TABLE 4.
Neurocognitive disease: characteristics and outcomes of eligible studies
| Author (year) | Study design | Location | Aim/outcome | Population | Sample size (n/% female) | Mean age (years) | Measures used | Relevant risk association examined for | Major findings |
|---|---|---|---|---|---|---|---|---|---|
| Chow, F et al. (2019)a | Cross‐sectional analysis of a prospective, multicentre observational study (HAILO) | USA | To evaluate the association between cardiometabolic risk factors and prevalent cognitive impairment in PLWH | PLWH > 40 | 795 (195/20%) | 52 |
Brief neurocognitive screen International Physical Activity Questionnaire Clinical assessment |
Sex |
A greater proportion of WLWH were cognitively impaired compared with MLWH (36% vs. 26%; p = 0.003). Increased physical activity (OR = 0.33 for ≥ 3 days/week; p = 0.003) was protective against cognitive impairment in WLWH but not MLWH. Higher HDL cholesterol was also associated with a lower risk of cognitive impairment in WLWH but not MLWH (OR = 0.78 for every 10 mg/dL higher HDL; p = 0.028). |
| Gustafson et al. (2013)b | Cross‐sectional analysis of a prospective, multicentre observational study (WIHS) | USA | To explore the relationship between BMI, waist circumference and waist‐to‐hip ratio with cognition in WLWH and HIV‐negative women |
WLWH HIV‐negative women |
1196 (1196/100%) 494 (494/100%) |
42.5 38.4 |
Standardized neurocognitive battery Anthropomorphic measurements |
HIV status | In WLWH, but not HIV‐negative women, a BMI < 18.5 kg/m2 was associated with worse performance in some domains of cognitive testing compared with WLWH with a BMI in the healthy range (BMI 18.5–25 kg/m2). |
| Maki et al. (2015)c | Cross‐sectional analysis of a prospective, multicentre observational study (WIHS) | USA |
1. To examine the association between HIV status and cognition in relation to other determinants of cognitive function 2. To examine the pattern and magnitude of impairment across cognitive outcomes |
WLWH HIV‐negative women |
1019 (1019/100%) 502 (502/100%) |
47.48 43.48 |
Standardized neurocognitive battery Clinical assessment |
HIV status |
WLWH performed worse on measures of verbal learning and memory, speed of information processing and attention (0.05–0.09 SD units). The effect of HIV on cognitive function was less than the effect of years of education, age, race/ethnicity, household income and reading level. WLWH with a low CD4 count, high VL, low education or an AIDS‐defining illness were more vulnerable to cognitive deficit. |
| Rubin (2018)d | Cross‐sectional analysis of a prospective, multicentre observational study (WIHS) | USA | To assess the cognitive effects of medications with known NC‐AE on WLWH and HIV negative women |
WLWH HIV‐negative women |
1037 (1037/100%) 521 (521/100%) |
47 43 |
Standardized neurocognitive battery Self‐reported NC‐AE medication history Clinical assessment |
HIV status |
WLWH performed worse than HIV‐negative women on global function (p = 0.01), memory (p = 0.04), attention/working memory (p = 0.02) and executive function (p = 0.02). WLWH reported using more NC‐AE medications than HIV‐negative women (p < 0.05). Opioid and anticonvulsant use was similar in both groups. Anticholinergic burden was negatively associated with learning and executive function. This association was greater in WLWH than in HIV‐negative women. |
| Meyer et al. (2013)e | Cross‐sectional analysis of a prospective, multicentre observational study (WIHS) | USA | To investigate the impact of HIV infection and illicit drug use on cognition in WLWH and HIV‐negative women |
WLWH HIV‐negative women |
952 (952/100%) 443 (443/100%) |
42.8 |
Neuropsychological testing, HVLT and Comalli Stroop test Self‐reported history of recreational drug use |
HIV status Recreational drug use |
Regardless of reported drug use, WLWH performed worse on total learning, learning slope, delayed recall and recognition (p‐values < 0.05). In WLWH, recent drug use was associated with a worse performance on learning slope (p = 0.04), delayed recall (p = 0.007) and recognition (p = 0.002) than non‐users. This was not seen in HIV‐negative women. |
| Rubin et al. (2015)f | Cross‐sectional analysis of a prospective, multicentre observational study (WIHS) | USA | To investigate the association between perceived stress and cognitive performance in WLWH and HIV‐negative women |
WLWH HIV‐negative women |
1003 (1003/100%) 496 (496/100%) |
46.2 |
Neuropsychological testing including HVLT PSS |
HIV status Higher vs. lower PSS |
Overall WLWH performed worse on verbal learning (p = 0.003), memory (p < 0.001), attention and concentration (p = 0.004), executive functioning (p = 0.005) and psychomotor speed (p = 0.01) than HIV‐negative women. A similar proportion of WLWH and HIV‐negative women reported higher perceived stress (38% vs. 36%; p = 0.41). Among WLWH, those with higher PSS had lower CD4 counts and higher plasma HIV RNA levels. Regardless of HIV status, PSS was inversely associated with cognitive performance, with those with higher perceived stress performing worse on all HVLT indices. In the WLWH, those with higher PSS performed worse on the verbal memory domain (B = −2.24, SE = 0.62; p < 0.001), specifically driven by delayed recall (B = −2.24, SE = 0.65; p < 0.001). This persisted after controlling for CD4 count, HIV VL, ART use and ART duration. This was not seen in HIV‐negative women. |
| Rubin et al. (2016)g | Cross‐sectional analysis of a prospective, multicentre observational study (WIHS) | USA | To investigate the association between PTSD and verbal learning and memory in WLWH and HIV‐negative women |
WLWH HIV‐negative women |
1004 (1004/100%) 496 (496/100%) |
47 43 |
PTSD Checklist‐Civilian version Neuropsychological testing including HVLT |
HIV status |
The proportion of women with PTSD was similar in WLWH and HIV‐negative women (18% vs. 16%; p = 0.49). Regardless of HIV status, PTSD was significantly associated with poor cognitive performance; with women performing worse on verbal learning (p < 0.001), memory (p < 0.001) and psychomotor speed (p < 0.001). Women |
| Rubin et al. (2016)h | Cross‐sectional analysis of a prospective, multicentre observational study (WIHS) | USA | To examine the association between stress, verbal memory and brain volumes in WLWH |
WLWH |
38 (38/100%) |
43.9 |
PSS PTSD Checklist‐Civilian version CES‐D scale Substance use history HVTL Structural MRI |
Higher vs. lower PSS |
Depressive symptoms were reported by 26% and an elevated PTSD symptom burden in 26%. 84% reported ever having experience abuse. Women with higher PSS performed worse than those with lower PSS on the verbal memory domain (p < 0.005). They had higher CD4 counts than those with lower PSS (p = 0.002). Higher PSS was associated with smaller volumes bilaterally in the medial temporal region (parahippocampal gyri) and prefrontal cortex regions, regions involved in verbal memory performance. |
| Rubin et al. (2016)i | Cross‐sectional analysis of a prospective, multicentre observational study (WIHS) | USA | To examine the association between stress and prefrontal cortical activation during verbal memory tasks | WLWH | 36 (36/100%) | 43.7 |
PSS PTSD Checklist‐Civilian version CES‐D scale Functional MRI In‐scanner verbal memory task similar to the HVLT |
Higher vs. lower PSS |
Women with higher PSS performed worse than those with lower PSS on the verbal memory domain (p < 0.005). They had higher CD4 counts than those with lower PSS (p = 0.002). Patterns of brain activation during recognition, but not encoding, differed between women with higher PSS than lower PSS. Women with higher PSS demonstrated greater deactivation in medial prefrontal cortex. |
Abbreviations: ART, antiretroviral therapy; BMI, body mass index; CES‐D, Center for Epidemiological Studies‐Depression; HAILO, Long‐term follow‐up of older HIV‐infected adults; HVLT, Hopkins Verbal Learning Test; MLWH, men living with HIV; MRI, magnetic resonance imaging; NC‐AE, neurocognitive‐adverse effects; OR, odds ratio; PLWH, people living with HIV; PSS, Perceived Stress Scale; PTSD, post‐traumatic stress disorder; VL, viral load; WIHS, Women’s Interagency HIV Study; WLWH, women living with HIV.
aChow FC, Makanjuola A, Wu K, Berzins B, Kim K‐YA, Ogunniyi A, et al. Physical Activity Is Associated with Lower Odds of Cognitive Impairment in Women but Not Men Living With Human Immunodeficiency Virus Infection. J Infect Dis. 2018;219(2):264–74.
bGustafson DR, Mielke MM, Tien PC, Valcour V, Cohen M, Anastos K, et al. Anthropometric measures and cognition in middle‐aged HIV‐infected and uninfected women. The Women’s Interagency HIV Study. J Neurovirol. 2013;19(6):574–85.
cMaki PM, Rubin LH, Valcour V, Martin E, Crystal H, Young M, et al. Cognitive function in women with HIV. Neurology. 2015;84(3):231–40.
dRubin LH, Radtke KK, Eum S, Tamraz B, Kumanan KN, Springer G, et al. Cognitive Burden of Common Non‐antiretroviral Medications in HIV‐Infected Women. Jaids J Acquir Immune Defic Syndromes. 2018;79(1):83–91.
eMeyer VJ, Rubin LH, Martin E, Weber KM, Cohen MH, Golub ET, et al. HIV and Recent Illicit Drug Use Interact to Affect Verbal Memory in Women. Jaids J Acquir Immune Defic Syndromes. 2013;63(1):67–76.
fRubin LH, Cook JA, Weber KM, Cohen MH, Martin E, Valcour V, et al. The association of perceived stress and verbal memory is greater in HIV‐infected versus HIV‐uninfected women. J Neurovirol. 2015;21(4):422–32.
gRubin LH, Pyra M, Cook JA, Weber KM, Cohen MH, Martin E, et al. Post‐traumatic stress is associated with verbal learning, memory, and psychomotor speed in HIV‐infected and HIV‐uninfected women. J Neurovirol. 2016;22(2):159–69.
hRubin LH, Meyer VJ, Conant RJ, Sundermann EE, Wu M, Weber KM, et al. Prefrontal cortical volume loss is associated with stress‐related deficits in verbal learning and memory in HIV‐infected women. Neurobiol Dis. 2016;92(Pt B):166–74.
iRubin LH, Wu M, Sundermann EE, Meyer VJ, Smith R, Weber KM, et al. Elevated stress is associated with prefrontal cortex dysfunction during a verbal memory task in women with HIV. J Neurovirol. 2016;22(6):840–51.