Effects of Androgen Deprivation Therapy on Preclinical Symptoms of Alzheimer's Disease

雄激素剥夺疗法对阿尔茨海默病临床前症状的影响

基本信息

  • 批准号:
    9364864
  • 负责人:
  • 金额:
    $ 65.48万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-07-15 至 2022-05-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Low levels of testosterone in older men have been associated with an increased risk of developing Alzheimer's disease (AlzD). Declines in testosterone begin as early as the mid-thirties, and by late-middle age contribute to many of the physiological and psychological complaints associated with male aging. The timing of these changes overlaps with the preclinical stage of AlzD, a period that has been targeted as the optimal time during which interventions for the disease may have the greatest effect. The degree to which declines in testosterone influence the preclinical markers of AlzD – cognition, beta-amyloid (Aβ), and tau – represents a significant knowledge gap that has yet to be adequately examined. In the proposed study we will examine cognitively normal men undergoing androgen deprivation therapy (ADT) for non-metastatic prostate cancer, as well as a non-ADT prostate cancer positive control group, with the goal of clarifying the effects of testosterone depletion on preclinical markers of AlzD. ADT is a commonly used treatment for prostate cancer, and offers a unique scenario through which to study the impact of dramatic testosterone depletion on the preclinical markers of AlzD. Although ADT is an effective cancer treatment, it is associated with a wide variety of side effects, including an increased risk for AlzD. In Aim 1, we will characterize the effects of ADT on cognitive function. We will assess an array of cognitive tests, and utilize a well validated measure of cognitive effort, task-evoked pupil dilation, to assess cognitive changes brought on by ADT. We hypothesize that ADT will tax cognitive resources, resulting in changes in effort and performance. In Aim 2, we will test whether the polygenic risk for AlzD alters the effects of ADT on cognition. We hypothesize that changes in AlzD sensitive cognitive abilities will be greater in individuals at greater genetic risk for AD. In Aim 3, will determine the extent to which measures of Aβ and tau are influenced by ADT. We will utilize gold standard CSF based measures, and neuronally-derived exosomes from plasma to acquire levels of Aβ40, Aβ42, total-tau, and phosphorylated-tau. We hypothesize that over the course of ADT we will observe significant changes in Aβ and tau levels, and that these changes will be more pronounced in those at greater genetic risk for AlzD. Moreover, we hypothesize that changes in Aβ and tau will be more strongly correlated with cognitive performance and cognitive effort in those at greater genetic risk for AlzD. Assessments will be conducted pre-treatment, and then again at 6 and 12 month follow-ups (three assessments in total). This naturalistic study of a unique clinical population offers a valuable opportunity to examine the impact of changes in a single AlzD risk factor (testosterone level). In contrast to the years or decades that it might take for clinically significant declines in testosterone to manifest in standard populations, we will be able to observe the impact of testosterone depletion on some of the earliest markers of AlzD-related processes over a condensed period of time. As a result, the proposed study will provide novel insights into the role of androgen action in the pathogenesis of AlzD.
项目总结

项目成果

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Matthew S Panizzon其他文献

Matthew S Panizzon的其他文献

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{{ truncateString('Matthew S Panizzon', 18)}}的其他基金

Understanding the relationship between female reproductive span and dementia risk
了解女性生育期与痴呆风险之间的关系
  • 批准号:
    10468823
  • 财政年份:
    2021
  • 资助金额:
    $ 65.48万
  • 项目类别:
Understanding the relationship between female reproductive span and dementia risk
了解女性生育期与痴呆风险之间的关系
  • 批准号:
    10301699
  • 财政年份:
    2021
  • 资助金额:
    $ 65.48万
  • 项目类别:
Effects of Androgen Deprivation Therapy on Preclinical Symptoms of Alzheimer's Disease
雄激素剥夺疗法对阿尔茨海默病临床前症状的影响
  • 批准号:
    10176322
  • 财政年份:
    2017
  • 资助金额:
    $ 65.48万
  • 项目类别:
Testosterone-Androgen Receptor Genetics: Role in Cognitive and Biological Aging
睾酮雄激素受体遗传学:在认知和生物衰老中的作用
  • 批准号:
    9281627
  • 财政年份:
    2014
  • 资助金额:
    $ 65.48万
  • 项目类别:
Testosterone-Androgen Receptor Genetics: Role in Cognitive and Biological Aging
睾酮雄激素受体遗传学:在认知和生物衰老中的作用
  • 批准号:
    8912967
  • 财政年份:
    2014
  • 资助金额:
    $ 65.48万
  • 项目类别:
Testosterone-Androgen Receptor Genetics: Role in Cognitive and Biological Aging
睾酮雄激素受体遗传学:在认知和生物衰老中的作用
  • 批准号:
    8750039
  • 财政年份:
    2014
  • 资助金额:
    $ 65.48万
  • 项目类别:
Testosterone-Androgen Receptor Genetics: Role in Cognitive and Biological Aging
睾酮雄激素受体遗传学:在认知和生物衰老中的作用
  • 批准号:
    9066056
  • 财政年份:
    2014
  • 资助金额:
    $ 65.48万
  • 项目类别:

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