Neuropsychiatric symptoms in MCI, AD, and healthy older adults: a network analysis perspective

OBJECTIVES: Alzheimer's Disease (AD), while traditionally classified as a cognitive disorder, is also characterized by neuropsychiatric symptoms (NPS). Despite their clinical relevance, NPS are often under-assessed or rarely examined in conjunction with cognitive symptoms. Here, we aimed to explore the dynamic interplay between cognitive and neuropsychiatric symptoms across the AD continuum. METHOD: We applied moderated Mixed Graphical Models (mMGMs) to a large sample from the Alzheimer's Disease Neuroimaging Initiative (ADNI), including Normal Controls (NC), individuals with Mild Cognitive Impairment (MCI), and patients with AD. RESULTS: Moderation analyses showed that diagnosis significantly influenced key relationships, such as those between visual hallucinations and visuoconstructive or memory functions, and between delusions and semantic fluency. Centrality analyses identified bridging symptoms-such as apathy, semantic fluency, and MMSE performance linking cognitive and psychiatric domains, highlighting their clinical relevance. In addition, diagnosis-specific patterns of symptom interaction were found, with AD patients displaying a denser and more interconnected network between cognitive and neuropsychiatric domains compared to the other groups. CONCLUSIONS: These findings support a more integrated conceptualization of AD pathology, where cognitive and neuropsychiatric symptoms co-evolve. Early identification and treatment of NPS may therefore be critical to improve quality of life and for informing comprehensive diagnostic and therapeutic strategies.