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Association of cognitive activity and neurocognitive function in blacks and whites with HIV

Krueger, Kristin R.; Adeyemi, Oluwatoyin; Leurgans, Sue; Shah, Raj C.; Jimenez, Antonio D.; Ouellet, Lawrence; Landay, Alan L.; Bennett, David A.; Barnes, Lisa L.

doi: 10.1097/QAD.0000000000001316

Objective: Older persons with HIV are at risk for impaired cognition, yet there is limited information on modifiable factors associated with neurocognitive function in this group.

Design: This is a cross-sectional observational study of cognitive activities and neurocognitive function.

Methods: We examined the relation between frequency of cognitive activity and current neurocognitive performance in 176 older persons with HIV [70% African American, 76% men; mean age = 58.7 (SD = 5.5); mean education = 13.2 (SD = 2.8)].

Results: In linear regression models adjusted for demographic variables, we found that higher frequency of cognitive activity was associated with better cognition in global cognition, semantic memory, and perceptual speed. Subsequent models that examined the role of race demonstrated that the association was significant only among Blacks for global cognition, episodic memory, working memory, and perceptual speed (interaction of cognitive activity by race: Estimate range = 0.38–0.55; all P < 0.05).

Conclusion: Greater frequency of cognitive activity is associated with better neurocognitive function in older persons with HIV, particularly older Blacks. Longitudinal studies are needed to assess the relation of cognitive activity to change in neurocognitive function in older persons with HIV.

aCook County Health and Hospital System

bRush Alzheimer's Disease Center, Rush University Medical Center

cDepartments of Neurological Sciences

dPreventive Medicine

eFamily Medicine

fDivision of Epidemiology and Biostatistics, School of Public Health, University of Illinois


hBehavioral Sciences, Rush University Medical Center, Chicago, Illinois, USA.

Correspondence to Kristin R. Krueger, John H Stroger Hospital of Cook County, Chicago, 122 W. Central Blvd, Villa Park, IL 60181IL USA. Tel: +1 312 343 8660; e-mail:

Received 23 June, 2016

Revised 16 September, 2016

Accepted 17 October, 2016

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Lifestyle factors can be modified to reduce one's risk of neurocognitive impairment associated with aging [1–4]. Identifying these protective factors among older HIV+ individuals has become critically important, particularly for those at higher risk for age-associated neurocognitive decline such as Blacks, a population also disproportionately affected by HIV [5].

The literature on aging has consistently shown that cognitive activity, or engaging in mentally stimulating tasks, is protective against neurocognitive decline [1,6–7]. The few available studies of cognitive activity associated with neurocognitive functioning among older HIV+ individuals [8–10] report promising results, but these studies were limited by small sample size [8], restriction to a single cognitive activity (e.g. internet-based stimulation) [9], and indirect or brief measures of cognitive activity [8–10].

In the present study, we investigated the frequency of cognitive activity and its association with current neurocognitive function among a group of older HIV+ individuals. Our sample was predominantly Black, which enabled us to explore possible racial differences in this association.

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Participants were 123 Black and 53 White, HIV-seropositive, primarily urban-dwelling men and women age 50 and older, enrolled in a longitudinal study of HIV and aging conducted by the National Institute on Minority Health and Health Disparities-funded Rush Center of Excellence on Disparities in HIV and Aging (CEDHA) at Rush Alzheimer's Disease Center in Chicago. The study protocol was approved by the IRBs in the study's catchment area (Rush University Medical Center, University of Illinois at Chicago, and the Cook County Health and Hospitals System). All participants provided written informed consent.

Table 1 shows participant characteristics. All participants were free of AIDS defining or other neurologic disorders, with no history of substance use for a minimum of 3 months. All participants were on combination antiretroviral therapy with a mean CD4+ cell count of 621 cells/mm3 and 167 (95%) participants had undetectable HIV-RNA. All participants undergo annual evaluations that include medical history, neurocognitive and motor function testing, and assessment of risk factors for neurocognitive decline.

Table 1

Table 1

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Materials and procedure

Cognitive activity

Participants completed a validated nine-item questionnaire [7] that assessed frequency of cognitive activities such as reading newspapers, magazines, or books; visiting museums or libraries; and attending a concert or play. Participants were asked to rate their participation frequency on a five-point Likert scale ranging from once or less per year (1) to almost every day (5). The final cognitive activity score consists of the mean of all nine items.

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Neurocognitive function

Participants completed a battery of 19 standardized neurocognitive tests that measured five neurocognitive domains: episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability. This battery has been used in multiple studies of aging and described in detail previously [1]. In particular, composite scores for the five neurocognitive domains were created by converting raw scores of the individual tests into z-scores, and averaging the z-scores. An index of global cognition was computed by averaging all of the individual z-scores [1].

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Age was determined from date of birth and date of enrollment; and education was determined as the number of years of formal education completed. Race and ethnicity were determined with questions from the 2000 US Census. Given the possible association with cognition, we included additional covariates in our analyses, in separate models. These included nadir CD4+ cell count, hepatitis C virus (HCV) serostatus, and index of past illicit drug (substance) use derived from the self-reported lifetime number of different drug types used (e.g. cannabis, opioids, amphetamines, etc.). Participants’ lifetime CD4+ nadir and diagnosis of Hepatitis C were extracted from their medical chart using the clinic visit closest in time to the neurocognitive evaluation. In total, eight medical conditions were identified in at least 10% of study participants based on self-report: hypertension, hypercholesterolemia, shingles, lung disease, neuropathy, liver disease, and poor circulation in the legs and feet. A vascular risk summary score analogous to Framingham Study indices [11] was also calculated based on history of diabetes mellitus, hypertension, and smoking (scored 0–3) as previously described by our group [12]. Depressive symptoms were assessed using a modified version of the Center for Epidemiological Studies Depression (CES-D) scale [13].

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Data analyses

We compared the average frequency of each of the nine cognitive activities for Blacks and Whites, with t-tests. We then examined the cross-sectional relationship of the cognitive activity and neurocognitive test scores using multiple linear regression models adjusting for age, sex, education, and race, and adding other covariates (CD4+ nadir, depressive symptoms, average number of drugs used in a lifetime, number of vascular risk factors, and number of medical conditions), one at a time to existing models. To examine whether the association between race and frequency of cognitive activity was comparable in Blacks and Whites, we added a term for the interaction between race and frequency of cognitive activity. A priori level of statistical significance was 0.05. Programming was done in SAS PROC NLMIX [14]. All models were examined graphically and analytically, with assumptions judged to be adequately met.

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Descriptive characteristics of participants

The majority of the 176 HIV+ participants were Black (70%), men (76%), with an average age of 58.7 years (SD = 5.5), and an average of 13.2 years of formal education (SD = 2.8). Years of education was significantly higher among Whites compared with Blacks (t = 4.4) P < 0.01). Whites also reported incomes of less than $25 000 less frequently compared with Blacks (49% vs. 81%; χ2 = 36.01; P < 0.001). Blacks and Whites were generally comparable on other demographic variables measured, including CD4+ nadir, medical conditions, vascular risk score, depressive symptoms, and MMSE score. There were no racial differences in percentage virally suppressed or in the number on combination antiretroviral therapy. Complete descriptive comparisons between Blacks and Whites are provided in Table 1.

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Cognitive activity

Compared with Whites, Blacks reported less frequent participation in three of the nine cognitive activities measured: reading per day, visiting a museum, and attending concerts. There were no significant differences in the other activities queried; however, there was a trend for Blacks to report spending more time playing games compared with Whites.

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Cognitive activity frequency and demographic variables

Neither age, nor sex was significantly associated with global cognition. As expected, a greater number of years of formal education were associated with better global cognition [Estimate = 0.06; standard error (SE) = 0.01, P < 0.001]. Compared with Whites, Blacks showed significantly lower global neurocognitive scores (Estimate = −0.37; SE = 0.08, P < 0.001). Broadly similar relationships were found for each of the five neurocognitive domains.

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Cognitive activity frequency and neurocognitive function

In a series of linear regression models, adjusted for demographics (age, sex, education, and race), we found that more frequent cognitive activity was associated with better global cognition (Estimate = 0.13; SE = .06, P = 0.026) and with two of the five neurocognitive domains, semantic memory (Estimate = 0.19; SE = .08, P = 0.017) and perceptual speed (Estimate = 0.28; SE = 0.08, P = 0.001) (Table 2).

Table 2

Table 2

The significant association between frequency of cognitive activity and global cognition was essentially unchanged after controlling for employment status, common medical conditions, vascular risk score, HCV serostatus, CD4+ nadir, and average number of lifetime drugs used. However, when number of depressive symptoms was entered, the association was reduced to a nonsignificant trend (Estimate = 0.10; SE = 0.10, P = 0.060). The associations of cognitive activity and the individual domains were essentially unchanged after controlling for all covariates.

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Cognitive activity frequency and race interaction

The race × cognitive activity interaction term was significant in subsequent models, suggesting that the association of cognitive activity and global neurocognitive function was only apparent among Blacks (Estimate for interaction = 0.38; SE = 0.11, P < 0.001). After controlling for all of the covariates listed above, this association remained significant, with P values ranging from P < 0.001 to P = 0.01 (controlling for Hepatitis C). Significant interactions between race and frequency of cognitive activity were also present for episodic memory (Estimate = 0.39; SE = 0.14, P = 0.006), working memory (Estimate = 0.54; SE = 0.19, P = 0.005), and perceptual speed (Estimate = 0. 41; SE = 0.17, P = 0.02) after controlling for covariates.

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In this study of 176 older persons with HIV, we found that, consistent with the aging literature [1,6–7], cognitive activity was significantly associated with better neurocognitive function. Specifically, more frequent participation in cognitive activity was associated with higher global neurocognitive function, and the following domains, episodic memory, working memory and perceptual speed, but only among Blacks. This relationship between current cognitive activity and neurocognitive function remained significant after controlling for demographic variables (age, sex, education), and important covariates, such as medical conditions, vascular risk score, HCV serostatus, CD4+ nadir, and average number of lifetime drugs. Furthermore, general health and HIV disease status were comparable for the two groups. Interestingly, when depressive symptoms were added to the model, the association between cognitive activity and neurocognitive function was reduced to a nonsignificant trend, suggesting that the association is not completely independent of depressive symptoms.

Overall, these results suggest the association between cognitive activity and neurocognitive function may be stronger in HIV+ Blacks compared with Whites. However, at present, the significance of this finding is unclear. Factors that contribute to racial disparities in neurocognitive health among older persons, such as years of education and income [15], were significantly higher among White participants in our study. Additionally, we note that Whites reported significantly more reading, museum visits, and attendance at plays or concerts, activities that are most likely more frequent among individuals with higher education and more disposable income.

Our study is limited by the use of a self-report measure of a restricted number of cognitive activities, although the measure has been used in numerous studies of older adults and has been shown to predict neurocognitive decline and risk of Alzheimer's disease [1,7,16–18]. Our measure of history of illicit drug was crude and does not take into account patterns of drug use over time. Future studies should use more sensitive measures that incorporate frequencies and patterns of past use. Also, we had a much smaller proportion of Whites among the study sample. Had our study included more Whites, we would have had slightly more power.

Our study is advantageous compared with previous reports from the cognitive activity literature among HIV+ individuals, in that the sample size was larger and neurocognitive testing was more comprehensive. Our study sample characteristics enabled us to observe potentially important demographic factors contributing to disparities in neurocognitive health and thereby help to establish factors associated with better neurocognitive outcomes in persons aging with HIV. An important implication of these findings for HIV+ Blacks and Whites suggest that improved access to cognitive activity interventions, in particular among middle to older aged Blacks, could be an important target to reduce late-life disparities in brain health and neurocognitive function.

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The authors gratefully thank the CEDHA participants, Tarisha Washington and Virginia Maravillas for study coordination and data collection, the CEDHA staff, the Ruth M. Rothstein staff, and the Rush Alzheimer's Disease Center Staff. We also thank Dr Eileen Martin in the Department of Psychiatry at Rush University Medical Center for her advice and comments on this version of the manuscript. This research was supported by National Institute on Minority Health and Health Disparities grant (P20MD6886).

Compliance with Ethical Standards: This research was supported by National Institute on Aging grant P20MD6886, and a grant from the Illinois Department of Public Health. A.L.L is on the Scientific Advisory Board for Merck. L.L.B is the recipient of grants mentioned above and has no other conflicts of interest. For the remaining authors no conflict of interests or funding sources have been declared.

All procedures performed in this study with human participants were in accordance with the ethical standards of the institutional review boards of Rush University Medical Center and the Cook County Health and Hospital System and with the 1964 Helsinki Declaration and its later amendments. Informed consent was obtained from all individual participants included in the study.

Author contributions: K.R.K commissioned the statistical analyses and drafted the manuscript. S.L performed the statistical analyses. L.L.B supervised the data analysis and interpretation. All authors critically reviewed the manuscript and approved the final draft.

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Conflicts of interest

There are no conflicts of interest.

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cognitive activity; health disparities; HIV/AIDS; neurocognitive function; older adults

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