DESCRIPTION (provided by applicant): The K99/R00 award will provide Dr. Fazeli with focused training and mentoring in the design and implementation of cognitive neurorehabilitation approaches for older HIV-infected (HIV+) adults, which will facilitate her goal of becoming an independent academic scientist conducting novel cognitive intervention research with older HIV+ adults. The K99 mentored phase of this award will augment existing expertise by providing intensive training in: 1) the design of randomized controlled trials of cognitive interventions in older HIV+ adults, and 2) the theory and application of a non-invasive brain stimulation technique. The training and proposed research is of considerable is of considerable

public health relevance because: 1) the older HIV+ population is growing, and 2) HIV and aging have additive detrimental effects on neurocognitive and everyday functioning. Cognitive intervention approaches grounded in the gerontological literature provide insights for strategies that may be effective for the treatment of HIV-associated neurocognitive disorders (HAND), which remain prevalent among the older HIV+ population. The present application will target speed of information processing (SOP) via cognitive remediation therapy (CRT), which is particularly germane given that: 1) HIV and age confer additive effects on SOP, 2) SOP may drive poorer performance in other neurocognitive domains, and 3) SOP is associated with performance of everyday functioning activities. Previous work by Dr. Fazeli showed that a computerized CRT improved SOP among older HIV+ adults; however, many important questions for future research remain, including: how can the effects of this intervention be strengthened? Transcranial direct current stimulation (tDCS) is a technique that has reemerged as a non-invasive therapeutic approach for a range of neurocognitive conditions and there is evidence that cognitive interventions coupled with tDCS yield stronger effects. No studies have examined the effect of tDCS on neurocognition among HIV+ persons. Both SOP CRT and tDCS have independently demonstrated positive effects on resting state functional connectivity, which is compromised in aging with HIV, therefore, a combined neurorehabilitation approach may be particularly valuable in older HIV+ adults. Thus, the purpose of the training and research objectives of the K99 and subsequent R00 is to test the hypothesis that combining tDCS with SOP CRT will improve neurocognitive outcomes. The K99 study will focus on feasibility and proximal (i.e., SOP) and secondary (e.g., executive functions) neurocognitive effects, while the R00 study will: 1) further examine generalizability to other domains, 2) examine translation to everyday function, 3) assess dosage and durability, and 4) examine the effect on neurocognitive trajectories over time (e.g., prophylaxis versus cognitive restoration) in a true randomized controlled trial fashion. The career development and training activities, including the carefully constructed multidisciplinary mentoring team, will facilitate the successful completion of these research projects and propel Dr. Fazeli's transition to research independence. These mentors include a Primary Mentor who is an expert in cognitive interventions among older adults (Dr. Karlene Ball) and Co-Mentors with expertise in HIV (Drs. David Moore and Michael Mugavero) and tDCS (Dr. Adam Woods). The hands-on research training, strong mentorship team, coursework, didactics, and scholarly activities proposed in this application will prepare Dr. Fazel for the R00 phase of this mechanism and will provide an unprecedented opportunity for Dr. Fazeli to transition from a Postdoctoral Fellow to an influential, independent academic scientist in the field. This training will facilitate her overarching goal of working to improve the health ad quality of life of older adults aging with HIV-infection. PUBLIC HEALTH RELEVANCE: HIV and aging confer additive deleterious effects on brain structure and function that may lead to problems with mental abilities and consequently, everyday functioning. Speed of information processing (SOP) is particularly compromised in aging with HIV, and the current study will use cognitive remediation therapy and non-invasive brain stimulation to improve SOP performance. If successful, the techniques will reduce the public health burden of HIV-associated neurocognitive disorders and promote successful cognitive aging with HIV.