Division of Neuroscience, National Institute on Aging/NIH, Bethesda, MD, USA.
Department of Neurosciences, University of California San Diego, La Jolla, CA, 92093, USA.
J Neurovirol. 2019 Oct;25(5):622-633. doi: 10.1007/s13365-019-00728-z. Epub 2019 Feb 21.
People over the age of 50 are the fastest growing segment of the HIV-infected population in the USA. Although antiretroviral therapy has remarkable success controlling the systemic HIV infection, HIV-associated neurocognitive disorder (HAND) prevalence has increased or remained the same among this group, and cognitive deficits appear more severe in aged patients with HIV. The mechanisms of HAND in the aged population are not completely understood; a leading hypothesis is that aged individuals with HIV might be at higher risk of developing Alzheimer's disease (AD) or one of the AD-related dementias (ADRD). There are a number of mechanisms through which chronic HIV disease alone or in combination with antiretroviral therapy and other comorbidities (e.g., drug use, hepatitis C virus (HCV)) might be contributing to HAND in individuals over the age of 50 years, including (1) overlapping pathogenic mechanisms between HIV and aging (e.g., decreased proteostasis, DNA damage, chronic inflammation, epigenetics, vascular), which could lead to accelerated cellular aging and neurodegeneration and/or (2) by promoting pathways involved in AD/ADRD neuropathogenesis (e.g., triggering amyloid β, Tau, or α-synuclein accumulation). In this manuscript, we will review some of the potential common mechanisms involved and evidence in favor and against a role of AD/ADRD in HAND.
50 岁以上人群是美国 HIV 感染人群中增长最快的年龄段。尽管抗逆转录病毒疗法在控制系统性 HIV 感染方面取得了显著成效，但在该人群中，与 HIV 相关的认知障碍（HAND）的患病率仍在增加或保持不变，并且在感染 HIV 的老年患者中，认知缺陷似乎更为严重。HAND 在老年人群中的发病机制尚不完全清楚；一个主要的假设是，HIV 感染的老年人可能面临更高的罹患阿尔茨海默病（AD）或 AD 相关痴呆症（ADRD）的风险。有许多机制可以解释为什么慢性 HIV 疾病本身，或与抗逆转录病毒疗法和其他合并症（例如，药物使用、丙型肝炎病毒（HCV））相结合，可能导致 50 岁以上人群发生 HAND，包括：（1）HIV 和衰老之间重叠的发病机制（例如，蛋白质稳态降低、DNA 损伤、慢性炎症、表观遗传学、血管），这可能导致细胞衰老和神经退行性变加速，和/或（2）通过促进 AD/ADRD 神经发病机制的相关途径（例如，触发淀粉样β、Tau 或α-突触核蛋白积累）。在本文中，我们将回顾一些潜在的共同机制，并提供支持和反对 AD/ADRD 在 HAND 中作用的证据。
