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Neuropsychiatric symptoms and brain morphology in patients with mild cognitive impairment and Alzheimer's disease with dementia

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Nikias Siafarikas, Dag Alnæs, Jennifer Monereo-Sanchez, Martina J. Lund, Geir Selbaek, Maria Stylianou-Korsnes, Karin Persson, Maria Lage Barca, Ina Selseth Almdahl, Tormod Fladby, Dag Aarsland, Ole A. Andreassen, Lars T. Westlye

Original languageEnglish
Pages (from-to)1217-1228
Number of pages12
JournalInternational Psychogeriatrics
Issue number11
Accepted/In press2021
Published17 Nov 2021

Bibliographical note

Funding Information: The study was funded by the Research Council of Norway (249795, 223273, and 276082), the South-Eastern Norway Regional Health Authority (2014097, 2019107, and 2020086), the European Research Council under the European Union’s Horizon 2020 research and Innovation program (ERC StG Grant 802998), and the Department of Psychology, University of Oslo. This paper represents independent research partly funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. Publisher Copyright: ©

King's Authors


Objectives: Neuropsychiatric symptoms (NPS) are common in mild cognitive impairment (MCI) and Alzheimer's disease with dementia (AD dementia), but their brain structural correlates are unknown. We tested for associations between NPS and MRI-based cortical and subcortical morphometry in patients with MCI and AD dementia. Design: Cross-sectional. Settings: Conducted in Norway. Participants: Patients with MCI (n = 102) and AD dementia (n = 133) from the Memory Clinic and the Geriatric Psychiatry Unit at Oslo University Hospital. Measurements: Neuropsychiatric Inventory - Questionnaire (NPI-Q) severity indices were reduced using principal component analysis (PCA) and tested for associations with 170 MRI features using linear models and false discovery rate (FDR) adjustment. We also tested for differences between groups. For transparency, we added analyses with selected NPI-Q items. Results: PCA revealed four factors: elation, psychosis, depression, and motor behavior. FDR adjustment revealed a significant positive association (B = 0.20, pFDR < 0.005) between elation and thickness of the right caudal anterior cingulate cortex (ACC) across groups, and significant interactions between diagnosis and psychosis (B = -0.48, pFDR < 0.0010) on the left post-central volume and between diagnosis and depression (B = -0.40, pFDR < 0.005) on the thickness of the banks of the left superior temporal sulcus. Associations of apathy, anxiety, and nighttime behavior to the left temporal lobe were replicated. Conclusions: The positive association between elation and ACC thickness suggests that mechanisms other than atrophy underly elation. Interactions between diagnosis and NPS on MRI features suggest different mechanisms of NPS in our MCI and AD dementia samples. The results contribute to a better understanding of NPS brain mechanisms in MCI and AD dementia.

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