Department of Internal Medicine, University of North Texas Health Science Center, Fort Worth, Texas, United States of America.
PLoS One. 2013 Jul 11;8(7):e68848. doi: 10.1371/journal.pone.0068848. Print 2013.
Alzheimer's disease (AD) is a devastating public health problem that affects over 5.4 million Americans. Depression increases the risk of Mild Cognitive Impairment (MCI) and AD. By understanding the influence of depression on cognition, the potential exists to identify subgroups of depressed elders at greater risk for cognitive decline and AD. The current study sought to: 1) clinically identify a sub group of geriatric patients who suffer from depression related cognitive impairment; 2) cross validate this depressive endophenotype of MCI/AD in an independent cohort.
Data was analyzed from 519 participants of Project FRONTIER. Depression was assessed with the GDS30 and cognition was assessed using the EXIT 25 and RBANS. Five GDS items were used to create the Depressive endophenotype of MCI and AD (DepE). DepE was significantly negatively related to RBANS index scores of Immediate Memory (B=-2.22, SE=.37, p<0.001), visuospatial skills (B=-1.11, SE=0.26, p<0.001), Language (B=-1.03, SE=0.21, p<0.001), Attention (B=-2.56, SE=0.49, p<0.001), and Delayed Memory (B=-1.54, SE = 037, p<0.001), and higher DepE scores were related to poorer executive functioning (EXIT25; B=0.65, SE=0.19, p=0.001). DepE scores significantly increased risk for MCI diagnosis (odds ratio [OR] = 2.04; 95% CI=1.54-2.69). Data from 235 participants in the TARCC (Texas Alzheimer's Research & Care Consortium) were analyzed for cross-validation of findings in an independent cohort. The DepE was significantly related to poorer scores on all measures, and a significantly predicted of cognitive change over 12- and 24-months.
The current findings suggest that a depressive endophenotype of MCI and AD exists and can be clinically identified using the GDS-30. Higher scores increased risk for MCI and was cross-validated by predicting AD in the TARCC. A key purpose for the search for distinct subgroups of individuals at risk for AD and MCI is to identify novel treatment and preventative opportunities.
阿尔茨海默病（AD）是一种严重的公共卫生问题，影响着超过 540 万的美国人。抑郁会增加轻度认知障碍（MCI）和 AD 的风险。通过了解抑郁对认知的影响，有可能确定抑郁的老年人中认知能力下降和 AD 风险更高的亚组。本研究旨在：1）从临床角度确定患有与抑郁相关认知障碍的老年患者亚组；2）在独立队列中验证 MCI/AD 的这种抑郁表型。
对 FRONTIER 项目的 519 名参与者进行了数据分析。使用 GDS30 评估抑郁，使用 EXIT25 和 RBANS 评估认知。使用五个 GDS 项目创建 MCI 和 AD 的抑郁表型（DepE）。DepE 与 RBANS 即时记忆指数得分（B=-2.22，SE=.37，p<0.001）、视空间技能（B=-1.11，SE=0.26，p<0.001）、语言（B=-1.03，SE=0.21，p<0.001）、注意力（B=-2.56，SE=0.49，p<0.001）和延迟记忆（B=-1.54，SE=0.37，p<0.001）显著负相关，更高的 DepE 分数与较差的执行功能相关（EXIT25；B=0.65，SE=0.19，p=0.001）。DepE 分数显著增加 MCI 诊断的风险（优势比[OR] = 2.04；95%CI=1.54-2.69）。对 TARCC（德克萨斯州阿尔茨海默病研究与护理联合会）的 235 名参与者的数据进行了分析，以验证独立队列中的发现。DepE 与所有测量结果的得分较差显著相关，并且在 12 个月和 24 个月的认知变化中具有显著的预测作用。
目前的研究结果表明，存在 MCI 和 AD 的抑郁表型，可以使用 GDS-30 进行临床识别。更高的分数增加了 MCI 的风险，并通过预测 TARCC 中的 AD 得到了交叉验证。寻找 AD 和 MCI 高危个体的不同亚组的一个主要目的是确定新的治疗和预防机会。
