Association. 2014 Alzheimer’s disease facts and figures. Alzheimer’s & Dementia. 2014 Mar 1;10(2):e47-92.
19. Doody RS, Raman R, Farlow M, Iwatsubo T, Vellas B, Joffe S, Kieburtz K, He F, Sun X, Thomas RG, Aisen PS. A phase 3 trial of semagacestat for treatment of Alzheimer’s disease. New England Journal of Medicine. 2013 Jul 25;369(4):341-50.
20. Jack Jr CR, Holtzman DM. Biomarker modeling of Alzheimer’s disease. Neuron. 2013 Dec 18;80(6):1347-58.
21. Blennow K, Mattsson N, Schöll M, Hansson O, Zetterberg H. Amyloid biomarkers in Alzheimer’s disease. Trends in pharmacological sciences. 2015 May 1;36(5):297-309.
22. Jessen F, Amariglio RE, Van Boxtel M, Breteler M, Ceccaldi M, Chételat G, Dubois B, Dufouil C, Ellis KA, Van Der Flier WM, Glodzik L. A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer’s disease. Alzheimer’s & Dementia. 2014 Nov 1;10(6):844-52.
23. Yan R, Vassar R. Targeting the β secretase BACE1 for Alzheimer’s disease therapy. The Lancet Neurology. 2014 Mar 1;13(3):319-29.
24. Jack Jr CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, Liu E. NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimer’s & Dementia. 2018 Apr 1;14(4):535-62.
25. Jack Jr CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, Liu E. NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimer’s & Dementia. 2018 Apr 1;14(4):535-62.
26. Heneka MT, Kummer MP, Stutz A, Delekate A, Schwartz S, Vieira-Saecker A, Griep A, Axt D, Remus A, Tzeng TC, Gelpi E. NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice. Nature. 2013 Jan;493(7434):674.
27. Lukiw W. Circular RNA (circRNA) in Alzheimer’s disease (AD). Frontiers in genetics. 2013 Dec 31;4:307.
28. De Strooper B, Karran E. The cellular phase of Alzheimer’s disease. Cell. 2016 Feb 11;164(4):603-15.
29. Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, Szoeke C, Macaulay SL, Martins R, Maruff P, Ames D. Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. The Lancet Neurology. 2013 Apr 1;12(4):357-67.
30. Alzheimer’s Association. 2017 Alzheimer’s disease facts and figures. Alzheimer’s & Dementia. 2017 Apr 1;13(4):325-73.

[1] Alzheimer’s A. 2015 Alzheimer’s disease facts and figures. Alzheimer’s & dementia: the journal of the Alzheimer’s Association. 2015 Mar;11(3):332.

[2] Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E, Cruchaga C, Sassi C, Kauwe JS, Younkin S, Hazrati L. TREM2 variants in Alzheimer’s disease. New England Journal of Medicine. 2013 Jan 10;368(2):117-27.

[3] Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, Jacobs AH, Wyss-Coray T, Vitorica J, Ransohoff RM, Herrup K. Neuroinflammation in Alzheimer’s disease. The Lancet Neurology. 2015 Apr 1;14(4):388-405.

[4], Birks JS, Evans JG. Rivastigmine for Alzheimer’s disease. Cochrane Database of Systematic Reviews.2015(4).

[5] Jonsson T, Stefansson H, Steinberg S, Jonsdottir I, Jonsson PV, Snaedal J, Bjornsson S, Huttenlocher J, Levey AI, Lah JJ, Rujescu D. Variant of TREM2 associated with the risk of Alzheimer’s disease. New England Journal of Medicine. 2013 Jan 10;368(2):107-16.

[6] Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO molecular medicine. 2016 Jun 1;8(6):595-608.

[7]. Doody RS, Thomas RG, Farlow M, Iwatsubo T, Vellas B, Joffe S, Kieburtz K, Raman R, Sun X, Aisen PS, Siemers E. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease. New England Journal of Medicine. 2014 Jan 23;370(4):311-21.

[8] Jack Jr CR, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, Shaw LM, Vemuri P, Wiste HJ, Weigand SD, Lesnick TG. Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. The Lancet Neurology. 2013 Feb 1;12(2):207-16.

[9] Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, DeKosky ST, Gauthier S, Selkoe D, Bateman R, Cappa S. Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. The Lancet Neurology. 2014 Jun 1;13(6):614-29.

[10] Lambert JC, Ibrahim-Verbaas CA, Harold D, Naj AC, Sims R, Bellenguez C, Jun G, DeStefano AL, Bis JC, Beecham GW, Grenier-Boley B. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nature genetics. 2013 Dec;45(12):1452.

[11] Salloway S, Sperling R, Fox NC, Blennow K, Klunk W, Raskind M, Sabbagh M, Honig LS, Porsteinsson AP, Ferris S, Reichert M. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. New England Journal of Medicine. 2014 Jan 23;370(4):322-33.

[12] of Alzheimer’s Association. 2016 Alzheimer’s disease facts and figures. Alzheimer’s & Dementia. 2016 Apr 1;12(4):459-509.

[13] Norton S, Matthews FE, Barnes DE, Yaffe K, Brayne C. Potential for primary prevention of Alzheimer’s disease: an analysis of population-based data. The Lancet Neurology. 2014 Aug 1;13(8):788-94.

[14] Sevigny J, Chiao P, Bussière T, Weinreb PH, Williams L, Maier M, Dunstan R, Salloway S, Chen T, Ling Y, O’Gorman J. The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. Nature. 2016 Sep;537(7618):50.

[15] Bettens K, Sleegers K, Van Broeckhoven C. Genetic insights in Alzheimer’s disease. The Lancet Neurology. 2013 Jan 1;12(1):92-104.

[16] Birks JS, Harvey RJ. Donepezil for dementia due to Alzheimer’s disease. Cochrane Database of systematic reviews. 2018(6).

[17]. Kumar A, Singh A. A review on Alzheimer’s disease pathophysiology and its management: an update. Pharmacological reports. 2015 Apr 1;67(2):195-203.

[18] Alzheimer’s Association. 2014 Alzheimer’s disease facts and figures. Alzheimer’s & Dementia. 2014 Mar 1;10(2):e47-92.

[19] Doody RS, Raman R, Farlow M, Iwatsubo T, Vellas B, Joffe S, Kieburtz K, He F, Sun X, Thomas RG, Aisen PS. A phase 3 trial of semagacestat for treatment of Alzheimer’s disease. New England Journal of Medicine. 2013 Jul 25;369(4):341-50.

[20] to Jack Jr CR, Holtzman DM. Biomarker modeling of Alzheimer’s disease. Neuron. 2013 Dec 18;80(6):1347-58.

[21] Blennow K, Mattsson N, Schöll M, Hansson O, Zetterberg H. Amyloid biomarkers in Alzheimer’s disease. Trends in pharmacological sciences. 2015 May 1;36(5):297-309.

[22] Jessen F, Amariglio RE, Van Boxtel M, Breteler M, Ceccaldi M, Chételat G, Dubois B, Dufouil C, Ellis KA, Van Der Flier WM, Glodzik L. A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer’s disease. Alzheimer’s & Dementia. 2014 Nov 1;10(6):844-52.

[23] Yan R, Vassar R. Targeting the β secretase BACE1 for Alzheimer’s disease therapy. The Lancet Neurology. 2014 Mar 1;13(3):319-29.

[24] Jack Jr CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, Liu E. NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimer’s & Dementia. 2018 Apr 1;14(4):535-62.

[25] Jack Jr CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, Liu E. NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimer’s & Dementia. 2018 Apr 1;14(4):535-62.

[26] Heneka MT, Kummer MP, Stutz A, Delekate A., Schwartz S, Vieira-Saecker A, Griep A, Axt D, Remus A, Tzeng TC, Gelpi E. NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice. Nature. 2013 Jan;493(7434):674.

[27] Lukiw W. Circular RNA (circRNA) in Alzheimer’s disease (AD). Frontiers in genetics. 2013 Dec 31;4:307.

[28] De Strooper B, Karran E. The cellular phase of Alzheimer’s disease. Cell. 2016 Feb 11;164(4):603-15.

[29] Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, Szoeke C, Macaulay SL, Martins R, Maruff P, Ames D. Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. The Lancet Neurology. 2013 Apr 1;12(4):357-67.

[30] Alzheimer’s Association. 2017 Alzheimer’s disease facts and figures. Alzheimer’s & Dementia. 2017 Apr 1;13(4):325-73.