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Brain Advance Access originally published online on July 11, 2008
Brain 2008 131(9):2455-2463; doi:10.1093/brain/awn151
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© The Author (2008). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Neuroanatomical correlates of neuropsychiatric symptoms in Alzheimer's disease

Peita D. Bruen1,2, William J. McGeown1, Michael F. Shanks1 and Annalena Venneri1,3

1Clinical Neuroscience Centre, University of Hull, Hull, UK, 2Department of Neuroscience, University of Parma, Parma and 3Department of Neuroscience, University of Modena and Reggio Emilia, Modena, Italy

Correspondence to: Prof. Annalena Venneri, Clinical Neuroscience Centre, University of Hull, Cottingham Road, Hull HU6 7RX, England, UK E-mail: a.venneri{at}hull.ac.uk

Alzheimer's disease research has largely concentrated on the study of cognitive decline, but the associated behavioural and neuropsychiatric symptoms are of equal importance in the clinical profile of the disease. There is emerging evidence that regional differences in brain atrophy may align with variant disease presentations. The objective of this study was to identify the regions of decreased grey matter (GM) volume which were associated with specific neuropsychiatric behaviours in patients with mild Alzheimer's disease. Voxel-based morphometry was used to correlate GM derived from T1-weighted MRI images of 31 patients with mild Alzheimer's disease and specific neuropsychiatric symptoms and behaviours measured by the Neuropsychiatric Inventory. Delusions were associated with decreased GM density in the left frontal lobe, in the right frontoparietal cortex and in the left claustrum. Apathy was associated with GM density loss in the anterior cingulate and frontal cortex bilaterally, the head of the left caudate nucleus and in bilateral putamen. Agitation was associated with decreased GM values in the left insula, and in anterior cingulate cortex bilaterally. Neuropsychiatric symptoms of Alzheimer's disease seem to associate with neurodegeneration of specific neural networks supporting personal memory, reality monitoring, processing of reward, interoceptive sensations and subjective emotional experience. The study of neurodegenerative disorders such as Alzheimer's disease using voxel-based morphometry and other imaging modalities may further the understanding of the neural structures that mediate the genesis of abnormal behaviours.

Key Words: delusions; apathy; agitation; dementia; voxel-based morphometry; MRI

Abbreviations: GM, grey matter; MMSE, Mini-Mental State Examination; NPI, Neuropsychiatric Inventory

Received March 31, 2008. Revised May 21, 2008. Accepted June 16, 2008.


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