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

Abstract

Abstract 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.