Variants at 21 genetic loci have been associated with an increased risk for Alzheimer’s disease (AD). An important unresolved question is whether multiple genetic risk factors can be combined to increase the power to detect changes in neuroimaging biomarkers for AD. We acquired high-resolution structural images of the hippocampus in 66 healthy, older human subjects. For 45 of these subjects, longitudinal 2-year follow-up data were also available. We calculated an additive AD genetic risk score for each participant and contrasted this with a weighted risk score (WRS) approach. Each score included APOE (apolipoprotein E), CLU (clusterin), PICALM (phosphatidylinositol binding clathrin assembly protein), and family history of AD. Both unweighted risk score (URS) and WRS correlated strongly with the percentage change in thickness across the whole hippocampal complex (URS: r = −0.40; p = 0.003; WRS: r = −0.25, p = 0.048), driven by a strong relationship to entorhinal cortex thinning (URS: r = −0.35; p = 0.009; WRS: r = −0.35, p = 0.009). By contrast, at baseline the risk scores showed no relationship to thickness in any hippocampal complex subregion. These results provide compelling evidence that polygenic AD risk scores may be especially sensitive to structural change over time in regions affected early in AD, like the hippocampus and adjacent entorhinal cortex. This work also supports the paradigm of studying genetic risk for disease in healthy volunteers. Together, these findings will inform clinical trial design by supporting the idea that genetic prescreening in healthy control subjects can be useful to maximize the ability to detect an effect on a longitudinal neuroimaging endpoint, like hippocampal complex cortical thickness.

The current study examined the independent and combined effects of HIV and marijuana use (no use, light use, and moderate-to-heavy use) on neurocognitive functioning among a convenience sample of HIV-positive (HIV+) and HIV-negative (HIV−) individuals recruited from HIV community care clinics and advertisements in the Greater Los Angeles area. Marijuana (MJ) users consisted of individuals who reported regular use of marijuana for at least 12 months, with last reported use within the past month. Participants included 89 HIV+ (n = 55) and HIV− (n = 34) individuals who were grouped into non-users, light users, and moderate-to-heavy users based on self-reported marijuana use. Participants were administered a brief cognitive test battery and underwent laboratory testing for CD4 count and viral load. HIV+ individuals demonstrated lower performance on neurocognitive testing than controls, and moderate-to-heavy MJ users performed more poorly on neurocognitive testing than light users or non-users. Moderate-to-heavy HIV+ users performed significantly lower on learning/memory than HIV− moderate-to-heavy users (MD = −8.34; 95% CI: −16.11 to −0.56) as well as all other comparison groups. In the domain of verbal fluency, HIV+ light users outperformed HIV− light users (MD = 7.28; 95% CI: 1.62 to 12.39), but no HIV group differences were observed at other MJ use levels. HIV+ MJ users demonstrated lower viral load (MD = −0.58; 95% CI: −1.30 to 0.14) and higher CD4 count than non-users (MD = 137.67; 95% CI: 9.48 to 265.85). The current study findings extend the literature by demonstrating the complex relationship between HIV status and marijuana use on neurocognitive and clinical outcomes.

Background The current study examined the independent and interactive effects of HIV and marijuana (MJ) use on brain structure and cognitive function among a sample of HIV-positive (HIV +) and HIV-negative (HIV–) individuals. Methods Participants (HIV+, n = 48; HIV–, n = 29) individuals underwent cognitive testing, questionnaires about substance use, and brain MRI. The HIV+ group was clinically stable based upon current plasma CD4 count, 50% had undetectable viral load (i.e., < 20 copies/mL), and all were on a stable regimen of cART. Results For HIV+ and HIV− participants, higher levels of MJ use were associated with smaller volumes in the entorhinal cortex and fusiform gyrus. HIV status (but not MJ use) was associated with cingulate thickness, such that HIV+ participants evidenced smaller thickness of the cingulate, as compared to HIV-controls. Regarding neurocognitive functioning, there was a HIV*MJ interactive effect on global cognition, such that when the amount of MJ use was less than 1.43 g per week, the HIV− group displayed significantly better neurocognitive performance than the HIV+ group (t = 3.14, p = 0.002). However, when MJ use reached 1.43 g per week, there were no significant HIV group differences in global cognitive performance (t = 1.39, p = 0.168). Conclusions Our results show independent and interactive effects of HIV and MJ on brain structure and cognition. However, our results do not support that HIV+ MJ users are at greater risk for adverse brain or cognitive outcomes compared to HIV− MJ users.

Among people with severe mental illnesses, neuropsychological abilities may contribute to vocational outcomes, such as job attainment, job tenure, and wages earned. The current study aimed to determine the strongest neuropsychological and other modifiable predictors of work outcomes in 153 people with severe mental illness (schizophrenia, 38%; bipolar disorder, 24%; and major depression, 38%) who participated in a 2-year supported employment study.Methods: Assessments of neuropsychological performance, functional capacity, social skills, and psychiatric symptom severity were administered at baseline; work outcomes (job attainment, weeks worked, and wages earned) were collected weekly for 2 years.