Age-Related Alterations in Gray Matter Microstructure in Older People With Remitted Major Depression at Risk for Dementia

John A E Anderson; Neda Rashidi-Ranjbar; Arash Nazeri; Jordan A Chad; Peter Zhukovsky; Benoit H Mulsant; Nathan Herrmann; Linda Mah; Alastair J Flint; Corinne E Fischer; Bruce G Pollock; Tarek K Rajji; Aristotle N Voineskos; PACt-MD Study Group

doi:10.1016/j.bpsgos.2023.08.018

Age-Related Alterations in Gray Matter Microstructure in Older People With Remitted Major Depression at Risk for Dementia

Biol Psychiatry Glob Open Sci. 2023 Sep 12;4(1):374-384. doi: 10.1016/j.bpsgos.2023.08.018. eCollection 2024 Jan.

Authors

John A E Anderson^{1

2

3}, Neda Rashidi-Ranjbar^{2

4}, Arash Nazeri⁵, Jordan A Chad^{6

7}, Peter Zhukovsky², Benoit H Mulsant^{2

8}, Nathan Herrmann^{8

9}, Linda Mah^{7

8}, Alastair J Flint^{8

10}, Corinne E Fischer^{4

8}, Bruce G Pollock^{2

8}, Tarek K Rajji^{2

8

11}, Aristotle N Voineskos^{2

4

8}; PACt-MD Study Group

Affiliations

¹ Department of Cognitive Science, Carleton University, Ottawa, Ontario, Canada.
² Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
³ Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
⁴ Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Ontario, Canada.
⁵ Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri (AN).
⁶ Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
⁷ Baycrest Health Sciences, Toronto, Ontario, Canada.
⁸ Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
⁹ Sunnybrook Health Sciences Centre, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
¹⁰ Centre for Mental Health, University Health Network, Toronto, Ontario, Canada.
¹¹ Toronto Dementia Research Alliance, University of Toronto, Toronto, Ontario, Canada.

Abstract

Background: Major depressive disorder (MDD) in late life is a risk factor for mild cognitive impairment (MCI) and Alzheimer's disease. However, studies of gray matter changes have produced varied estimates of which structures are implicated in MDD and dementia. Changes in gray matter volume and cortical thickness are macrostructural measures for the microstructural processes of free water accumulation and dendritic spine loss.

Methods: We conducted multishell diffusion imaging to assess gray matter microstructure in 244 older adults with remitted MDD (n = 44), MCI (n = 115), remitted MDD+MCI (n = 61), or without psychiatric disorders or cognitive impairment (healthy control participants; n = 24). We estimated measures related to neurite density, orientation dispersion, and free water (isotropic volume fraction) using a biophysically plausible model (neurite orientation dispersion and density imaging).

Results: Results showed that increasing age was correlated with an increase in isotropic volume fraction and a decrease in orientation dispersion index, which is consistent with neuropathology dendritic loss. In addition, this relationship between age and increased isotropic volume fraction was more disrupted in the MCI group than in the remitted MDD or healthy control groups. However, the association between age and orientation dispersion index was similar for all 3 groups.

Conclusions: The findings suggest that the neurite orientation dispersion and density imaging measures could be used to identify biological risk factors for Alzheimer's disease, signifying both conventional neurodegeneration observed with MCI and dendritic loss seen in MDD.

Keywords: Corticolimbic circuit; Dementia; Diffusion-weighted imaging; Fractional anisotropy; Frontal-executive circuit; Geriatric; Gray matter; MRI; Major depressive disorder; Mild cognitive impairment; Structural covariance; T1-weighted image.