Cognitive impact of anticholinergic and sedative burden in people living with HIV.

OBJECTIVE: This study aims to estimate the extent to which anticholinergic and sedative burden is associated with cognitive ability and self-reported cognitive difficulties (SCD) in middle-aged and older adults living with HIV. DESIGN: This cross-sectional analysis examined data from the inaugural visit of participants enrolled in the Positive Brain Health Now (BHN) study. METHODS: Cognitive ability was measured using the Brief Cognitive Ability Measure (B-CAM; higher is better) and SCD using the Perceived Deficits Questionnaire (PDQ; higher is worse). Medication burden was quantified using several scoring systems, including the Anticholinergic Cognitive Burden (ACB), Anticholinergic and Sedative Burden Catalog (ACSBC), Anticholinergic Drug Scale (ADS), Anticholinergic Risk Scale (ARS), and the Sedative Load Model (SLM). Multivariable Ordinary Least Squares and quantile regression were utilized to estimate average effects and distribution-specific impacts, respectively. RESULTS: Of 824 participants (mean age 53 years, 84.7% men), 41.4% used anticholinergics (ACSBC) and 39% used sedatives (SLM). High anticholinergic burden was linked to worse cognitive ability (ß = -3.81; 95% CI: -7.16, -0.46) and SCD (ß = 3.89; 95% CI: 1.08, 6.71). Using three or more anticholinergics worsened cognitive ability (ß = -4.45; 95% CI: -8.54, -0.35), and using three or more sedatives increased SCD (ß = 4.35; 95% CI: 0.92 -7.78). Stronger negative associations were observed in participants with lower cognitive ability and more difficulties. CONCLUSIONS: These results suggest that anticholinergic and sedative burden may contribute to cognitive impairment in people with HIV. Personalized medication management and regular cognitive assessments could mitigate these adverse effects.

Portrait of mental health identified by people with the post-covid syndrome.

OBJECTIVES: This study aimed to produce a patient-centered understanding of mental health symptoms of people with the post-COVID-19 syndrome (PCS). METHODS: A cross-sectional analysis of 414 participants in a longitudinal study was carried out involving people who self-identified as having symptoms of PCS. People were asked to name their most frequent and most bothersome mental health symptoms affected by PCS using the structure of the Patient Generated Index (PGI). The text threads from the PGI were grouped into topics using BERTopic analysis. RESULTS: 20 topics were identified from 818 text threads referring to PCS mental health symptoms. 35% of threads were identified as relating to anxiety, discussed in terms of five topics: generalized/social anxiety, fear/worry, post-traumatic stress, panic, and nervous. 29% of threads were identified as relating to low mood, represented by five topics: depression, discouragement, emotional distress, sadness, and loneliness. A cognitive domain (22% of threads) was covered by four topics referring to concentration, memory, brain fog, and mental fatigue. Topics related to frustration, anger, irritability. and mood swings (7%) were considered as one domain and there were separate topics related to motivation, insomnia, and isolation. CONCLUSIONS: This novel method of digital transformation of unstructured text data uncovered different ways in which people think about classical mental health domains. This information could be used to evaluate whether existing measures cover the content identified by people with PCS, to initiate a clinical conversation, or to justify the development of a new measure of the mental health impact of PCS.

In Support of Multidimensional Frailty: A Structural Equation Model from the Canadian Positive Brain Health Now Cohort.

The objective of this study was to estimate the structure and relationships between four h ypothesized frailty dimensions (physical, emotional, cognitive, and social) and the extent to which personal and HIV-related factors and comorbidity associate with these frailty dimensions. This is a secondary analysis of an existing dataset arising from Positive Brain Health Now study (n = 856) in people aging with HIV (mean age: 52.3 ± 8.1 years). Structural equation modeling (SEM) models were applied to two cross-sections of the data: one at study entry and one at second visit, 9-month apart. Multidimensional frailty was modeled based on the combined Wilson-Cleary and International Classification of Functioning, Disability and Health framework. Four dimensions were operationalized with patient-reported and self-report measures from standardized questionnaires. The SEM model from the first visit was replicated using data from the second visit, testing measurement invariance. The proposed model showed acceptable fit at both visits (including no violation of measurement invariance). The final model for the first visit showed that sex, body mass index, HIV diagnosis pre-1997, current or nadir CD4 counts, and comorbidity did not associate with any frailty dimension; however, age (ß range: 0.12-0.25), symptoms (ß range: -0.35 to -0.58), and measured cognition (ß range: 0.10-0.24) directly associated with all frailty dimensions. The model remained stable across the two visits. This study contributes evidence for operationalizing multidimensional frailty. Evidence-based interventions are available for many of the measures considered here, offering opportunities to improve the lives of people with frailty in the context of HIV.

Medication utilization patterns in patients with post-COVID syndrome (PCS): Implications for polypharmacy and drug-drug interactions.

BACKGROUND: Post-COVID syndrome (PCS) causes lasting symptoms like fatigue and cognitive issues. PCS treatment is nonspecific, focusing on symptom management, potentially increasing the risk of polypharmacy. OBJECTIVES: To describe medication use patterns among patients with Post-COVID Syndrome (PCS) and estimate the prevalence of polypharmacy, potential drug-drug interactions, and anticholinergic/sedative burden. METHODS: A cross-sectional analysis of baseline data from the Quebec Action for Post-COVID cohort, consisting of individuals self-identifying with persistent COVID-19 symptoms beyond 12 weeks. Medications were categorized using Anatomical Therapeutic Classification (ATC) codes. Polypharmacy was defined as using 5 or more concurrent medications. The Anticholinergic and Sedative Burden Catalog assessed anticholinergic and sedative loads. The Lexi-Interact checker identified potential drug-drug interactions, which were categorized into 3 severity tiers. RESULTS: Out of 414 respondents, 154 (average age 47.7 years) were prescribed medications related to persistent COVID-19 symptoms. Drugs targeting the nervous system were predominant at 54.5%. The median number of medications was 2, while 11.7% reported polypharmacy. Over half of the participants prescribed medications used at least 1 anticholinergic or sedative medication, and 25% had the potential risk for clinically significant drug-drug interactions, primarily needing therapy monitoring. CONCLUSIONS: Our study reveals prescription patterns for PCS, underscoring the targeted management of nervous system symptoms. The risks associated with polypharmacy, potential drug-drug interactions, and anticholinergic/sedative burden stress the importance of judicious prescribing. While limitations like recall bias and a regional cohort are present, the findings underscore the imperative need for vigilant PCS symptom management.

An umbrella review of the literature on the effectiveness of goal setting interventions in improving health outcomes in chronic conditions.

PURPOSE: To identify the contexts in which goal setting has been used in chronic disease management interventions and to estimate the magnitude of its effect on improvement of health outcomes. METHODS: The strength of evidence and extent of potential bias in the published systematic reviews of goal setting interventions in chronic conditions were summarized using AMSTAR2 quality appraisal tool, number of participants, 95% prediction intervals, and between-study heterogeneity. Components of goal setting interventions were also extracted. RESULTS: Nine publications and 35 meta-analysis models were identified, investigating 25 health outcomes. Of the 35 meta-analyses, none found strong evidence and three provided some suggestive evidence on symptom reduction and perceived well-being. There was weak evidence for effects on eight health outcomes (HbA1c, self-efficacy, depression, anxiety, distress, medication adherence, health-related quality of life and physical activity), with the rest classified as non-significant. Half of the meta-analyses had high level of heterogeneity. CONCLUSION: Goal setting by itself affects outcomes of chronic diseases only to a small degree. This is not unexpected finding as changing outcomes in chronic diseases requires a complex and individualized approach. Implementing goal setting in a standardized way in the management of chronic conditions would seem to be a way forward.IMPLICATIONS FOR REHABILITATIONThe link between goal setting and health outcomes seems to be weak.Some levels of positive behavioural change could be of benefits to patients as seen by improved self-efficacy, patients' satisfaction and overall quality of life.Systematic and consistent application of personalized goal-oriented interventions considering patient's readiness to change could better predict improved outcomes.Incorporation of various goal setting components while actively engaging patient and/or their care givers in the process could appraise how goal setting could help with challenges in faced by people living with chronic conditions in different areas.

The association between anticholinergic/sedative burden and physical frailty in people aging with HIV.

OBJECTIVE: This study aimed to estimate the strength of the association between anticholinergic/sedative burden and concurrent physical frailty in people aging with HIV. DESIGN: This cross-sectional analysis examined baseline data from 824 adults with a mean age of 53 enrolled in the Positive Brain Health Now study. METHODS: Anticholinergic medications were identified using four methods: Anticholinergic Cognitive Burden (ACB) Scale, Anticholinergic Risk Scale (ARS), Anticholinergic Drug Scale (ADS), and the anticholinergic list of the Anticholinergic and Sedative Burden Catalog (ACSBC). Sedatives were identified using the Sedative Load Model (SLM) and the sedative list of the ACSBC. Physical frailty was assessed using a modified Fried Frailty Phenotype (FFP) based on self-report items. Multivariable logistic regression models, adjusted for sociodemographic factors, lifestyle considerations, HIV-related variables, comorbidities, and co-medication use, were used to estimate odds ratios (ORs). RESULTS: Anticholinergic burden demonstrated associations with frailty across various methods: total anticholinergic burden (OR range: 1.22-1.32; 95% confidence interval (CI) range: 1.03-1.66), sedative burden (OR range: 1.18-1.24; 95% CI range: 1.02-1.45), high anticholinergic burden (OR range: 2.12-2.74; 95% CI range: 1.03-6.19), and high sedative burden (OR range: 1.94-2.18; 95% CI: 1.01-4.34). CONCLUSION: The anticholinergic and sedative burdens may represent modifiable risk factors for frailty in people aging with HIV. Future studies should evaluate the effects of reducing anticholinergic and sedative burdens on frailty outcomes and explore the prognostic value of diverse scoring methods.

Dorsomedial frontal cortex damage impairs error-based, but not reinforcement-based motor learning in humans.

We adapt our movements to new and changing environments through multiple processes. Sensory error-based learning counteracts environmental perturbations that affect the sensory consequences of movements. Sensory errors also cause the upregulation of reflexes and muscle co-contraction. Reinforcement-based learning enhances the selection of movements that produce rewarding outcomes. Although some findings have identified dissociable neural substrates of sensory error- and reinforcement-based learning, correlative methods have implicated dorsomedial frontal cortex in both. Here, we tested the causal contributions of dorsomedial frontal to adaptive motor control, studying people with chronic damage to this region. Seven human participants with focal brain lesions affecting the dorsomedial frontal and 20 controls performed a battery of arm movement tasks. Three experiments tested: (i) the upregulation of visuomotor reflexes and muscle co-contraction in response to unpredictable mechanical perturbations, (ii) sensory error-based learning in which participants learned to compensate predictively for mechanical force-field perturbations, and (iii) reinforcement-based motor learning based on binary feedback in the absence of sensory error feedback. Participants with dorsomedial frontal damage were impaired in the early stages of force field adaptation, but performed similarly to controls in all other measures. These results provide evidence for a specific and selective causal role for the dorsomedial frontal in sensory error-based learning.

Gaze differences in configural and elemental evaluation during multi-attribute decision-making.

Introduction: While many everyday choices are between multi-attribute options, how attribute values are integrated to allow such choices remains unclear. Recent findings suggest a distinction between elemental (attribute-by-attribute) and configural (holistic) evaluation of multi-attribute options, with different neural substrates. Here, we asked if there are behavioral or gaze pattern differences between these putatively distinct modes of multi-attribute decision-making. Methods: Thirty-nine healthy men and women learned the monetary values of novel multi-attribute pseudo-objects (fribbles) and then made choices between pairs of these objects while eye movements were tracked. Value was associated with individual attributes in the elemental condition, and with unique combinations of attributes in the configural condition. Choice, reaction time, gaze fixation time on options and individual attributes, and within- and between-option gaze transitions were recorded. Results: There were systematic behavioral differences between elemental and configural conditions. Elemental trials had longer reaction times and more between-option transitions, while configural trials had more within-option transitions. The effect of last fixation on choice was more pronounced in the configural condition. Discussion: We observed differences in gaze patterns and the influence of last fixation location on choice in multi-attribute value-based choices depending on how value is associated with those attributes. This adds support for the claim that multi-attribute option values may emerge either elementally or holistically, reminiscent of similar distinctions in multi-attribute object recognition. This may be important to consider in neuroeconomics research that involve visually-presented complex objects.

The Patient Generated Index (PGI) as an early-warning system for predicting brain health challenges: a prospective cohort study for people living with Human Immunodeficiency Virus (HIV).

PURPOSE: In research people are often asked to fill out questionnaires about their health and functioning and some of the questions refer to serious health concerns. Typically, these concerns are not identified until the statistician analyses the data. An alternative is to use an individualized measure, the Patient Generated Index (PGI) where people are asked to self-nominate areas of concern which can then be dealt with in real-time. This study estimates the extent to which self-nominated areas of concern related to mood, anxiety and cognition predict the presence or occurrence of brain health outcomes such as depression, anxiety, psychological distress, or cognitive impairment among people aging with HIV at study entry and for successive assessments over 27 months. METHODS: The data comes from participants enrolled in the Positive Brain Health Now (+ BHN) cohort (n = 856). We analyzed the self-nominated areas that participants wrote on the PGI and classified them into seven sentiment groups according to the type of sentiment expressed: emotional, interpersonal, anxiety, depressogenic, somatic, cognitive and positive sentiments. Tokenization was used to convert qualitative data into quantifiable tokens. A longitudinal design was used to link these sentiment groups to the presence or emergence of brain health outcomes as assessed using standardized measures of these constructs: the Hospital Anxiety and Depression Scale (HADS), the Mental Health Index (MHI) of the RAND-36, the Communicating Cognitive Concerns Questionnaire (C3Q) and the Brief Cognitive Ability Measure (B-CAM). Logistic regressions were used to estimate the goodness of fit of each model using the c-statistic. RESULTS: Emotional sentiments predicted all of the brain health outcomes at all visits with adjusted odds ratios (OR) ranging from 1.61 to 2.00 and c-statistics > 0.73 (good to excellent prediction). Nominating an anxiety sentiment was specific to predicting anxiety and psychological distress (OR 1.65 & 1.52); nominating a cognitive concern was specific to predicting self-reported cognitive ability (OR 4.78). Positive sentiments were predictive of good cognitive function (OR 0.36) and protective of depressive symptoms (OR 0.55). CONCLUSIONS: This study indicates the value of using this semi-qualitative approach as an early-warning system in predicting brain health outcomes.

The Prognostic Utility of Anticholinergic Burden Scales: An Integrative Review and Gap Analysis.

BACKGROUND: Anticholinergic drugs are commonly prescribed, especially to older adults. Anticholinergic burden scales (ABS) have been used to evaluate the cumulative effects of multiple anticholinergics. However, studies have shown inconsistent results regarding the association between anticholinergic burden assessed with ABS and adverse clinical outcomes such as cognitive impairment, functional decline, and frailty. This review aims to identify gaps in research on the development, validation, and evaluation of ABS, and provide recommendations for future studies. METHOD: A comprehensive search of five databases (MEDLINE, Embase, PsychInfo, CINAHL, CENTRAL) was conducted for relevant studies published from inception until 25 May 2023. Two reviewers screened for eligibility and assessed the quality of studies using different tools based on the study design and stage of the review framework. Research evidence was evaluated, and gaps were identified and grouped into evidence, knowledge, and methodological gaps, using evidence tables to summarize data. RESULTS: Several evidence, knowledge, and methodological gaps in existing development, validation, and evaluation studies of ABS were identified. There is no universally accepted scale, and there is a need to define a clinically relevant threshold for measuring total anticholinergic burden. The current evidence has limitations, underrepresenting low- and middle-income countries, younger individuals, and populations with cognitive disabilities. The impact of anticholinergic burden on frailty is also understudied. Existing evaluation studies provide limited evidence on the benefit of reducing anticholinergic burden on clinical outcomes or the safety of anticholinergic deprescribing. There is also uncertainty regarding optimal reduction, clinically significant anticholinergic burden thresholds, and cost effectiveness. CONCLUSIONS: Future research recommendations to bridge knowledge gaps include developing a risk assessment framework, refining ABS scales, establishing a standardized consensus scale, and creating a longitudinal measure of cumulative anticholinergic risk. Strategies to minimize bias, consider frailty, and promote multidisciplinary and multinational collaborations are also necessary to improve patient outcomes.

Translocation of bacterial LPS is associated with self-reported cognitive abilities in men living with HIV receiving antiretroviral therapy.

BACKGROUND: Gut damage allows translocation of bacterial lipopolysaccharide (LPS) and fungal ß-D-glucan (BDG) into the blood. This microbial translocation contributes to systemic inflammation and risk of non-AIDS comorbidities in people living with HIV, including those receiving antiretroviral therapy (ART). We assessed whether markers of gut damage and microbial translocation were associated with cognition in ART-treated PLWH. METHODS: Eighty ART-treated men living with HIV from the Positive Brain Health Now Canadian cohort were included. Brief cognitive ability measure (B-CAM) and 20-item patient deficit questionnaire (PDQ) were administered to all participants. Three groups were selected based on their B-CAM levels. We excluded participants who received proton pump inhibitors or antiacids in the past 3 months. Cannabis users were also excluded. Plasma levels of intestinal fatty acid binding protein (I-FABP), regenerating islet-derived protein 3 α (REG3α), and lipopolysaccharides (LPS = were quantified by ELISA, while 1-3-ß-D-glucan BDG) levels were assessed using the Fungitell assay. Univariable, multivariable, and splines analyses were performed. RESULTS: Plasma levels of I-FABP, REG3α, LPS and BDG were not different between groups of low, intermediate and high B-CAM levels. However, LPS and REG3α levels were higher in participants with PDQ higher than the median. Multivariable analyses showed that LPS association with PDQ, but not B-CAM, was independent of age and level of education. I-FABP, REG3α, and BDG levels were not associated with B-CAM nor PDQ levels in multivariable analyses. CONCLUSION: In this well characterized cohort of ART-treated men living with HIV, bacterial but not fungal translocation was associated with presence of cognitive difficulties. These results need replication in larger samples.

"Alone, there is nobody": A qualitative study of the lived experience of loneliness in older men living with HIV.

Loneliness has been shown to be a predictor of poor health and early mortality in the general population. Older men living with human immunodeficiency virus (HIV) are at heightened risk of experiencing loneliness. Here, we aim to describe the lived experience of loneliness in older men living with HIV and identify targets for intervention. We used grounded theory with a theoretical framework of narrative phenomenology to focus data collection and analysis on significant experiences related to loneliness. Based on individual narrative interviews with 10 older men living with HIV, experiences of loneliness related to "multiple losses," "being invisible" and "hiding out" as emergent themes. Participants also described living with loneliness by "finding meaning," "creating social experiences," "pursuing interests and things to 'live for'" and attending events in which "everyone is welcome." The discussion situates experiences of loneliness within the accumulation of losses and stigmas over time and how the participants strategies for living with loneliness could inform interventions to reduce loneliness in older men living with HIV at individual and societal levels.

Effectiveness of a personalized health profile on specificity of self-management goals among people living with HIV in Canada: findings from a blinded pragmatic randomized controlled trial.

PURPOSE: To estimate among people living with chronic HIV, to what extent providing feedback on their health outcomes will affect the number and specificity of patient-formulated self-management goals. METHODS: A personalized feedback profile was produced for individuals enrolled in a Canadian HIV Brain Health Now study. Goal specificity was measured by total number of specific words (matched to a domain-specific developed lexicon) per person-words using text mining techniques. RESULTS: Of 176 participants enrolled and randomly assigned to feedback and control groups, 110 responses were received. The average number of goals was similar for both groups (3.7 vs 3.9). The number of specific words used in the goals formulated by the feedback and control group were 642 and 739, respectively. Specific nouns and actionable verbs were present to some extent and "measurable" and "time-bound" words were mainly missing. Negative binomial regression showed no difference in goal specificity among groups (RR = 0.93, 95% CI 0.78-1.10). Goals set by both groups overlapped in 8 areas and had little difference in rank. CONCLUSION: Personalized feedback profile did not help with formulation of high-quality goals. Text mining has the potential to help with difficulties of goal evaluation outside of the face-to-face setting. With more data and use of learning models automated answers could be generated to provide a more dynamic platform.

Development of a self-report measure of cognitive change: assessment of interpretability in two samples, people with HIV and people without HIV.

AIM: The overall aim of this study was to develop a method of measuring change in cognitive ability from the person's perspective. METHODS: Cognitive change items came from an item pool that was used to develop the Communicating Cognitive Concerns Questionnaire (C3Q). The change items were administered to a test sample of 211 people with HIV + and a sample of 484 people drawn from the general population (HIV- sample). Rasch analysis was used to identify items that formed a linear continuum and correlations with measures of related constructs were used to support the interpretability of the new measure. RESULTS: Eleven of the original 12 change items fit the unidimensional Rasch model in both samples with a near similar ordering of the items. The average value for cognitive change of the HIV + sample was greater than that of the HIV- sample. Values on C3Q-Change correlated most highly (> 0.7) with current self-reported cognitive status and measures of depression and anxiety (> 0.6). The lowest correlation was with performance-based cognitive ability (r = 0.2). CONCLUSION: The items of C3Q-Change fit a strong measurement model and related to converging constructs in an expected way. Further work needs to be done to assess the meaning of self-reported cognitive change in relationship to measured change and to examine sources of differential item functioning.

Development of a Prototype for a Bilingual Patient-Reported Outcome Measure of the Important Health Aspects of Quality of Life in People Living with HIV: The Preference Based HIV Index (PB-HIV).

(1) Background: The aim of this project was to develop a short, HIV-specific, health-related quality of life measure with a scoring system based on patient preferences for the different dimensions of the Preference-Based HIV Index (PB-HIV). (2) Methods: This study is a cross-sectional analysis of data from the Canadian Positive Brain Health Now cohort (n = 854; mean age 53 years). Items from the standardized measures were mapped to the areas from the Patient-Generated Index and formed the domains. A Rasch analysis was used to identify the best performing item to represent each dimension. Each item was then regressed on self-rated health (scored 0 to 100) and the regression parameters were used as scaling weights to form an index score for the prototype measure. (3) Results: Seven independent dimensions with three declarative statements ordered as response options formed the PB-HIV Index (pain, fatigue, memory/concentration, sleep, physical appearance/body image, depression, motivation). Regression parameters from a multivariable model yielded a measure with a scoring range from 0 (worst health) to 100 (perfect health). (4) Conclusions: Preference-based measures are optimal, as the total score reflects gains in some dimensions balanced against losses in others. The PB-HIV Index is the first HIV-specific preference-based measure.

Efficacy potential of Goal Management Training to improve cognitive function in older people living with HIV.

Goal Management Training® (GMT) teaches strategies to reduce cognitive load and improve focus in everyday tasks. The aim of this study was to ascertain feasibility, acceptability, and efficacy potential of GMT for people (≥50 years) with stable HIV infection scoring low on tests of cognitive ability. A two-sample, parallel, controlled trial was carried out. Feasibility was demonstrated, as 21/30 participants in the GMT group attended ≥8 of the 9 sessions and completed at least half of the homework. There was no change on the primary performance-based cognitive outcomes in the GMT group or in the control group (n = 23). There was a meaningful improvement in self-reported cognition in those adherent to the intervention. GMT is a promising intervention for people aging with HIV who are dealing with cognitive difficulties affecting their everyday life and should be further investigated.

Characterization of structural and functional network organization after focal prefrontal lesions in humans in proof of principle study.

Lesion research classically maps behavioral effects of focal damage to the directly injured brain region. However, such damage can also have distant effects that can be assessed with modern imaging methods. Furthermore, the combination and comparison of imaging methods in a lesion model may shed light on the biological basis of structural and functional networks in the healthy brain. We characterized network organization assessed with multiple MRI imaging modalities in 13 patients with chronic focal damage affecting either superior or inferior frontal gyrus (SFG, IFG) and 18 demographically matched healthy Controls. We first defined structural and functional network parameters in Controls and then investigated grey matter (GM) and white matter (WM) differences between patients and Controls. Finally, we examined the differences in functional coupling to large-scale resting state networks (RSNs). The results suggest lesions are associated with widespread within-network GM loss at distal sites, yet leave WM and RSNs relatively preserved. Lesions to either prefrontal region also had a similar relative level of impact on structural and functional networks. The findings provide initial evidence for causal contributions of specific prefrontal regions to brain networks in humans that will ultimately help to refine models of the human brain.

Relationship between reward-related evoked potentials and real-world motivation in older people living with human immunodeficiency virus.

Apathy, a clinical disorder characterized by low motivation, is prevalent in people living with Human Immunodeficiency Virus (HIV). It affects mental and physical health-related quality-of-life, medication adherence, and is associated with cognitive decline. However, the causes of apathy and the underlying brain mechanisms in HIV are unknown. Brain responses to reward may be relevant to understanding apathy and might serve as biomarkers for diagnosis or treatment response. Electroencephalogram (EEG) responses to gain and loss feedback in simple guessing tasks have been related to apathy in neurodegenerative conditions and healthy individuals. The primary aim of this study is to contribute evidence regarding the relationship between two EEG correlates of reward processing, the Reward Positivity, and the Feedback-P300, and real-world motivated behavior indicated by self-reported hours engaged in goal-directed leisure activities per week, in older individuals with well-controlled HIV infection. High-density EEG was collected from 75 participants while they performed a guessing task with gain or loss feedback. We found that a later component of reward processing, the Feedback-P300, was related to real-world engagement, while the earlier Reward Positivity was not. The Feedback-P300 measured with EEG holds promise as a biomarker for motivated behavior in older people living with HIV. These findings lay the groundwork for a better understanding of the neurobiology of apathy in this condition.

Factors partitioning physical frailty in people aging with HIV: A classification and regression tree approach.

OBJECTIVE: To estimate the extent to which comorbidity and lifestyle factors were associated with physical frailty in middle-aged and older Canadians living with HIV. DESIGN: Cross-sectional analysis of 856 participants from the Canadian Positive Brain Health Now cohort. METHODS: The frailty indicator phenotype was adapted from Fried's criteria using self-report items. Univariate logistic regression and classification and regression tree (CaRT) models were used to identify the most relevant independent contributors to frailty. RESULTS: In all, 100 men (14.0%) and 26 women (19.7%) were identified as frail (≥ 3/5 criteria) for an overall prevalence of 15.2%. Nine comorbidities showed an influential association with frailty. The most influential comorbidities were hypothyroidism [odds ratio (OR) = 2.55, 95% confidence interval (CI): 1.29-5.03] and arthritis (OR = 2.54, 95% CI: 1.58-4.09). Additionally, tobacco (OR = 1.79, 95% CI: 1.05-3.04) showed an association. Any level of alcohol consumption showed a protective effect for frailty. The CaRT model showed nine pathways that led to frailty. Arthritis was the most discriminatory variable followed by alcohol, hypothyroidism, tobacco, cancer, cannabis, liver disease, kidney disease, osteoporosis, lung disease and peripheral vascular disease. The prevalence of physical frailty for people with arthritis was 27.4%; with additional cancer or tobacco and alcohol the prevalence rates were 47.1% and 46.1%, respectively. The protective effect of alcohol consumption evident in the univariate model appeared again in the CaRT model, but this effect varied. Cognitive frailty (19.5% overall) and emotional frailty (37.9% overall) were higher than the prevalence of physical frailty. CONCLUSIONS: Specific comorbidities and tobacco use were implicated in frailty, suggesting that it is comorbidities causing frailty. However, some frailty still appears to be HIV-related. The higher prevalence of cognitive and emotional frailty highlights the fact that physical frailty should not be the only focus in HIV.