Decreased Cerebral Amyloid-β Depositions in Patients With a Lifetime History of Major Depression With Suspected Non-Alzheimer Pathophysiology

Kuan-Yi Wu; Kun-Ju Lin; Chia-Hsiang Chen; Chia-Yih Liu; Yi-Ming Wu; Cheng-Sheng Chen; Tzu-Chen Yen; Ing-Tsung Hsiao

doi:10.3389/fnagi.2022.857940

Decreased Cerebral Amyloid-β Depositions in Patients With a Lifetime History of Major Depression With Suspected Non-Alzheimer Pathophysiology

Front Aging Neurosci. 2022 May 26:14:857940. doi: 10.3389/fnagi.2022.857940. eCollection 2022.

Authors

Kuan-Yi Wu¹, Kun-Ju Lin^{2

3

4}, Chia-Hsiang Chen¹, Chia-Yih Liu¹, Yi-Ming Wu⁵, Cheng-Sheng Chen⁶, Tzu-Chen Yen^{2

3}, Ing-Tsung Hsiao^{2

3

4}

Affiliations

¹ Department of Psychiatry, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan City, Taiwan.
² Department of Nuclear Medicine, Center for Advanced Molecular Imaging and Translation, Chang Gung Memorial Hospital, Taoyuan City, Taiwan.
³ Department of Medical Imaging and Radiological Sciences, College of Medicine and Healthy Aging Research Center, Chang Gung University, Taoyuan City, Taiwan.
⁴ Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City, Taiwan.
⁵ Department of Radiology, Chang Gung Memorial Hospital, Taoyuan City, Taiwan.
⁶ Department of Psychiatry, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan.

Abstract

Cerebral amyloid-β (Aβ) depositions in depression in old age are controversial. A substantial proportion of individuals with late-life major depressive disorder (MDD) could be classified as having suspected non-Alzheimer's disease pathophysiology (SNAP) by a negative test for the biomarker amyloid-β (Aβ-) but positive neurodegeneration (ND+). This study aimed to evaluate subthreshold Aβ loads in amyloid-negative MDD, particularly in SNAP MDD patients. This study included 46 amyloid-negative MDD patients: 23 SNAP (Aβ-/ND+) MDD and 23 Aβ-/ND- MDD, and 22 Aβ-/ND- control subjects. All subjects underwent ¹⁸F-florbetapir PET, FDG-PET, and MRI. Regions of interest (ROIs) and voxel-wise group comparisons were performed with adjustment for age, gender, and level of education. The SNAP MDD patients exhibited significantly deceased ¹⁸F-florbetapir uptakes in most cortical regions but not the parietal and precuneus cortex, as compared with the Aβ-/ND- MDD and control subjects (FDR correction, p < 0.05). No correlations of neuropsychological tests or depression characteristics with global cortical uptakes, but significant positive correlations between cognitive functions and adjusted hippocampal volumes among different groups were observed. The reduced Aβ depositions in the amyloid-negative MDD patients might be attributed mainly to the SNAP MDD patients. Our results indicated that meaningfully low amounts of subclinical Aβ might contain critical information on the non-amyloid-mediated pathogenesis.

Keywords: 18F-florbetapir (AV-45/Amyvid); amyloid-β (Aβ); depression in old age; major depressive disorder (MDD); neurodegeneration; suspected non-Alzheimer pathophysiology (SNAP).