The Relationship Between Brain Structure and Neuropsychiatric Symptoms in Patients With Mild Cognitive Impairment and Alzheimer's Dementia

Introduction Neuropsychiatric symptoms (NPS) are highly prevalent from mild cognitive impairment (MCI) to Alzheimer's dementia (AD). Understanding the link between NPS and regional brain changes can provide insight into neural correlates of disease progression. Methods This cross‐sectional study analyzed 1536 older adults from the National Alzheimer's Coordinating Center comprising 860 healthy controls, 389 patients with MCI, and 287 patients with AD. The NPSs were evaluated with the Neuropsychiatric Inventory (NPI), which measures severity in four domains: mood, psychosis, frontal, and total symptoms. Magnetic resonance imaging quantified regional gray matter volumes (GM), cerebrospinal fluid volume (CSF), and white matter hyperintensity (WMH) volumes to see their correlations with NPS. Results All volumes showed the smallest in dementia, the intermediate in MCI, and the largest in healthy controls. Higher total NPI scores were significantly associated with smaller volumes of hippocampal and gray matter volumes and larger cerebrospinal fluid volume, with the strongest correlations in the dementia group. By domain, NPI‐mood symptoms were correlated with reduced hippocampal, temporal, and frontal volumes. NPI‐psychosis symptoms also correlated with frontotemporal regions, but less extensively. Mood symptoms were most strongly linked to temporolimbic atrophy. Conclusion The study supports associations between emerging neuropsychiatric manifestations and accumulating structural brain damage along the pathological cascade.