Objectives: Neuropsychiatric symptoms (NPS) are common in mild cognitive impairment (MCI) and even more so in Alzheimer's disease (AD). The affective/vegetative NPS cluster model (sleep disorders, depression, appetite changes, anxiety, and apathy) has been asso-ciated with an increased risk of dementia in patients with MCI and these five NPS have common neuroanatomical associations. Hence, in this study, we examined how brain morphology is influenced by the severity of affective/vegetative NPS

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... cross different stages of cognitive performance. Participants: 175 AD, 367 MCI and 223 cognitively normal (CN) participants. Setting: Participants were recruited at multiple centers in North America included in the ADNI project. Design: A GLM was established to test for intergroup differences (CN -MCI, CN-AD, AD-MCI) of the effects of the five NPS on brain structures. A regression model was also per-formed to show slope directionality of the regions of interest as NPS severity increases. Measurements: 3T MRI data (cortical volumes, areas and thickness) and severity scores of the five NPS. Results: Associations within AD were predominantly stronger compared to MCI. Increased severity of sleep disorders and appetite changes were associated with a decrease in frontal surface areas in AD. Furthermore, increased severity of all NPS (except apathy) were asso-ciated with changes in the temporal regions, predominantly with decreased volumes and sur-face areas. Conclusion: These findings show the implication of fronto-temporal regions with sleep disorders, depression and appetite changes, and contribute to a better understanding of brain morphological differences between CN, MCI and AD with respect to all five NPS.