Developmental principles informing human pluripotent stem cell differentiation to cartilage and bone.

Human pluripotent stem cells can differentiate into any cell type given appropriate signals and hence have been used to research early human development of many tissues and diseases. Here, we review the major biological factors that regulate cartilage and bone development through the three main routes of neural crest, lateral plate mesoderm and paraxial mesoderm. We examine how these routes have been used in differentiation protocols that replicate skeletal development using human pluripotent stem cells and how these methods have been refined and improved over time. Finally, we discuss how pluripotent stem cells can be employed to understand human skeletal genetic diseases with a developmental origin and phenotype, and how developmental protocols have been applied to gain a better understanding of these conditions.

Implications of vascular depression for successful cognitive aging in HIV Disease.

Although older adults with HIV are at high risk for mild neurocognitive disorders, a subset experience successful cognitive aging (SCA). HIV is associated with an increased risk of vascular depression (VasDep), which can affect cognitive and daily functioning. The current study examined whether VasDep impedes SCA among older adults with HIV. 136 persons with HIV aged 50 years and older were classified as either SCA+ (n = 37) or SCA- (n = 99) based on a battery of demographically adjusted neurocognitive tests and self-reported cognitive symptoms. Participants were also stratified on the presence of vascular disease (e.g., hypertension) and current depression as determined by the Composite International Diagnostic Interview and the Depression/Dejection scale of the Profile of Mood States. A Cochran-Armitage test revealed a significant additive effect of vascular disease and depression on SCA in this sample of older adults with HIV (z = 4.13, p <.0001). Individuals with VasDep had the lowest frequency of SCA+ (0%), which differed significantly from the group with only vascular disease (30%, OR = 0.04, CI = 0.002,0.68)) and the group with neither vascular disease nor depression (47% OR = 0.02, CI = 0.33,0.001). Findings were not confounded by demographics, HIV disease severity, or other psychiatric and medical factors (ps > 0.05). These data suggest that presence of VasDep may be a barrier to SCA in older adults with HIV disease. Prospective, longitudinal studies with neuroimaging-based operationalizations of VasDep are needed to further clarify this risk factor's role in the maintenance of cognitive and brain health in persons with HIV disease.

Ecological validity of cognitive fluctuations in dementia with Lewy bodies.

OBJECTIVES: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Successful Aging is Associated with Better Health Literacy in Older Adults with HIV Disease.

People with HIV (PWH) are susceptible to neurocognitive, physical, and mental health problems that may decrease their likelihood of experiencing successful aging. This cross-sectional, retrospective study estimated the extent to which health literacy is associated with successful aging among 116 older PWH and 60 persons without HIV. Successful aging was defined using indicators of biological health, cognitive efficiency, mental health, and productivity. Health literacy was measured using the Rapid Estimate of Adult Literacy in Medicine, Newest Vital Sign, Brief Health Literacy Screening, and Beliefs Related to Medication Adherence. A series of logistic regressions covarying for education showed that better health literacy was associated with a higher frequency of successful aging among older PWH. Older PWH were approximately three times less likely to experience successful aging as compared to older adults without HIV. Future studies may examine whether improving health literacy among younger PWH increases the likelihood of successful aging.

Does Social Support Play a Role in the Expression and Everyday Functioning Impact of Apathy in HIV Disease?

Clinically notable apathy occurs in approximately one-third of persons living with HIV (PLWH). Drawing from psychological theory, this cross-sectional study examined the interplay between apathy and social support in persons with (n = 143) and without (n = 61) HIV disease. Analyses were conducted using multiple regression and mediation procedures with 95th percentile bootstrap confidence intervals. Positive HIV serostatus and lower social support were associated with more frequent apathy, independent of other mood symptoms. Social support did not moderate apathy's associations with everyday functioning among PLWH, but post hoc analyses revealed that apathy mediated the relationship between social support and everyday functioning among PLWH. Stronger social support may provide a buffer against the frequency of apathy symptoms in persons with and without HIV disease. The relationship between lower social support and poorer everyday functioning in HIV might be partly explained by apathy. Longitudinal research is needed to examine the mechanisms of these relationships.

RESUMEN: La apatía clínicamente notable se produce en aproximadamente un tercio de las personas que viven con el VIH (PVVS). A partir de la teoría psicológica, este estudio transversal examinó la interacción entre la apatía y el apoyo social en personas con (n = 143) y sin (n = 61) enfermedad de VIH. Los análisis se llevaron utilizando procedimientos de regresión múltiple y mediación con intervalos de confianza bootstrap del 95º percentil. El estado serológico positivo respecto al VIH y un menor apoyo social se asociaron con una apatía más frecuente, independientemente de otros síntomas del estado de ánimo. El apoyo social no moderó las asociaciones de la apatía con el funcionamiento cotidiano entre las PVVS, pero los análisis post hoc revelaron que la apatía mediaba la relación entre el apoyo social y el funcionamiento cotidiano entre las PVVS. Un apoyo social más fuerte puede atenuar la frecuencia de los síntomas de apatía en personas con y sin VIH. La relación entre un menor apoyo social y un peor funcionamiento cotidiano en personas con VIH podría explicarse en parte por la apatía. Se necesitan investigaciones longitudinales para examinar los mecanismos de estas relaciones.

The Relationship Between Apathy and Cognitive Impairment Among Hispanic/Latin Americans: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses Systematic Review.

OBJECTIVES: The primary aim was to evaluate apathy assessment measures in relation to cognitive impairment among Hispanic/Latin Americans. METHODS: A systematic review on the relationship between apathy and cognitive impairment among Hispanic/Latin Americans across normal aging and neurocognitive disorders was conducted according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and using APA PsycInfo, Embase, and PubMed databases. Inclusion criteria required (1) a sample of English or Spanish-speaking adults ages 18 years and older, (2) with measures of apathy, (3) assessment of cognitive functioning or diagnosis of neurocognitive disorder, (4) with at least 18.5% Hispanic/Latin American represented in the sample. RESULTS: Only 14 papers met criteria to be included in this review. Of the 12 cross-sectional studies, 9 demonstrated significant associations between increased apathy and cognitive impairment, 1 demonstrated a descriptive difference between apathy and cognitive status (ie, no hypothesis test conducted), while 2 demonstrated null effects. These cross-sectional studies consisted of community and clinic samples of participants across North and South America. Two longitudinal studies conducted in North America demonstrated non-significant associations of apathy with cognitive status. CONCLUSIONS: The Neuropsychiatric Inventory (NPI) and Neuropsychiatric Inventory Questionnaire (NPI-Q) apathy subscales were the most used measures for apathy in this review (85.7% of included studies). However, validity evidence from a review of apathy measures has warranted caution against the use of the NPI outside the context of screening for apathy. This potential measurement bias with Hispanic/Latin Americans apathy research limits conclusions drawn from the present review.

Cognitive Intra-individual Variability in the Laboratory Is Associated With Greater Executive Dysfunction in the Daily Lives of Older Adults With HIV.

BACKGROUND: Executive dysfunction, which is common among persons with HIV (PWH), can have an adverse impact on health behaviors and quality of life. Intra-individual variability (IIV) is a measure of within-person variability across cognitive tests that is higher in PWH and is thought to reflect cognitive dyscontrol. OBJECTIVE: To assess whether cognitive IIV in the laboratory is associated with self-reported executive dysfunction in daily life among older PWH. METHOD: Participants included 71 PWH aged ≥50 years who completed six subtests from the Cogstate battery and two subscales from the Frontal Systems Behavior Scale (FrSBe; self-report version). Cognitive IIV was calculated from the Cogstate as the coefficient of variation derived from age-adjusted normative T scores. RESULTS: Cognitive IIV as measured by the Cogstate showed a significant, positive, medium-sized association with current FrSBe ratings of executive dysfunction but not disinhibition. CONCLUSION: Higher cognitive IIV in the laboratory as measured by the Cogstate may be related to the expression of HIV-associated symptoms of executive dysfunction in daily life for older PWH.

Recent Advances in Neuropsychological Test Interpretation for Clinical Practice.

Much attention in the field of clinical neuropsychology has focused on adapting to the modern healthcare environment by advancing telehealth and promoting technological innovation in assessment. Perhaps as important (but less discussed) are advances in the development and interpretation of normative neuropsychological test data. These techniques can yield improvement in diagnostic decision-making and treatment planning with little additional cost. Brooks and colleagues (Can Psychol 50: 196-209, 2009) eloquently summarized best practices in normative data creation and interpretation, providing a practical overview of norm development, measurement error, the base rates of low scores, and methods for assessing change. Since the publication of this seminal work, there have been several important advances in research on development and interpretation of normative neuropsychological test data, which may be less familiar to the practicing clinician. Specifically, we provide a review of the literature on regression-based normed scores, item response theory, multivariate base rates, summary/factor scores, cognitive intraindividual variability, and measuring change over time. For each topic, we include (1) an overview of the method, (2) a rapid review of the recent literature, (3) a relevant case example, and (4) a discussion of limitations and controversies. Our goal was to provide a primer for use of normative neuropsychological test data in neuropsychological practice.

Lower prospective memory is associated with higher neurocognitive dispersion in two samples of people with HIV: A conceptual replication study.

OBJECTIVES: People living with HIV (PLWH) often experience deficits in the strategic/executive aspects of prospective memory (PM) that can interfere with instrumental activities of daily living. This study used a conceptual replication design to determine whether cognitive intraindividual variability, as measured by dispersion (IIV-dispersion), contributes to PM performance and symptoms among PLWH. METHODS: Study 1 included 367 PLWH who completed a comprehensive clinical neuropsychological test battery, the Memory for Intentions Test (MIsT), and the Prospective and Retrospective Memory Questionnaire (PRMQ). Study 2 included 79 older PLWH who completed the Cogstate cognitive battery, the Cambridge Prospective Memory Test (CAMPROMPT), an experimental measure of time-based PM, and the PRMQ. In both studies, a mean-adjusted coefficient of variation was derived to measure IIV-dispersion using normative T-scores from the cognitive battery. RESULTS: Higher IIV-dispersion was significantly associated with lower time-based PM performance at small-to-medium effect sizes in both studies (mean r s  = -0.30). The relationship between IIV-dispersion and event-based PM performance was comparably small in magnitude in both studies (r s  = -0.19, -0.20), but it was only statistically significant in Study 1. IIV-dispersion showed very small, nonsignificant relationships with self-reported PM symptoms in both samples (r s < 0.10). CONCLUSIONS: Extending prior work in healthy adults, these findings suggest that variability in performance across a cognitive battery contributes to laboratory-based PM accuracy, but not perceived PM symptoms, among PLWH. Future studies might examine whether daily fluctuations in cognition or other aspects of IIV (e.g., inconsistency) play a role in PM failures in everyday life.

Historical trends in reporting effect sizes in clinical neuropsychology journals: A call to venture beyond the results section.

OBJECTIVE: For decades, quantitative psychologists have recommended that authors report effect sizes to convey the magnitude and potential clinical relevance of statistical associations. However, fewer than one-third of neuropsychology articles published in the early 2000s reported effect sizes. This study re-examines the frequency and extent of effect size reporting in neuropsychology journal articles by manuscript section and over time. METHODS: A sample of 326 empirical articles were drawn from 36 randomly selected issues of six neuropsychology journals at 5-year intervals between 1995 and 2020. Four raters used a novel, reliable coding system to quantify the extent to which effect sizes were included in the major sections of all 326 articles. RESULTS: Findings showed medium-to-large increases in effect size reporting in the Methods and Results sections of neuropsychology journal articles that plateaued in recent years; however, there were only very small and nonsignificant changes in effect size reporting in the Abstract, Introduction, and Discussion sections. CONCLUSIONS: Authors in neuropsychology journals have markedly improved their effect size reporting in the core Methods and Results sections, but are still unlikely to consider these valuable metrics when motivating their study hypotheses and interpreting the conceptual and clinical implications of their findings. Recommendations are provided to encourage more widespread integration of effect sizes in neuropsychological research.

Does neurocognition contribute to age-related deficits in the online navigation of electronic patient health portals?

OBJECTIVE: The internet serves an increasingly critical role in how older adults manage their personal health. Electronic patient portals, for example, provide a centralized platform for older adults to access lab results, manage prescriptions and appointments, and communicate with providers. This study examined whether neurocognition mediates the effect of older age on electronic patient portal navigation. METHOD: Forty-nine younger (18-35 years) and 35 older adults (50-75 years) completed the Test of Online Health Records Navigation (TOHRN), which is an experimenter-controlled website on which participants were asked to log-in, review laboratory results, read provider messages, and schedule an appointment. Participants also completed a neuropsychological battery, self-report questionnaires, and measures of health literacy and functional capacity. RESULTS: Mediation analyses revealed a significant indirect effect of older age on lower TOHRN accuracy, which was fully mediated by the total cognitive composite. CONCLUSIONS: Findings indicate that neurocognition may help explain some of the variance in age-related difficulties navigating electronic patient health portals. Future studies might examine the possible benefits of both structural (e.g., human factors web design enhancement) and individual (e.g., training and compensation) cognitive supports to improve the navigability of electronic patient health portals for older adults.

Was the COVID-19 Pandemic Associated with Gender Disparities in Authorship of Manuscripts Submitted to Clinical Neuropsychology Journals?

OBJECTIVE: The COVID-19 pandemic exacerbated gender disparities in some academic disciplines. This study examined the association of the pandemic with gender authorship disparities in clinical neuropsychology (CN) journals. METHOD: Author bylines of 1,018 initial manuscript submissions to four major CN journals from March 15 through September 15 of both 2019 and 2020 were coded for binary gender. Additionally, authorship of 40 articles published on pandemic-related topics (COVID-19, teleneuropsychology) across nine CN journals were coded for binary gender. RESULTS: Initial submissions to these four CN journals increased during the pandemic (+27.2%), with comparable increases in total number of authors coded as either women (+23.0%) or men (+25.4%). Neither the average percentage of women on manuscript bylines nor the proportion of women who were lead and/or corresponding authors differed significantly across time. Moreover, the representation of women as authors of pandemic-related articles did not differ from expected frequencies in the field. CONCLUSIONS: Findings suggest that representation of women as authors of peer-reviewed manuscript submissions to some CN journals did not change during the initial months of the COVID-19 pandemic. Future studies might examine how risk and protective factors may have influenced individual differences in scientific productivity during the pandemic.

Neuropsychological Correlates of Adherence in Youth with Behaviorally Acquired HIV.

Youth living with behaviorally acquired HIV (YLWH) are at-risk for both neuropsychological disorders and antiretroviral therapy (ART) non-adherence; little is known about their interrelationship over time in YLWH. Neuropsychological and psychiatric functioning, substance use, and self-report of 7-day/week and weekend ART adherence were assessed at baseline and Weeks 24, 48, 96 and 144 of a longitudinal study evaluating the impact of early (CD4>350) versus standard of care (CD4≤350) treatment initiation on neuropsychological functioning in 111 treatment-naïve YLWH age 18-24 years at entry. Bayesian multi-level models for adherence (≥ 90% vs. <90%) were fit using random intercepts for repeated measures. Adjusted odds ratios (OR [95% credible interval]) for higher versus lower baseline Motor function for visit adherence were 0.58 (0.25, 1.16), 0.5 (0.15, 1.38), 0.52 (0.16, 1.52), and 0.94 (0.3, 2.8) at Weeks 24, 48, 96, and 144, respectively. Week 24 adherence was associated with higher adjusted odds of Motor function at Week 48 (week: 0.27, -0.05-0.59; weekend: 0.28, -0.07-0.62). Week 96 Complex Executive functioning was associated with higher adjusted odds of adherence at Week 144, OR = 4.26 (1.50, 14.33). Higher Motor functioning emerged most consistently associated with lower odds of adherence in YLWH. Complex Executive functioning was associated with adherence only at end of study, suggesting potential contribution in adherence over the long-term.

Racial differences in scores on the HIV Dementia Scale: mediating effects of literacy and screening utility among Black and White persons with HIV disease.

There are many obstacles to screening for HIV-associated neurocognitive disorders (HAND), including the influence of various sociodemographic effects on screening measures. This study examined possible racial bias on the HIV Dementia Scale (HDS) in screening for HAND among 39 Black and 84 White persons living with HIV (PLWH). Black PLWH had significantly lower raw HDS scores than White PLWH, which was mediated by lower oral word reading scores. Nevertheless, HDS scores were comparably predictive of clinical HAND diagnoses for Black and White PLWH as determined by a comprehensive battery; overall, individuals who failed the HDS were three times as likely to have HAND as compared to those who performed within normal limits (sensitivity = .26, specificity = .94). Consistent with prior literature exploring race-group differences, findings suggest that lower scores among Black PLWH compared to White PLWH on a commonly-used screening measure for HAND are partly explained by reading scores, perhaps reflecting differences in educational quality and opportunities. However, race-group differences did not affect the classification accuracy of the HDS in detecting HAND, although overall diagnostic accuracy was modest in both groups. Future work should determine the optimal neurocognitive screening methods for Black PLWH and other under-represented ethnoracial groups.

Executive functions mediate the association between alcohol use and declarative memory symptoms in daily life.

Alcohol use is associated with memory problems in young adults with HIV, but the cognitive mechanisms of that association are not known. Sixty adults (aged 19-24 years) living with HIV were administered the Alcohol, Smoking, and Substance Involvement Screening Test to assess alcohol use, Behavior Rating Inventory of Executive Function for self-reported executive functions, and the Prospective and Retrospective Memory Questionnaire (PRMQ) for dailiy memory functioning. Controlling for mood, self-reported executive functions fully mediated the relationship between alcohol use and memory (indirect effect b=.568, 95%CI [.209,.888]). Findings suggest that self-reported executive dysregulation of memory processes (e.g., Strategic encoding and retrieval) may drive the effects of alcohol use on daily memory symptoms.

Computer use: a protective factor for cognition in aging and HIV disease?

BACKGROUND: Modifiable lifestyle factors such as engagement with technology may be beneficial to cognition in older adults, but we know little about these relationships in older persons with chronic medical conditions. AIMS: The current study examined the association between computer use frequency and cognition in younger and older adults with and without HIV disease. METHODS: Participants included 110 older persons with HIV (pwHIV; age ≥ 50 years), 84 younger pwHIV (age ≤ 40 years), 76 older HIV-, and 66 younger HIV- adults who completed a comprehensive medical, psychiatric, and cognitive research assessment. Demographically adjusted scores were derived from a well-validated clinical battery of performance-based neuropsychological tests. Participants also completed self-reported measures of cognitive symptoms in daily life and the Brief Computer Use and Anxiety Questionnaire (BCUAQ). RESULTS: Older age was associated with less frequent computer use among persons with and without HIV disease. More frequent computer use was strongly and independently related to better cognitive performance, particularly in higher order domains (e.g., episodic memory and executive functions) and among the older seronegative adults. A small, univariable correlation between more frequent computer use and fewer cognitive symptoms in daily life was observed in the full sample, but that relationship was better explained by computer-related anxiety and HIV/age study group. DISCUSSION: These findings add to the existing literature that suggests regular engagement with digital technologies may have a beneficial impact on cognitive functioning, consistent with the technological reserve hypothesis.

Indirect Effects of Negative Mood on Opioid Misuse and Dependence via Anxiety Sensitivity Subfacets: Evidence from Adults Reporting Chronic Pain.

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, Mage = 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.

Are accuracy discernment and sharing of COVID-19 misinformation associated with older age and lower neurocognitive functioning?

The online proliferation of COVID-19 misinformation led to adverse health and societal consequences. This study investigated possible differences in COVID-19 headline accuracy discernment and online sharing of COVID-19 misinformation between older and younger adults, as well as the role of individual differences in global cognition, health literacy and verbal IQ. Fifty-two younger (18-35 years old) and fifty older adults (age 50 and older) completed a neurocognitive battery, health literacy and numeracy measures, and self-report questionnaires via telephone. Participants also completed a social media headline-sharing experiment (Pennycook et al., Psychological science, 31(7), 770-780, 2020) in which they were presented with true and false COVID-19 headlines about which they indicated: 1) the likelihood that they would share the story on social media; and 2) the factual accuracy of the story. A repeated measures multivariate analysis of variance controlling for gender and race/ethnicity showed no effects of age (p = .099) but a significant interaction between actual COVID-19 headline accuracy and the likelihood of sharing (p < .001), such that accuracy was more strongly related to sharing false headlines (r = -.64) versus true headlines (r = -.43). Moreover, a higher likelihood of sharing false COVID-19 headlines was associated with lower verbal IQ and numeracy skills in older adults (rs = -.51--.40) and with lower verbal IQ, numeracy, and global cognition in younger adults (rs = -.66--.60). Findings indicate that headline accuracy judgements, numeracy, and verbal IQ are important contributors to sharing COVID-19 misinformation in both older and younger adults. Future work might examine the benefits of psychoeducation for improving health and science literacy for COVID-19. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-023-04464-w.

microRNA-seq of cartilage reveals an overabundance of miR-140-3p which contains functional isomiRs.

miR-140 is selectively expressed in cartilage. Deletion of the entire Mir140 locus in mice results in growth retardation and early-onset osteoarthritis-like pathology; however, the relative contribution of miR-140-5p or miR-140-3p to the phenotype remains to be determined. An unbiased small RNA sequencing approach identified miR-140-3p as significantly more abundant (>10-fold) than miR-140-5p in human cartilage. Analysis of these data identified multiple miR-140-3p isomiRs differing from the miRBase annotation at both the 5' and 3' end, with >99% having one of two seed sequences (5' bases 2-8). Canonical (miR-140-3p.2) and shifted (miR-140-3p.1) seed isomiRs were overexpressed in chondrocytes and transcriptomics performed to identify targets. miR-140-3p.1 and miR-140-3p.2 significantly down-regulated 694 and 238 genes, respectively, of which only 162 genes were commonly down-regulated. IsomiR targets were validated using 3'UTR luciferase assays. miR-140-3p.1 targets were enriched within up-regulated genes in rib chondrocytes of Mir140-null mice and within down-regulated genes during human chondrogenesis. Finally, through imputing the expression of miR-140 from the expression of the host gene WWP2 in 124 previously published data sets, an inverse correlation with miR-140-3p.1 predicted targets was identified. Together these data suggest the novel seed containing isomiR miR-140-3p.1 is more functional than original consensus miR-140-3p seed containing isomiR.

Combined effects of older age and HIV disease on changes in everyday functioning over one year.

Older age and HIV disease are independent risk factors for problems in many aspects of everyday functioning. However, less is known about how these risk factors may combine to influence everyday functioning over time. The current study examined the possible combined effects of age and HIV serostatus on change in everyday functioning over a 1-year period and its specific associations with changes in neurocognition. A repeated measures factorial design was employed. Participants included 77 older persons with HIV (PWH), 35 younger PWH, 44 older HIV-, and 27 younger HIV-adults who each completed baseline and follow-up visits approximately 14 months apart. Everyday functioning was assessed using a standardized self-report measure of activities of daily living (ADLs) at each visit. A comprehensive clinical battery assessed six domains of neurocognition. Raw scores on each neurocognitive measure were converted to sample-based z-scores, from which a global neurocognitive z-score was derived. Older PWH reported the poorest everyday functioning at baseline and follow-up visits at medium-to-large effect sizes. However, these ADL disruptions among older PWH were relatively stable over time, differing significantly from younger PWH who evidenced mild ADL improvements from baseline to follow-up. Within the entire sample, everyday functioning at baseline predicted neurocognitive performance at follow-up, but the reciprocal relationship was not significant. Older adults with HIV have high rates of ADL problems, which appear stable over 1 year, the trajectory of which differed from younger adults with HIV for whom mild improvements were observed. Importantly, the results also suggest that problems with ADLs may sometimes precede neurocognitive declines. Further examination of longitudinal data is needed to elucidate the long-term trajectory of neurocognitive and functional changes in older PWH to support early detection and proper management of clinical care.