There are over 35 million people worldwide infected with the Human Immunodeficiency Virus (HIV) and its progression to Acquired Immunodeficiency Syndrome (AIDS; WHO, 2014). With the advent of ...combined antiretroviral therapy (i.e., cART) in 1996, persons living with HIV/AIDS (PLWHA) now have much longer life expectancies. However, living with HIV remains challenging, as it is associated with a number of significant and recurrent (chronic) stressors including physical pain, side effects of cART, social stigma, and discrimination, among other social stressors. Presumably, as a result of these types of stressors, a disproportionately high number of PLWHA struggle with clinically-significant psychiatric symptoms and disorders. Although much scientific and clinical attention has focused on depressed mood and psychopathology among PLWHA, there has been comparably less focus on anxiety and its disorders. The paucity of work in this area is concerning from a public health perspective, as anxiety symptoms and disorders are the most common class of psychiatric disorders and often maintain a large negative impact on life functioning.
•A review of the rates and impact of clinically-significant anxiety among persons living with HIV/AIDS (PLWHA) is presented.•Anxiety disorders and clinically-relevant symptoms have negative physical and emotional effects on PLWHA.•Certain transdiagnostic variables may impact the rates and impact of anxiety among PLWHA.•A heuristic model is proposed outlining the interrelations of anxiety and poor physical and psychological symptoms.
Objective: Cognitive fluctuations are characteristic of dementia with Lewy bodies (DLB) but challenging to measure. Dispersion-based intra-individual variability (IIV-d) captures neurocognitive ...performance fluctuations across a test battery and may be sensitive to cognitive fluctuations but has not been studied in DLB. Method: We report on 5,976 participants that completed the uniform data set 3.0 neuropsychological battery (UDS3NB). IIV-d was calculated via the intra-individual standard deviation across 12 primary UDS3NB indicators. Separate models using mean USD3NB score and the Montreal cognitive assessment (MoCA) total score tested the reproducibility of the incremental value of IIV-d over-and-above global cognition. Binary logistic regressions tested whether IIV-d could classify individuals with and without clinician-rated cognitive fluctuations. Multinomial logistic regressions tested whether IIV-d could differentiate participants with DLB, participants with Alzheimer's disease (AD), and participants with healthy cognition (CH), as well as the incremental diagnostic utility of IIV-d over-and-above clinician-rated cognitive fluctuations. Results: IIV-d exhibited large univariate associations with clinician-rated and non-clinician-informant reported cognitive fluctuations, which persisted when adjusting for MoCA but not the full battery mean. Of diagnostic relevance, greater IIV-d was consistently associated with DLB and AD relative to CH over-and-above global cognition and clinician-rated cognitive fluctuations. Greater IIV-d was less consistently associated with an increased probability of DLB relative to AD when controlling for global cognition. Conclusions: IIV-d accurately differentiates DLB from CH over-and-above global cognition and clinician-rated cognitive fluctuations. IIV-d may supplement a thorough clinical interview of cognitive fluctuations and serve as a standardized performance-based indicator of this transdiagnostic phenomenon.
Key Points
Question: Does neurocognitive dispersion (IIV-d) differentiate participants with dementia with Lewy bodies (DLB) from cognitively healthy (CH) participants and participants with Alzheimer's disease (AD)? Findings: Greater IIV-d was consistently associated with an increased probability of DLB and AD relative to CH (but not DLB relative to AD) over-and-above global cognition and clinician-rated cognitive fluctuations, but the large univariate associations between IIV-d and clinician-rated/non-clinician-informant reported cognitive fluctuations were inconsistently observed when controlling for global cognition. Importance: IIV-d may serve as a standardized performance-based indicator of cognitive fluctuations that may be used to enhance diagnosis and allocation of treatment resources for those with DLB. Next Steps: Future research would benefit from testing the relationship between IIV-d and non-clinician-informant reported cognitive fluctuations in a larger sample and from developing norms for IIV-d to facilitate use in research and clinical practice.
Here we evaluated whether neurocognitive disorders in HIV-infected individuals on effective antiretroviral therapy (ART) are associated with persistent monocyte activation as indexed by levels of ...soluble CD163 (sCD163), shed by monocyte/macrophages.
Chronically, HIV-infected individuals were examined at two consecutive visits median interquartile range (IQR) 16 (7-32) months apart. All patients were on ART and durably virologically suppressed (plasma HIV RNA <50 copies/ml) at all visits. Thirty-four age-matched HIV-seronegative patients were used as controls.
A global deficit score (GDS) was calculated based on comprehensive neuropsychological assessment according to standard methods. Neuropsychological and medical data were used to assign neurocognitive status according to published guidelines for HIV-associated neurocognitive disorders (HAND) as follows: neuropsychologically normal (NP-nml), asymptomatic neuropsychological impairment (ANI) and minor neurocognitive disorder (MND). sCD163 in plasma and cerebrospinal fluid was measured using ELISA.
GDS-impaired patients had higher plasma sCD163 than those who were not impaired median (IQR) 1401 ng/ml (1057-2258) versus 955 ng/ml (586-1313); Wilcoxon P=0.028. Patients with MND (N=6) had significantly higher plasma sCD163 than ANI (P=0.04) or NP-nml (P=0.02). Whereas plasma sCD163 levels dropped in patients who were stably GDS-unimpaired after the first visit (P<0.032), levels remained elevated in those who remained GDS-impaired (P=0.50).
These findings are consistent with persistent monocyte/macrophage activation in neurophysiologically impaired HIV-infected individuals despite virally suppressive ART. Overall, these observations underscore the significance of monocyte/macrophage immune responses in HIV, persistent monocyte activation in HAND and the value of sCD163, as a plasma marker of neurocognitive impairment.
Cognitive fluctuations are a core clinical feature of dementia with Lewy bodies (DLB), but their contribution to the everyday functioning difficulties evident DLB are not well understood. The current ...study evaluated whether intraindividual variability across a battery of neurocognitive tests (intraindividual variability-dispersion) and daily cognitive fluctuations as measured by informant report are associated with worse daily functioning in DLB.
The study sample included 97 participants with consensus-defined DLB from the National Alzheimer's Coordinating Center (NACC). Intraindividual variability-dispersion was measured using the coefficient of variation, which divides the standard deviation of an individual's performance scores across 12 normed neurocognitive indices from the NACC neuropsychological battery by that individual's performance mean. Informants reported on daily cognitive fluctuations using the Mayo Fluctuations Scale (MFS) and on daily functioning using the functional activities questionnaire (FAQ).
Logistic regression identified a large univariate association of intraindividual variability-dispersion and presence of daily cognitive fluctuations on the MFS (Odds Ratio = 73.27, 95% Confidence Interval = 1.38, 3,895.05). Multiple linear regression demonstrated that higher intraindividual variability-dispersion and presence of daily cognitive fluctuations as assessed by the MFS were significantly and independently related to worse daily functioning (FAQ scores).
Among those with DLB, informant-rated daily cognitive fluctuations and cognitive fluctuations measured in the clinic (as indexed by intraindividual variability-dispersion across a battery of tests) were independently associated with poorer everyday functioning. These data demonstrate ecological validity in measures of cognitive fluctuations in DLB.
Brain-derived neurotrophic factor (BDNF) shows consistent associations with memory across many clinical populations, including dementia. Less is understood about the association between BDNF and ...memory functioning in people living with HIV (PWH).
A sample of 173 adults aged 50+ (n = 100 HIV+ and n = 73 HIV seronegative) completed a comprehensive neurobehavioral assessment and blood draw. Linear regressions predicting memory domains (learning, delayed recall, and recognition) were conducted including race (White vs. Black/African American), HIV status, BDNF, and their interactions.
For learning and delayed recall, significant (P < 0.05) main effects for race and interactions for BDNF x race and HIV status x race were found, whereas for recognition, only a BDNF x race interaction emerged. In adjusted models, BDNF x race interactions remained for learning and delayed recall. To determine effect size, correlations were conducted between BDNF and memory domains stratified by HIV serostatus and race, and small-medium associations between BDNF and learning and delayed recall (rho = 0.29, P < 0.01; rho = 0.22, P = 0.045), but no recognition (rho = 0.12, P = 0.29) were found among Black/African American PWH. BDNF was not significantly associated with memory domains in White PWH or either HIV- sample. Follow-up analyses showed BDNF-memory specificity, such that race X BDNF interactions did not emerge for other cognitive domains.
While limited by cross-sectional design among a small sample, particularly of White individuals, results indicate that BDNF may serve as a promising biomarker reflecting memory functioning in PWH, particularly Black/African Americans. Further work is needed to replicate findings and determine mechanisms for racial differences in BDNF associations with memory.
OBJECTIVE:While HIV-associated neurocognitive disorders (HAND) remain prevalent despite combination antiretroviral therapy (CART), the clinical relevance of asymptomatic neurocognitive impairment ...(ANI), the most common HAND diagnosis, remains unclear. We investigated whether HIV-infected persons with ANI were more likely than those who were neurocognitively normal (NCN) to experience a decline in everyday functioning (symptomatic decline).
METHODS:A total of 347 human participants from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) cohort were NCN (n = 226) or had ANI (n = 121) at baseline. Neurocognitive assessments occurred approximately every 6 months, with median (interquartile range) follow-up of 45.2 (28.7–63.7) months. Symptomatic decline was based on self-report (SR) or objective, performance-based (PB) problems in everyday functioning. Proportional hazards modeling was used to generate risk ratios for progression to symptomatic HAND after adjusting for baseline and time-dependent covariates, including CD4+ T-lymphocyte count (CD4), virologic suppression, CART, and mood.
RESULTS:The ANI group had a shorter time to symptomatic HAND than the NCN after adjusting for baseline predictorsadjusted risk ratios for symptomatic HAND were 2.0 (confidence interval CI 1.1–3.6; p = 0.02) for SR, 5.8 (CI 3.2–10.7; p < 0.0001) for PB, and 3.2 (CI 2.0–5.0; p < 0.0001) for either SR or PB. Current CD4 and depression were significant time-dependent covariates, but antiretroviral regimen, virologic suppression, and substance abuse or dependence were not.
CONCLUSIONS:This longitudinal study demonstrates that ANI conveys a 2-fold to 6-fold increase in risk for earlier development of symptomatic HAND, supporting the prognostic value of the ANI diagnosis in clinical settings. Identifying those at highest risk for symptomatic decline may offer an opportunity to modify treatment to delay progression.
OBJECTIVE:To determine whether HIV infection and aging act synergistically to disrupt everyday functioning.
DESIGN:Cross-sectional factorial study of everyday functioning in the context of HIV ...serostatus and age (≤40 years vs. ≥50 years).
METHODS:One hundred three HIV+ and 87 HIV− participants were administered several measures of everyday functioning, including self-report indices of health-related quality of life (HRQoL) and instrumental and basic activities of daily living (IADLs and BADLs), and objective measures of functioning, including employment and Karnofsky Performance Scale ratings.
RESULTS:Significant interaction effects of HIV and aging were observed for IADL and BADL declines, and for Karnofsky Performance Scale ratings (Ps < 0.05), independent of potentially confounding factors. Follow-up contrasts revealed significantly worse functioning in the older HIV+ group for most functional outcome measures relative to the other study groups (Ps < 0.05). A significant interaction effect was also observed on the emotional functioning HRQoL subscale, and additive effects of both age and HIV were observed for the physical functioning and general health perceptions HRQoL subscales (Ps < 0.05). Significant predictors of poorer functioning in the older HIV+ group included current major depressive disorder for all outcomes, and comorbid medical conditions, lower estimated premorbid functioning, neurocognitive impairment, and nadir CD4 count for selected outcomes.
CONCLUSION:Findings suggest that older age may exacerbate the adverse effects of HIV on daily functioning, which highlights the importance of evaluating and monitoring the functional status of older HIV-infected adults. Early detection of functional difficulties could facilitate delivery of compensatory strategies (eg, cognitive remediation) or assistive services.
There is significant overlap between reading and writing, but no known standardized measure assesses these jointly. The goal of the present study is to evaluate the properties of a novel measure, the ...Assessment of Writing, Self-Monitoring, and Reading (AWSM Reader), that simultaneously evaluates both reading comprehension and writing. In doing so, we evaluate reliability (Cronbach’s alpha) and various aspects of construct-related validity, including separate criterion measures of reading and writing, and the AWSM Reader’s relations with other variables, including language and executive function (EF), both of which are implicated for both reading and writing. Participants were 377 3rd, 4th, and 5th graders with or at-risk for reading and writing difficulties. Reliability was low for the AWSM Reader reading comprehension (α = 0.58), but good for writing (α = 0.75-0.80). Criterion-related validity indices revealed moderate correlations with other standardized and commonly used reading and writing measures,
r =
.47 to 0.50 (all
p
s < 0.001). Additionally, validity data supported the relations of both language and EF to AWSM Reader reading and writing, with EF showing unique prediction in both reading and writing domains. Results provide initial support for the measure per se but stress the difficulty in constructing combined reading and writing measures; directions are given for future work. Results also add to data on the contributions of language and EF to both reading and writing.
Background: Opioid misuse in the context of pain management exacts a significant public health burden. Past work has established linkages between negative mood (i.e., symptoms of anxiety and ...depression) and opioid misuse/dependence, yet the mechanisms underlying these associations have received little scientific investigation. Anxiety sensitivity (AS), the fear of the negative consequences of internal states, may be relevant to better understanding negative mood-opioid relations among adults with chronic pain. Methods: Simultaneous indirect effects of negative mood on opioid misuse and opioid dependence via lower-order factors of AS (physical, cognitive, and social concerns) were examined cross-sectionally in the present study. The study sample consisted of 428 adults (74.1% female, M
age
= 38.27 years, SD = 11.06) who self-reported current moderate to severe chronic pain and opioid use for chronic pain. Results: Results indicated that negative mood was (in part) indirectly related to opioid misuse (in part) via AS physical and cognitive concerns and was (in part) indirectly related to opioid dependence via AS cognitive concerns only. No significant indirect effects via social concerns were observed. Discussion and Conclusions: Findings suggest the importance of further exploring the role of anxiety sensitivity cognitive and physical concerns in terms of opioid misuse and dependence among adults with chronic pain.
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