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

Nov 11, 2025Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics

Brain-related symptoms in Alzheimer's disease: Understanding causes, treatments, and new approaches

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Abstract

Neuropsychiatric symptoms (NPS) affect the vast majority of individuals with Alzheimer's disease (AD) and are associated with faster decline and increased caregiver burden.

NPS include symptoms such as apathy, depression, agitation, and psychosis, which significantly worsen quality of life.
Current understanding highlights biological factors contributing to NPS, including network dysfunction, neurotransmitter imbalances, and neuroinflammation.
Pharmacologic treatments can offer benefits but may carry significant risks, necessitating careful consideration.
Non-pharmacological approaches, especially those involving caregiver training and environmental design, show promise but are not consistently implemented.
Innovative therapies like neuromodulation and digital tools are emerging as potential new treatment options.
Future strategies should focus on integrating both pharmacologic and non-pharmacologic interventions, informed by biological mechanisms and patient experiences.

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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.

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

Abstract

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