Department of Cell and Molecular Medicine, Rush University Medical Center, Chicago, IL.
New York Medical College, Valhalla, NY.
J Acquir Immune Defic Syndr. 2022 Oct 1;91(2):162-167. doi: 10.1097/QAI.0000000000003043.
Bone loss and cognitive impairment are common in women living with HIV (WLWH) and are exacerbated by menopause. Bone-derived undercarboxylated osteocalcin (ucOCN) and sclerostin appear to influence cognition. The current study investigated whether the circulating levels of these 2 proteins are associated with cognition in midlife WLWH and demographically similar HIV seronegative women.
Plasma samples from women enrolled in a musculoskeletal substudy within the Women's Interagency HIV Study were used to measure ucOCN and sclerostin. A neuropsychological (NP) test battery assessing executive function, processing speed, attention/working memory, learning, memory, verbal fluency, and motor function was administered within 6 months of musculoskeletal enrollment and every 2 years after (1-4 follow-up visits per participant). A series of generalized estimating equations were conducted to examine the association between biomarkers and NP performance at the initial assessment and over time in the total sample and in WLWH only. Primary predictors included biomarkers, time, and biomarker by time interactions. If the interaction terms were not significant, models were re-run without interactions.
Neither biomarker predicted changes in NP performance over time in the total sample or in WLWH. ucOCN was positively associated with executive function in the total sample and in WLWH and with motor skills in WLWH. ucOCN was negatively associated with attention/working memory in the total sample. There were no significant associations between sclerostin and NP performance.
The current study suggests an association between bone-derived ucOCN and cognition in women with and without HIV infection.
骨质疏松和认知障碍在感染 HIV 的女性(WLWH)中很常见,且会因更年期而加重。骨源性非羧化骨钙素(ucOCN)和硬化蛋白似乎会影响认知。本研究旨在调查这 2 种蛋白的循环水平是否与中年 WLWH 和具有相似人口统计学特征的 HIV 阴性女性的认知功能相关。
本研究使用 Women's Interagency HIV Study 中肌肉骨骼子研究纳入的女性的血浆样本来测量 ucOCN 和硬化蛋白。神经心理学(NP)测试套件用于评估执行功能、处理速度、注意力/工作记忆、学习、记忆、言语流畅性和运动功能,在肌肉骨骼入组后 6 个月内以及之后每 2 年进行一次(每位参与者进行 1-4 次随访)。采用广义估计方程来研究在总样本中和仅在 WLWH 中,生物标志物与 NP 表现之间在初始评估和随时间的关联。主要预测因子包括生物标志物、时间以及生物标志物与时间的相互作用。如果交互项不显著,则不包含交互项重新运行模型。
在总样本和仅在 WLWH 中,均没有生物标志物预测 NP 表现随时间的变化。ucOCN 与总样本和 WLWH 中的执行功能以及 WLWH 中的运动技能呈正相关,与总样本中的注意力/工作记忆呈负相关。硬化蛋白与 NP 表现之间无显著相关性。
本研究表明,在感染 HIV 的女性和未感染 HIV 的女性中,骨源性 ucOCN 与认知之间存在关联。