NC change is common in HIV infection and appears to be driven by a complex set of risk factors involving HIV disease, its treatment, and comorbid conditions.

Objective We examined the influence of a broad spectrum of life experiences on longitudinal cognitive trajectories in a demographically diverse sample of older adults. Method Participants were 333 educationally, ethnically, and cognitively diverse older adults enrolled in a longitudinal aging study. Mixed-effects regression was used to measure baseline status in episodic memory, executive functioning, and semantic memory and change in a global cognition factor defined by change in these three domain-specific measures. We examined effects of life experience variables (literacy, childhood socioeconomic status, morphometric measures of physical development, life course physical and recreational activity) on longitudinal cognitive trajectories, covarying for age, APOE genotype and demographics (education, ethnicity, language). Results Non-Latino whites had higher baseline cognition, but life experience variables attenuated ethnic differences in cognitive scores. Age, literacy, childhood socioeconomic status and physical activity significantly influenced baseline cognition. Age, APOE ε4 and decline in intellectually and socially stimulating recreational activity from mid to late life were independently associated with increased late life cognitive decline. Higher literacy and late life recreational activity were associated with less decline. Literacy had similar effects for English and Spanish readers/speakers. Bilingual English and Spanish speakers did not differ from English Speakers in cognitive performance. Conclusions Life experience variables, especially literacy level, were strongly related to baseline cognition and substantially attenuated effects of race/ethnicity and education. Cognitive change was best explained by age, APOE ε4, literacy, and current recreational activities. Literacy had robust associations with baseline cognition and cognitive change in both English and Spanish speakers.

The beneficial effects of self-referential processing on memory have been demonstrated in numerous experiments with younger adults but have rarely been studied in older individuals. In the present study we tested young people, younger-older adults, and older-older adults in a self-reference paradigm, and compared self-referential processing to general semantic processing. Findings indicated that older adults over the age of 75 and those with below average episodic memory function showed a decreased benefit from both semantic and self-referential processing relative to a structural baseline condition. However, these effects appeared to be confined to the shared semantic processes for the two conditions, leaving the added advantage for self-referential processing unaffected These results suggest that reference to the self engages qualitatively different processes compared to general semantic processing. These processes seem relatively impervious to age and to declining memory and executive function, suggesting that they might provide a particularly useful way for older adults to improve their memories.

These findings demonstrate that early life experiences influence the trajectory of cognitive aging. Early life development and experience appears to provide a distal basis upon which additional risk and protective factors interact in the development of dementia.

Objective The Veterans Aging Cohort Study (VACS) Index is predictive of mortality, and combines age, traditional HIV biomarkers (HIV-1 plasma RNA and current CD4 count) and non-HIV biomarkers (indicators of renal and liver function, anemia, and Hepatitis C co-infection). We examined the association between the VACS Index and HIV-associated neurocognitive impairment (NCI). Design and Methods Participants included 601 HIV-infected adults enrolled in cohort studies at the UCSD HIV Neurobehavioral Research Program (Ages: 18-76 years; 88% male; 63% White; Median current CD4=364; 63% on antiretroviral therapy; AIDS=64%). Biomarkers used in calculating the VACS Index were measured in prospectively collected blood samples using conventional laboratory methods. NCI was defined using global and seven domain deficit scores. Results Higher VACS Index scores were associated with concurrent risk for global NCI (p<.001; OR=1.21, CI=1.12-1.32), even when adjusting for psychiatric comorbidities. This relation was statistically significant for most cognitive domains in adjusted models. Furthermore, the VACS Index predicted concurrent NCI beyond nadir CD4 and estimated duration of infection. Older age, lower hemoglobin and lower CD4 counts were the VACS components most strongly linked to NCI. Conclusions The findings extend prior research on the potential usefulness of the VACS Index in predicting HIV-associated outcomes to include NCI. Although the effect size was relatively small, our findings suggest that demographic information, HIV-disease factors, and common comorbidities might each play important roles in the clinical manifestation of cognitive impairment among HIV-infected individuals. Additional research is needed to determine if a more sensitive and specific index can be developed.

Neurocognitive impairment (NCI) remains prevalent in HIV-infection. Randomized trials have shown that physical exercise improves NCI in non HIV-infected adults, but data on HIV-infected populations is limited. Community-dwelling HIV-infected participants (n=335) completed a comprehensive neurocognitive battery that was utilized to define both global and domain-specific NCI. Participants were divided into “Exercise” (n=83) and “No Exercise” (n=252) groups based on whether they self-reported engaging in any activity that increased heart rate in the last 72 hours or not. We also measured and evaluated a series of potential confounding factors, including demographics, HIV-disease characteristics, substance use and psychiatric comorbidities, and physical functioning. Lower rates of global NCI were observed among the Exercise group (15.7%) as compared to those in the No Exercise group (31.0%; p<.01). A multivariable logistic regression controlling for potential confounds (i.e., education, AIDS status, current CD4+ lymphocyte count, self-reported physical function, current depression) showed that being in the Exercise group remained significantly associated with lower global NCI (OR=2.63, p<.05). Similar models of domain-specific NCI showed that Exercise was associated with reduced impairment in working memory (p<.05) and speed of information processing (p<.05). The present findings suggest that HIV-infected adults who exercise are approximately half as likely to show NCI as compared to those who do not. Future longitudinal studies might be best suited to address causality and intervention trials in HIV-infected individuals will determine whether exercise can prevent or ameliorate NCI in this population.

We examined the association between physical activity (PA), neurocognitive impairment (NCI), and instrumental activities of daily living (IADLs) among older HIV+ persons. One hundred older HIV+ adults completed the International Physical Activity Questionnaire (IPAQ), a neurocognitive battery, and IADL scale. Higher levels of moderate PA were associated with lower odds of NCI (p=0.01), even when covariates were modeled. The association between moderate PA and NCI was driven by executive function (p=0.04). Higher levels of moderate PA were also associated with lower odds of IADL Dependence (p = 0.03), although this fell to a trend (p = 0.08) when including covariates. Follow-up analysis showed those with both NCI and IADL Dependence had lower moderate PA than those with neither (p=0.03). While these cross-sectional findings suggest PA is associated with better neurocognitive and everyday functioning in older HIV+ adults, longitudinal studies utilizing objective PA methods are needed to evaluate directionality and mechanisms.

Grit and ambition are psychological factors that may protect neurocognitive function among persons living with HIV (PLWH). We examined associations between grit, ambition, premorbid verbal intellectual function, and current neurocognitive and everyday functioning among PLWH and persons without HIV (HIV-). 120 PLWH and 94 HIV- adults completed the Grit Scale (includes total score and consistency of interests and perseverance of effort subscales), ambition scale, and a comprehensive neurobehavioral battery. PLWH had lower grit scores than HIV- adults. The two groups did not differ on ambition. No relationship was observed between grit and cognition among HIV- adults. Among PLWH, however, higher perseverance of effort and more ambition was related to better global neurocognitive functioning, and higher grit, but not ambition, was related to independence in daily functioning. Longitudinal studies are needed to elucidate these relationships over time and examine whether grit or ambition have protective effects on cognitive outcomes among PLWH.