Impact of neuropsychiatric symptoms on limbic structures in age-related cognitive decline

Abstract ObjectivesNeuropsychiatric symptoms (NPS) are known to increase the risk of cognitive decline in aging. Several studies have investigated the brain substrates of these symptoms, reporting a broad involvement of the limbic regions. ParticipantsUsing the Alzheimer’s Disease Neuroimaging Initiative database, we investigated 223 participants with normal cognition, 367 with mild cognitive impairment (MCI) and 175 with Alzheimer’s disease (AD). MeasurementsNeuropsychiatric symptoms were assessed with the Neuropsychiatric Inventory and MRIs were processed with FreeSurfer. We used a general linear model (FreeSurfer) and multivariate analysis of covariance (IBM SPSS software) to establish the associations between the severity of neuropsychiatric symptoms and morphometry in cortical and subcortical structures in each clinical group. ResultsThe results outlined significant associations between cortical and subcortical structures and neuropsychiatric symptoms. In cognitively normal participants, only a positive association between nighttime behaviors and bilateral caudate nuclei volumes was found. In patients with MCI, agitation, depression, apathy and nighttime behaviors were respectively negatively associated with (i) left precentral and inferior frontal and inferior parietal volumes; (ii) left fusiform volume and area; (iii) right precentral thickness, left frontopolar area and bilateral ventral diencephalon volumes; (iv) right lingual thickness, whereas depression and nighttime behaviors were also respectively positively associated with right ventral diencephalon volume; and left temporal volume and area. In patients with Alzheimer’s disease, broader association were outlined between NPS severity and cortical structures notably agitation, apathy, irritability and nighttime behaviors outlined respectively positive associations with : (i) volumes in the right temporal regions and with surface area in the frontal region; (ii) the cortical thickness of the right pericalcarine region; (iii) volumes in the frontal, temporal and parietal regions; (iv) volume of the right cuneus region; whereas depression and apathy were also respectively negatively associated with the cortical thickness of the left parietal superior region; and cortical volume and area of the parietal regions. ConclusionsThese results showed that NPS have broad association patterns with associative brain structures and few associations with limbic structures. These associations were also dependent on the clinical stage of cognitive impairment.