Anatomical Correlates of the Neuropsychiatric Symptoms in Alzheimer’s Disease
2015
The current study aimed to assess the relationship between the neuropsychiatric symptoms in Alzheimer’s disease
(AD) and the regional grey matter (GM) volume using voxel based morphometry (VBM). Data of 85 AD patients,
208 subjects with mild cognitive impairment (MCI), and 131 healthy controls were selected from the Alzheimer’s Disease
Neuroimaging Initiative. Individual VBM models across the entire sample for each items of the Neuropsychiatric Inventory
Questionnaire as variables of interest were specified with four nuisance covariates, including age, sex, total intracranial
volume (TIV), and Mini-Mental State Examination (MMSE) score. Agitation was related to the GM atrophy in the
left inferior frontal/insula and bilateral retrosplenial cortices. Aberrant motor behavior (AMB) was related to the GM reductions
in the right basal ganglia. The VBM models were recalculated by specifying three nuisance covariates (age, sex,
TIV), and by excluding voxels related to AD severity by applying a MMSE mask. This procedure confirmed the first results,
and additionally revealed associations between depression and GM atrophy in the left middle frontal cortex, between
agitation and the GM atrophy in the left middle frontal cortex, and between AMB and GM reduction in the right inferior
frontal cortex. Hierarchical multiple regression analyses using extracted mean GM value in these additional regions
confirmed these associations. Finally, VBM analyses within a subgroup (85 AD patients and 41 MCI converters) largely
confirmed the results. Our results suggest that specific patterns of GM atrophy within AD related neurodegeneration predispose
to certain neuropsychiatric symptoms, suggesting distinct neurobiological mechanisms.
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