Androgen Deprivation Therapy Unrelated to Alzheimer’s Disease in the UK Biobank Cohort

In a meta-analysis of 14 studies, men who received androgen deprivation therapy (ADT) for prostate cancer had a higher risk of dementia and/or Alzheimer disease (AD) than men who did not receive ADT. The effect was more pronounced when ADT was given for more than 12 months. However, in all these analyses, two of the strongest AD risk factors after age, family history of AD and the apolipoprotein e4 allele, were not included. In the current study, we have used data from the UK Biobank (UKB) that incorporates these two factors.Our analysis included all subjects with prostate cancer and AD. Prostate cancer diagnosis was ascertained using the 10th Revision of the International Classification of Diseases (ICD10), C61. AD diagnosis was ascertained using the 10th Revision of the International Classification of Diseases (ICD10) G30. Single nucleotide polymorphism (SNP) data for rs429358 and rs7412 were used to determine ApoE genotypes. ADT was in UKB field 20003, Treatment/medication code, Medications. Family history of AD was in UKB data fields 20107, Illnesses of father; 20110, Illnesses of mother; 20111, Illnesses of siblings.We studied 13,203 men with prostate cancer. The age of 132 subjects that received ADT was 64±5.6 (mean±standard deviation), and the age of 13,071 subjects that did not receive ADT was 62±5.6 (p<0.001). ADT was not associated with AD, but Apoe3e3 was significantly associated with diminished risk of AD when compared to e4e4. Moreover, every year of age was associated with increased risk of AD. ADT was unrelated to AD (p=0.997).Our UK Biobank data analysis does not confirm that ADT causes AD in men with prostate cancer. Large studies that include family history of AD and ApoeE genotype are needed. Mendelian randomization would also be desirable for a more definitive result.