Distinct Longitudinal Brain White Matter Microstructure Changes and Associated Polygenic Risk of Common Psychiatric Disorders and Alzheimer's Disease in the UK Biobank

Max Korbmacher; Dennis van der Meer; Dani Beck; Daniel E Askeland-Gjerde; Eli Eikefjord; Arvid Lundervold; Ole A Andreassen; Lars T Westlye; Ivan I Maximov

doi:10.1016/j.bpsgos.2024.100323

Distinct Longitudinal Brain White Matter Microstructure Changes and Associated Polygenic Risk of Common Psychiatric Disorders and Alzheimer's Disease in the UK Biobank

Biol Psychiatry Glob Open Sci. 2024 Apr 26;4(4):100323. doi: 10.1016/j.bpsgos.2024.100323. eCollection 2024 Jul.

Authors

Max Korbmacher^{1

2

3}, Dennis van der Meer^{2

4}, Dani Beck^{2

5

6}, Daniel E Askeland-Gjerde², Eli Eikefjord^{1

3}, Arvid Lundervold^{3

7}, Ole A Andreassen^{2

8}, Lars T Westlye^{2

6

8}, Ivan I Maximov^{1

2}

Affiliations

¹ Department of Health and Functioning, Western Norway University of Applied Sciences, Bergen, Norway.
² NORMENT Centre for Psychosis Research, Division of Mental Health and Addiction, University of Oslo and Oslo University Hospital, Oslo, Norway.
³ Mohn Medical Imaging and Visualization Centre, Bergen, Norway.
⁴ Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
⁵ Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
⁶ Department of Psychology, University of Oslo, Oslo, Norway.
⁷ Department of Biomedicine, University of Bergen, Bergen, Norway.
⁸ KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.

Abstract

Background: During the course of adulthood and aging, white matter (WM) structure and organization are characterized by slow degradation processes such as demyelination and shrinkage. An acceleration of such aging processes has been linked to the development of a range of diseases. Thus, an accurate description of healthy brain maturation, particularly in terms of WM features, is fundamental to the understanding of aging.

Methods: We used longitudinal diffusion magnetic resonance imaging to provide an overview of WM changes at different spatial and temporal scales in the UK Biobank (UKB) (n = 2678; age_{scan 1} = 62.38 ± 7.23 years; age_{scan 2} = 64.81 ± 7.1 years). To examine the genetic overlap between WM structure and common clinical conditions, we tested the associations between WM structure and polygenic risk scores for the most common neurodegenerative disorder, Alzheimer's disease, and common psychiatric disorders (unipolar and bipolar depression, anxiety, obsessive-compulsive disorder, autism, schizophrenia, attention-deficit/hyperactivity disorder) in longitudinal (n = 2329) and cross-sectional (n = 31,056) UKB validation data.

Results: Our findings indicate spatially distributed WM changes across the brain, as well as distributed associations of polygenic risk scores with WM. Importantly, brain longitudinal changes reflected genetic risk for disorder development better than the utilized cross-sectional measures, with regional differences giving more specific insights into gene-brain change associations than global averages.

Conclusions: We extend recent findings by providing a detailed overview of WM microstructure degeneration on different spatial levels, helping to understand fundamental brain aging processes. Further longitudinal research is warranted to examine aging-related gene-brain associations.

Keywords: Aging; Diffusion MRI; Magnetic resonance imaging; Microstructure; Polygenic risk; White matter.

Plain language summary

In their study, Korbmacher et al. benchmark healthy aging processes in the brain’s white matter. Findings of degrading white matter at higher ages were consistent with recent cross-sectional and longitudinal findings, particularly outlining changes in ventricle-near and cerebellar white matter. Degenerative processes were also found to accelerate at a higher age. Finally, the polygenic risk to develop psychiatric and neurodegenerative disorders was weakly associated with the white matter change in the otherwise healthily aging participants.