Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
J Neurovirol. 2019 Oct;25(5):661-672. doi: 10.1007/s13365-018-0702-9. Epub 2019 Jan 22.
The advent of effective antiretroviral medications (ARVs) has led to an aging of the HIV population with approximately 50% of people with HIV (PWH) being over the age of 50 years. Neurocognitive complications, typically known as HIV-associated neurocognitive disorders (HAND), persist in the era of ARVs and, in addition to risk of HAND, older PWH are also at risk for age-associated, neurodegenerative disorders including Alzheimer's disease (AD). It has been postulated that risk for AD may be greater among PWH due to potential compounding effects of HIV and aging on mechanisms of neural insult. We are now faced with the challenge of disentangling AD from HAND, which has important prognostic and treatment implications given the more rapidly debilitating trajectory of AD. Herein, we review the evidence to date demonstrating both parallels and differences in the profiles of HAND and AD. We specifically address similarities and difference of AD and HAND as it relates to (1) neuropsychological profiles (cross-sectional/longitudinal), (2) AD-associated neuropathological features as evidenced from neuropathological, cerebrospinal fluid and neuroimaging assessments, (3) biological mechanisms underlying cortical amyloid deposition, (4) parallels in mechanisms of neural insult, and (5) common risk factors. Our current understanding of the similarities and dissimilarities of AD and HAND should be further delineated and leveraged in the development of differential diagnostic methods that will allow for the early identification of AD and more suitable and effective treatment interventions among graying PWH.
有效的抗逆转录病毒药物 (ARV) 的出现导致 HIV 人群老龄化,大约 50% 的 HIV 感染者 (PWH) 年龄在 50 岁以上。神经认知并发症,通常称为 HIV 相关神经认知障碍 (HAND),在 ARV 时代仍然存在,除了 HAND 的风险外,老年 PWH 还面临与年龄相关的神经退行性疾病的风险,包括阿尔茨海默病 (AD)。有人推测,由于 HIV 和衰老对神经损伤机制的潜在复合作用,PWH 患 AD 的风险可能更高。我们现在面临着将 AD 与 HAND 区分开来的挑战,鉴于 AD 更迅速地使人衰弱的轨迹,这具有重要的预后和治疗意义。在此,我们回顾了迄今为止的证据,这些证据表明 HAND 和 AD 的特征既有相似之处,也有不同之处。我们特别讨论了 AD 和 HAND 在以下方面的相似性和差异性:(1) 神经心理学特征(横断面/纵向);(2) 神经病理学、脑脊液和神经影像学评估证实的 AD 相关神经病理学特征;(3) 皮质淀粉样蛋白沉积的生物学机制;(4) 神经损伤机制的相似性;(5) 共同的风险因素。我们对 AD 和 HAND 的相似性和差异性的当前理解应该进一步阐述和利用,以开发差异化诊断方法,从而能够早期识别 AD,并为老龄化 PWH 提供更合适和有效的治疗干预措施。