Latent Profile Analysis of Cognitive Performance and Depressive Symptoms Among People with HIV.

Depression and cognitive impairment are prevalent conditions among people with HIV (PWH), likely attributable to shared causes and common risk factors. Identifying subtypes of PWH with similar patterns of neurocognitive impairment (NCI) and depressive symptoms may inform development of patient-centered interventions that target-specific profiles. This study aimed to (1) classify PWH based on patterns of domain-specific NCI and depression; and (2) determine the relationship between latent class membership and pertinent clinical characteristics. PWH (N = 580, 86.2% male, 57.1% non-Hispanic White, 69.2% unemployed) completed a comprehensive neuropsychological test battery assessing global and domain-specific cognition. Domain-specific NCI was classified as deficit score >0.5. Participants completed the Beck Depression Inventory-II (BDI-II), and domain-specific BDI-II scores reflecting cognitive, affective, and somatic symptoms were computed. Latent profile analysis (LPA) was used to determine latent subgroups of NCI and depression. The optimal LPA solution consisted of five classes: minimal NCI and minimal depression (Class 1), amnestic and minimal depression (Class 2), severe multi-domain NCI and moderate depression (somatic and affective; Class 3), mild NCI and mild depression (Class 4), and moderate multi-domain NCI and severe depression (Class 5). Despite similar levels of functional impairment, Class 5 had a significant psychiatric profile, whereas Class 3 had a complex medical profile (i.e., higher frailty index, higher medications, greater proportion of AIDS diagnosis). In contrast, Class 1 had the lowest medication use and frailty index, with similar HIV disease characteristics to Classes 3 and 5. Our results suggest there are multiple pathways to cognitive and functional impairment among PWH with co-occurring depression and cognitive impairment, and these groups may respond differently to interventions. Of note, our sample was majority non-Hispanic White and male, which is nonrepresentative of the US population of PWH. Future interventions should consider a more integrated, person-centered approach that addresses cognitive and emotional health to optimize health outcomes in PWH.

Neurocognitive Dysfunction With Neuronal Injury in People With HIV on Long-Duration Antiretroviral Therapy.

BACKGROUND AND OBJECTIVES: Neurologic outcomes in people with HIV (PWH) on long-duration antiretroviral therapy (ART) are not fully understood, and the underlying pathophysiology is unclear. To address this, we established a cohort of such individuals and compared them with HIV-negative controls using a novel matching technique. Both groups underwent extensive cognitive testing, evaluation for psychiatric measures, and MRI and CSF analyses. METHODS: Participants underwent comprehensive neuropsychological testing and completed standardized questionnaires measuring depressive symptoms, perceptions of own functioning, and activities of daily living as part of an observational study. Brain MRI and lumbar puncture were optional. Coarsened Exact Matching was used to reduce between-group differences in age and sex, and weighted linear/logistic regression models were used to assess the effect of HIV on outcomes. RESULTS: Data were analyzed from 155 PWH on ART for at least 15 years and 100 HIV-negative controls. Compared with controls, PWH scored lower in the domains of attention/working memory (PWH least square mean [LSM] = 50.4 vs controls LSM = 53.1, p = 0.008) and motor function (44.6 vs 47.7, p = 0.009) and a test of information processing speed (symbol search 30.3 vs 32.2, p = 0.003). They were more likely to self-report a higher number of cognitive difficulties in everyday life (p = 0.011). PWH also reported more depressive symptoms, general anxiety, and use of psychiatric medications (all with p < 0.05). PWH had reduced proportions of subcortical gray matter on MRI (ß = -0.001, p < 0.001), and CSF showed elevated levels of neurofilament light chain (664 vs 529 pg/mL, p = 0.01) and tumor necrosis factor α (0.229 vs 0.156 ng/mL, p = 0.0008). DISCUSSION: PWH, despite effective ART for over a decade, displayed neurocognitive deficits and mood abnormalities. MRI and CSF analyses revealed reduced brain volume and signs of ongoing neuronal injury and neuroinflammation. As the already large proportion of virologically controlled PWH continues to grow, longitudinal studies should be conducted to elucidate the implications of cognitive, psychiatric, MRI, and CSF abnormalities in this group.

High Psychosocial Burden Relates to Poorer Antiretroviral Treatment Adherence Among Black/African American People with HIV.

Black/African American communities continue to be disproportionately impacted by HIV with Black people with HIV (PWH) exhibiting poorer outcomes along the HIV treatment cascade. Psychosocial burden may, in part, explain these health disparities among PWH. We implemented a culturally adapted intervention [individualized Texting for Adherence Building (iTAB)] to improve ART adherence among 89 Black PWH in San Diego, CA. We aimed to (1) characterize psychosocial risk factors (depression, negative life events, discrimination, medical mistrust) hypothesized to be barriers to HIV outcomes among Black PWH and (2) determine if these factors influence intervention engagement, HIV outcomes, and self-reported physical and mental health. We identified three levels of psychosocial burden (low, moderate, high) through hierarchical cluster analysis. Participants in the high burden cluster (n = 25) experienced the highest levels of depression, negative life events, and discrimination, in addition to the poorest intervention outcomes, HIV outcomes, and physical and mental health compared to low and moderate burden clusters. Participants in the low (n = 29) burden cluster had less medical mistrust than the moderate (n = 34) and high burden clusters, but low and moderate clusters did not differ on any outcomes. Overall, self-reported ART adherence was 83%, which is above estimates of ART adherence in the Western region of the United States. The iTAB intervention shows promise in improving HIV-related outcomes among Black PWH with low to moderate psychosocial burden; however, additional supports may need to be identified for those with high psychosocial burden.

Four-Year Trajectories of Internal Strengths and Socioemotional Support Among Middle-Aged and Older Adults with HIV.

Positive psychological attributes are associated with better health outcomes, yet few studies have identified their underlying constructs and none have examined their temporal trajectories in clinical vs. non-clinical samples. From data collected over 4 years from people with HIV (PWH) and HIV-uninfected (HIV-) participants, we identified two latent factors (internal strengths; socioemotional support) based on responses to seven positive psychological attributes. Internal strengths increased over 4 years for PWH, but not for HIV- comparisons. Socioemotional support did not change significantly in either group. Lower internal strengths and worse socioemotional support were related to greater depressive symptoms. We speculate that improvement in internal strengths in PWH could reflect their being in care, but this requires further study to include PWH not in care. Given the apparent malleability of internal strengths and their association with improved health outcomes, these attributes can serve as promising intervention targets for PWH.

Medical Symptom Validity Test (MSVT) profiles in individuals being evaluated for Alzheimer's disease.

Objective:Our purpose was to determine whether Medical Symptom Validity Test (MSVT) profiles could differentiate performance invalidity from true impairment in patients with varying levels of memory impairment and functional ability being evaluated for Alzheimer's disease (AD). Method: Seventy-three older adults (13 healthy controls, 25 mild cognitive impairment [MCI], 16 mild AD, 19 moderate AD) were evaluated with a neuropsychological battery including the MSVT and activities of daily living (ADL) measures. Using MSVT classification guidelines, examinees' MSVT profiles were categorized as: 1) valid, 2) invalid, 3) weak memory, or 4) genuine memory impairment (GMIP). Results: Eighty-four percent of moderate AD examinees produced a GMIP. Among MCI and mild AD examinees, who had only modestly affected ADLs, a substantial proportion manifested a GMIP (40% and 62.5%, respectively). An invalid profile was uncommon across patient groups (12.5% in mild AD, 5.3% in moderate AD, and 0% in MCI). Conclusions: The MSVT functions reasonably well in a dementia sample to determine if an examinee has an invalid profile, although for mild AD examinees, the false positive rate is slightly above the recommended 10% cut-off. However, even individuals with MCI, mild AD and relative preservation of ADLs may manifest a GMIP, demonstrating that such profile is found across patients with lower and higher degrees of functional impairment. Given this finding, the usefulness of the GMIP in differentiating performance invalidity from true impairment in patients being evaluated for AD appears limited.

Association of White Matter Hyperintensities With HIV Status and Vascular Risk Factors.

OBJECTIVE: To test the hypothesis that brain white matter hyperintensities (WMH) are more common in people living with HIV (PLWH), even in the setting of well-controlled infection, and to identify clinical measures that correlate with these abnormalities. METHODS: Research brain MRI scans, acquired within longitudinal studies evaluating neurocognitive outcomes, were reviewed to determine WMH load using the Fazekas visual rating scale in PLWH with well-controlled infection (antiretroviral therapy for at least 1 year and plasma viral load <200 copies/mL) and in sociodemographically matched controls without HIV (CWOH). The primary outcome measure of this cross-sectional analysis was increased WMH load, determined by total Fazekas score ≥2. Multiple logistic regression analysis was performed to evaluate the effect of HIV serostatus on WMH load and to identify MRI, CSF, and clinical variables that associate with WMH in the PLWH group. RESULTS: The study included 203 PLWH and 58 CWOH who completed a brain MRI scan between April 2014 and March 2019. The multiple logistic regression analysis, with age and history of tobacco use as covariates, showed that the adjusted odds ratio of the PLWH group for increased WMH load is 3.7 (95% confidence interval 1.8-7.5; p = 0.0004). For the PLWH group, increased WMH load was associated with older age, male sex, tobacco use, hypertension, and hepatitis C virus coinfection, and also with the presence of measurable tumor necrosis factor α in CSF. CONCLUSION: Our results suggest that HIV serostatus affects the extent of brain WMH. This effect is mainly associated with aging and modifiable comorbidities.

Quality of life of HIV-negative, previously healthy individuals following cryptococcal meningoencephalitis.

The morbidity and mortality of cryptococcal meningoencephalitis (CM) in previously healthy, HIV-negative individuals is increasingly recognized. We administered a healthcare associated quality of life (QOL) survey to the largest longitudinally followed cohort of these patients in the United States. We identified moderate or severe self-reported impairment in at least one QOL domain in 61% of subjects at least one year following diagnosis. Self-reported cognitive impairment was noted in 52% and sleep disturbance was noted in 55%. This is the first comprehensive study of cross-sectional long-term QOL in previously healthy patients following cryptococcal infection.

When and how did you go wrong? Characterizing mild functional difficulties in older adults during an everyday task.

Mild functional difficulties associated with cognitive aging may be reliably measured by coding "micro-errors" during everyday tasks, like meal preparation. Micro-errors made by 25 older adult and 48 younger adults were coded on four dimensions to evaluate the influence of: 1) poor error monitoring; 2) goal decay; 3) competition for response selection when switching to a new subtask; and 4) interference from distractor objects. Micro-errors made by young adults under a dual task load also were analyzed to determine the influence of overall performance level. Older adults' micro-errors were observed when switching to a new subtask and to unrelated distractors. Slowed error monitoring and goal decay also influenced micro-errors in older adults, but not significantly more so than younger adults under the dual task. Interventions to reduce interference from distractors and to increase attention at critical choice points during tasks may optimize everyday functioning and preclude decline in older adults.

HIV-Negative Cryptococcal Meningoencephalitis Results in a Persistent Frontal-Subcortical Syndrome.

Twenty-seven previously healthy (of 36 consecutive eligible patients), HIV-negative cryptococcal meningoencephalitis (CM) patients underwent comprehensive neuropsychological evaluation during the late post-treatment period (1.3-4 years post diagnosis), assessing attention, language, learning, memory, visuospatial, executive function, information processing, psychomotor functioning, as well as mood symptoms. Seven of eight domains (all except attention) showed increased percentages of CM patients scoring in the less than 16th percentile range compared to standardized normative test averages, adjusted for education level and age. Comparison with a matched archival dataset of mild cognitive impairment/Alzheimer's disease patients showed that CM patients exhibited relative deficits in psychomotor and executive function with fewer deficits in memory and learning, consistent with a frontal-subcortical syndrome. MRI evaluation at the time of testing demonstrated an association of lower neuropsychological functioning with ventriculomegaly. These studies suggest that CM should be included in the list of treatable causes of dementia in neurological work ups. Future studies are needed to identify diagnostic and treatment regimens that may enhance neurological function after therapy.

The neuropsychological phenotype of Chediak-Higashi disease.

BACKGROUND/OBJECTIVES: Chediak-Higashi Disease (CHD) is a rare autosomal disorder, purported to have cognitive and neurological impairments. Prior descriptions of cognitive impairment, however, are solely based on subjective, unstructured observations rather than on formal neuropsychological measures. METHODS: Four pediatric and 14 adult patients with diagnostically confirmed CHD were administered a neuropsychological battery assessing memory, attention, processing speed, psychomotor speed, language fluency, executive function, and general intelligence. Nine of the adult patients received follow-up evaluations to elucidate the longitudinal progression or stability of cognition over time. RESULTS: Pediatric CHD patients performed within the average range. Adult patients, however, performed below average on nearly all measures administered, and endorsed subjective reports of learning difficulties and poor academic performance in childhood. In particular, patients struggled with memory and psychomotor speed tasks, with 75% or more of patients scoring in the bottom 2.3 percentile in these two domains. No significant declines in cognition were observed among the patients who completed follow-up evaluations (M = 39.90, SD = 8.03 months between visits). Exploratory analyses suggested that adult patients who had classic CHD and previously received bone marrow transplants (BMTs; n = 3) exhibited moderately greater cognitive impairment than adult patients who had atypical CHD and had not received BMTs (n = 10). CONCLUSIONS: Adult patients with CHD uniformly exhibit deficits in multiple domains, but in psychomotor speed and memory, in particular. Based on their neuropsychological profile, their ability to hold jobs and succeed in school may require support and special accommodations. The source of cognitive deficits is probably multifactorial including central nervous system involvement in CHD, and, for those transplanted, BMT-related side effects and complications. Absence of cognitive decline at three-year follow-up is encouraging but does not exclude progression at a slower time-scale. Future work should elucidate the possible effects and timing of BMT on cognition, as well as the mechanisms driving neuropsychological impairment in CHD.

The Virtual Kitchen Challenge: preliminary data from a novel virtual reality test of mild difficulties in everyday functioning.

Background: Efficient, objective measures of mild functional difficulties are lacking. Preliminary data from a novel, non-immersive virtual reality, performance-based task (Virtual Kitchen Challenge; VKC) were obtained to address this gap. Methods: 14 older and 21 younger adults completed cognitive tests and two everyday tasks (breakfast, lunch) in the VKC with virtual objects and a touch-screen and in the Real Kitchen with real objects (order counterbalanced). Automated performance measures were obtained from the VKC program and human coders scored VKC and Real Kitchen videos for errors. Results: Older adults made more errors than younger adults on the VKC and Real Kitchen, with similar error patterns across measures. VKC automated measures were significantly related to measures from human coders, performance on the Real Kitchen, and cognitive test scores. Conclusion: The VKC is a valid and highly efficient performance-based measure of subtle functional difficulties with great potential for future clinical and research applications.