Etiology of Late-Onset Alzheimer's Disease, Biomarker Efficacy, and the Role of Machine Learning in Stage Diagnosis

Late-onset Alzheimer's disease (LOAD) is a subtype of dementia that manifests after the age of 65. It is characterized by progressive impairments in cognitive functions, behavioral changes, and learning difficulties. Given the progressive nature of the disease, early diagnosis is crucial. Early-onset Alzheimer's disease (EOAD) is solely attributable to genetic factors, whereas LOAD has multiple contributing factors. A complex pathway mechanism involving multiple factors contributes to LOAD progression. Employing a systems biology approach, our analysis encompassed the genetic, epigenetic, metabolic, and environmental factors that modulate the molecular networks and pathways. These factors affect the brain's structural integrity, functional capacity, and connectivity, ultimately leading to the manifestation of the disease. This study has aggregated diverse biomarkers associated with factors capable of altering the molecular networks and pathways that influence brain structure, functionality, and connectivity. These biomarkers serve as potential early indicators for AD diagnosis and are designated as early biomarkers. The other biomarker datasets associated with the brain structure, functionality, connectivity, and related parameters of an individual are broadly categorized as clinical-stage biomarkers. This study has compiled research papers on Alzheimer's disease (AD) diagnosis utilizing machine learning (ML) methodologies from both categories of biomarker data, including the applications of ML techniques for AD diagnosis. The broad objectives of our study are research gap identification, assessment of biomarker efficacy, and the most effective or prevalent ML technology used in AD diagnosis. This paper examines the predominant use of deep learning (DL) and convolutional neural networks (CNNs) in Alzheimer's disease (AD) diagnosis utilizing various types of biomarker data. Furthermore, this study has addressed the potential scope of using generative AI and the Synthetic Minority Oversampling Technique (SMOTE) for data augmentation.