An Augmented Aging Process in Brain White Matter in HIV

T. Kuhn; T. Kaufmann; N.T. Doan; L.T. Westlye; J. Jones; R.A. Nunez; S.Y. Bookheimer; E.J. Singer; C.H. Hinkin; A.D. Thames

Further, these findings indicate the significant advantages of using BAG to predict HIV-associated white matter aging over other methods. The BAG findings were much stronger than our conventional age-trajectory findings, indicating that the SVRbased brain age approach we used is a sensitive approach to reveal group differences beyond simple differences in mean DTI measures. Additionally, BAG outperformed each individual DTI metric in its ability to discriminate between HIV+ and HIVparticipants and demonstrate the effect of HIV infection on advancing brain white matter age. BAG also may be more useful than, or at the very least a meaningful compliment to, hyper/hypo-intense lesion volume and count which has been shown to relate to HIV infection and cognitive performance, but not to HIV clinical variables or HIV-associated aging 41, 42, 43 . Additionally, BAG is a relatively easy metric to understand and thus it circumvents the cumbersome and difficult to interpret multivariate score often used with DTI metrics which are inherently difficult to connect to clinical variables. In contrast, BAG was successfully and clearly connected to both HIV clinical variables (e.g. HIV RNA viral load) and neurocognitive performance. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/265199 doi: bioRxiv preprint It is important to consider these findings also in the context of the psychosocial stressors and associated comorbidities associated with living with HIV. For example, the HIV+ sample evidenced greater rates of comorbidities, both medical (which were included in the model herein) and psychiatric (e.g. depression, which was not included in the model). It is unclear in the literature to what extent depression is a secondary reaction to living with HIV or is a neurologic symptom of the predominantly frontalsubcortical clinical profile of the disease. Therefore, it remains unclear whether the augmented aging findings are related directly and solely to the effects of the HIV virus on the brain or if they are also related to secondary effects of these HIV-associated increased comorbidities. This is particularly worthy of follow up investigation given that depressive disorders are the most prevalent mental health disorders associated with HIV 44 and studies have shown that depression can be associated with neurodegeneration and increased brain age 45 .