Effects of androgen deprivation on cerebral morphometry in prostate cancer patients--an exploratory study

Abstract

Background: Androgen deprivation therapy (ADT) is a common treatment for non-metastatic, low-risk prostate cancer, but a potential side effect of ADT is impaired brain functioning. Previous work with functional magnetic resonance imaging (MRI) demonstrated altered prefrontal cortical activations in cognitive control, with undetectable changes in behavioral performance. Given the utility of brain imaging in identifying the potentially deleterious effects of ADT on brain functions, the current study examined the effects of ADT on cerebral structures using high resolution MRI and voxel-based morphometry (VBM).

Methods: High resolution T1 weighted image of the whole brain were acquired at baseline and six months after ADT for 12 prostate cancer patients and 12 demographically matched non-exposed control participants imaged at the same time points. Brain images were segmented into gray matter, white matter and cerebral ventricles using the VBM toolbox as implemented in Statistical Parametric Mapping 8.

Results: Compared to baseline scan, prostate cancer patients undergoing ADT showed decreased gray matter volume in frontopolar cortex, dorsolateral prefrontal cortex and primary motor cortex, whereas the non-exposed control participants did not show such changes. In addition, the decrease in gray matter volume of the primary motor cortex showed a significant correlation with longer reaction time to target detection in a working memory task.

Conclusions: ADT can affect cerebral gray matter volumes in prostate cancer patients. If replicated, these results may facilitate future studies of cognitive function and quality of life in men receiving ADT, and can also help clinicians weigh the benefits and risks of hormonal therapy in the treatment of prostate cancer.

Figure 1. Changes in cerebral gray matter volumes in frontal cortices as demonstrated by voxel-based morphometry.

Voxelwise paired t test between baseline and 6 months for ADT (patients who received 6 months of androgen deprivation therapy) and Control (patients who did not receive any hormonal therapy) group, at p<0.001, uncorrected. The difference in gray matter volume, as reflected by a map of T values (color bar), is shown here on a structural brain image in axial sections, from z = -26 to z = +62, with adjacent sections 4 mm apart. Warm color: baseline >6 months; Cool color: 6 months>baseline. Neurological orientation: Right (R) = right. ADT but not control patients showed decreased gray matter volume in the primary motor cortex (PMC), frontopolar cortex (FPC), and dorsolateral prefrontal cortex (DLPFC).

Figure 2. Changes (mean ± s.d.) in Gray matter volume (GMV) for the three regions of interest: primary motor cortex (PMC), frontopolar cortex (FPC), and dorsolateral prefrontal cortex (DLPFC), for the ADT (blue) and control (red) group (upper panel).

A decrease in the GMV of the PMC correlated with prolonged reaction time to target detection during the zero-back condition in the ADT group (lower panel). Because of the small sample size, we used a Spearman regression for correlation (p<0.0042, rho = −0.7832). The result of Pearson regression was also significant: p<0.0049.