Rajendrakumar Aravind Lathika, Arbeev Konstantin G, Bagley Olivia, Duan Matt, Yashin Anatoliy I, Ukraintseva Svetlana
Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, North Carolina, United States of America.
medRxiv. 2024 Oct 1:2024.09.13.24313582. doi: 10.1101/2024.09.13.24313582.
Impaired brain glucose metabolism is a preclinical feature of neurodegenerative diseases such as Alzheimer's disease (AD). Infections may promote AD-related pathology. Therefore, we investigated the interplay between infections and , a strong genetic risk factor for AD.
We analyzed data on 1,509 participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database using multivariate linear regression models. The outcomes were rank-normalized hypometabolic convergence index (HCI), statistical regions of interest (SROI) for AD, and mild cognitive impairment (MCI). Marginal mean estimates for infections, stratified by carrier status, were then computed.
Prior infections were associated with greater HCI [β=0.15, 95% CI: 0.03, 0.27, p=0.01]. The combined effects of infections and carriers on HCI levels were significantly greater than either variable alone. Among carriers, the estimated marginal mean was 0.62, rising to 0.77, with infections (p<0.001), indicating an interaction effect. Carriers with multiple infections showed greater hypometabolism (higher HCI), with an estimate of 0.44 (p=0.01) compared to 0.11 (p=0.08) for those with a single infection, revealing a dose-response relationship. The estimates for the association of infections with SROI AD and SROI MCI were β=-0.01 (p=0.02) and β=-0.01 (p=0.04), respectively.
Our findings suggest that infections and jointly contribute to brain glucose hypometabolism and AD pathology, supporting a "multi-hit" mechanism in AD development.
脑葡萄糖代谢受损是阿尔茨海默病（AD）等神经退行性疾病的临床前特征。感染可能会促进AD相关病理变化。因此，我们研究了感染与AD的一个强大遗传风险因素之间的相互作用。
我们使用多元线性回归模型分析了阿尔茨海默病神经影像倡议（ADNI）数据库中1509名参与者的数据。结果指标为秩正态化低代谢收敛指数（HCI）、AD的统计感兴趣区域（SROI）和轻度认知障碍（MCI）。然后计算按 携带者状态分层的感染的边际均值估计值。
既往感染与更高的HCI相关[β=0.15，95%置信区间：0.03，0.27，p=0.01]。感染和 携带者对HCI水平的综合影响显著大于单独的任何一个变量。在 携带者中，估计的边际均值为0.62，有感染时升至0.77（p<0.001），表明存在交互作用。有多次感染的携带者表现出更高的低代谢（更高的HCI），估计值为0.44（p=0.01），而单次感染的携带者为0.11（p=0.08），显示出剂量反应关系。感染与SROI AD和SROI MCI的关联估计值分别为β=-0.01（p=0.02）和β=-0.01（p=0.04）。
我们的研究结果表明，感染和 共同导致脑葡萄糖低代谢和AD病理变化，支持AD发展中的“多重打击”机制。
