Diversity of neurodegenerative pathophysiology in nondemented patients with major depressive disorder: Evidence of cerebral amyloidosis and hippocampal atrophy

Background: Patients with late-life depression may be at the preclinical stage of dementia. However, the neurodegenerative processes in late-life depression are poorly understood. This study aimed to investigate the distribution patterns of amyloid pathology and neurodegeneration in a depressive population without dementia. Methods: The study recruited 63 middle-aged and elderly patients with major depressive disorder (MDD) and 22 control subjects. The MDD patients were further subdivided into those with mild cognitive impairment (MCI) (n = 24) and non-MCI (n = 39) patients. We used the global standardized uptake value ratio of ¹⁸ F-florbetapir (AV-45/Amyvid) positron emission tomography imaging as a biomarker of cerebral amyloidosis and the hippocampal volume as a biomarker for neurodegeneration. Cutoff points of brain amyloid positivity and hippocampal atrophy were determined using independent data obtained from clinically diagnosed Alzheimer's disease (AD) patients in a previous study. Results: Most of the control subjects (81.8%) were biomarker-negative, in contrast to the MCI MDD patients (37.5%). A relatively high proportion of the MCI MDD patients (12.5%) exhibited both amyloid positivity and hippocampal atrophy as compared to the control subjects (4.5%) and non-MCI patients (5.1%). However, a considerable proportion of the MCI MDD patients (29.2%) were categorized into the group with hippocampal atrophy alone, and negative amyloid deposition, as compared to the control subjects (0%) and non-MCI patients (5.1%). Conclusions: This study highlights the expected heterogeneity of the processes of neurodegeneration in MDD patients. The diverse neurodegenerative processes may have important etiologic and therapeutic implications regarding neurodegenerative pathophysiology in late-life depression.