Neuroanatomical correlates of neuropsychiatric symptoms in Alzheimer's disease

TLDR

Alzheimer’s disease research has focused on cognitive decline, yet behavioural and neuropsychiatric symptoms are equally important, and regional brain atrophy differences may correspond to distinct disease presentations. The study aimed to pinpoint grey‑matter regions linked to specific neuropsychiatric behaviours in mild Alzheimer’s disease and to advance understanding of neural structures underlying abnormal behaviours. Voxel‑based morphometry of T1‑weighted MRI from 31 mild Alzheimer’s patients was used to correlate grey‑matter volume with Neuropsychiatric Inventory‑measured symptoms. Decreased grey‑matter density in frontal, frontoparietal, claustrum, anterior cingulate, caudate, putamen, insula, and other regions was linked to delusions, apathy, and agitation, indicating that neuropsychiatric symptoms in Alzheimer’s associate with degeneration of networks supporting memory, reality monitoring, reward processing, interoception, and emotion.

Abstract

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 T(1)-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.