White matter brain aging in relationship to schizophrenia and its cognitive deficit

We hypothesized that cerebral white matter deficits in schizophrenia (SZ) are driven in part by accelerated white matter aging and are associated with cognitive deficits. We used a machine learning model to predict individual age from diffusion tensor imaging features and calculated the delta age (Aage) as the difference between predicted and chronological age. Through this approach, we translated multivariate white matter imaging features into an age-scaled metric and used it to test the temporal trends of accelerated aging-related white matter deficit in SZ and its association with the cognition. A feature selection procedure was first employed to choose fractional anisotropy values in 34 of 43 white fiber tracts. Using these features, a machine learning model was trained based on a training set consisted of 107 healthy controls (HC). The brain age of 166 SZs and 107 HCs in the testing set were calculated using this model. Then, we examined the SZ-HC group effect on Aage and whether this effect was moderated by chronological age using the regression spline model. The results showed that Aage was significantly elevated in the age > 30 group in patients (p < 0.001) but not in age <= 30 group (p = 0.364). Aage in patients was significantly and negatively associated with both working memory (3 = & minus;0.176, p = 0.007) and processing speed (3 = & minus;0.519, p = 0.035) while adjusting sex and chronological age. Overall, these findings indicate that the Aage is elevated in SZs and become significantly from the third decade of life; the increase of Aage in SZs is associated with the declined neurocognitive performance. (c) 2021 Elsevier B.V. All rights reserved.

Automated summary

Cerebral white matter deficits in schizophrenia may be partially due to accelerated white matter aging, as evidenced by the machine learning analysis of diffusion tensor imaging features. The study found that the increase of brain age in patients with schizophrenia is associated with declined neurocognitive performance.