OBJECTIVE Neuropsychiatric symptoms (NPS) are common in Alzheimer disease (AD) and vascular dementia (VaD), and are distressful to patients and caregivers. NPS are likely related to the underlying pathology. Previous studies suggest that frontal lobe lesions and vascular changes such as white matter hyperintensities (WMH) have a significant association with specific NPS. The current study aimed to compare NPS in patients with AD, VaD, and mixed AD/VaD, and to evaluate the differences in the prevalence of NPS in relation to frontal WMH volume. METHODS In total, 180 patients with NPS and MRI data (92 probable AD, 51%; 34 probable VaD, 19%; and 54 probable mixed AD/VaD, 30%) were included in the study. Regression analyses were performed to determine the relationships between NPS prevalence and diagnosis, and between NPS and frontal WMH. RESULTS VaD patients had significantly more agitation (p < 0.05; 40 vs. 14%) and sleep disturbances (p < 0.05; 57 vs. 32%) than AD patients, and significantly more depression (p < 0.05; 48 vs. 20%) and aberrant motor behaviors (p < 0.05; 31 vs. 13%) than mixed AD/VaD patients. AD patients with delusions had significantly greater right frontal WMH volumes than those without (p < 0.05; delusions 1/0 = 314.8/112.6 mm3). CONCLUSIONS Differences in NPS prevalence are likely related to the underlying pathology and warrant further study as they have implications for treatment.