Australian Alzheimer's Research Foundation, Ralph and Patricia Sarich Neuroscience Research Institute, Nedlands, Western Australia, Australia; School of Psychological Science, University of Western Australia, Nedlands, Western Australia, Australia.
Collaborative Genomics and Translation Group, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia; Centre for Precision Health, Edith Cowan University, Joondalup, Western Australia, Australia; School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley, Western Australia, Australia.
Horm Behav. 2021 May;131:104966. doi: 10.1016/j.yhbeh.2021.104966. Epub 2021 Mar 11.
Age-related decrease in testosterone levels is a potential risk factor for cognitive decline in older men. However, observational studies and clinical trials have reported inconsistent results on the effects of testosterone on individual cognitive domains. Null findings may be attributed to factors that studies have yet to consider. In particular, individual variations in polyglutamine (CAG) length in the androgen receptor (AR) gene could alter androgenic activity in brain regions associated with cognitive processes including memory and executive functions. However, the role of AR CAG repeat length as a moderator of the relationship between testosterone levels and cognition has not been investigated. Therefore, we aimed to examine the relationship between baseline calculated free testosterone (cFT) levels, change in cFT levels over 18 months and CAG repeat length on cognitive performance in memory, executive function, language, attention and processing speed domains. These relationships were examined in 304 cognitively normal older male participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Ageing. In the attention and processing speed domain, a short CAG repeat length appears to exacerbate the effects of low baseline cFT levels that are also lower than expected at follow-up. These results highlight that individual variations in AR CAG repeat length should be considered in future studies and clinical trials that examine the complex relationship between testosterone and cognition.
随着年龄增长，睾丸激素水平下降是老年男性认知能力下降的一个潜在风险因素。然而，观察性研究和临床试验报告的睾丸激素对个体认知领域的影响结果并不一致。阴性结果可能归因于研究尚未考虑的因素。特别是，雄激素受体（AR）基因中的多聚谷氨酰胺（CAG）长度的个体差异可能改变与认知过程（包括记忆和执行功能）相关的大脑区域的雄激素活性。然而，AR CAG 重复长度作为睾丸激素水平与认知之间关系的调节剂的作用尚未得到研究。因此，我们旨在研究基线计算游离睾酮（cFT）水平、18 个月内 cFT 水平变化与记忆、执行功能、语言、注意力和处理速度领域认知表现的 CAG 重复长度之间的关系。这些关系在澳大利亚影像学、生物标志物和生活方式（AIBL）衰老研究的 304 名认知正常的老年男性参与者中进行了研究。在注意力和处理速度领域，短的 CAG 重复长度似乎会加剧低基线 cFT 水平的影响，而这些低水平在随访时也低于预期。这些结果强调，在未来研究和临床试验中，应考虑 AR CAG 重复长度的个体差异，以研究睾丸激素和认知之间复杂的关系。
