Alzheimer's Disease - A Comprehensive Review
DOI:
https://doi.org/10.12775/JEHS.2024.56.013Keywords
Alzheimer's disease, Psychiatry, Dementia, NeurodegenerationAbstract
Introduction: Alzheimer's disease (AD) remains a pervasive and challenging neurodegenerative disorder with profound implications for individuals, families, and societies. As the most prevalent cause of dementia globally, AD's prevalence is set to rise significantly in the context of an aging population. This introductory section emphasizes the urgent need for a comprehensive understanding of the disease, encompassing both its molecular intricacies and the socio-economic burden. With age being the primary risk factor, recent research has delved into the complex interplay of genetic predisposition and environmental influences, reshaping our understanding of AD from a multifactorial perspective.
Current State of Knowledge: Advancements in Alzheimer's research have led to a nuanced understanding of its pathology. Traditionally characterized by amyloid-beta plaques and tau tangles, recent insights from neuroimaging and biomarker studies have revealed the intricate nature of these pathologies and their roles in disease progression. Genetic studies, including genome-wide association analyses, have identified susceptibility loci, notably the APOE gene. Simultaneously, environmental factors, such as air pollution and lifestyle choices, are recognized contributors to AD risk. The therapeutic landscape has evolved, with ongoing investigations into anti-amyloid and anti-tau therapies, lifestyle interventions, and precision medicine approaches. The synthesis of these diverse findings highlights the dynamic nature of Alzheimer's research and its potential to shape future treatment modalities.
Summary: In summary, this article provides a comprehensive overview of the current state of knowledge regarding Alzheimer's disease. From understanding its evolving pathology to exploring the interplay of genetic and environmental factors, the multifactorial nature of AD is underscored. The therapeutic landscape is actively advancing, presenting a hopeful outlook for future treatments.
References
2021 Alzheimer's disease facts and figures. Alzheimers Dement. 2021;17(3):327-406. doi:10.1002/alz.12328
Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement. 2013;9(1):63-75.e2. doi:10.1016/j.jalz.2012.11.007
Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):280-292. doi:10.1016/j.jalz.2011.03.003
Lambert JC, Ibrahim-Verbaas CA, Harold D, et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nat Genet. 2013;45(12):1452-1458. doi:10.1038/ng.2802
Long JM, Holtzman DM. Alzheimer Disease: An Update on Pathobiology and Treatment Strategies. Cell. 2019;179(2):312-339. doi:10.1016/j.cell.2019.09.001
Hardy JA, Higgins GA. Alzheimer's disease: the amyloid cascade hypothesis. Science. 1992;256(5054):184-185. doi:10.1126/science.1566067
Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol Med. 2016 Jun 1;8(6):595-608. doi: 10.15252/emmm.201606210.
Holtzman DM, Carrillo MC, Hendrix JA, et al. Tau: From research to clinical development. Alzheimers Dement. 2016;12(10):1033-1039. doi:10.1016/j.jalz.2016.03.018
Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K. Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci U S A. 1985;82(12):4245-4249. doi:10.1073/pnas.82.12.4245
Bertram L, Tanzi RE. The genetics of Alzheimer's disease. Prog Mol Biol Transl Sci. 2012;107:79-100. doi:10.1016/B978-0-12-385883-2.00008-4
Cacciottolo M, Wang X, Driscoll I, et al. Particulate air pollutants, APOE alleles and their contributions to cognitive impairment in older women and to amyloidogenesis in experimental models. Transl Psychiatry. 2017;7(1):e1022. Published 2017 Jan 31. doi:10.1038/tp.2016.280
Gorelick PB, Scuteri A, Black SE, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the american heart association/american stroke association. Stroke. 2011;42(9):2672-2713. doi:10.1161/STR.0b013e3182299496
Stern Y. Cognitive reserve in ageing and Alzheimer's disease. Lancet Neurol. 2012;11(11):1006-1012. doi:10.1016/S1474-4422(12)70191-6
Livingston G, Sommerlad A, Orgeta V, et al. Dementia prevention, intervention, and care. Lancet. 2017;390(10113):2673-2734. doi:10.1016/S0140-6736(17)31363-6
Fratiglioni L, Paillard-Borg S, Winblad B. An active and socially integrated lifestyle in late life might protect against dementia. Lancet Neurol. 2004;3(6):343-353. doi:10.1016/S1474-4422(04)00767-7
Dubois B, Feldman HH, Jacova C, et al. Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria [published correction appears in Lancet Neurol. 2014 Aug;13(8):757]. Lancet Neurol. 2014;13(6):614-629. doi:10.1016/S1474-4422(14)70090-0
Jack CR Jr, Bennett DA, Blennow K, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018;14(4):535-562. doi:10.1016/j.jalz.2018.02.018
Janelidze S, Mattsson N, Palmqvist S, et al. Plasma P-tau181 in Alzheimer's disease: relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer's dementia. Nat Med. 2020;26(3):379-386. doi:10.1038/s41591-020-0755-1
Perneczky R, Jessen F, Grimmer T, et al. Anti-amyloid antibody therapies in Alzheimer's disease. Brain. 2023;146(3):842-849. doi:10.1093/brain/awad005
Doody RS, Farlow M, Aisen PS; Alzheimer’s Disease Cooperative Study Data Analysis and Publication Committee. Phase 3 trials of solanezumab and bapineuzumab for Alzheimer's disease. N Engl J Med. 2014;370(15):1460. doi:10.1056/NEJMc1402193
Holtzman DM, Carrillo MC, Hendrix JA, et al. Tau: From research to clinical development. Alzheimers Dement. 2016;12(10):1033-1039. doi:10.1016/j.jalz.2016.03.018
Heneka MT, Carson MJ, El Khoury J, et al. Neuroinflammation in Alzheimer's disease. Lancet Neurol. 2015;14(4):388-405. doi:10.1016/S1474-4422(15)70016-5
Ngandu T, Lehtisalo J, Solomon A, et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015;385(9984):2255-2263. doi:10.1016/S0140-6736(15)60461-5
Honig LS, Vellas B, Woodward M, et al. Trial of Solanezumab for Mild Dementia Due to Alzheimer's Disease. N Engl J Med. 2018;378(4):321-330. doi:10.1056/NEJMoa1705971
Cummings J, Lee G, Ritter A, Sabbagh M, Zhong K. Alzheimer's disease drug development pipeline: 2020. Alzheimers Dement (N Y). 2020;6(1):e12050. Published 2020 Jul 16. doi:10.1002/trc2.12050
Hampel, H., O'Bryant, S. E., Durrleman, S., Younesi, E., et al. (2018). A precision medicine initiative for Alzheimer's disease: the road ahead to biomarker-guided integrative disease modeling. Climacteric, 21(5), 509-518.
Kunkle, B. W., Schmidt, M., Klein, H. U., Naj, A. C., Hamilton-Nelson, et al. (2019). Novel Alzheimer disease risk loci and pathways in African American individuals using the African Genome Resources panel: a meta-analysis. JAMA neurology, 76(4), 442-451.
Goldman, J. S., & Hahn, S. E. (2016). Clinical implementation of integrated genomic profiling in individuals with Alzheimer's and other neurodegenerative diseases. Molecular Case Studies, 2(6), a001297.
Birks J, Harvey RJ. Donepezil for dementia due to Alzheimer's disease. Cochrane Database Syst Rev. 2006;(1):CD001190. Published 2006 Jan 25. doi:10.1002/14651858.CD001190.pub2
Reisberg B, Doody R, Stöffler A, et al. Memantine in moderate-to-severe Alzheimer's disease. N Engl J Med. 2003;348(14):1333-1341. doi:10.1056/NEJMoa013128
Scheltens P, Blennow K, Breteler MM, et al. Alzheimer's disease. Lancet. 2016;388(10043):505-517. doi:10.1016/S0140-6736(15)01124-1
Gauthier S, Feldman HH, Schneider LS, et al. Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer's disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial. Lancet. 2016;388(10062):2873-2884. doi:10.1016/S0140-6736(16)31275-2
Aisen PS, Schafer KA, Grundman M, et al. Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA. 2003;289(21):2819-2826. doi:10.1001/jama.289.21.2819
Petersen RC, Thomas RG, Grundman M, et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med. 2005;352(23):2379-2388. doi:10.1056/NEJMoa050151
Sitzer DI, Twamley EW, Jeste DV. Cognitive training in Alzheimer's disease: a meta-analysis of the literature. Acta Psychiatr Scand. 2006;114(2):75-90. doi:10.1111/j.1600-0447.2006.00789.x
Lautenschlager NT, Cox KL, Flicker L, et al. Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial [published correction appears in JAMA. 2009 Jan 21;301(3):276]. JAMA. 2008;300(9):1027-1037. doi:10.1001/jama.300.9.1027
Eskelinen MH, Ngandu T, Helkala EL, et al. Fat intake at midlife and cognitive impairment later in life: a population-based CAIDE study. Int J Geriatr Psychiatry. 2008;23(7):741-747. doi:10.1002/gps.1969
Särkämö T, Tervaniemi M, Laitinen S, et al. Cognitive, emotional, and social benefits of regular musical activities in early dementia: randomized controlled study. Gerontologist. 2014;54(4):634-650. doi:10.1093/geront/gnt100
Gitlin LN, Winter L, Corcoran M, Dennis MP, Schinfeld S, Hauck WW. Effects of the home environmental skill-building program on the caregiver-care recipient dyad: 6-month outcomes from the Philadelphia REACH Initiative. Gerontologist. 2003;43(4):532-546. doi:10.1093/geront/43.4.532
Brodaty H, Donkin M. Family caregivers of people with dementia. Dialogues Clin Neurosci. 2009;11(2):217-228. doi:10.31887/DCNS.2009.11.2/hbrodaty
Cacabelos R. Pharmacogenomics in Alzheimer's disease. Methods Mol Biol. 2008;448:213-357. doi:10.1007/978-1-59745-205-2_10
Skowronek, A., Bojkowska-Otrębska, K., & Łabuz-Roszak, B. (2023). Public Knowledge about Dementia in Poland—A Survey Study. Journal of Clinical Medicine, 12(24), 7675. doi: 10.3390/jcm12247675.
Alorfi NM. Public Awareness of Alzheimer's Disease: A Cross-Sectional Study from Saudi Arabia. Int J Gen Med. 2022 Sep 28;15:7535-7546. doi: 10.2147/IJGM.S373447. PMID: 36199585; PMCID: PMC9527696.
Muglan J, Alkhaldi RM, Alsharif MM, Almuwallad SI, Alotaibi RS. Public Awareness, Knowledge, and Attitude Toward Alzheimer's Disease in Makkah, Saudi Arabia. Cureus. 2023 Nov 19;15(11):e49047. doi: 10.7759/cureus.49047. PMID: 38116357; PMCID: PMC10728572.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Kinga Woźniak, Monika Gardian-Baj, Magdalena Jung, Patryk Hedesz, Maximilian Jung, Aleksandra Żuk-Łapan, Aleksandra Doryń, Krystian Jędral, Aleksandra Włodarczyk, Alicja Szczerbiak, Justyna Popczyńska
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 736
Number of citations: 0
