Major depressive disorder, cognitive symptoms, and neuropsychological performance among ethnically diverse HIV+ men and women.

Major depressive disorder (MDD), cognitive symptoms, and mild cognitive deficits commonly occur in HIV-infected individuals, despite highly active antiretroviral therapies. In this study, we compared neuropsychological performance and cognitive symptoms of 191 HIV-infected participants. Results indicated that participants with a formal diagnosis of current MDD performed significantly worse than participants without MDD in all seven neuropsychological domains evaluated, with the largest effect sizes in information processing speed, learning, and memory. In addition, a brief assessment of cognitive symptoms, derived from a comprehensive neuromedical interview, correlated significantly with neurocognitive functioning. Participants with MDD reported more cognitive symptoms and showed greater neurocognitive deficits than participants without MDD. These findings indicate that HIV-infected adults with MDD have more cognitive symptoms and worse neuropsychological performance than HIV-infected individuals without MDD. The results of this study have important implications for the diagnosis of HIV-associated neurocognitive disorders (HAND).

Distal sensory polyneuropathy is associated with neuropsychological test performance among persons with HIV.

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).

Pathological functional impairment: Neuropsychological correlates of the shared variance between everyday functioning and brain volumetrics.

Objective: Given that several non-cognitive factors can contribute to difficulties with everyday functioning, examining the extent to which cognition is associated with brain-related changes in everyday functioning is critical to accurate characterization of cognitive disorders. In this study, we examined neuropsychological correlates of the shared variance between everyday functioning and pathological indicators of cognitive aging using MRI brain volumetrics. Participants and methods: Participants were 600 adults aged 55 and older without dementia [432 cognitively normal; 168 mild cognitive impairment (MCI)] from the National Alzheimer's Coordinating Center cohort who underwent neuropsychological testing, informant-rated everyday functioning, and brain MRI scanning at baseline. The shared variance between everyday functioning and brain volumetrics (i.e., hippocampal volume, white matter hyperintensity volume) was extracted using the predicted value from multiple regression. The shared variance was used as an indicator of pathological everyday functional impairment. The residual variance from the regression analysis was used to examine functional reserve. Results: Larger white matter hyperintensity volumes (p = 0.002) and smaller hippocampal volumes (p < 0.001) were significantly correlated with worse informant-rated everyday functioning. Among individuals with MCI, worse performances on delayed recall (p = 0.013) and category fluency (p = 0.012) were significantly correlated with pathological functional impairment in multiple regression analysis. In the cognitively normal group, only worse auditory working memory (i.e., digit span backward; p = 0.025) significantly correlated with pathological functioning. Functional reserve was inversely related to anxiety (p < 0.001) in the MCI group and was associated with depressive symptoms (p = 0.003) and apathy (p < 0.001) in the cognitively normal group. Conclusion: Subtle brain-related everyday functioning difficulties are evident in MCI and track with expected preclinical Alzheimer's disease cognitive phenotypes in this largely amnestic sample. Our findings indicate that functional changes occur early in the disease process and that interventions to target neuropsychiatric symptoms may help to bolster functional reserve in those at risk.

Multimethod assessment of everyday functioning and memory abilities in Parkinson's disease.

OBJECTIVE: This study compared functional abilities in individuals with Parkinson's disease (PD) with normal cognition (PD-CN) and mild cognitive impairment (PD-MCI) using multiple assessment methods. Cognitive and physical correlates were also examined. METHOD: Participants were 42 nondemented individuals with PD (24 PD-CN, 18 PD-MCI) and 42 age-matched healthy controls. Functional abilities were assessed through direct observation and self- and informant-report questionnaires. Participants were administered an activity-based memory paradigm that assessed prospective, content, and temporal order memory as well as a test of mobility. RESULTS: Compared to the PD-CN and healthy control groups, participants with PD-MCI performed significantly worse on directly observed everyday activities, self- and informant-reports of instrumental activities of daily living (IADLs), and self-report of everyday activities requiring physical capacity. No significant differences were observed between PD-CN and healthy controls. Among participants with PD, content memory correlated with all of the functional outcome measures, temporal order memory correlated with self-reported IADLs, and physical mobility correlated with self-reported physical capacity and content memory. CONCLUSIONS: The results indicated that PD-MCI is associated with decreased ability to perform everyday activities. Reduced ability to correctly recall and sequence activities may contribute to lower functional abilities on IADLs, whereas noncognitive factors (i.e., mobility) may become more salient when the everyday task requires physical capacity. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Symbol Digit Modalities Test: Regression-Based Normative Data and Clinical Utility.

OBJECTIVE: The purpose of this study was to provide regression-based normative data for the written, oral, and incidental recall trials of the Symbol Digit Modalities Test (SDMT). METHOD: Regression-based normative equations for the written and oral trials were derived from 536 healthy men and women between the ages of 18 and 91. Normative equations for the incidental recall trial are provided for a subset of the normative sample (age range = 60-91). The clinical utility of the newly developed norms was examined by comparing mean performance and rates of impaired scores for participants with traumatic brain injury (TBI), mild cognitive impairment (MCI), and dementia. Within-group analyses were used to compare the new norms to the original published norms. RESULTS: Age, education, and sex were all significant predictors of written trial performance, age and education were significant predictors of oral trial performance, and only age predicted incidental recall trial performance. As expected, the TBI group demonstrated the highest rates of impaired performance on both written and oral trials. Participants with dementia showed the highest rate of impaired scores on the incidental recall trial, followed by participants with amnestic MCI. Compared to traditional norming methods, the regression-based norms classified more clinical participants as impaired on both the written and oral trials. CONCLUSIONS: Comprehensive regression-based normative equations with demonstrated clinical utility are provided to improve the detection of cerebral dysfunction using the SDMT. A calculator with the normative equations is provided so that raw scores can be easily converted to demographically-corrected standardized scores.

Independent and Differential Effects of Obesity and Hypertension on Cognitive and Functional Abilities.

OBJECTIVE: The primary aim of this study was to identify the independent and differential associations of obesity and hypertension with cognitive, physical, and directly observed functional abilities among middle age and older adults. METHOD: Participants were 119 adults between the ages of 51 and 89, who underwent a cross-sectional assessment of cognitive, physical, functional and relevant health-related variables. RESULTS: Obesity predicted significantly poorer executive functions (ß = -.301, t = -3.86, p < .001), mobility (ß = .329, t = 3.59, p < .001), observed functional abilities (ß = .220, t = 2.52, p = .013), and self-reported ability to perform activities of daily living that require physical capability (ß = -.365, t = -4.23, p < .001). In contrast, hypertension was not independently associated with any of the outcome measures (ps > .05). Results from the path analysis revealed that executive functions mediated the association between obesity and poorer directly observed functional abilities. Additionally, obesity had a direct and indirect (through mobility) effect on self-reported basic activities of daily living. CONCLUSIONS: These findings suggest a link between obesity, executive functions, and limitations in physical function and instrumental activities of daily living among middle age and older adults, however, longitudinal research is needed to further delineate the trajectory of these factors.

Multicomponent analysis of a digital Trail Making Test.

OBJECTIVE: The purpose of the current study was to use a newly developed digital tablet-based variant of the TMT to isolate component cognitive processes underlying TMT performance. METHOD: Similar to the paper-based trail making test, this digital variant consists of two conditions, Part A and Part B. However, this digital version automatically collects additional data to create component subtest scores to isolate cognitive abilities. Specifically, in addition to the total time to completion and number of errors, the digital Trail Making Test (dTMT) records several unique components including the number of pauses, pause duration, lifts, lift duration, time inside each circle, and time between circles. Participants were community-dwelling older adults who completed a neuropsychological evaluation including measures of processing speed, inhibitory control, visual working memory/sequencing, and set-switching. The abilities underlying TMT performance were assessed through regression analyses of component scores from the dTMT with traditional neuropsychological measures. RESULTS: Results revealed significant correlations between paper and digital variants of Part A (rs = .541, p < .001) and paper and digital versions of Part B (rs = .799, p < .001). Regression analyses with traditional neuropsychological measures revealed that Part A components were best predicted by speeded processing, while inhibitory control and visual/spatial sequencing were predictors of specific components of Part B. Exploratory analyses revealed that specific dTMT-B components were associated with a performance-based medication management task. CONCLUSIONS: Taken together, these results elucidate specific cognitive abilities underlying TMT performance, as well as the utility of isolating digital components.

Between-domain cognitive dispersion and functional abilities in older adults.

OBJECTIVE: Within-person variability in cognitive performance is related to neurological integrity, but the association with functional abilities is less clear. The primary aim of this study was to examine the association between cognitive dispersion, or within-person variability, and everyday multitasking and the way in which these variables may influence performance on a naturalistic assessment of functional abilities. METHOD: Participants were 156 community-dwelling adults, age 50 or older. Cognitive dispersion was calculated by measuring within-person variability in cognitive domains, established through principal components analysis. Path analysis was used to determine the independent contribution of cognitive dispersion to functional ability, mediated by multitasking. RESULTS: Results of the path analysis revealed that the number of subtasks interweaved (i.e., multitasked) mediated the association between cognitive dispersion and task sequencing and accuracy. Although increased multitasking was associated with worse task performance in the path model, secondary analyses revealed that for individuals with low cognitive dispersion, increased multitasking was associated with better task performance, whereas for those with higher levels of dispersion multitasking was negatively correlated with task performance. CONCLUSION: These results suggest that cognitive dispersion between domains may be a useful indicator of multitasking and daily living skills among older adults.

Psychological trauma exposure and co-morbid psychopathologies in HIV+Men and Women.

This study examined the association between trauma exposure, PTSD, suicide attempts, and other psychopathology among 316 racially/ethnically diverse HIV-infected men and women who underwent semi-structured psychiatric assessment. In addition, the role of psychological resilience in trauma exposure was examined in the context of neurological symptoms and functional status. Nearly half (47.8%; 151/316) of the participants reported trauma exposure, of which 47.0% (71/151) developed PTSD. Among trauma-exposed individuals, those with a current psychiatric diagnosis reported more neurological symptoms and lower functional status. Trauma exposure without PTSD was associated with a higher rate of panic disorder and substance-induced mental disorders. Trauma-exposed individuals who did not develop PTSD were less likely than those who reported no trauma exposure to meet criteria for major depressive disorder (MDD). Trauma exposure, MDD, borderline personality disorder, and substance-induced mental disorders were independently associated with increased odds of suicide attempt. These results indicate that co-morbid psychiatric disorders are common among trauma exposed individuals with a history of PTSD, but those with trauma exposure who do not develop PTSD are less likely to experience MDD. The role of other co-morbid psychopathologies in the genesis of suicidal behavior among individuals living with HIV deserves further study.

Reading Ability as an Estimator of Premorbid Intelligence: Does It Remain Stable Among Ethnically Diverse HIV+ Adults?

UNLABELLED: The Wide Range Achievement Test, 3rd edition, Reading Recognition subtest (WRAT-3 RR) is an established measure of premorbid ability. Furthermore, its long-term reliability is not well documented, particularly in diverse populations with CNS-relevant disease. OBJECTIVE: We examined test-retest reliability of the WRAT-3 RR over time in an HIV+ sample of predominantly racial/ethnic minority adults. METHOD: Participants (N = 88) completed a comprehensive neuropsychological battery, including the WRAT-3 RR, on at least two separate study visits. Intraclass correlation coefficients (ICCs) were computed using scores from baseline and follow-up assessments to determine the test-retest reliability of the WRAT-3 RR across racial/ethnic groups and changes in medical (immunological) and clinical (neurocognitive) factors. Additionally, Fisher's Z tests were used to determine the significance of the differences between ICCs. RESULTS: The average test-retest interval was 58.7 months (SD = 36.4). The overall WRAT-3 RR test-retest reliability was high (r = .97, p < .001) and remained robust across all demographic, medical, and clinical variables (all r's > .92). ICCs did not differ significantly between the subgroups tested (all Fisher's Z p's > .05). CONCLUSIONS: Overall, this study supports the appropriateness of word-reading tests, such as the WRAT-3 RR, for use as stable premorbid IQ estimates among ethnically diverse groups. Moreover, this study supports the reliability of this measure in the context of change in health and neurocognitive status and in lengthy inter-test intervals. These findings offer strong rationale for reading as a "hold" test, even in the presence of a chronic, variable disease such as HIV.

Effects of information processing speed on learning, memory, and executive functioning in people living with HIV/AIDS.

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.

Neurocognitive impact of substance use in HIV infection.

BACKGROUND: : To determine how serious a confound substance use (SU) might be in studies on HIV-associated neurocognitive disorder (HAND), we examined the relationship of SU history to neurocognitive impairment (NCI) in participants enrolled in the Central Nervous System HIV Antiretroviral Therapy Effects Research study. METHODS: : After excluding cases with behavioral evidence of acute intoxication and histories of factors that independently could account for NCI (eg, stroke), baseline demographic, medical, SU, and neurocognitive data were analyzed from 399 participants. Potential SU risk for NCI was determined by the following criteria: lifetime SU Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis, self-report of marked lifetime SU, or positive urine toxicology. Participants were divided into 3 groups as follows: no SU (n = 134), nonsyndromic SU (n = 131), syndromic SU (n = 134) and matched on literacy level, nadir CD4, and depressive symptoms. RESULTS: : Although approximately 50% of the participants were diagnosed with HAND, a multivariate analysis of covariance of neurocogntive summary scores, covarying for urine toxicology, revealed no significant effect of SU status. Correlational analyses indicated weak associations between lifetime heroin dosage and poor recall and working memory and between cannabis and cocaine use and better verbal fluency. CONCLUSIONS: : These data indicate that HIV neurocognitive effects are seen at about the same frequency in those with and without historic substance abuse in cases that are equated on other factors that might contribute to NCI. Therefore, studies on neuroAIDS and its treatment need not exclude such cases. However, the effects of acute SU and current SU disorders on HAND require further study.