Abstract
New research on assessing neuropsychiatric manifestations of Alzheimer´s Disease (AD) involves grouping neuropsychiatric symptoms into syndromes. Yet this approach is limited by high inter-subject variability in neuropsychiatric symptoms and a relatively low degree of concordance across studies attempting to cluster neuropsychiatric symptoms into syndromes. An alternative strategy that involves dichotomizing AD subjects into those with few versus multiple neuropsychiatric symptoms is both consonant with real-world clinical practice and can contribute to understanding neurobiological underpinnings of neuropsychiatric symptoms in AD patients. The aim of this study was to address whether the number of neuropsychiatric symptoms (i.e., presence of few [≤2] versus multiple [≥3] symptoms) in AD would be associated with degree of significant gray matter (GM) volume loss. Of particular interest was volume loss in brain regions involved in memory, emotional processing and salience brain networks, including the prefrontal, lateral temporal and parietal cortices, anterior cingulate gyrus, temporo-limbic structures and insula. We recruited 19 AD patients and 13 healthy controls, which underwent an MRI and neuropsychiatric assessment. Regional brain volumes were determined using voxel-based morphometry and other advanced imaging processing methods. Our results indicated the presence of different patterns of GM atrophy in the two AD subgroups relative to healthy controls. AD patients with multiple neuropsychiatric manifestations showed more evident GM atrophy in the left superior temporal gyrus and insula as compared with healthy controls. In contrast, AD subjects with few neuropsychiatric symptoms displayed more GM atrophy in prefrontal regions, as well as in the dorsal anterior cingulate ad post-central gyri, as compared with healthy controls. Our findings suggest that the presence of multiple neuropsychiatric symptoms is more related to the degree of atrophy in specific brain networks rather than dependent on the global severity of widespread neurodegenerative brain changes.
Highlights
Neuropsychiatric symptoms are highly prevalent when there is an established diagnosis of a dementing condition, such as Alzheimers Disease (AD) [1,2,3]
The associations between neuropsychiatric symptoms and brain volume abnormalities highlighted in these voxel-based morphometry (VBM) studies have a variety of results, including: psychotic symptoms, agitation and disinhibition related to gray matter (GM) volume deficits in regions previously implicated in salience brain networks [14,15], as well as portions of the frontal, temporal, parietal and occipital cortices and the hippocampus [8,9,12,13]; and apathy and/or depression associated with GM atrophy in frontal and cingulated regions relevant to emotional processing [8,11,13]
When these analyses were repeated using the small volume correction (SVC) approach, the presence of sleep disorders was correlated to decreased GM volume in a cluster involving the right middle temporal pole (BA 38) extending towards the middle and inferior temporal gyri (MNI coordinates x y z 37 20–41, k = 269, Z score = 3.84, p
Summary
Neuropsychiatric symptoms are highly prevalent when there is an established diagnosis of a dementing condition, such as Alzheimers Disease (AD) [1,2,3]. Neuroimaging studies in patients with dementia may help to identify the neurobiological underpinnings of the emergence of NPI-assessed neuropsychiatric manifestations in AD, linking neuropsychiatric symptoms to the neurodegenerative process that characterize AD This approach has been applied in a number of structural neuroimaging studies using magnetic resonance imaging (MRI), several of which have used voxel-based morphometry (VBM) methods that allow voxel wise inspections of foci of gray matter (GM) volume abnormalities across the entire brain, in an automated fashion [8,9,10,11,12,13]. The associations between neuropsychiatric symptoms and brain volume abnormalities highlighted in these VBM studies have a variety of results, including: psychotic symptoms, agitation and disinhibition related to GM volume deficits in regions previously implicated in salience brain networks (namely the insular and anterior cingulate cortices) [14,15], as well as portions of the frontal, temporal, parietal and occipital cortices and the hippocampus [8,9,12,13]; and apathy and/or depression associated with GM atrophy in frontal and cingulated regions relevant to emotional processing [8,11,13]
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