Kolpakov Stanislav, Yashkin Arseniy, Akushevich Igor
Social Science Research Institute, Duke University, Durham, NC 27710.
Ann Biostat Biom Appl. 2024;6(1). doi: 10.33552/abba.2024.06.000630. Epub 2024 Jun 26.
Elevated concentration of amyloids in the cerebrum results in elevated risks for cerebral hemorrhage and early AD onset following early depression/dementia onset. In this study, we compare patterns of amyloid depositions across eight regions of interest of the human brain between U.S. Veterans and non-Veterans adults aged 62+.
Data were taken from the ADNI and DoD-ADNI studies. A pseudo-randomization algorithm was applied to achieve comparability, reduce bias due to age mismatching, and account for non-treatment-related differences between subsamples extracted from DoD-ADNI and ADNI databases. The pool of participants included data about age, race, apolipoprotein ε4 allele (APOE) status, modified Hachinski Ischemic Score, education level, and geriatric depression score, which were used to build a propensity score.
Aβ concentration, resulting from the PET image analysis, in key brain regions of interest, and two categorical variables describing the 0.79 and 1.11 cutoffs were used as outcomes, while the Veteran and AD status were used as predictors.
To balance subsamples, we applied a pseudo-randomization algorithm, eliminating the observed sources of heterogeneity. We used a generalized linear model for continuous variables and the logistic regression model for binary variables.
The pattern of the Aβ distribution in Veteran's brains was found to be different from the classic AD pattern. The amyloid depositions following Veteran status were concentrated in cerebellar gray matter and the cerebellum in general. In contrast, the AD pattern shows more Aβ depositions in the frontal lobe, cingulate cortex, parietal, and temporal lobes, along with higher whole-cerebrum concentration of amyloids. Since Florbetapir PET cannot distinguish between senile plaques and depositions in blood vessels, the elevated concentration of amyloids in a cerebellum for participants with the Veteran status may suppose elevated risks for cerebral hemorrhage and early AD onset following early depression/dementia onset.
大脑中淀粉样蛋白浓度升高会导致脑出血风险增加,以及在早期抑郁/痴呆发作后阿尔茨海默病(AD)早期发病风险增加。在本研究中,我们比较了美国退伍军人和62岁以上非退伍军人成年人脑内八个感兴趣区域的淀粉样蛋白沉积模式。
数据取自阿尔茨海默病神经影像学计划(ADNI)和国防部-ADNI研究。应用伪随机化算法以实现可比性,减少因年龄不匹配导致的偏差,并考虑从国防部-ADNI和ADNI数据库中提取的子样本之间与治疗无关的差异。参与者库包含有关年龄、种族、载脂蛋白ε4等位基因(APOE)状态、改良哈金斯基缺血评分、教育水平和老年抑郁评分的数据,这些数据用于构建倾向得分。
通过PET图像分析得出的关键脑感兴趣区域的β淀粉样蛋白(Aβ)浓度,以及描述0.79和1.11临界值的两个分类变量用作结果,而退伍军人身份和AD状态用作预测因素。
为了平衡子样本,我们应用了伪随机化算法,消除了观察到的异质性来源。我们对连续变量使用广义线性模型,对二元变量使用逻辑回归模型。
发现退伍军人脑中Aβ分布模式与经典AD模式不同。退伍军人身份后的淀粉样蛋白沉积集中在小脑灰质和整个小脑中。相比之下,AD模式显示额叶、扣带回皮质、顶叶和颞叶中有更多的Aβ沉积,同时全脑淀粉样蛋白浓度更高。由于氟代硼吡咯正电子发射断层扫描(Florbetapir PET)无法区分老年斑和血管中的沉积物,退伍军人身份参与者小脑中淀粉样蛋白浓度升高可能意味着脑出血风险增加,以及在早期抑郁/痴呆发作后AD早期发病风险增加。