Neuropsychiatric symptoms in Alzheimer's disease: Bridging mechanisms, management, and emerging innovations

Neuropsychiatric symptoms (NPS) are among the most distressing and functionally disruptive features of Alzheimer's disease (AD), affecting the vast majority of individuals across the disease continuum. These symptoms, ranging from apathy and depression to agitation and psychosis, not only worsen quality of life but also predict faster decline, earlier institutionalization, and heightened caregiver burden. Yet, despite their clinical significance, NPS remain under-recognized and undertreated. This review synthesizes current understanding of the biological underpinnings of NPS in AD, highlighting network-level dysfunction, neurotransmitter imbalances, neuroinflammation, and emerging roles for tau pathology and circadian disruption. We critically examine current treatment paradigms, noting that pharmacologic interventions offer benefit but often carry significant risks. In contrast, non-pharmacological approaches, particularly those that integrate caregiver training, environmental design, and sensory engagement, hold promise but are inconsistently applied in routine care. Emerging innovations, including neuromodulation, repurposed agents (e.g., beta-blockers, cannabinoids), and digital therapeutics such as virtual reality and AI-enabled monitoring tools, offer new therapeutic avenues. We call for a paradigm shift toward person-centered, mechanistically-informed care that aligns intervention strategies with biological drivers of NPS. Future progress hinges on inclusive clinical trials, implementation of first-line behavioral strategies, and development of biomarker-guided, precision approaches to symptom management. Effective care for NPS in AD demands integration, not substitution, of pharmacologic and non-pharmacologic strategies, grounded in a deeper understanding of both disease biology and lived patient experience.