AUTHOR=Safiri Saeid , Ghaffari Jolfayi Amir , Fazlollahi Asra , Morsali Soroush , Sarkesh Aila , Daei Sorkhabi Amin , Golabi Behnam , Aletaha Reza , Motlagh Asghari Kimia , Hamidi Sana , Mousavi Seyed Ehsan , Jamalkhani Sepehr , Karamzad Nahid , Shamekh Ali , Mohammadinasab Reza , Sullman Mark J. M. , Şahin Fikrettin , Kolahi Ali-Asghar TITLE=Alzheimer's disease: a comprehensive review of epidemiology, risk factors, symptoms diagnosis, management, caregiving, advanced treatments and associated challenges JOURNAL=Frontiers in Medicine VOLUME=11 YEAR=2024 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1474043 DOI=10.3389/fmed.2024.1474043 ISSN=2296-858X ABSTRACT=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 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 and caregivers.