The Study Of Prostate Cancer Patients With Androgen-deprivation Therapy Induced Cognitive Impairment

Objective Prostate cancer is the second most frequently diagnosed cancer of men wordwide.Documented incidence rates of prostate cancer differ considerably across countries worldwide because of geographic and racial differences, higher in Australia/New Zealand, Europe and America, with lower incidence rates in Asia and North Africa.Although the incidence rate of our country is lower than the incidence rate of prostate cancer in the United States and Europe. But the trend is rising in recent years. According to the survey results worldwide in 2012,the annual growth rate of incidence rate in China is 2.1% during 1988-1994.The incidence rate of prostate cancer growed 13.4% every year during 1994-2002. Although PC can occur at any age, its onset is typically between the ages 75 and 79.In our country, less than 60 year old men had relatively low incidence rates. In USA, more than 70% PC patients are at the age of 65 and older, the age of 50 years old is rare. The elderly male population is susceptible to cognitive impairment related to drug. For years, androgen-ablation therapy was indicated solely for patients with late-stage prostate cancer. However, researchers have proven a survival benefit for androgen deprivation therapy(ADT) in certain situations for earlier stages of prostate cancer. studies have indicated that androgen-ablation therapy in conjunction with primary radiotherapy and surgery could lead to improved overall survival compared with radiotherapy or surgery alone.The men with PC may use ADT for a long duration, such that ADT for men with risingPSA may last for as long as 5 to 10 years or more.Moreover,PC have a relatively long survival time.Given the above factors, side effects are important to consider, especially since adverse effects and complications of treatment may impact health and quality of life more than the cancer itself.ADT leads to prolonged testosterone deficiency, which is associated with numerous adverse effects, including an increased risk for cardiovascular disease, increased serum cholesterol, triglycerides, insulin resistance,body mass index and fat body mass. Recently,PC patients frequently complain of memory or attention problems during or after ADT.The objective of our study is how to use the scientific method to measure and evaluate the association between ADT and cognition.Prior studies using traditional neuropsychological testing in patients with prostate cancer treated with ADT showed equivocal findings; results were interpreted as showing either no effect,impaired function, or a mixed effect of ADT(with patients improving on some tests but doing worse on others) There are rarely reported about the ADT effect on cognition in Chinese PCa patients in previous studies.The neural mechanisms of cognitive impairment caused by ADT are still unclear.Therefore,The primary purpose of this study was to evaluate the effects of ADT on cognition in Chinese PCa patients with cross-sectional case control study.At the same time,we use prospective memory paradigm to assess their prospective memory, and speculate on its possible mechanism of injury.Methods Participants are choosed from PCa patients in the wards and outpatient Department, Radiation Oncology Department and Urology Department of Anhui Provincial Hospital and the First Affiliated Hospital of Anhui Medical University during August 2011 to Desember 2013, and all had been diagnosed with non-metastatic PC. Participants included PC patients who had undergone ADT(ADT group, n=33) and patients who did not undergo ADT(non-ADT group, n=32),as well as age- and education- matched healthy controls(HC group, n=35). All participants were examined using the neuropsychological battery aimed at assessing severalcognitive domains including attention, memory and information processing performance. In the study of prospective memory we incorporated the larger sample size. The ADT group, which consisted of 45 patients, had received ADT treatment for 6 months. The non-ADT group, which consisted of 38 PC patients who did not receive ADT, served as a control group. The healthy control group consisted of 41 healthy elderly male subjects who were undergoing physical examinations in the outpatient clinic during the same time. For the ADT group, non-ADT group, and healthy control group, there were 43, 35, and 40 subjects, respectively, all of whom provided complete medical histories and personal information as instructed and completed all neuropsychological tests. All participants were administered with a neuropsychological battery of tests including EBPM and TBPM tasks. We analysed neuropsychological characteristics of three groups, to find the differences among the PM performances in three groups and the correlation between PM and the scores of the neuropsychological background tests.Results As compared with HC and non-ADT groups, there were no significant differences in Immediate Recall,Delayed Recall,the Backward,VFT,TMT test A, Stroop test A and Stroop test B among three groups(p>0.05).Recognition and the correct number of Forward were lower in the ADT group(p<0.05). The reaction time of Stroop test B, Stroop test C and TMT test B were longer in the ADT group(p<0.05). There were no significant differences in neuropsychological background tests between the non-ADT group and the healthy control group(p>0.05).During the EBPM task, the ADT group obtained significantly lower scores than the non-ADT and HC group did, while no significant differences in the TBPM task scores were found among these three groups. There were no significant differences in the EBPM task scores(p > 0.05) between the non-ADT group and the healthy control group.Correlation analyses within the ADT group indicated that the patients’ EBPM scores were significantly correlated with a measure of episodic memory as well as with executive function. No significantcorrelations were found between scores of prospective memory tests and the ages of the participants or the Mo CA, HAMD or HAMA scores(all p’s > 0.10). Within the non-ADT group and the healthy controls, no correlations were found demonstrated among these variables.Conclusions The findings revealed that the Chinese PC patients receiving ADT showed cognitive impairments in several domains including memory, attention and information processing performance.This study demonstrated that PC patients receiving ADT may have selective reductions in EBPM performance but unimpaired TBPM performance and that these deficits may result from the changes of function and structure of the Prefrontal Cortex induced by ADT.