Whitman Ethan T, Elliott Maxwell L, Knodt Annchen R, Abraham Wickliffe C, Anderson Tim J, Cutfield Nick, Hogan Sean, Ireland David, Melzer Tracy R, Ramrakha Sandhya, Sugden Karen, Theodore Reremoana, Williams Benjamin S, Caspi Avshalom, Moffitt Terrie E, Hariri Ahmad R
Department of Psychology and Neuroscience, Duke University, Durham, NC, USA.
Department of Psychology, Center for Brain Science, Harvard University, Cambridge, MA, USA.
bioRxiv. 2024 Aug 22:2024.08.19.608305. doi: 10.1101/2024.08.19.608305.
To understand how aging affects functional decline and increases disease risk, it is necessary to develop accurate and reliable measures of how fast a person is aging. Epigenetic clocks measure aging but require DNA methylation data, which many studies lack. Using data from the Dunedin Study, we introduce an accurate and reliable measure for the rate of longitudinal aging derived from cross-sectional brain MRI: the Dunedin Pace of Aging Calculated from NeuroImaging or DunedinPACNI. Exporting this measure to the Alzheimer's Disease Neuroimaging Initiative and UK Biobank neuroimaging datasets revealed that faster DunedinPACNI predicted participants' cognitive impairment, accelerated brain atrophy, and conversion to diagnosed dementia. Underscoring close links between longitudinal aging of the body and brain, faster DunedinPACNI also predicted physical frailty, poor health, future chronic diseases, and mortality in older adults. Furthermore, DunedinPACNI followed the expected socioeconomic health gradient. When compared to brain age gap, an existing MRI aging biomarker, DunedinPACNI was similarly or more strongly related to clinical outcomes. DunedinPACNI is a "next generation" MRI measure that will be made publicly available to the research community to help accelerate aging research and evaluate the effectiveness of dementia prevention and anti-aging strategies.
为了了解衰老如何影响功能衰退并增加疾病风险，有必要开发出准确可靠的方法来衡量一个人的衰老速度。表观遗传时钟可测量衰老，但需要DNA甲基化数据，而许多研究都缺乏这些数据。利用达尼丁研究的数据，我们引入了一种基于横断面脑磁共振成像（MRI）得出的准确可靠的纵向衰老速度测量方法：即通过神经影像计算得出的达尼丁衰老速度（Dunedin Pace of Aging Calculated from NeuroImaging，简称DunedinPACNI）。将该测量方法应用于阿尔茨海默病神经影像倡议组织（Alzheimer's Disease Neuroimaging Initiative）和英国生物银行（UK Biobank）的神经影像数据集后发现，DunedinPACNI值越高预示着参与者会出现认知障碍、脑萎缩加速以及发展为确诊痴呆症。DunedinPACNI值越高还预示着老年人身体虚弱、健康状况不佳、未来患慢性病以及死亡，这突出了身体和大脑纵向衰老之间的紧密联系。此外，DunedinPACNI呈现出预期的社会经济健康梯度。与现有的MRI衰老生物标志物脑年龄差距相比，DunedinPACNI与临床结果的相关性相似或更强。DunedinPACNI是一种“下一代”MRI测量方法，将向研究界公开提供，以帮助加速衰老研究，并评估痴呆症预防和抗衰老策略的有效性。
