The American Journal of Geriatric Psychiatry: White Noise—Is Anxiety in Late-Life Associated With White Matter Hyperintensity Burden?

Anxiety disorders are prevalent in late life, with symptoms including severe (uncontrollable) worry and rumination. Late-life anxiety, worry, and rumination in the context of the aging brain can be associated with differences in volume and thickness of gray matter regions in the brain, as well as altered functional connectivity in the networks involved in emotion generation and regulation, but these changes may differ by anxiety phenotypes. 

To improve our understanding of age-related changes in white matter on late-life anxiety, a team including Andrew Gerlach, PhD (Assistant Professor of Psychiatry); Helmet Karim, PhD (Assistant Professor of Psychiatry and Bioengineering); Dana Tudorascu, PhD (Associate Professor of Psychiatry and Biostatistics); Meryl Butters, PhD (Professor of Psychiatry and Clinical and Translational Science); and Carmen Andreescu, MD (Professor of Psychiatry), from the University of Pittsburgh, investigated the relationship between global anxiety, worry, and rumination and white matter hyperintensities. The presence of white matter hyperintensities on magnetic resonance imaging (MRI) is a sign of age-related deterioration of the white matter, and are robustly associated with depression in late life. 

The investigators recruited 110 individuals aged 50 or older, who did or did not have anxiety and/or mood disorders, and assessed their worry severity and cognitive function. Participants underwent one MRI session.

Results of the study, recently published in the American Journal of Geriatric Psychiatry, revealed higher white matter hyperintensities burden was associated with lower global anxiety and worry severity. Further analysis of the results revealed the complexities of this relationship, with executive function playing an important role: In the older half of the cohort and individuals with accelerated white matter hyperintensity accumulation, executive function was correlated with both worry severity and white matter hyperintensities, but this was not the case in the younger half or individuals with a normal level of white matter hyperintensities.

“These surprising findings underscore how complex the relationship between the brain and behavior are. I'm very excited for the longitudinal follow-up study currently underway that will help clarify some of the causal mechanisms,” said Dr. Gerlach, the study’s first author. 

“These results also underscore the different neural underpinning of anxiety and depression later in life," said Dr. Andreescu, the study’s senior author.

White Noise—Is Anxiety in Late-Life Associated with White Matter Hyperintensity Burden?
Gerlach AR, Karim HT, Lee S, Kolobaric A, Tudorascu DL, Butters MA, Andreescu C.
The American Journal of Geriatric Psychiatry. Volume 32, Issue 1, January 2024, Pages 83-97