Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, 670 W. Baltimore Street, HSF III, Baltimore, MD, 21201, USA.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
J Neuroinflammation. 2020 Aug 6;17(1):230. doi: 10.1186/s12974-020-01910-5.
Cognitive deficits and microstructural brain abnormalities are well documented in HIV-positive individuals (HIV+). This study evaluated whether chronic marijuana (MJ) use contributes to additional cognitive deficits or brain microstructural abnormalities that may reflect neuroinflammation or neuronal injury in HIV+.
Using a 2 × 2 design, 44 HIV+ participants [23 minimal/no MJ users (HIV+), 21 chronic active MJ users (HIV + MJ)] were compared to 46 seronegative participants [24 minimal/no MJ users (SN) and 22 chronic MJ users (SN + MJ)] on neuropsychological performance (7 cognitive domains) and diffusion tensor imaging metrics, using an automated atlas to assess fractional anisotropy (FA), axial (AD), radial (RD), and mean (MD) diffusivities, in 18 cortical and 4 subcortical brain regions.
Compared to SN and regardless of MJ use, the HIV+ group had lower FA and higher diffusivities in multiple white matter and subcortical structures (p < 0.001-0.050), as well as poorer cognition in Fluency (p = 0.039), Attention/Working Memory (p = 0.009), Learning (p = 0.014), and Memory (p = 0.028). Regardless of HIV serostatus, MJ users had lower AD in uncinate fasciculus (p = 0.024) but similar cognition as nonusers. HIV serostatus and MJ use showed an interactive effect on mean diffusivity in the right globus pallidus but not on cognitive function. Furthermore, lower FA in left anterior internal capsule predicted poorer Fluency across all participants and worse Attention/Working Memory in all except SN subjects, while higher diffusivities in several white matter tracts also predicted lower cognitive domain Z-scores. Lastly, MJ users with or without HIV infection showed greater than normal age-dependent FA declines in superior longitudinal fasciculus, external capsule, and globus pallidus.
Our findings suggest that, except in the globus pallidus, chronic MJ use had no additional negative influence on brain microstructure or neurocognitive deficits in HIV+ individuals. However, lower AD in the uncinate fasciculus of MJ users suggests axonal loss in this white matter tract that connects to cannabinoid receptor rich brain regions that are involved in verbal memory and emotion. Furthermore, the greater than normal age-dependent FA declines in the white matter tracts and globus pallidus in MJ users suggest that older chronic MJ users may eventually have lesser neuronal integrity in these brain regions.
认知缺陷和大脑微观结构异常在 HIV 阳性个体（HIV+）中已有充分记录。本研究评估了慢性大麻（MJ）使用是否会导致额外的认知缺陷或大脑微观结构异常，这些异常可能反映了 HIV+中的神经炎症或神经元损伤。
使用 2×2 设计，将 44 名 HIV+参与者[23 名最低/无 MJ 使用（HIV+），21 名慢性活跃 MJ 使用（HIV+MJ）]与 46 名血清阴性参与者[24 名最低/无 MJ 使用（SN）和 22 名慢性 MJ 使用（SN+MJ）]进行比较，使用自动图谱评估各皮质和 4 个皮质下脑区的分数各向异性（FA）、轴向（AD）、径向（RD）和平均（MD）扩散率，以评估神经心理学表现（7 个认知领域）和弥散张量成像指标。
与 SN 相比，无论 MJ 使用情况如何，HIV+组在多个白质和皮质下结构中的 FA 降低，各向异性升高（p<0.001-0.050），流畅性（p=0.039）、注意力/工作记忆（p=0.009）、学习（p=0.014）和记忆（p=0.028）认知能力更差。无论 HIV 血清状态如何，MJ 使用者在钩束（uncinate fasciculus）的 AD 降低（p=0.024），但认知功能与非使用者相似。HIV 血清状态和 MJ 使用呈交互作用，影响右苍白球的平均弥散率，但不影响认知功能。此外，左前内囊的 FA 降低预测所有参与者的流畅性较差，除 SN 受试者外，注意力/工作记忆较差，而几个白质束的弥散率升高也预测认知域 Z 分数较低。最后，无论是否感染 HIV，MJ 使用者的上纵束、外囊和苍白球的 FA 随年龄的正常下降幅度更大。
我们的研究结果表明，除了苍白球外，慢性 MJ 使用对 HIV+个体的大脑微观结构或神经认知缺陷没有额外的负面影响。然而，MJ 使用者钩束的 AD 降低提示该白质束的轴突丢失，该白质束与富含大麻素受体的大脑区域相连，这些区域参与语言记忆和情绪。此外，MJ 使用者的白质束和苍白球的 FA 随年龄的正常下降幅度大于正常，提示年龄较大的慢性 MJ 使用者最终可能会出现这些大脑区域的神经元完整性降低。
