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Men Treated For Prostate Cancer Have A Decreased Incidence of Dementia Fill box to show platform used: PC Macintosh Richard L. Bowen1, Heather Beaird2, Craig S. Atwood3, Mark A. Smith2, Alfred A. Rimm2 Pharmaceutical Corp., Raleigh, NC, USA; 2Case Western Reserve University, Cleveland, OH, USA; 3University of Wisconsin, Madison, WI, USA. Years Probability of Developing Dementia (Patients Aged 70 to 72 at Time of Procedure) Cholecystectomy Group Exclusions Transurethral Prostatectomy Group Exclusions Hypothalamic-Pituitary-Gonadal Axis Years Probability of Developing Dementia (Patients Aged 73 to 75 at Time of Procedure) Gallbladder Enlarged Prostate Inguinal Hernia Age 67-69 1.0 1.8 2.2 2.4 Age 70-72 1.0 1.8 2.1 2.2 Age 73-75 1.0 2.0 2.8 2.9 Email: Prostate Cancer Phone: Transurethral prostatectomy Herniorrhaphy Cholecystectomy Prostatectomy 5 Year Relative Risk of Dementia DISCUSSION This study provides convincing evidence that, regarding hormones, it is the age-related increase in gonadotropins rather than the loss of sex steroids that contributes to the pathogenesis of Alzheimer’s disease. This statement is based on the fact that more than 10 prospective studies have failed to demonstrate a statistically significant association between circulating levels of androgens and prostate cancer risk. In other words, since there is a clearly an inverse relationship between prostate cancer and dementia, but no relationship between prostate cancer and testosterone, it is unlikely testosterone is playing a direct role in the pathogenesis of Alzheimer’s disease. The most common treatment, GnRH agonists, suppresses both gonadotropins and sex steroids. If the difference in the rate of dementia seen in this study is due to the GnRH agonist, its effect would be exceptional. For example, among the 73 to 75 year age group, if it is assumed that the 59% of patients in the prostatectomy group (whose risk is shown to be 0.062) really has a risk of developing D/AD equivalent to that of say, the cholecystectomy group (0.095). Then the 41% of patients believed to have received a GnRH agonist would actually have an exceptionally decreased risk of 0.015 for dementia. CONCLUSION At five years, men who underwent surgical prostatectomy for prostate cancer have approximately half the risk of developing dementia as men who undergo other common surgical procedures. Further research is needed to determine if this difference is due to GnRH agonist therapy. Phase II clinical trials using the GnRH agonist leuprolide to treat patients with Alzheimer’s disease are currently underway and should provide important information as to its effect. Alt. Contact (Last, First): Herniorrhaphy Group Exclusions Email: Prostatectomy Group Exclusions Phone: A serendipitous encounter with a patient has led us to examine the possibility that hormones of the hypothalamic-pituitary-gonadal axis other than the sex steroids may directly contribute to the pathogenesis of Alzheimer’s disease. After he patient received the gonadotropin releasing hormone (GnRH) agonist leuprolide acetate a common hormonal treatment for prostate cancer, his wife noticed an improvement in his cognitive function which subsequently remained stable for more than five years. To ascertain whether treatment with GnRH agonists such as leuprolide has a beneficial effect in Alzheimer’s disease, an epidemiological study was performed. The study was designed to determine the incidence of dementia in men who underwent prostatectomy for prostate cancer and would have likely received a GnRH agonist (it is estimated that approximately 40% of prostatectomy patients will experience disease recurrence and undergo GnRH agonist therapy). All in-patient Medicare hospitalization claims for men aged 67 to 75 during the years 1984 through 1997 were analyzed and the incidence of dementia in men who underwent prostatectomy for prostate cancer (n=139,414) was compared to three control groups who would not have received GnRH agonist therapy. The control groups included men with; gallbladder disease who underwent cholecystectomy (n=255,493), inguinal hernia who underwent herniorrhaphy (n=162,115), and benign prostatic hyperplasia who underwent transurethral prostatectomy (n=635,615). The cohorts were separated into three groups based on their age at the time of the procedure; A) 67-69, B) 70-72, and C) 73-75. The prostate cancer group was designated the reference group with a risk of developing dementia of 1.0 At five years post-procedure, the relative risk of dementia for men with BPH was 2.2, 2.1, and 2.8 for age groups A, B, and C respectively. For men with gallbladder surgery the risk was 1.8, 1.8, 2.0 and for the hernia group it was 2.4, 2.2, and 2.9. Along with our other findings, these results lend further support to the premise that gonadotropins promote the development of AD and that GnRH agonists are a potential therapeutic agent for its treatment. Clinical trials using leuprolide acetate in the treatment of mild to moderate Alzheimer’s disease are currently underway. Probability of Developing Dementia (Patients Aged 67 to 69 at Time of Procedure) Dept: ABSTRACT Name (Last, First): 1Voyager On your proof: check one box & return to ITAC: OK Printed for Research ShowCASE by Instructional Technology & Academic Computing (ITAC), 368-3777 Years Changes marked on proof; a disk with corrections is being submitted