Abstract

Alzheimer's disease (AD) research has largely concentrated on the study of cognitive decline, but the associated behavioral and neuropsychiatric symptoms are of equal importance in the clinical profile of the disease. Apathy is the most common neuropsychiatric manifestation in AD. Clinical, multimodal neuroimaging studies and pathologic studies of apathy in AD have suggested an association with frontal dysfunction but without a definitive localization. In this study, we examined the association between apathy and white matter integrity using diffusion tensor imaging (DTI). Twenty-one AD patients underwent DTI and neuropsychiatric and cognitive assessments. All fractional anisotropy (FA) maps were normalized to the standard space, and the association between the apathy scale and DTI metrics were evaluated voxel basically. Statistical parametric mapping analysis showed that there were statistically negative correlations between the apathy scale and FA values in the right anterior cingulate, right thalamus, and bilateral parietal regions using age, Mini-Mental State Examination score and sex as nuisance variables. Apathy in AD is associated with impaired white matter integrity in the anterior cingulate and medial thalamus. These results reinforce the confluence of evidence from other investigational modalities in implicating limbic dysfunction and related neuronal circuits in the neurobiology of apathy in AD.

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