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Global cognitive dysfunction and β-amyloid neuropathology in late-life and treatment-resistant major depression

Published online by Cambridge University Press:  26 October 2021

Cheng-Ta Li*
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Division of Psychiatry, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan Institute of Brain Science and Brain Research Center, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan Institute of Cognitive Neuroscience, National Central University, Jhongli, Taiwan
Jong-Ling Fuh
Affiliation:
Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan
Bang-Hung Yang
Affiliation:
Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
Chen-Ji Hong
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Division of Psychiatry, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Chi-Wei Chang
Affiliation:
Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
Pei-Chi Tu
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Division of Psychiatry, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Jia-Shyun Jeng
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
Mu-Hong Chen
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Division of Psychiatry, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan Institute of Brain Science and Brain Research Center, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Shih-Jen Tsai
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Division of Psychiatry, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Ya-Mei Bai
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Division of Psychiatry, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Tung-Ping Su
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Division of Psychiatry, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan Institute of Brain Science and Brain Research Center, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan Department of Psychiatry, Cheng Hsin General Hospital, Taipei, Taiwan
Hsuan Lee
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
Wen-Sheng Huang*
Affiliation:
Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
*
Author for correspondence: Cheng-Ta Li, E-mail: ctil2@vghtpe.gov.tw; Wen-Sheng Huang, E-mail: wshuang01@gmail.com
Author for correspondence: Cheng-Ta Li, E-mail: ctil2@vghtpe.gov.tw; Wen-Sheng Huang, E-mail: wshuang01@gmail.com

Abstract

Background

Cognitive impairment is common in late-life depression, which may increase Alzheimer disease (AD) risk. Therefore, we aimed to investigate whether late-life major depressive disorder (MDD) has worse cognition and increases the characteristic AD neuropathology. Furthermore, we carried out a comparison between treatment-resistant depression (TRD) and non-TRD. We hypothesized that patients with late-life depression and TRD may have increased β-amyloid (Aβ) deposits in brain regions responsible for global cognition.

Methods

We recruited 81 subjects, including 54 MDD patients (27 TRD and 27 non-TRD) and 27 matched healthy controls (HCs). Neurocognitive tasks were examined, including Mini-Mental State Examination and Montreal Cognitive Assessment to detect global cognitive functions. PET with Pittsburgh compound-B and fluorodeoxyglucose were used to capture brain Aβ pathology and glucose use, respectively, in some patients.

Results

MDD patients performed worse in Montreal Cognitive Assessment (p = 0.003) and had more Aβ deposits than HCs across the brain (family-wise error-corrected p < 0.001), with the most significant finding in the left middle frontal gyrus. Significant negative correlations between global cognition and prefrontal Aβ deposits existed in MDD patients, whereas positive correlations were noted in HCs. TRD patients had significantly more deposits in the left-sided brain regions (corrected p < 0.001). The findings were not explained by APOE genotypes. No between-group fluorodeoxyglucose difference was detected.

Conclusions

Late-life depression, particularly TRD, had increased brain Aβ deposits and showed vulnerability to Aβ deposits. A detrimental role of Aβ deposits in global cognition in patients with late-onset or non-late-onset MDD supported the theory that late-life MDD could be a risk factor for AD.

Type
Original Article
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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