Alzheimer’s Disease and Cognitive Disorders: From Molecular Drivers to Multilevel Clinical Solutions
Abstract Alzheimer’s disease (AD) represents the leading cause of dementia worldwide, accounting for approximately 70% of all dementia cases, and is characterized by progressive cognitive decline arising from complex interactions among molecular, genetic, environmental, and systemic factors. This review integrates current mechanistic insights with evolving diagnostic and therapeutic approaches. Central pathogenic processes include amyloid-β (Aβ) aggregation, tau hyperphosphorylation and propagation, neuroimmune dysregulation, synaptic failure, and network-level circuit disruption. Genetic and epigenetic contributors such as APOE genotype, aging-related inflammatory signaling, oxidative stress, and lifestyle-associated risk factors further modify susceptibility and disease trajectory. Recent advances in fluid biomarkers, amyloid and tau molecular imaging, and digital phenotyping—such as AI-driven cognitive assessments, gait analysis, voice analytics, and passive activity monitoring—have improved early detection and patient stratification. Emerging therapeutic strategies include disease-modifying agents, neuroprotective interventions, neurotrophin mimetics, and hormesis-based lifestyle approaches such as structured exercise, caloric modulation, and intermittent fasting. Precision-medicine trial designs and biomarker-guided therapeutic selection are transforming clinical research. At the clinical and public health level, caregiver-centered care models, community-based support systems, and multidomain prevention strategies emphasize the need for equitable, culturally informed dementia care. Future progress will depend on large-scale, diverse cohort studies, multi-omics integration, single-cell brain atlases, and AI-supported neuropathology pipelines to enable prevention and intervention during the preclinical window. This review highlights the importance of bridging mechanistic research with real-world clinical practice to generate impactful diagnostic, therapeutic, and policy outcomes. Keywords: Alzheimer’s disease, amyloid-β and tau pathology, neurodegeneration, biomarkers and digital phenotyping, precision medicine.