Validating the Stanford Gender-Related Variables for Health Research (SGVHR) in a Canadian population.

In addition to biological sex, the impact of gender on health outcomes is now well-recognized. Gender norms are changing rapidly, demanding contemporary gender assessment tools. This study sought to validate the recent US-based Stanford Gender-Related Variables for Health Research (SGVHR) scale in Canada. We also aimed to improve gender prediction by including socio-demographic information on education, income and occupations. We recruited 2445 Canadian online participants (~50% female; mean age: 49.3). Multigroup confirmatory factor analyses confirmed the SGVHR factor structure in our sample, indicating its generalizability beyond the USA. Regression analyses indicated that the SGVHR subscales were moderately predictive of self-reported gender. Incorporating socio-demographic factors Significantly enhanced gender prediction via the SGVHR. This study underscores the SGVHR's applicability in diverse Western populations and encourages the inclusion of easily accessible sociodemographic variables to approximate a gender metric. Future studies should test the health-relevance of such indicators along with the SGVHR.

Effects of healthy aging and mnemonic strategies on verbal memory performance across the adult lifespan: Mediating role of posterior hippocampus.

In this study, we aimed to understand the contributions of hippocampal anteroposterior subregions (head, body, tail) and subfields (cornu ammonis 1-3 [CA1-3], dentate gyrus [DG], and subiculum [Sub]) and encoding strategies to the age-related verbal memory decline. Healthy participants were administered the California Verbal Learning Test-II to evaluate verbal memory performance and encoding strategies and underwent 4.7 T magnetic resonance imaging brain scan with subsequent hippocampal subregions and subfields manual segmentation. While total hippocampal volume was not associated with verbal memory performance, we found the volumes of the posterior hippocampus (body) and Sub showed significant effects on verbal memory performance. Additionally, the age-related volume decline in hippocampal body volume contributed to lower use of semantic clustering, resulting in lower verbal memory performance. The effect of Sub on verbal memory was statistically independent of encoding strategies. While total CA1-3 and DG volumes did not show direct or indirect effects on verbal memory, exploratory analyses with DG and CA1-3 volumes within the hippocampal body subregion suggested an indirect effect of age-related volumetric reduction on verbal memory performance through semantic clustering. As semantic clustering is sensitive to age-related hippocampal volumetric decline but not to the direct effect of age, further investigation of mechanisms supporting semantic clustering can have implications for early detection of cognitive impairments and decline.

Verbal Memory Performance and Depressive Symptoms in Persons with Treated HIV.

The link between memory and comorbid depression in persons with HIV (PWH) is unclear based on evidence from published cohorts. We compared verbal memory in the HVLT-R in a well-characterized HIV cohort (n = 354) with (n = 102) or without (n = 252) comorbid depressive symptoms, and examined memory correlates in both scenarios. Memory fell within unimpaired ranges, but was lower in depressed than non-depressed PWH. Memory was related to quality of life, sociodemographic, and mental health factors, but not to assessed HIV-related or antiretroviral factors. However, longitudinally (n = 52) memory declined with presence and severity of depressive symptoms. In this treated cohort, verbal memory was unrelated to HIV-related variables but to quality of life and depressive symptoms. Greater performance decline over time also related to acute or ongoing depressive symptoms. These findings highlight the importance of addressing comorbid depressive symptoms to improve quality of life in persons with treated HIV.

Pharmacological Interventions for Primary Psychodermatologic Disorders: An Evidence Mapping and Appraisal of Randomized Controlled Trials.

BACKGROUND: The lack of clinical guidelines for the treatment of primary psychodermatologic disorders (PPDs) hinders the delivery of optimal care to patients. The review aimed to identify, appraise, and summarize the currently available evidence about the safety and effectiveness of pharmacological management of PPDs through randomized controlled trials (RCTs). METHODS: The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRIMSA) statement and the Global Evidence Mapping Initiative guidance were followed. Medline, Embase, PsycInfo, Cochrane and Scopus were searched, and two reviewers independently completed article review, data extraction, and quality assessment. RESULTS: Among 2618 unique studies, full texts of 83 were reviewed and 21 RCTs were included. Five PDDs were identified: trichotillomania (n = 12), pathologic skin picking (n = 5), nail biting (n = 2), delusional parasitosis (n = 1), and dermatitis from compulsive hand washing (n = 1). Seven different classes of medications were investigated: SSRIs (i.e., fluoxetine, sertraline, and citalopram), tricyclic antidepressants (i.e., clomipramine and desipramine), antipsychotics (i.e., olanzapine and pimozide), anticonvulsant (i.e., lamotrigine), N-acetylcysteine, inositol, and milk thistle. RCT-derived evidence supports the use of antidepressants in trichotillomania (sertraline and clomipramine), pathologic skin picking (fluoxetine), pathologic nail biting and dermatitis from compulsive hand washing (clomipramine or desipramine); antipsychotics in trichotillomania (olanzapine) and delusional parasitosis (pimozide); N-acetyl cysteine in trichotillomania and skin picking. CONCLUSION: Few pharmacotherapies for primary psychodermatologic disorders are assessed through controlled trials in the literature. This review serves as a roadmap for researchers and clinicians to reach informed decisions with current evidence, and to build on it to establish guidelines in the future.

Emotional recognition across the adult lifespan: Effects of age, sex, cognitive empathy, alexithymia traits, and amygdala subnuclei volumes.

The ability to recognize others' emotions is vital to everyday life. The goal of this study was to assess which emotions show age-related decline in recognition accuracy of facial emotional expressions across the entire adult lifespan and how this process is related to cognitive empathy (Theory of Mind [ToM]), alexithymia traits, and amygdala subnuclei volumes in a large cohort of healthy individuals. We recruited 140 healthy participants 18-85 years old. Facial affect processing was assessed with the Penn Emotion Recognition task (ER40) that contains images of the five basic emotions: Neutral, Happy, Sad, Angry, and Fearful. Structural magnetic resonance imaging (MRI) datasets were acquired on a 4.7T MRI system. Structural equation modeling was used to test the relationship between studied variables. We found that while both sexes demonstrated age-related reduction in recognition of happy emotions and preserved recognition of sadness, male participants showed age-related reduction in recognition of fear, while in female participants, age-related decline was linked to recognition of neutral and angry facial expressions. In both sexes, accurate recognition of sadness negatively correlated with alexithymia traits. On the other hand, better ToM capabilities in male participants were associated with improvement in recognition of positive and neutral emotions. Finally, none of the observed age-related reductions in emotional recognition were related to amygdala and its subnuclei volumes. In contrast, both global volume of amygdala and its cortical and centromedial subnuclei had significant direct effects on recognition of sad images.

Effects of acute exercise on emotional memory.

Research has demonstrated beneficial effects of acute exercise on memory for neutral materials, such as word lists of neutral valence/low arousal. However, the impacts of exercise on emotional memory is less understood. Across three laboratory experiments in college students, we tested if acute exercise could enhance both neutral and emotional memory performance, anticipating a greater effect for emotional memory. We examined effects of exercise at varying intensities (Experiment 1: high-intensity; Experiment 2: low- and high-intensity; Experiment 3: moderate-intensity), of diverse modalities (Experiment 1: treadmill jogging; Experiment 2: cycling; Experiment 3: open-skill (racquetball) and closed-skill (treadmill jogging) exercise), and on emotional memory performance assessed at increasing levels of hippocampal dependency (Experiment 1: Y/N recognition task; Experiment 2: paired-associative recognition task; Experiment 3: cued-recall task). We found that, in all experiments, acute exercise did not significantly influence emotional or neutral memory performance relative to sedentary control conditions. However, we observed several noteworthy outcomes indicating that acute exercise may be linked to improvements in memory confidence and accuracy for central aspects of emotional memory stimuli, and that select exercise modalities (e.g. treadmill exercise) may also be associated with increased frequency of memory intrusions.

An Overview of the Involvement of D-Serine in Cognitive Impairment in Normal Aging and Dementia.

Dementia, of which Alzheimer's disease (AD) is the most common form, is characterized by progressive cognitive deterioration, including profound memory loss, which affects functioning in many aspects of life. Although cognitive deterioration is relatively common in aging and aging is a risk factor for AD, the condition is not necessarily a part of the aging process. The N-methyl-D-aspartate glutamate receptor (NMDAR) and its co-agonist D-serine are currently of great interest as potential important contributors to cognitive function in normal aging and dementia. D-Serine is necessary for activation of the NMDAR and in maintenance of long-term potentiation (LTP) and is involved in brain development, neuronal connectivity, synaptic plasticity and regulation of learning and memory. In this paper, we review evidence, from both preclinical and human studies, on the involvement of D-serine (and the enzymes involved in its metabolism) in regulation of cognition. Potential mechanisms of action of D-serine are discussed in the context of normal aging and in dementia, as is the potential for using D-serine as a potential biomarker and/or therapeutic agent in dementia. Although there is some controversy in the literature, it has been proposed that in normal aging there is decreased expression of serine racemase and decreased levels of D-serine and down-regulation of NMDARs, resulting in impaired synaptic plasticity and deficits in learning and memory. In contrast, in AD there appears to be activation of serine racemase, increased levels of D-serine and overstimulation of NMDARs, resulting in cytotoxicity, synaptic deficits, and dementia.

Plasma microRNAs are associated with domain-specific cognitive function in people with HIV.

OBJECTIVE: Cognitive impairment remains common in people with HIV (PWH) on antiretroviral therapy (ART). The clinical presentation and severity are highly variable in PWH suggesting that the pathophysiological mechanisms of cognitive complications are likely complex and multifactorial. MicroRNA (miRNA) expression changes may be linked to cognition as they are gene regulators involved in immune and stress responses as well as the development, plasticity, and differentiation of neurons. We examined plasma miRNA expression changes in relation to domain-specific and global cognitive function in PWH. DESIGN: Cross-sectional observational study. METHODS: Thirty-three PWH receiving care at the Southern Alberta Clinic, Canada completed neuropsychological (NP) testing and blood draw. Plasma miRNA extraction was followed by array hybridization. Random forest analysis was used to identify the top 10 miRNAs upregulated and downregulated in relation to cognition. RESULTS: Few miRNAs were identified across cognitive domains; however, when evident a miRNA was only associated with two or three domains. Notably, miR-127-3p was related to learning/memory and miR-485-5p to motor function, miRNAs previously identified in CSF or plasma in Alzheimer's and Parkinson's, respectively. Using miRNET 2.0, a software-platform for understanding the biological relevance of the miRNA-targets (genes) relating to cognition through a network-based approach, we identified genes involved in signaling, cell cycle, and transcription relating to executive function, learning/memory, and language. CONCLUSION: Findings support the idea that evaluating miRNA expression (or any molecular measure) in the context of global NP function might exclude miRNAs that could be important contributors to the domain-specific mechanisms leading to the variable neuropsychiatric outcomes seen in PWH.

Construct and Criterion-Related Validity of the Clinical Frailty Scale in Persons With HIV.

BACKGROUND: The co-occurrence of frailty and cognitive impairment in older (50+ years) persons with HIV (PWH) is common and increases the risk of poor outcomes. In HIV clinics, the most commonly used frailty measures are the frailty phenotype (FP), which requires measuring grip strength and gait speed to implement, and the frailty index (FI) based on comprehensive health data collected on patients. We examined construct and criterion-related validity (as it predicts cognition) of the Clinical Frailty Scale (CFS), a less resource-intensive approach for assessing frailty, in relation to these more commonly used frailty assessments (FP and FI). SETTING/METHODS: A total of 143 older (age 50+) PWH (mean age 57 years; 88% male) seen at the Southern Alberta Clinic underwent both frailty screening with the FP, CFS, and FI and neuropsychological testing. Mixed-effects regressions examined the associations between frailty status and cognition. RESULTS: Concordance with the FP was slightly superior for the CFS than the FI. The FP and CFS had similar associations with domain-specific cognitive performance with frail PWH performing worse than nonfrail individuals on tests requiring manual dexterity (Trail Making Part A and B; Symbol Digit; and Grooved Pegboard; P values <0.05). Neither were associated with executive function, learning, or memory performance. The FI was associated with worse fluency, fine motor skills (Grooved Pegboard), and Trail Making Part A. CONCLUSION: The CFS is a simple screening tool with good construct and criterion-related validity. It was associated with a similar pattern of cognitive deficits as the FP. If confirmed and the associations are extended to other clinically significant characteristics and outcomes, the CFS can be considered as an alternative to the FP and FI in assessing frailty in older PWH.

Predictive variables for peripheral neuropathy in treated HIV type 1 infection revealed by machine learning.

OBJECTIVE: Peripheral neuropathies (PNPs) in HIV-infected patients are highly debilitating because of neuropathic pain and physical disabilities. We defined prevalence and associated predictive variables for PNP subtypes in a cohort of persons living with HIV. DESIGN: Adult persons living with HIV in clinical care were recruited to a longitudinal study examining neurological complications. METHODS: Each patient was assessed for symptoms and signs of PNP with demographic, laboratory, and clinical variables. Univariate, multiple logistic regression and machine learning analyses were performed by comparing patients with and without PNP. RESULTS: Three patient groups were identified: PNP (n = 111) that included HIV-associated distal sensory polyneuropathy (n = 90) or mononeuropathy (n = 21), and non-neuropathy (n = 408). Univariate analyses showed multiple variables differed significantly between the non-neuropathy and PNP groups including age, estimated HIV type 1 (HIV-1) duration, education, employment, neuropathic pain, peak viral load, polypharmacy, diabetes, cardiovascular disorders, AIDS, and prior neurotoxic nucleoside antiretroviral drug exposure. Classification algorithms distinguished those with PNP, all with area under the receiver operating characteristic curve values of more than 0.80. Random forest models showed greater accuracy and area under the receiver operating characteristic curve values compared with the multiple logistic regression analysis. Relative importance plots showed that the foremost predictive variables of PNP were HIV-1 duration, peak plasma viral load, age, and low CD4+ T-cell levels. CONCLUSION: PNP in HIV-1 infection remains common affecting 21.4% of patients in care. Machine-learning models uncovered variables related to PNP that were undetected by conventional analyses, emphasizing the importance of statistical algorithmic approaches to understanding complex neurological syndromes.

Psychodermatology in Canada: A National Survey Assessment of Dermatologists' Perception, Practice Patterns, and Challenges.

OBJECTIVES: We aimed to assess the perception of psychodermatology, practice patterns, and challenges reported by Canadian dermatologists. METHODS: We designed an online questionnaire based on previous literature, including questions about practitioners' perceptions, practice patterns, training, and challenges in psychodermatology. We solicited their opinions on desired training, research needs, and clinical approach recommendations. Our survey was distributed nationally by the Canadian Dermatology Association (CDA). RESULTS: Of the total of 78 participating dermatologists, >75% reported treating patients with psychodermatological conditions, with higher frequencies of secondary than primary psychodermatological conditions. While practitioners had some confidence in their understanding of psychodermatology (median = 4 on a 5-point scale), their comfort levels to approach these patients were lower (median = 3), and their confidence in prescribing psychotropic medication was markedly low (median = 2). A total of 50% reported that a "multidisciplinary approach" would be best for these patients. Poor access to psychiatry was the most reported (26.9%) challenge, together with time constraints, lack of training, poor communication with patients, and lack of patient insight and resources. While 46.2% reported having never participated in psychodermatology training, 55.1% expressed interest in doing so. CONCLUSION: We identified several challenges with knowledge, awareness, and healthcare delivery in psychodermatological practice in Canada. Increasing dermatologists' access to psychiatric consultations/services, a multidisciplinary approach with dermatologists and psychiatrists co-providing care, and more specialized training in this area are recommended to narrow the identified gaps.

Exploratory study on neurochemical effects of low-intensity pulsed ultrasound in brains of mice.

There is now a relatively large body of evidence suggesting a relationship between dysfunction of myelin and oligodendrocytes and the etiology of several neuropsychiatric disorders, including depression and schizophrenia, and also suggesting that ultrasound methods may alleviate some of the symptoms of depression. We have applied low-intensity pulsed ultrasound (LIPUS) to the brains of mice treated with the demyelinating drug cuprizone, a drug that has been used as the basis for a rodent model relevant to a number of psychiatric and neurologic disorders including depression, schizophrenia, and multiple sclerosis. Prior to conducting the studies in mice, preliminary studies were carried out on the effects of LIPUS in vitro in neuron-like SH-SY5Y cells and primary glial cells. In subsequent studies in mice, female C57BL/6 mice were restrained in plastic tubes for 20 min daily with the ultrasound transducer near the end of the tube directly above the mouse's head. LIPUS was used at an intensity of 25 mW/cm2 once daily for 22 days in control mice and in mice undergoing daily repetitive restraint stress (RRS). Behavioral or neurochemical studies were done on the mice or the brain tissue obtained from them. The studies in vitro indicated that LIPUS stimulation at an intensity of 15 mW/cm2 delivered for 5 min daily for 3 days in an enclosed sterile cell culture plate in an incubator increased the viability of SH-SY5Y and primary glial cells. In the studies in mice, LIPUS elevated levels of doublecortin, a marker for neurogenesis, in the cortex compared to levels in the RRS mice and caused a trend in elevation of brain levels of brain-derived neurotrophic factor in the hippocampus relative to control levels. LIPUS also increased sucrose preference (a measure of the attenuation of anhedonia, a common symptom of several psychiatric disorders) in the RRS model in mice. The ability of LIPUS administered daily to rescue damaged myelin and oligodendrocytes was studied in mice treated chronically with cuprizone for 35 days. LIPUS increased cortex and corpus callosum levels of myelin basic protein, a protein marker for mature oligodendrocytes, and neural/glial antigen 2, a protein marker for oligodendrocyte precursor cells, relative to levels in the cuprizone + sham animals. These results of this exploratory study suggest that future comprehensive time-related studies with LIPUS on brain chemistry and behavior related to neuropsychiatric disorders are warranted. Exploratory Study on Neurochemical Effects of Low Intensity Pulsed Ultrasound in Brains of Mice. Upper part of figure: LIPUS device and in-vitro cell experimental set-up. The center image is the LIPUS generating box; the image in the upper left shows the cell experiment set-up; the image in the upper right shows a zoomed-in sketch for the cell experiment; the image in the lower left shows the set-up of repetitive restraint stress (RRS) with a mouse; the image in the lower middle shows the set-up of LIPUS treatment of a mouse; the image in the lower right shows a zoomed-in sketch for the LIPUS treatment of a mouse.

Emotional arousal impairs association memory: roles of prefrontal cortex regions.

The brain processes underlying impairing effects of emotional arousal on associative memory were previously attributed to two dissociable routes using high-resolution fMRI of the MTL (Madan et al. 2017). Extrahippocampal MTL regions supporting associative encoding of neutral pairs suggested unitization; conversely, associative encoding of negative pairs involved compensatory hippocampal activity. Here, whole-brain fMRI revealed prefrontal contributions: dmPFC was more involved in hippocampal-dependent negative pair learning and vmPFC in extrahippocampal neutral pair learning. Successful encoding of emotional memory associations may require emotion regulation/conflict resolution (dmPFC), while neutral memory associations may be accomplished by anchoring new information to prior knowledge (vmPFC).

Long-term consequences of interpersonal violence experiences on treatment engagement and health status in people living with HIV.

OBJECTIVE: To examine the impact of previous interpersonal violence (IPersV) experiences on long-term healthcare engagement and health outcomes in a large Canadian HIV-cohort. DESIGN: People living with HIV (PLHIV) were screened for IPersV, and their healthcare outcomes over the nine subsequent years were analyzed. METHODS: A total of 1064 PLHIV were screened for past and present IPersV experiences through semistructured interviews. Follow-up included core treatment engagement (e.g. clinic visits) and health-status variables (HIV viral load, CD4+ T-cell count, mortality, comorbidities), analyzed descriptively and with longitudinal Cox regressions. RESULTS: At intake, 385 (36%) PLHIV reported past or present IPersV including childhood (n = 224, 21%) or adulthood experiences (n = 161, 15%) and were offered conventional social work support. Over 9 years, individuals with any IPersV experiences were 36% more likely to discontinue care, 81% more likely to experience viremia, 47% more likely to experience a drop in CD4+ cell counts below 200/µl, and 65% more likely to die compared with patients not reporting IPersV (P < 0.05). Outcomes were similar when adjusted for sociodemographic factors. Childhood IPersV in particular was linked to several of the outcomes, with higher rates of discontinuation of care, viremia, and mortality related to mental health/addiction or HIV-related complications. CONCLUSION: IPersV is associated with an increased risk over time of healthcare discontinuation, poorer long-term HIV-related health outcomes, and increased mortality, especially for patients victimized in childhood. Apart from targeted IPersV screening to initiate conventional supports (e.g. through social work), increased efforts to engage vulnerable populations in their long-term care seems warranted.

Neurocognitive Impairment and Associated Genetic Aspects in HIV Infection.

HIV enters the central nervous system (CNS) early after infection. HIV-associated neurocognitive disorders (HAND) remain a serious complication of HIV infection despite available antiretroviral therapy (ART). Neurocognitive deficits observed in HAND are heterogeneous, suggesting a variability in individuals' susceptibility or resiliency to the detrimental CNS effects of HIV infection. This chapter reviews primary host genomic changes (immune-related genes, genes implicated in cognitive changes in primary neurodegenerative diseases), epigenetic mechanisms, and genetic interactions with ART implicated in HIV progression or HAND/neurocognitive complications of HIV. Limitations of the current findings include diversity of the HAND phenotype and limited replication of findings across cohorts. Strategies to improve the precision of future (epi)genetic studies of neurocognitive consequences of HIV infection are offered.

Estimated Frequency of Psychodermatologic Conditions in Alberta, Canada.

BACKGROUND: Psychodermatologic disorders are difficult to identify and treat. Knowledge about the prevalence of these conditions in dermatological practice in Canada is scarce. This hampers our ability to address potential gaps and establish optimal care pathways. OBJECTIVES: To provide an estimate of the frequencies of psychodermatologic conditions in dermatological practice in Alberta, Canada. METHODS: Two administrative provincial databases were used to estimate the prevalence of potential psychodermatological conditions in Alberta from 2014 to 2018. Province-wide dermatology claims data were examined to extract relevant International Classification of Disease codes as available. Claims were linked with pharmacy dispensation data to identify patients who received at least 1 psychoactive medication within 90 days of the dermatology claim. RESULTS: Of 243 963 patients identified, 28.6% had received at least 1 psychotropic medication (mean age: 47.9 years; 67.5% female). Rates of concurrent psychotropic medications were highest for pruritus and related conditions (46.7%), followed by urticaria (44.5%) and hyperhidrosis (32.8%). Among patients with psychotropic medications, rates of antidepressants were highest (56.3%), followed by anxiolytics (37.1%). Across billing codes, besides hyperhidrosis (71.2%), diseases of hair (61.4%) and psoriasis (59.1%) had the highest rates of antidepressant dispensations. Patients with atopic dermatitis had the highest rates for anxiolytic prescriptions (54.3%). CONCLUSION: In a 5-year window, more than a quarter of the identified dermatology patients in Alberta received at least 1 psychotropic medication, pointing to high rates of potential psychodermatologic conditions and/or concurrent mental health issues in dermatology. Diagnostic and care pathways should include a multidisciplinary approach to better identify and treat these conditions.

Neuroanatomical associations of the Edinburgh cognitive and Behavioural ALS screen (ECAS).

Cognitive impairment is now recognized in a subset of patients with amyotrophic lateral sclerosis (ALS). The objective of the study was to identify group differences and neuroanatomical correlates of the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) in participants ALS. Fifty-three ALS patients and 43 healthy controls recruited as a part of our multicentre study (CALSNIC) were administered the ECAS and underwent an MRI scan. Voxel-based morphometry and tract based spatial statistics (TBSS) was performed to identify structural changes and associations with impaired ECAS scores. Lower performance in the ECAS verbal fluency and executive domains were noted in ALS patients as compared to controls (p < 0.01). Extensive white matter degeneration was noted in the corticospinal tract in all ALS patients, while ALS patients with impaired verbal fluency or executive domains (ALS-exi, n = 22), displayed additional degeneration in the corpus callosum, cingulum and superior longitudinal fasciculus as compared to controls (p < 0.05, TFCE corrected). Mild grey matter changes and associations with ECAS verbal fluency or executive performance were noted at lenient statistical thresholds (p < 0.001, uncorrected). Executive impairment was detected using the ECAS in our multicentre sample of Canadian ALS patients. White matter degeneration in motor regions was revealed in ALS patients with extensive spread to frontal regions in the ALS-exi sub-group. Mild associations between ECAS verbal fluency, executive function scores and MRI metrics suggest that reduced performance may be associated with widespread structural integrity.

Comorbidities in Older Persons with Controlled HIV Infection: Correlations with Frailty Index Subtypes.

Frailty is prevalent in persons with human immunodeficiency virus (PWH), but factors predisposing older PWH to frailty remain uncertain. We examined factors associated with frailty and determined whether there were multiple frailty subtypes in older adults with controlled HIV infection. This was a cross-sectional outpatient study in an urban HIV clinic. Twenty-nine clinical indicators were extracted from medical records to compute a Frailty Index (FI) for 389 older (age 50+) PWH (range = 50-93; mean = 61.1, standard deviation = 7.2; 85% men) receiving HIV treatment in Calgary, Canada. We used regressions to identify factors associated with FI values. Latent class analysis was used to identify FI subtypes. Age, employment status, and duration of known HIV infection were the strongest predictors of FI (p's < 0.05). Four FI subtypes were identified. Subtype 1 (severe metabolic dysfunction+polypharmacy) had the highest mean FI (0.30). Subtype 2 (less severe metabolic dysfunction+polypharmacy) and Subtype 3 (lung and liver dysfunction+polypharmacy) had lower but equivalent mean FIs (0.20 for each). Subtype 4 (least severe metabolic dysfunction) had the lowest mean FI (0.13; p's < 0.001). Sociodemographic and behavioral characteristics differed among the subtypes. Individuals with Subtype 1 were older and more frequently unemployed/retired, whereas those with Subtype 3 were more likely to smoke, use crack/cocaine, have heavy alcohol use, and live in temporary/unstable housing. The clinical presentation of frailty in older PWH is heterogeneous. The metabolic syndrome, hepatitis C virus coinfection, cirrhosis, lung disease, and polypharmacy were associated with frailty as were unemployment/retirement, unstable housing, and substance use.

Lifetime antiretroviral exposure and neurocognitive impairment in HIV.

Despite the availability of modern antiretroviral therapy (ART), neurocognitive impairment persists among some persons with HIV (PWH). We investigated the role of exposure to four major classes of ARTs in neurocognitive impairment in PWH. A single-site cohort of 343 PWH was recruited. Lifetime ART medication history was obtained from medical health records. We evaluated the role of ART exposure as a predictor of neurocognitive impairment using univariate analyses and machine learning, while accounting for potential effects of demographic, clinical, and comorbidity-related risk factors. Out of a total of 26 tested variables, two random forest analyses identified the most important characteristics of a neurocognitively impaired group (N = 59): Compared with a neurocognitively high-performing group (N = 132; F1-score = 0.79), we uncovered 13 important risk factors; compared with an intermediate-performing group (N = 152; F1-score = 0.75), 16 risk factors emerged. Longer lifetime ART exposure, especially to integrase inhibitors, was one of the most important predictors of neurocognitive impairment in both analyses (rank 2 of 13 and rank 4 of 16, respectively), superseding effects of age (rank 11/13, rank 15/16) and HIV duration (rank 13/13, rank 16/16). Concerning specific integrase inhibitors, the impaired group had significantly longer dolutegravir exposure (p = 0.011) compared with the high-performing group (p = 0.012; trend compared with the intermediate group p = 0.063). A longer duration to integrase inhibitor intake was negatively related to cognition in this cohort. Our findings suggest that possible cognitive complications of long-term exposure to integrase inhibitors, in particular dolutegravir, should be closely monitored in PWH.

The associations of the BDNF and APOE polymorphisms, hippocampal subfield volumes, and episodic memory performance across the lifespan.

In this study, we explored the associations between the brain derived neurotrophic factor (BDNF) and the apolipoprotein E (APOE) polymorphisms and hippocampal subfields in 127 healthy participants (18-85 years). MRI datasets were collected on a 4.7 T system. Participants were administered the Wechsler Memory Scale to evaluate episodic memory function. Significant associations of both polymorphisms were present only in older adults (≥50 years). BDNF polymorphism was associated with larger dentate gyrus volumes within the anterior hippocampus (head) in Met-carriers compared to Val/Val homozygotes. We found that in Met-carriers total hippocampal volume predicted performance on visuospatial memory tasks. APOE polymorphism was associated with larger total hippocampal volume, especially in cornu ammonis 1-3 and subiculum in APOE ɛ2 carriers compared to both ɛ4 and ɛ3 carriers, while APOE ɛ3 and ɛ4 carriers did not differ from each other. APOE polymorphism was associated with better performance on visuospatial memory tasks in APOE ε2 carriers in comparison to ε4 carriers.