Saeid Safiri ^1,2* Amir Ghaffari ³ Asra Fazlollahi ² Soroush Morsali ² Aila Sarkesh ² Amin Daei Sorkhabi ² Behnam Golabi ² Reza Aletaha ¹ Kimia Motlagh Asghari ⁴ Sana Hamidi ¹ Seyed Ehsan Mousavi ¹ Sepehr Jamalkhani ⁵ Nahid Karamzad ^6,7 Ali Shamekh ¹ Reza Mohammadinasab ⁸ Mark J M Sullman ^10,9 Fikrettin Şahin ¹¹ Ali-Asghar Kolahi ^12*

• ¹ Neurosciences Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
• ² Social Determinants of Health Research Center, Department of Community Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
• ³ Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
• ⁴ Research Center for Integrative Medicine in Aging, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
• ⁵ Aalborg University, Aalborg, Denmark
• ⁶ Department of Persian Medicine, School of Traditional Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
• ⁷ Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
• ⁸ Department of History of Medicine, School of Traditional Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
• ⁹ Department of Life and Health Sciences, University of Nicosia, Nicosia, Cyprus
• ¹⁰ Department of Social Sciences, University of Nicosia, Nicosia, Cyprus
• ¹¹ Faculty of Engineering, Department of Genetics and Bioengineering, Yeditepe University, Istanbul, Türkiye
• ¹² Social Determinants of Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Alborz, Iran

Background: Alzheimer's disease (AD) is a chronic, progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and impaired reasoning. It is the leading cause of dementia in older adults, marked by the pathological accumulation of amyloid-beta plaques and neurofibrillary tangles. These pathological changes lead to widespread neuronal damage, significantly impacting daily functioning and quality of life. Objective: This comprehensive review aims to explore various aspects of Alzheimer's disease, including its epidemiology, risk factors, clinical presentation, diagnostic advancements, management strategies, caregiving challenges, and emerging therapeutic interventions. Methods: A systematic literature review was conducted across multiple electronic databases, including PubMed, MEDLINE, Cochrane Library, and Scopus, from their inception to May 2024. The search strategy incorporated a combination of keywords and Medical Subject Headings (MeSH) terms such as "Alzheimer's disease," "epidemiology," "risk factors," "symptoms," "diagnosis," "management," "caregiving," "treatment," and "novel therapies." Boolean operators (AND, OR) were used to refine the search, ensuring a comprehensive analysis of the existing literature on Alzheimer's disease. Results: AD is significantly influenced by genetic predispositions, such as the apolipoprotein E (APOE) ε4 allele, along with modifiable environmental factors like diet, physical activity, and cognitive engagement. Diagnostic approaches have evolved with advances in neuroimaging techniques (MRI, PET), and biomarker analysis, allowing for earlier detection and intervention. The National Institute on Aging and the Alzheimer's Association have updated diagnostic criteria to include biomarker data, enhancing early diagnosis. Conclusion: The management of AD includes pharmacological treatments, such as cholinesterase inhibitors and NMDA receptor antagonists, which provide symptomatic relief but do not slow disease progression. Emerging therapies, including amyloid-beta and tau-targeting treatments, gene therapy, and immunotherapy, offer potential for disease modification. The critical role of caregivers is underscored, as they face considerable emotional, physical, and financial burdens. Support programs, communication strategies, and educational interventions are essential to for improving caregiving outcomes. While significant advancements have been made in understanding and managing AD, ongoing research is necessary to identify new therapeutic targets and enhance diagnostic and treatment strategies. A holistic approach, integrating clinical, genetic, and environmental factors, is essential for addressing the multifaceted challenges of Alzheimer's disease and improving outcomes for both patients.