PROJECT SUMMARY/ABSTRACT There is compelling but scant evidence that the increasingly common combination of HIV, methamphetamine use (MU), and aging form a deleterious trio that undermines cognitive functioning. HIV and MU are both risk factors for decreased neurocognitive function and evidence shows that continued substance use (SU) after HIV infection may erode cognitive functioning. Estimates indicate that over 70% of people living with HIV (PWH) will be >50 years of age in the next decade and older PWH experience a high burden of both lifetime SU and cognitive impairment. A gap exists in our understanding of the intertwining relationships of SU, HIV, and cognitive function across biological ages and over time. Examining cognitive change over time and across ages will help identify potential points of intervention to maintain brain health across the life course. Interventions to reduce MU and support brain health among aging PWH are vital and improving social relationships is a promising area of intervention. By applying advanced statistical modeling methods and capitalizing on an exceptional analytic cohort of 527 adults with and without HIV (ages 18-87) and people who use meth, the proposed study is uniquely positioned to rigorously advance scientific understanding of these intertwining relationships across ages and over time among adults with and without HIV. The specific aims of this study are to 1) Assess the validity and reliability of the social relationship measures in the NIH Toolbox Emotions Battery in adults aging with vs. without HIV, to inform Aims 2 and 3 analyses; 2) Examine a) age-varying cognitive impairment among our sample, and Identify a) the reciprocal associations between MU and cognitive function over time among people with and without HIV and b) examine the extent to which social relationships mediate the longitudinal associations between MU and cognitive function among adults with and without HIV. b) variations in cognitive function across age by HIV status, MU, and social relationships; and 3) The proposed K01 will also provide me with a rich opportunity to become an NIH-funded leader in life course research who applies advanced quantitative and qualitative methods to conduct high impact, rigorous NIH-funded about the psychosocial needs of PWH with co-occurring SU and other mental and physical health comorbidities across the lifespan by: (1) deepening my expertise in the substantive content and measurement of SU and cognitive function; (2) expanding my knowledge about the measurement of social relationship factors that might mediate relationships of HIV, SU, and cognitive function; (3) gaining expertise in time-varying effect modeling; and (4) developing my expertise in longitudinal structural equation modeling, including cross-lagged panel analysis, to examine reciprocal change over time. This research team of mentors. The findings and skills obtained from this award will result in scientific publications that provid...