Structural Neuroimaging Correlates of Neuropsychiatric Symptoms in Alzheimer's Disease: A Systematic Literature Review

Introduction: Neuropsychiatric symptoms (NPS) such as increased apathy, affective symptoms, psychosis and hyperactivity are common in Alzheimer s disease (AD) and are associated with increased disease severity and caregiver burden. In contrast to well-characterized associations between AD-related cognitive deficits and focal neuropathology (e.g., memory and hippocampal atrophy), fewer studies have focused on associations between NPS-brain associations in AD. Furthermore, studies focusing on magnetic resonance imaging measures of gray matter (GM) abnormalities associated with NPS in AD have not been systematically reviewed. Methods: To address this gap, a systematic literature review was undertaken to identify articles that assessed structural brain differences associated with NPS in AD. This review identified 29 such articles that tested associations between NPS and gray matter loss (GML: reduced GM density, reduced GM volume, decreased cortical thickness, etc.). Results: Across all NPS, most symptoms were associated with GML in the prefrontal cortex and medial temporal lobe, highlighting key limbic/limbic adjacent structures including orbitofrontal cortex and parahippocampal regions. Other regions exhibiting associations included the superior and middle temporal gyri as well as anterior and posterior cingulate cortex. Conclusion: Understanding how GM changes in the brain relate to NPS in AD may not only improve our understanding of NPS and AD but may also provide help identify homologies/ correspondence with brain changes in psychiatric diseases. 2025 S. Karger AG, Basel.