Alzheimer's disease with depression: clinical characteristics and potential mechanisms involving orexin and brain atrophy.

This study aimed to explore the clinical characteristics and alteration of orexinergic level in cerebrospinal fluid (CSF) and the volumes of brain grey and white matters, and investigate the roles of orexinergic level on the association between brain atrophy and depression in Alzheimer's disease (AD) patients. The demographic variables of 156 participants were collected. Orexinergic level in CSF and the volumes of brain grey and white matters were evaluated. The correlations of orexinergic level in CSF with depression and brain volume in AD patients were analyzed. The mediating effect of orexinergic level in CSF on the association between brain atrophy and depression in AD patients was investigated. The joint predictive value of orexinergic level in CSF and brain volume for depression in AD patients was established. AD with depression patients showed significantly elevated levels of orexin A and orexin B in CSF; orexin A level in CSF was positively correlated with HAMD score in AD patients. The elevated orexin A level in CSF mediated 49.6% of total association between the decreased grey matter volume of right dorsal medial thalamic nucleus and depression, and 50.3% of total association between the reduced white matter volume of left amygdala and depression. Combinations of above parameters could predict depression in AD patients with a significantly high area under the curve (AUC = 0.841). Therefore, the elevated orexin A level in CSF mediates its effect on the atrophy of the right dorsal medial thalamic nucleus and the white matter of the left amygdala, eventually alleviating depression in AD.