Effects of Androgen Deprivation on Cerebral Morphometry in Prostate Cancer Patients – An Exploratory Study

Abstract

BackgroundAndrogen 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).MethodsHigh 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.ResultsCompared 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.ConclusionsADT 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.

Changes in cerebral metabolic activity in men undergoing androgen deprivation therapy for non-metastatic prostate cancer

“…3–5 While not all studies support this connection, 6 there is an indication that ADT decreases cognitive function 7–9 , brain function 10 and neuronal structure in humans, all of which are prodromal indices of progressive cognitive decline and possible AD. 11 The disease mechanism of AD is unknown, and complex. However, several side effects and impacts of ADT are known to be involved in proposed AD disease mechanisms including loss of testosterone and estradiol.…”

No increased risk of dementia in patients receiving androgen deprivation therapy for prostate cancer: a 5-year follow-up study

“…Recent studies suggest that ADT use may be associated with structural and functional changes in brain areas relevant to dementia 14151617. Some studies have suggested that the use of ADT might cause the impairment of cognitive function, which is one of the common symptoms of dementia; however, the association between ADT and cognitive impairment still remains controversial 181920212223.…”

Cognitive impairment following hormone therapy: current opinion of research in breast and prostate cancer patients

“…So far, only a few studies have explored biomarkers and other potential correlates of cognitive functioning in hormone therapy patients. For example, investigators have examined neuronal activation in ADT patients and have found altered activation patterns [62, 63] and changes in brain structure [64]. However, until there is more definitive evidence regarding the association between hormone therapy use and cognitive impairment, investigations into neurobiological and pathophysiological mechanisms should, in our opinion, be secondary or an adjunct to well controlled neuropsychological studies.…”