Distal Sensory Polyneuropathy is Associated with Neuropsychological Test Performance among Persons with HIV
ABSTRACT While distal sensory polyneuropathy (DSP) is the most common neurological condition associated with HIV, causing nerve damage in upper and lower extremities, its impact on neuropsychological test performance is unclear. In this study, we analyzed baseline data for 278 HIV-infected participants with comprehensive neurological and neurocognitive evaluations to examine the contribution of DSP and anatomic distribution of neuropathic signs (upper extremity or lower extremity) on standardized domain scores. We found that participants with DSP performed significantly worse in multiple domains containing timed psychomotor tests (i.e., motor, information processing speed and executive functioning). With regard to executive functioning, differences were limited to a test with a motor component (Trail Making Test, Part B). The group with clinically detectable neuropathic signs in the upper extremities and the group with signs limited to the lower extremities both performed worse in the motor domain than the group without DSP. Participants with DSP demonstrated a unique pattern of impairment limited to neuropsychological domains with timed psychomotor tests. These results suggest that caution should be used in interpretation of neuropsychological tests in patients with DSP, as some abnormalities may be exacerbated by peripheral nervous system pathology. (JINS, 2012, 19, 1-10).
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ABSTRACT: HIV sensory neuropathy and distal neuropathic pain (DNP) are common, disabling complications associated with combination antiretroviral therapy (cART). We previously associated iron-regulatory genetic polymorphisms with a reduced risk of HIV sensory neuropathy during more neurotoxic types of cART. We here evaluated the impact of polymorphisms in 19 iron-regulatory genes on DNP in 560 HIV-infected subjects from a prospective, observational study, who underwent neurological examinations to ascertain peripheral neuropathy and structured interviews to ascertain DNP. Genotype-DNP associations were explored by logistic regression and permutation-based analytical methods. Among 559 evaluable subjects, 331 (59%) developed HIV-SN, and 168 (30%) reported DNP. Fifteen polymorphisms in 8 genes (p<0.05) and 5 variants in 4 genes (p<0.01) were nominally associated with DNP: polymorphisms in TF, TFRC, BMP6, ACO1, SLC11A2, and FXN conferred reduced risk (adjusted odds ratios [ORs] ranging from 0.2 to 0.7, all p<0.05); other variants in TF, CP, ACO1, BMP6, and B2M conferred increased risk (ORs ranging from 1.3 to 3.1, all p<0.05). Risks associated with some variants were statistically significant either in black or white subgroups but were consistent in direction. ACO1 rs2026739 remained significantly associated with DNP in whites (permutation p<0.0001) after correction for multiple tests. Several of the same iron-regulatory-gene polymorphisms, including ACO1 rs2026739, were also associated with severity of DNP (all p<0.05). Common polymorphisms in iron-management genes are associated with DNP and with DNP severity in HIV-infected persons receiving cART. Consistent risk estimates across population subgroups and persistence of the ACO1 rs2026739 association after adjustment for multiple testing suggest that genetic variation in iron-regulation and transport modulates susceptibility to DNP.PLoS ONE 08/2014; 9(8):e103123. DOI:10.1371/journal.pone.0103123 · 3.53 Impact Factor
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ABSTRACT: Introduction: It is unclear whether or to what degree literacy, aging, and other neurologic abnormalities relate to cognitive deficits among people living with HIV/AIDS in the combined antiretroviral therapy (CART) era. The primary aim of this study was to simultaneously examine the association of age, HIV-associated motor abnormalities, major depressive disorder, and reading level with information processing speed, learning, memory, and executive functions, and to determine whether processing speed mediated any of the relationships between cognitive and noncognitive variables. Method: Participants were 186 racially and ethnically diverse men and women living with HIV/AIDS who underwent comprehensive neurological, neuropsychological, and medical evaluations. Structural equation modeling was utilized to assess the extent to which information processing speed mediated the relationship between age, motor abnormalities, major depressive disorder, and reading level with other cognitive abilities. Results: Age, motor dysfunction, reading level, and current major depressive disorder were all significantly associated with information processing speed. Information processing speed fully mediated the effects of age on learning, memory, and executive functioning and partially mediated the effect of major depressive disorder on learning and memory. The effect of motor dysfunction on learning and memory was fully mediated by processing speed. Conclusions: These findings provide support for information processing speed as a primary deficit, which may account, at least in part, for many of the other cognitive abnormalities recognized in complex HIV/AIDS populations. The association of age and information processing speed may account for HIV/aging synergies in the generation of CART-era cognitive abnormalities.Journal of Clinical and Experimental Neuropsychology 08/2014; 36(8):1-12. DOI:10.1080/13803395.2014.943696 · 2.16 Impact Factor
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ABSTRACT: Controversy exists as to whether effects of HIV infection can be detected in the cognitive profiles of substance users, with methodological differences in degree of control for confounding factors a major contributor to empirical discrepancies. To address this shortcoming, we conducted a small but well-controlled study aimed at isolating HIV neurocognitive (NC) effects in a group of chronic substance users. Thirty HIV-negative substance users were individually matched to 30 HIV-positive substance users on relevant medical and demographic factors, including reading level and methadone therapy status. Results revealed that reading level, methadone maintenance therapy, and positive urine toxicology each exerted significant influence on NC function, and that HIV status was a significant predictor of learning and speeded processing after these control factors were considered. The HIV-positive group also displayed significantly more neurologically assessed motor impairment (p < .05), which was specifically related to impaired cognition in this group and independent of degree of immunocompromise. These data demonstrate the need for increased attention to clinical/demographic characteristics of groups under study. They also show that with applied methodological rigor, the deleterious effects of HIV on cognition can be parsed from substance use, even in small samples with chronic and active use histories. (JINS, 2013, 19, 1-11).Journal of the International Neuropsychological Society 02/2013; DOI:10.1017/S1355617712001634 · 2.70 Impact Factor