Depression and Agitation Factors Are Related to Regional Brain Atrophy and Faster Longitudinal Cognitive Decline in Mild Cognitive Impairment

Background: Neuropsychiatric symptoms (NPS) are a common aspect of Alzheimer’s disease (AD). Multiple studies have investigated its brain correlates, but it still remains unclear how they relate with brain atrophy in mild cognitive impairment (MCI). Objective: Our objective was to investigate brain volume in MCI patients as a function of NPS. Methods: We measured grey matter volume, neuropsychological status and NPS (Neuropsychiatric Inventory, NPI), in a sample of 81 MCI patients (43 females). Participants were divided in groups depending on presence (NPS+) or absence (NPS–) of NPS and on type of NPS. Results: We found lower volume of left temporal pole in patients with depression compared to NPS– (p = 0.012), and in patients with agitation compared to NPS– in the right middle occipital gyrus (p = 0.003). We also found a significant correlation between volume of left temporal pole and MMSE (r (78)  = 0.232, p = 0.019). Finally, NPS+ presented lower cross-sectional cognitive level than NPS– (t (79)  = 1.79, p = 0.038), and faster cognitive decline (t (48)  = –1.74, p = 0.044). Conclusions: Our results support the colocalization of structural damage as a possible mechanism underlying the relationship between MCI and depression and provide novel evidence regarding agitation. Moreover, our longitudinal evidence highlights the relevance of an adequate identification of NPS in MCI patients to identify those at risk of faster cognitive decline.