New research on assessing neuropsychiatric manifestations of Alzheimer´s Disease (AD) involves grouping neuropsychiatric symptoms into syndromes. Yet this approach is limited by high inter-subject variability in neuropsychiatric symptoms and a relatively low degree of concordance across studies attempting to cluster neuropsychiatric symptoms into syndromes. An alternative strategy that involves dichotomizing AD subjects into those with few versus multiple neuropsychiatric symptoms is both consonant with real-world clinical practice and can contribute to understanding neurobiological underpinnings of neuropsychiatric symptoms in AD patients. The aim of this study was to address whether the number of neuropsychiatric symptoms (i.e., presence of few [≤2] versus multiple [≥3] symptoms) in AD would be associated with degree of significant gray matter (GM) volume loss. Of particular interest was volume loss in brain regions involved in memory, emotional processing and salience brain networks, including the prefrontal, lateral temporal and parietal cortices, anterior cingulate gyrus, temporo-limbic structures and insula. We recruited 19 AD patients and 13 healthy controls, which underwent an MRI and neuropsychiatric assessment. Regional brain volumes were determined using voxel-based morphometry and other advanced imaging processing methods. Our results indicated the presence of different patterns of GM atrophy in the two AD subgroups relative to healthy controls. AD patients with multiple neuropsychiatric manifestations showed more evident GM atrophy in the left superior temporal gyrus and insula as compared with healthy controls. In contrast, AD subjects with few neuropsychiatric symptoms displayed more GM atrophy in prefrontal regions, as well as in the dorsal anterior cingulate ad post-central gyri, as compared with healthy controls. Our findings suggest that the presence of multiple neuropsychiatric symptoms is more related to the degree of atrophy in specific brain networks rather than dependent on the global severity of widespread neurodegenerative brain changes.