White matter alterations in brain strongly associated with cognitive impairment

Key takeaways:

• Those with major depressive disorder had lower cognitive performance and more depressive episodes vs. healthy controls.
• Alterations of white matter integrity were more significant in those with MDD.

Alterations in white matter integrity were linked to cognitive impairment, and associations were strongest in those with major depressive disorder compared with healthy controls, according to new research.

“Approximately 94% of individuals with [major depressive disorder] have cognitive deficits during acute depression and these symptoms persist even after remission in approximately 73% of individuals,” Kira Flinkenflugel, MSc, doctoral student at the Institute for Translational Psychiatry at the University of Münster in Germany, and colleagues wrote.

“Cognitive deficits are predictors of poor treatment response and have been prospectively associated with adverse disease outcomes.”

As the underlying mechanisms of cognitive deficits are poorly understood, effective treatment strategies remain elusive, while new evidence suggests that alterations in the brain’s white matter may trigger cognitive dysfunction in MDD, Flunkenflugel and colleagues wrote.

They sought to examine the associations between alterations in white matter integrity, cognitive decline and MDD disease course in a cohort of individuals from Germany.

They conducted the Marburg-Münster Affective Disorders Cohort Study, a prospective, observational case-control clinical trial. It included 881 adults of Caucasian ancestry, who were largely recruited from local psychiatric hospitals in Münster, Germany, and Marburg, Germany. A total of 418 individuals had a diagnosis of MDD (mean age, 36.8 years; 66% women) along with 463 healthy controls (mean age 35.6 years; 64% women).

At baseline, which occurred between September 2014 and June 2019, all participants underwent diffusion-weighted imaging, submitted to seven neuropsychological tests and had detailed clinical data collected. Follow-up assessments were made between October 2016 and May 2021 for all enrollees by the same methods at baseline.

Tracking of disease course was accomplished by patient-led life charting, in which participants recounted the type, time and duration of their depressive episodes, along with sick leave and/or hospitalizations. Changes in depression symptom severity were measured by the 21-item Hamilton Depression Rating Scale.

According to results, those with MDD registered lower cognitive performance, more depressive episodes, longer duration and more hospitalizations compared with healthy controls at all time points across the study and follow-up intervals.

The researchers found a significant association between cognitive impairment and white matter integrity decline for both groups for all time intervals; for those with MDD, white matter integrity alteration and negative disease course independently predicted lower cognitive performance at follow-up.

Diffusion-weighted imaging analyses revealed a significant interaction between diagnosis and time, coupled with a steeper decline in white matter integrity of the superior longitudinal fasciculus over time in participants with MDD, compared with healthy counterparts.

“Our study highlights the relevance of white matter microstructure in participants with [major depressive disorder] and provides evidence that changes in white matter integrity might be a possible neural mechanism associated with cognitive performance alterations,” Flinkenflugel and colleagues wrote.