Lyndaker Anna, Lau Chuen-Yen, Shah Swati, Wakim Paul, Kelly Erin, Horne Elizabeth, McMahan Cynthia, Spiegel Alicia, Gollomp Elyse, Chien Alice, Mitchell Amelia, Monroe Cynthia, Kim Alan, Nair Govind, Snow Joseph, Smith Bryan, Nath Avindra, Hammoud Dima A
Center for Infectious Disease Imaging, Radiology and Imaging Sciences, National Institutes of Health Clinical Center, Bethesda, Maryland, USA.
HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Open Forum Infect Dis. 2024 Sep 20;11(10):ofae552. doi: 10.1093/ofid/ofae552. eCollection 2024 Oct.
Cardiovascular disease (CVD) and neuroinflammation are thought to exacerbate neurocognitive dysfunction in treated people with human immunodeficiency virus (PWH). Here, we longitudinally measured brain glucose metabolism as a measure of neuronal integrity in treated PWH using [F]Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in correlation with atherosclerotic cardiovascular disease (ASCVD) scores, cerebrospinal fluid (CSF) neuroinflammatory markers, neurocognitive outcomes, and other clinical and laboratory variables (CLVs).
Well-controlled PWH (n = 36) underwent baseline and follow-up FDG PET/CT obtained 3.5 years apart on average. Longitudinal changes in whole brain and regional relative FDG uptake, brain volumes, CLVs, CSF cytokines, and neuropsychological measures were measured. A variable selection model identified baseline variables related to future brain metabolic changes while multivariable models explored neuropsychological implications of brain metabolism and volumetrics.
High ASCVD scores predicted future decreased thalamic uptake (slope = -0.0068, = .027) and decreasing thalamic uptake correlated with worsening cognition (slope = 15.80, = .020). Despite longitudinal greater than expected gray matter loss, whole brain FDG uptake did not change over the follow-up period. Most CSF cytokines decreased longitudinally but were not predictive of FDG changes.
We found that high ASCVD scores in a group of treated PWH were related to thalamic hypometabolism, which in turn correlated with neurocognitive decline. Our findings support the contribution of CVD to neurocognitive dysfunction. More proactive CVD management may have a role in mitigating progression of cognitive impairment. Lack of change in global brain glucose metabolism despite documented accelerated gray matter volume loss over the same period suggests that FDG PET might underestimate neuronal injury in PWH compared to structural magnetic resonance imaging.
心血管疾病（CVD）和神经炎症被认为会加重接受治疗的人类免疫缺陷病毒感染者（PWH）的神经认知功能障碍。在此，我们使用[F]氟脱氧葡萄糖（FDG）正电子发射断层扫描/计算机断层扫描（PET/CT）纵向测量接受治疗的PWH的脑葡萄糖代谢，作为神经元完整性的一项指标，并将其与动脉粥样硬化性心血管疾病（ASCVD）评分、脑脊液（CSF）神经炎症标志物、神经认知结果以及其他临床和实验室变量（CLV）进行关联分析。
病情得到良好控制的PWH（n = 36）平均间隔3.5年接受了基线和随访FDG PET/CT检查。测量了全脑和区域相对FDG摄取、脑容量、CLV、脑脊液细胞因子以及神经心理学指标的纵向变化。一个变量选择模型确定了与未来脑代谢变化相关的基线变量，而多变量模型探讨了脑代谢和容积测量的神经心理学意义。
高ASCVD评分预测未来丘脑摄取量降低（斜率 = -0.0068，P = 0.027），而丘脑摄取量降低与认知功能恶化相关（斜率 = 15.80，P = 0.020）。尽管纵向灰质损失大于预期，但在随访期间全脑FDG摄取量并未改变。大多数脑脊液细胞因子纵向下降，但不能预测FDG变化。
我们发现一组接受治疗的PWH中高ASCVD评分与丘脑代谢减退有关，而丘脑代谢减退又与神经认知衰退相关。我们的研究结果支持CVD对神经认知功能障碍有影响。更积极的CVD管理可能在减轻认知障碍进展方面发挥作用。尽管同期有记录显示灰质体积加速损失，但全脑葡萄糖代谢缺乏变化，这表明与结构磁共振成像相比，FDG PET可能低估了PWH中的神经元损伤。
