Sex in Alzheimer disease

阿尔茨海默病中的性行为

基本信息

批准号：
9896747
负责人：
Jennifer S Yokoyama
金额：
$ 16.1万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2020-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9896747
关键词：
Adopted Age Age of Onset Aging Alleles Alzheimer disease screening Alzheimer&apos s Disease Alzheimer&apos s disease risk Amyloid Apolipoprotein E Architecture Area Autopsy Caring Clinical Clinical Research Cognitive Data Dementia Development Disease Early Diagnosis Early Intervention Elderly Funding Future Genetic Genomics Genotype Goals Healthcare High Risk Woman Hippocampus (Brain)Impaired cognition Individual Late Onset Alzheimer Disease Measures Medial Methods Nerve Degeneration Neurofibrillary Tangles Onset of illness Patient Recruitments Population Positron-Emission Tomography Public Health Research Risk Senile Plaques Sex Differences Survival Analysis Temporal Lobe Testing Time United States National Institutes of Health Woman age related aging brain amyloid pathology clinical predictors cognitive development cohort cost direct application effective therapy entorhinal cortex genetic variant hazard health care settings human very old age (85+)implementation research improved in vivo innovation men multimodality neuropathology novel older men older women phenotypic data programs sex tau Proteins tool

项目摘要

PROJECT SUMMARY With the aging of the US population and high costs associated with caring for the cognitively impaired elderly, identifying older individuals at greatest risk for developing Alzheimer's disease (AD) is of utmost societal and clinical importance. Currently no treatments effectively slow the progression of AD or other causes of cognitive decline, but billions of dollars are being invested to develop effective treatments. Development of inexpensive, genomic methods that go beyond APOE to identify individuals at risk for cognitive decline has the potential to greatly accelerate the development of new treatments. The overall significance of this project is that it will use a validated polygenic score to more comprehensively understand when older men and women are at highest risk for cognitive decline and Alzheimer's neurodegeneration. Using an age-dependent approach, we have recently developed and validated a novel `polygenic hazard score' (PHS) for quantifying AD dementia age of onset, even among APOE E3/3 individuals, who constitute the majority of all US individuals with AD dementia. In this proposal, our objective is to comprehensively assess whether sex differences influence how PHS predicts cognitive decline and AD neurodegeneration and how age influences this relationship. Leveraging genotypic and multi-modal phenotypic data from several existing NIH-funded cohorts (total n > 7,000), we will investigate whether age-dependent sex differences modify cognitive decline, postmortem and in vivo AD neuropathology and medial temporal lobe volume loss.

项目概要随着美国人口老龄化以及照顾认知障碍老年人的高昂费用，确定罹患阿尔茨海默氏病 (AD) 风险最高的老年人对于社会和社会至关重要临床重要性。目前尚无治疗方法能有效减缓 AD 或其他认知障碍的进展下降，但正在投资数十亿美元来开发有效的治疗方法。开发物美价廉，超越 APOE 来识别有认知能力下降风险的个体的基因组方法有可能大大加速了新疗法的开发。该项目的总体意义在于，它将利用经过验证的多基因评分，可以更全面地了解老年男性和女性何时处于最高水平认知能力下降和阿尔茨海默氏症神经变性的风险。使用与年龄相关的方法，我们有最近开发并验证了一种新的“多基因危险评分”（PHS），用于量化 AD 痴呆症年龄即使在 APOE E3/3 个体中，他们也占美国所有 AD 痴呆症患者的大多数。在本提案中，我们的目标是全面评估性别差异是否影响 PHS 预测认知能力下降和 AD 神经变性以及年龄如何影响这种关系。杠杆作用来自 NIH 资助的几个现有队列（总数 > 7,000）的基因型和多模式表型数据，我们将研究年龄依赖性性别差异是否会影响认知能力下降、死后和体内AD 神经病理学和内侧颞叶容量损失。