White matter integrity change across the lifespan: a systematic review and meta-analysis

1249 

Abstract Submission 

Karis Colyer-Patel¹, Jalmar Teeuw¹, Vivien maes², Rachel Brouwer³, Paul Thompson⁴, Hilleke Hulshoff Pol²

¹University Medical Center Utrecht, UMC Brain Center, Department of Psychiatry, Utrecht, Netherlands, ²Utrecht University, Department of Experimental Psychology, Helmholtz Institute, Utrecht, Netherlands, ³Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam, Netherlands, ⁴Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Los Angeles, USA

Karis Colyer-Patel  
University Medical Center Utrecht, UMC Brain Center, Department of Psychiatry
Utrecht, Netherlands

Jalmar Teeuw  
University Medical Center Utrecht, UMC Brain Center, Department of Psychiatry
Utrecht, Netherlands

Vivien maes  
Utrecht University, Department of Experimental Psychology, Helmholtz Institute
Utrecht, Netherlands

Rachel Brouwer  
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research
Amsterdam, Netherlands

Paul Thompson  
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute
Los Angeles, USA

Hilleke Hulshoff Pol  
Utrecht University, Department of Experimental Psychology, Helmholtz Institute
Utrecht, Netherlands

Across the lifespan the brain undergoes significant changes during development and aging which coincide with the maturation of cognition and behaviour during development, and with functional decline later in life. White matter (WM) microstucture changes with development and aging (Lebel et al., 2019; Madden et al., 2012) and is associated with risk and resilience to psychiatric and neurological disorders (Meyer & Lee, 2019; Sorond & Gorelick, 2019). The extent to which and how measures of WM microstructure, including fractional anisotropy (FA), evolve over the lifespan is still not fully understood. Genetic factors influence various metrics of WM microstructure (Kochunov et al., 2015; Koenis et al., 2015) and change-rates of WM volume (Brouwer et al., 2022). However, it is less clear whether change-rates of WM microstructure across the lifespan are also influenced by genetics. The aims of this systematic review are twofold: (1) to investigate how FA changes across the lifespan based on longitudinal data, and (2) to investigate evidence of genetic influences on change rates.

We systematically reviewed longitudinal studies investigating FA changes across the lifespan. Searches were conducted in Medline, PsycInfo, and EMBASE up to 9th August 2023, with terms related to DTI/FA and longitudinal/change. Inclusion criteria included participants in the age range of 0-99 and included both healthy and patient groups with a sample size of ≥ 75. For the meta-analysis investigating annual whole-brain FA change, a cubic-spline function was applied. When estimating the trajectories of whole-brain FA values across the lifespan, a LOESS curve was used to fit the data. To review the evidence of influences of genetic variants on WM integrity change, we conducted an additional search adding the following search terms: i.e., genes, genome-wide association study, polygenic, family, twins and heritability. The search terms were broadened to include other DTI measures: i.e., mean diffusivity (MD), global and local efficiency.

Our systematic search resulted in 3,017 studies, of which 125 studies measured FA across two timepoints. From these studies, 9 studies had quantified whole-brain FA change and had reported the actual annual changes. A further 9 studies which did not report the actual annual whole-brain FA change, but annual changes could be estimated were also included. Across childhood and adolescence, FA increased and started to plateau in adulthood. Between ages 25-50 there was non-significant change. Beyond 50, significant decreases emerged, which continued to the upper limit of our age range (age 65). Longitudinal studies of FA change above the age of 65 that met are inclusion criteria were sparse. Maximum annual increase in FA was 0.02 and maximum decrease was -0.025. The additional systematic search focusing on genetic studies resulted in 828 studies, of which thirteen were identified as suitable for the systematic review, including 3 familial risk studies, 1 heritability study and 9 studies investigating specific genetic variants. Overall, findings from the familial and heritability studies provide limited evidence of genetic influences on change in WM integrity across time. In the studies of specific genetic variants, five provided evidence of an influence on changes of both FA and MD over time. These studies investigated genetic variants associated with Alzheimer's disease, schizophrenia, Huntington's disease and frontotemporal dementia.

There are significant changes in FA across the lifespan, with average increases up to age 25, non-significant change between 25-50 years, and beyond age 50 decreases up to (at least) age 65. While WM microstructure is substantially heritable, in the sparse studies investigating heritability of change in WM integrity so far, most evidence suggests there is no significant influence of genes. GWAS in larger samples may be required to identify robust effects of specific common genetic variants.

Genetics Other

Early life, Adolescence, Aging ¹

Diffusion MRI Modeling and Analysis ²

White Matter Anatomy, Fiber Pathways and Connectivity

Aging

Development

Meta- Analysis

Plasticity

Statistical Methods

White Matter

WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC