Department of Neuroscience.
Department of Psychiatry.
AIDS. 2021 Apr 1;35(5):727-736. doi: 10.1097/QAD.0000000000002840.
Nearly half of individuals living with HIV in the USA are now 50 or older. This rapidly ageing populace may be at an increasingly greater risk of Alzheimer's disease. However, the potential interaction between HIV-disease and Alzheimer's disease pathogenesis (i.e. Alzheimer's disease genetic risk factors) on brain function remains an open question. The present study aimed to investigate the impact of APOE ε4 on brain function in middle-aged to older people with HIV (PWH), as well as the putative interaction between ε4 and HIV disease severity.
Ninety-nine PWH participated in a cross-sectional study (56.3 ± 6.5 years, range 41-70 years, 27 women, 26 ε4 carriers and 73 noncarriers). Structural MRI and resting-state functional MRI were collected to assess alterations in brain structure and functional connectivity, respectively.
APOE ε4 was associated with worse memory performance and reduced functional connectivity in the memory network. The functional connectivity reduction was centred at the caudate nucleus rather than hippocampus and correlated with worse memory performance. In ε4 carriers, low CD4+ cell count nadir was associated with reduced functional connectivity in the memory network, but this association was absent in noncarriers. Furthermore, there was an indirect detrimental impact of ε4 on memory performance through memory network functional connectivity. However, this indirect effect was contingent on CD4+ cell count nadir, that is the indirect effect of ε4 on memory was only significant when CD4+ cell count nadir was low.
APOE ε4 is associated with reduced memory and reduced functional connectivity within the memory network, and low CD4+ cell count nadir -- indicating a history of severe immunosuppression -- may exacerbate the effects of ε4.
目前美国近一半的艾滋病毒感染者年龄在 50 岁或以上。这一快速老龄化的人群可能面临更大的阿尔茨海默病风险。然而，艾滋病毒疾病与阿尔茨海默病发病机制（即阿尔茨海默病遗传风险因素）之间的潜在相互作用对大脑功能的影响仍是一个悬而未决的问题。本研究旨在探讨 APOE ε4 对艾滋病毒感染者（PWH）中年至老年人群大脑功能的影响，以及 ε4 与艾滋病毒疾病严重程度之间的潜在相互作用。
99 名 PWH 参与了一项横断面研究（年龄 56.3±6.5 岁，年龄范围为 41-70 岁，27 名女性，26 名 ε4 携带者和 73 名非携带者）。采集结构 MRI 和静息态功能 MRI 以分别评估大脑结构和功能连接的变化。
APOE ε4 与记忆表现下降和记忆网络功能连接减少有关。功能连接减少的中心位于尾状核，而不是海马体，并且与记忆表现下降有关。在 ε4 携带者中，最低 CD4+细胞计数与记忆网络的功能连接减少有关，但在非携带者中则不存在这种关联。此外，ε4 通过记忆网络功能连接对记忆表现有间接的不良影响。然而，这种间接效应取决于 CD4+细胞计数的最低点，即当 CD4+细胞计数的最低点较低时，ε4 对记忆的间接影响才具有统计学意义。
APOE ε4 与记忆下降和记忆网络内功能连接减少有关，而最低 CD4+细胞计数——表明曾有严重免疫抑制史——可能会加剧 ε4 的影响。
