Background: and Purpose Neuropsychiatric symptoms (NPS) are frequent in dementia and mild cognitive impairment (MCI), yet their reported associations with white matter hyperintensities (WMHs) remain inconsistent. We examined item-level associations between WMHs and NPS across Alzheimer’s disease dementia (ADD), dementia with Lewy bodies (DLB), and amnestic MCI (aMCI). Methods: This multicenter retrospective study involved 523 patients: 276 with ADD, 67 with DLB, and 180 with aMCI. Three-dimensional T1-weighted and T2–fluid-attenuated inversion recovery magnetic resonance images were processed with BAAD (Brain Anatomical Analysis using Diffeomorphic Deformation) software to quantify WMH volume (WMHV) and gray matter volume (GMV), normalized to total intracranial volume (TIV). NPS were assessed using the Neuropsychiatric Inventory. Multiple regression analyses were performed within each group, adjusting for GMV/TIV, age, sex, years of education, Clinical Dementia Rating–Sum of Boxes score, and institution. Results: In the aMCI group, higher WMHV/TIV was positively associated with depression, apathy, and disinhibition, and negatively with delusions. Subregional analyses revealed NPSspecific topographic patterns. No significant associations were detected in the ADD or DLB group. GMV/TIV was positively associated with delusions in the ADD group, but negatively associated with hallucinations in the DLB group. Conclusions Associations between WMHs and NPS were evident in the aMCI group but absent in the ADD and DLB groups, suggesting a stage-dependent effect. WMHs may contribute to NPS primarily in prodromal stages, whereas their influence may be overshadowed by neurodegenerative pathology in dementia. Clarifying the mechanisms underlying WMHs is critical for evaluating their potential as intervention targets.

Objective : The objective of the present study was to clarify the differences in statistical imaging analysis of functional and morphologic imaging between neuropsychological impairments (NPI) and nonorganic mental disorder (MD) after traumatic head injury. Methods : Six depressive patients after head injury without abnormal findings on conventional MRI (MD group), six nondepressive patients with NPI after diffuse axonal injury (NPI group), and six healthy subjects with a history of head injury (control group) were enrolled in this study. For all subjects, ^99mTc-ethylcysteinate dimmer (Tc-ECD) SPECT and MRI 3D volumetry were performed. Imaging data were analyzed using statistical parametric mapping, and then, the analyzed data were compared among the three groups (2 sample t test, uncorrected p<0.01). Results : Compared to the Control group, significant low Tc-ECD uptake and regional grey matter volume reduction were noticed bilaterally in the anterior medial brain aspects such as the anterior cingulate cortex in both the MD group and the NPI group. These findings were significantly greater in the NPI group than in the MD group. Moreover, these functional and morphologic abnormalities were also spread to more medial and deep aspects such as the posterior limbic and the brain stem in the NPI group. Conversely, in the MD group without morphologic abnormalities, only functional abnormalities spread above the common lesions to the dorsolateral brain aspects such as the superior frontal lobe. Conclusion : Our results revealed some characteristics of statistical imaging analysis in functional and morphologic imaging of MD and NPI patients after head injury. These findings seem to be novel and can serve as useful information for future investigation of neural correlates with both NPI and MD after head injury.