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A comparison of the Wherry-Gaylord iterative factor analysis procedure and the Thurstone multiple-group analysis of sub-tests shows that the two methods result in the same factors. The Wherry-Gaylord method has the advantage of giving factor loadings for items. The number of iterations needed can be reduced by doing a factor analysis of sub-tests, re-grouping sub-tests according to factors, and using each group as a starting point for iterations.
To co-design support strategies to enable sustainable, healthy, affordable food provision, including waste mitigation practices, in Australian Early Childhood Education and Care (ECEC) settings.
Design:
Based on the co-design IDEAS framework (Ideate, DEsign, Assess & Share), this co-design process involved iterative interviews and focus groups with ECEC centre staff and workshops with Nutrition Australia. Interview and workshop themes were coded to the Theoretical Domains Framework (TDF) to develop initial prototypes for support strategies that were further developed and refined in focus groups.
Setting:
ECEC with onsite food provision, in Victoria, Australia.
Participants:
ECEC staff and a Victorian Government-funded programme delivered through Nutrition Australia that provides nutrition support to ECEC services.
Results:
ECEC staff interviews (n 17) suggested a lack of knowledge on the topic of sustainable healthy food provision and a need for resources and support for all staff and children. Workshops with Nutrition Australia built on interviews and suggested a focus on lower intensity strategies and a suggestion to embed knowledge-related activities into the children’s curriculum. Focus groups (n 8) further informed co-design of strategies, producing a visual representation of sustainable healthy food provision with supporting tips and a whole-of-centre approach that includes children through a classroom activity.
Conclusions:
The co-designed resources could provide feasible strategies for the adoption of sustainable, healthy and affordable provision practices in the ECEC setting. Involvement of a local government-funded health promotion service provides valuable research-to-practice contribution as well opportunity for scalable dissemination of resources through existing infrastructure.
Racial and ethnic variations in antibiotic utilization are well-reported in outpatient settings but little is known about inpatient settings. Our objective was to describe national inpatient antibiotic utilization among children by race and ethnicity.
Methods:
This study included hospital visit data from the Pediatric Health Information System between 01/01/2022 and 12/31/2022 for patients <20 years. Primary outcomes were the percentage of hospitalization encounters that received an antibiotic and antibiotic days of therapy (DOT) per 1000 patient days. Mixed-effect regression models were used to determine the association of race-ethnicity with outcomes, adjusting for covariates.
Results:
There were 846,530 hospitalizations. 45.2% of children were Non-Hispanic (NH) White, 27.1% were Hispanic, 19.2% were NH Black, 4.5% were NH Other, 3.5% were NH Asian, 0.3% were NH Native Hawaiian/Other Pacific Islander (NHPI) and 0.2% were NH American Indian. Adjusting for covariates, NH Black children had lower odds of receiving antibiotics compared to NH White children (aOR 0.96, 95%CI 0.94–0.97), while NH NHPI had higher odds of receiving antibiotics (aOR 1.16, 95%CI 1.05–1.29). Children who were Hispanic, NH Asian, NH American Indian, and children who were NH Other received antibiotic DOT compared to NH White children, while NH NHPI children received more antibiotic DOT.
Conclusions:
Antibiotic utilization in children’s hospitals differs by race and ethnicity. Hospitals should assess policies and practices that may contribute to disparities in treatment; antibiotic stewardship programs may play an important role in promoting inpatient pharmacoequity. Additional research is needed to examine individual diagnoses, clinical outcomes, and drivers of variation.
Isopods infest fish worldwide, but their role as disease vectors remains poorly understood. Here, we describe infestation of Atlantic bonefish (Albula vulpes) in Belize with isopods in two of three locations studied, with infestation rates of 15 and 44%. Isopods fed aggressively, and infested fish showed missing scales and scars. Gross morphologic and molecular phylogenetic analyses revealed the isopods to cluster within the family Aegidae and to be most closely related to members of the genus Rocinela, which are globally distributed micro-predators of fish. Metagenomic analysis of 10 isopods identified 11 viruses, including two novel reoviruses (Reovirales) in the families Sedoreoviridae and Spinareoviridae. The novel sedoreovirus clustered phylogenetically within an invertebrate-specific clade of viruses related to the genus Orbivirus, which contains arboviruses of global concern for mammal health. The novel spinareovirus clustered within the fish-infecting genus Aquareovirus, which contains viruses of global concern for fish health. Metagenomic analyses revealed no evidence of infection of bonefish with the novel aquareovirus, suggesting that viremia in bonefish is absent, low, or transient, or that isopods may have acquired the virus from other fish. During field collections, isopods aggressively bit humans, and blood meal analysis confirmed that isopods had fed on bonefish, other fish, and humans. Vector-borne transmission may be an underappreciated mechanism for aquareovirus transmission and for virus host switching between fish and other species, which has been inferred across viral families from studies of deep virus evolution.
Identifying persons with HIV (PWH) at increased risk for Alzheimer’s disease (AD) is complicated because memory deficits are common in HIV-associated neurocognitive disorders (HAND) and a defining feature of amnestic mild cognitive impairment (aMCI; a precursor to AD). Recognition memory deficits may be useful in differentiating these etiologies. Therefore, neuroimaging correlates of different memory deficits (i.e., recall, recognition) and their longitudinal trajectories in PWH were examined.
Design:
We examined 92 PWH from the CHARTER Program, ages 45–68, without severe comorbid conditions, who received baseline structural MRI and baseline and longitudinal neuropsychological testing. Linear and logistic regression examined neuroanatomical correlates (i.e., cortical thickness and volumes of regions associated with HAND and/or AD) of memory performance at baseline and multilevel modeling examined neuroanatomical correlates of memory decline (average follow-up = 6.5 years).
Results:
At baseline, thinner pars opercularis cortex was associated with impaired recognition (p = 0.012; p = 0.060 after correcting for multiple comparisons). Worse delayed recall was associated with thinner pars opercularis (p = 0.001) and thinner rostral middle frontal cortex (p = 0.006) cross sectionally even after correcting for multiple comparisons. Delayed recall and recognition were not associated with medial temporal lobe (MTL), basal ganglia, or other prefrontal structures. Recognition impairment was variable over time, and there was little decline in delayed recall. Baseline MTL and prefrontal structures were not associated with delayed recall.
Conclusions:
Episodic memory was associated with prefrontal structures, and MTL and prefrontal structures did not predict memory decline. There was relative stability in memory over time. Findings suggest that episodic memory is more related to frontal structures, rather than encroaching AD pathology, in middle-aged PWH. Additional research should clarify if recognition is useful clinically to differentiate aMCI and HAND.
Carbohydrate intake and key food sources of carbohydrates in early childhood are poorly understood. The present study described total carbohydrate intake and subtypes (i.e. starch, sugar), their primary food sources and their tracking among young Australian children. Data from children at ages 9 months (n 393), 18 months (n 284), 3·5 years (n 244) and 5 years (n 240) from the Melbourne InFANT Program were used. Three 24-hour recalls assessed dietary intakes. The 2007 AUSNUT Food Composition Database was used to calculate carbohydrates intake and food groups. Descriptive statistics summarised total carbohydrate and subtype intake and their main food sources. Tracking was examined using Pearson correlations of residualised scores between time points. Total carbohydrate, starch and sugar intakes (g/d) increased across early childhood. The percentage of energy from total carbohydrates (% E) remained stable overtime (48·4–50·5 %). From ages 9 months to 5 years, the %E from total sugar decreased from 29·4 % to 22·6 %, while the %E from starch increased from 16·7 % to 26·0 %. Sources of total carbohydrate intake changed from infant formula at 9 months to bread/cereals, fruits and milk/milk products at 18 months, 3·5 and 5 years. Across all time points, the primary sources of total sugar intake were fruit, milk/milk products and cakes/cookies, whereas main food groups for starch intake included bread/cereals, cakes/cookies and pasta. Weak to moderate tracking of total carbohydrates, total sugar and starch (g/d) was observed. These findings may have the potential to inform the refinement of carbohydrate intake recommendations and design of interventions to improve children’s carbohydrate intake.
Field schools are foundational training for archaeologists and the corresponding methods for instruction are largely consistent within the discipline. The expectation is that at some point early in their careers students will enroll in a field school. To participate, students must pay summer tuition, dedicate a minimum of four weeks (usually longer) to full-time fieldwork, and in many cases travel to remote locations. The reality is that for many students such expectations make field school participation an impossibility—and ultimately make archaeology a nonviable career option for students from historically underrepresented backgrounds. Offering local field opportunities within the context of a regular school year alleviates those problems. A recent field school in north Idaho demonstrated how traditional field school structure excludes many students and how archaeologists can adjust instruction to make field training more accessible to students.
Globally, there is seasonal variation in tuberculosis (TB) incidence, yet the biological and behavioural or social factors driving TB seasonality differ across countries. Understanding season-specific risk factors that may be specific to the UK could help shape future decision-making for TB control. We conducted a time-series analysis using data from 152,424 UK TB notifications between 2000 and 2018. Notifications were aggregated by year, month, and socio-demographic covariates, and negative binomial regression models fitted to the aggregate data. For each covariate, we calculated the size of the seasonal effect as the incidence risk ratio (IRR) for the peak versus the trough months within the year and the timing of the peak, whilst accounting for the overall trend. There was strong evidence for seasonality (p < 0.0001) with an IRR of 1.27 (95% CI 1.23–1.30). The peak was estimated to occur at the beginning of May. Significant differences in seasonal amplitude were identified across age groups, ethnicity, site of disease, latitude and, for those born abroad, time since entry to the UK. The smaller amplitude in older adults, and greater amplitude among South Asians and people who recently entered the UK may indicate the role of latent TB reactivation and vitamin D deficiency in driving seasonality.
Background: Cerebral venous thrombosis (CVT) is a rare cause of stroke, with 10–15% of patients experiencing dependence or death. The role of endovascular therapy (EVT) in the management of CVT remains controversial and practice patterns are not well-known. Methods: We distributed a comprehensive 53-question survey to neurologists, neuro-interventionalists, neurosurgeons and other relevant clinicians globally from May 2023 to October 2023. The survey asked about practice patterns and perspectives on EVT for CVT and assessed opinions regarding future clinical trials. Results: The overall response rate was 31% (863 respondents from 2744 invited participants) across 61 countries. A majority (74%) supported use of EVT for certain CVT cases. Key considerations for EVT included worsening level of consciousness (86%) and other clinical deficits (76%). Mechanical thrombectomy with aspiration (22%) and stent retriever (19%) were the most utilized techniques, with regional variations. Post-procedurally, low molecular weight heparin was the predominant anticoagulant administered (40%), although North American respondents favored unfractionated heparin. Most respondents supported future trials of EVT (90%). Conclusions: Our survey reveals significant heterogeneity in approaches to EVT for CVT, highlighting the necessity for adequately powered clinical trials to guide standard-of-care practices.
Background: Spinal Muscular Atrophy (SMA) is a rare, genetic disorder marked by motor neuron degeneration, causing progressive muscle weakness. SMA significantly impacts patients and their families. This study investigates HRQOL in a longitudinal SMA cohort. Methods: The study used the Canadian Neuromuscular Disease Registry to examine HRQOL in children aged 6-10 years with genetically confirmed SMA. HRQOL was evaluated using the PedsQL™ Measurement Model. This tool is validated in children and adolescents with various health conditions. The PedsQL Neuromuscular Module which has been validated in SMA was also used. Results: Eight participants completed the PedsQL generic and Neuromuscular Module at timepoint 1 (TP1) and 2 (TP2). The mean scores at TP1 were 49.66 (SD=5.05) for the generic PedsQL and 61.06 (SD=18.37) for the Neuromuscular Module. At TP2, mean scores increased to 59.32 (SD=13.08) and 74.86 (SD=9.88), respectively. The overall mean change over the two timepoints was +9.66 (SD=15.16) for the Generic PedQL and +13.80 (SD=23.03) for the Neuromuscular Module. Six participants were on disease modifying treatment. Conclusions: HRQOL scores in SMA patients improved over the study period. The enhancement in HRQOL may indicate the positive impact of diseases modifying treatments of SMA that became available during that time.
The UK Diabetes Remission Clinical Trial (DiRECT) demonstrated that a weight loss strategy consisting of: (1) 12 weeks total diet replacement; (2) 4 to 6 weeks food reintroduction; and (3) a longer period of weight loss maintenance, is effective in reducing body weight, improving glycaemic control, and facilitating type 2 diabetes remission(1). The DiRECT protocol is now funded for type 2 diabetes management in the UK(2). Type 2 diabetes is a growing problem in Aotearoa New Zealand(3), but the acceptability and feasibility of the DiRECT intervention in our diverse sociocultural context remains unclear. We conducted a randomised controlled trial of DiRECT within a Māori primary healthcare provider in O¯tepoti Dunedin. Forty participants with diabetes and obesity who wanted to lose weight were randomised to receive the DiRECT intervention or usual care. Both groups received the same level of individualised support from an in-house dietitian. We conducted individual, semi-structured interviews with 26 participants after 3 months. Questions explored perspectives and experiences, barriers and facilitators, and future expectations regarding dietary habits and weight loss. Interview transcripts were analysed using inductive thematic analysis(4). Participants struggled with weight management prior to the study. Advice from doctors, friends and whānau, and the internet was prolific, yet often impractical or unclear. The DiRECT intervention was mentally and physically challenging, but rapid weight loss and an improved sense of health and wellbeing enhanced motivation. Participants identified strategies which supported adaptation and adherence. Food reintroduction beyond 3 months was an exciting milestone, but the risk of reverting to previous habits was daunting. Participants feared weight regain and felt ongoing guidance was required for a successful transition to a real-food diet. Conversely, usual care participants described a gradual and ongoing process of health-focused dietary modification. While this approach did support behaviour change, a perceived slow rate of weight loss was often frustrating. Across both interventions, self-motivation and whānau support contributed to perceived success, whereas busy lifestyles, social and cultural norms, and financial concerns presented additional challenges. The role of individualised and non-judgemental dietetic support was a central theme across both groups. In addition to nutrition education and practical guidance, the in-house dietitian offered encouragement and promoted self-acceptance among participants. At 3 months, positive shifts in perspectives surrounding food, health, and sense of self were identified, which participants largely attributed to the level of nutrition support received: a new experience for many. The DiRECT protocol appears an acceptable weight loss approach among New Zealanders with diabetes and obesity, but tailored dietetic and behavioural support must be prioritised in its implementation. Future research should examine the broader health benefits associated with providing greater dietetic support and the cost-effectiveness of employing nutrition-trained health professionals within the primary care workforce.
Methods to reduce obesity and type 2 diabetes in Aotearoa New Zealand are desperately needed, with obesity one of the greatest predisposing factors for type 2 diabetes as well as heart disease, and certain cancers.1 A recent New Zealand report2 identified several interventions that might benefit people with established diabetes, the most promising being a period of rapid weight loss, followed by supported weight-loss maintenance. Such weight loss has shown to achieve what was previously thought impossible, diabetes remission,3 as well as appreciably reduce the risk of cardiovascular disease and prevent diabetes-related chronic kidney disease, retinopathy, nephropathy, and lower limb amputation.2 While the findings from the studies of low energy total meal replacement diets have stimulated great interest, their use in Aotearoa New Zealand has not been considered. The purpose of this primary-care led intervention therefore was to consider the acceptability and efficacy of such a weight loss programme, DiRECT, in Aotearoa New Zealand. Te Kāika DiRECT is a 12-month study conducted within a Māori primary healthcare provider in O¯tepoti Dunedin. The DiRECT protocol is three months of total meal replacement for rapid weight loss followed by food reintroduction and a longer period of supported weight loss maintenance. Participants were adults with prediabetes or T2 diabetes and obesity wanting to lose weight. Twenty participants (70% female, age 46 (SD 10), BMI 41 (9), HbA1c 51 (11)) were randomised to receive the DiRECT protocol, twenty more (70% female, age 50 (SD 8), BMI 40 (7), HbA1c 54 (14)) were randomised to receive best practice weight loss support (usual care). All participants had the same number of visits with the in-house Dietitian and free access to the onsite gym. Participants in the control group also received regular grocery vouchers to purchase the foods encouraged by healthy eating guidelines. Recruitment began in February, 2022. After the initial three month study period, DiRECT participants reported consuming 3.0MJ (95% CI 1.2 to 4.8MJ) less energy per day than those in usual care. Mean weight loss was 6kg (2.3-9.6kg) greater for DiRECT participants than usual care participants, while medication use and systolic blood pressure (12mmHg (0-24mmHg)) were lower. Continuous glucose monitoring identified that at baseline, participants on average only spent 10% of the day with a blood glucose reading under 8mmol/L (normoglycaemia). After three months, the usual care group spent on average 48% of the day within the normoglycaemic range, while DiRECT participants spent 78% of the day within the normoglycaemic range. Results at 12 months will enable comment on longer term markers of blood glucose control (HbA1c) and diabetes remission rates, as well as indicate if the body weight, medication, and blood pressure improvements observed at three months are sustained.
Identifying thrombus formation in Fontan circulation has been highly variable, with reports between 17 and 33%. Initially, thrombus detection was mainly done through echocardiograms. Delayed-enhancement cardiac MRI is emerging as a more effective imaging technique for thrombus identification. This study aims to determine the prevalence of occult cardiac thrombosis in patients undergoing clinically indicated cardiac MRI.
Methods:
A retrospective chart review of children and adults in the Duke University Hospital Fontan registry who underwent delayed-enhancement cardiac MRI. Individuals were excluded if they never received a delayed-enhancement cardiac MRI or had insufficient data. Demographic characteristics, native heart anatomy, cardiac MRI measurements, and thromboembolic events were collected for all patients.
Results:
In total, 119 unique individuals met inclusion criteria with a total of 171 scans. The median age at Fontan procedure was 3 (interquartile range 1, 4) years. The majority of patients had dominant systemic right ventricle. Cardiac function was relatively unchanged from the first cardiac MRI to the third cardiac MRI. While 36.4% had a thrombotic event by history, only 0.5% (1 patient) had an intracardiac thrombus detected by delayed-enhancement cardiac MRI.
Conclusions:
Despite previous echocardiographic reports of high prevalence of occult thrombosis in patients with Fontan circulation, we found very low prevalence using delayed-enhancement cardiac MRI. As more individuals are reaching adulthood after requiring early Fontan procedures in childhood, further work is needed to develop thrombus-screening protocols as a part of anticoagulation management.
FoodRx is a 12-month healthy food prescription incentive program for people with type 2 diabetes (T2DM) and experiences of household food insecurity. In this study, we aimed to explore potential users’ prospective acceptability (acceptability prior to program use) of the design and delivery of the FoodRx incentive and identify factors influencing prospective acceptability.
Design:
We used a qualitative descriptive approach and purposive sampling to recruit individuals who were interested or uninterested in using the FoodRx incentive. Semi-structured interviews were guided by the theoretical framework of acceptability, and corresponding interview transcripts were analysed using differential qualitative analysis guided by the socioecological model.
Setting:
Individuals living in Alberta, Canada.
Participants:
In total, fifteen adults with T2DM and experiences of household food insecurity.
Results:
People who were interested in using the FoodRx incentive (n 10) perceived it to be more acceptable than those who were uninterested (n 5). We identified four themes that captured factors that influenced users’ prospective acceptability: (i) participants’ confidence, views and beliefs of FoodRx design and delivery and its future use (intrapersonal), (ii) the shopping routines and roles of individuals in participants’ social networks (interpersonal), (iii) access to and experience with food retail outlets (community), and (iv) income and food access support to cope with the cost of living (policy).
Conclusion:
Future healthy food prescription programs should consider how factors at all levels of the socioecological model influence program acceptability and use these data to inform program design and delivery.
There is much discussion in archaeological circles about challenges associated with the millions of artifacts generated by fieldwork. Most of these discussions are limited to issues within the profession, such as care of collections, accessibility for research, orphaned collections, and shortcomings in training on collections awareness. An underrecognized third party in these discussions is the public. Despite a broadly held ethos of the importance of archaeology for all, archaeologists have paid comparatively little attention to sharing/exposing collections (and the outcomes of excavations) with audiences outside of the profession. This research discusses negative ramifications of not sharing collections with broader audiences and then presents some options for broadening this much-needed engagement through developing more public outreach efforts, providing alternative uses of collections, collaborating with private collectors, and using digital technology to increase access to collections.
Organic ligands, such as EDTA, accelerate the dissolution of silicate and oxide minerals. In natural systems, oxyanions can compete with organic ligands for mineral surface sites thereby affecting ligand-promoted dissolution rates, either enhancing or inhibiting dissolution, depending upon pH. The influence of selenite, molybdate and phosphate on the EDTA-promoted dissolution of goethite has been examined and a mechanism proposed for the observed differences in dissolution rates over a pH range of 4–8. We propose that the surface complex formed by EDTA is the controlling factor for the observed dissolution rate, with mononuclear complexes accelerating dissolution compared to bi- or multinuclear complexes. Dissolution results from our experiments suggest that EDTA forms multinuclear complexes at pH values ⩾6 and mononuclear complexes at pH values <6. Dissolution results show that when the oxyanion and the EDTA are present in the system at concentrations nearly equalling the surface sites available for adsorption, the oxyanion reduces the adsorption of EDTA and inhibits dissolution. However, if the oxyanion is present at lower concentrations at pH values ⩾6, EDTA is adsorbed but the number of carboxylic groups that can bind to the surface is reduced causing the formation of mononuclear complexes. This shift to a weaker surface complex enhances the EDTA-promoted dissolution of goethite in the presence of the oxyanions compared to EDTA-promoted dissolution in their absence.
Older people with HIV (PWH) are at-risk for Alzheimer’s disease (AD) and its precursor, amnestic mild cognitive impairment (aMCI). Identifying aMCI among PWH is challenging because memory impairment is also common in HIV-associated neurocognitive disorders (HAND). The neuropathological hallmarks of aMCI/AD are amyloid-ß42 (Aß42) plaque and phosphorylated tau (p-tau) accumulation. Neurofilament light chain protein (NfL) is a marker of neuronal injury in AD and other neurodegenerative diseases. In this study, we assessed the prognostic value of the CSF AD pathology markers of lower Aß42, and higher p-tau, p-tau/Aß42 ratio, and NfL levels to identify an aMCI-like profile among older PWH and differentiating it from HAND. We assessed the relationship between aMCI and HAND diagnosis and AD biomarker levels
Participants and Methods:
Participants included 74 PWH (Mean age=48 [SD=8.5]; 87.4% male, 56.5% White) from the National NeuroAIDS Tissue Consortium (NNTC). CSF Aß42, Aß40, p-tau and NfL were measured by commercial immunoassay. Participants completed a neurocognitive evaluation assessing the domains of learning, recall, executive function, speed of information processing, working memory, verbal fluency, and motor. Memory domains were assessed with the Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised, and aMCI was defined as impairment (<1.0 SD below normative mean) on two or more memory outcomes among HVLT-R and BVMT-R learning, delayed recall and recognition with at-least one recognition impairment required. HAND was defined as impairment (<1.0 SD below normative mean) in 2 or more cognitive domains. A series of separate linear regression models were used to examine how the levels of CSF p-tau, Aß42, p-tau/Aß42 ratio, and NfL relate to aMCI and HAND status while controlling for demographic variables (age, gender, race and education). Covariates were excluded from the model if they did not reach statistical significance.
Results:
58% percent of participants were diagnosed with HAND, 50.5% were diagnosed with aMCI. PWH with aMCI had higher levels of CSF p-tau/Aß42 ratio compared to PWH without aMCI (ß=.222, SE=.001, p=.043) while controlling for age (ß=.363, p=.001). No other AD biomarker significantly differed by aMCI or HAND status.
Conclusions:
Our results indicate that the CSF p-tau/Aß42 ratio relates specifically to an aMCI-like profile among PWH with high rates of cognitive impairment across multiple domains in this advanced HIV disease cohort. Thus, the p-tau/Aß42 ratio may have utility in disentangling aMCI from HAND and informing the need for further diagnostic procedures and intervention. Further research is needed to fully identify, among a broader group of PWH, who is at greatest risk for aMCI/AD and whether there is increased risk for aMCI/AD among PWH as compared to those without HIV.
Among people with HIV (PWH), the apolipoprotein e4 (APOE-e4) allele, a genetic marker associated with Alzheimer’s disease (AD), and self-reported family history of dementia (FHD), considered a proxy for higher AD genetic risk, are independently associated with worse neurocognition. However, research has not addressed the potential additive effect of FHD and APOE-e4 on global and domain-specific neurocognition among PWH. Thus, the aim of the current investigation is to examine the associations between FHD, APOE-e4, and neurocognition among PWH.
Participants and Methods:
283 PWH (Mage=50.9; SDage=5.6) from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study completed comprehensive neuropsychological and neuromedical evaluations and underwent APOE genotyping. APOE status was dichotomized into APOE-e4+ and APOE-e4-. APOE-e4+ status included heterozygous and homozygous carriers. Participants completed a free-response question capturing FHD of a first- or second-degree relative (i.e., biologic parent, sibling, children, grandparent, grandchild, uncle, aunt, nephew, niece, half-sibling). A dichotomized (yes/no), FHD variable was used in analyses. Neurocognition was measured using global and domain-specific demographically corrected (i.e., age, education, sex, race/ethnicity) T-scores. t-tests were used to compare global and domain-specific demographically-corrected T-scores by FHD status and APOE-e4 status. A 2x2 factorial analysis of variance (ANOVA) was used to model the interactive effects of FHD and APOE-e4 status. Tukey’s HSD test was used to follow-up on significant ANOVAs.
Results:
Results revealed significant differences by FHD status in executive functioning (t(281)=-2.3, p=0.03) and motor skills (t(278)=-2.0, p=0.03) such that FHD+ performed worse compared to FHD-. Differences in global neurocognition by FHD status approached significance (t(281)=-1.8, p=.069). Global and domain-specific neurocognitive performance were comparable among APOE-e4 carriers and noncarriers (ps>0.05). Results evaluating the interactive effects of FHD and APOE-e4 showed significant differences in motor skills (F(3)=2.7, p=0.04) between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups such that the FHD+/APOE-e4- performed worse than the FHD-/APOE-e4+ group (p=0.02).
Conclusions:
PWH with FHD exhibited worse neurocognitive performance within the domains of executive functioning and motor skills, however, there were no significant differences in neurocognition between APOE-e4 carriers and noncarriers. Furthermore, global neurocognitive performance was comparable across FHD/APOE-e4 groups. Differences between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups in motor skills were likely driven by FHD status, considering there were no independent effects of APOE-e4 status. This suggests that FHD may be a predispositional risk factor for poor neurocognitive performance among PWH. Considering FHD is easily captured through self-report, compared to blood based APOE-e4 status, PWH with FHD should be more closely monitored. Future research is warranted to address the potential additive effect of FHD and APOE-e4 on rates of global and domain-specific neurocognitive decline and impairment over time among in an older cohort of PWH, where APOE-e4 status may have stronger effects.
Many people with HIV (PWH) are at risk for age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Studies on the association between cognition, neuroimaging outcomes, and the Apolipoprotein E4 (APOE4) genotype, which is associated with greater risk of AD, have yielded mixed results in PWH; however, many of these studies have examined a wide age range of PWH and have not examined APOE by race interactions that are observed in HIV-negative older adults. Thus, we examined how APOE status relates to cognition and medial temporal lobe (MTL) structures (implicated in AD pathogenesis) in mid- to older-aged PWH. In exploratory analyses, we also examined race (African American (AA)/Black and non-Hispanic (NH) White) by APOE status interactions on cognition and MTL structures.
Participants and Methods:
The analysis included 88 PWH between the ages of 45 and 68 (mean age=51±5.9 years; 86% male; 51% AA/Black, 38% NH-White, 9% Hispanic/Latinx, 2% other) from the CNS HIV Antiretroviral Therapy Effects Research multi-site study. Participants underwent APOE genotyping, neuropsychological testing, and structural MRI; APOE groups were defined as APOE4+ (at least one APOE4 allele) and APOE4- (no APOE4 alleles). Eighty-nine percent of participants were on antiretroviral therapy, 74% had undetectable plasma HIV RNA (<50 copies/ml), and 25% were APOE4+ (32% AA/Black/15% NH-White). Neuropsychological testing assessed seven domains, and demographically-corrected T-scores were calculated. FreeSurfer 7.1.1 was used to measure MTL structures (hippocampal volume, entorhinal cortex thickness, and parahippocampal thickness) and the effect of scanner was regressed out prior to analyses. Multivariable linear regressions tested the association between APOE status and cognitive and imaging outcomes. Models examining cognition covaried for comorbid conditions and HIV disease characteristics related to global cognition (i.e., AIDS status, lifetime methamphetamine use disorder). Models examining the MTL covaried for age, sex, and
relevant imaging covariates (i.e., intracranial volume or mean cortical thickness).
Results:
APOE4+ carriers had worse learning (ß=-0.27, p=.01) and delayed recall (ß=-0.25, p=.02) compared to the APOE4- group, but APOE status was not significantly associated with any other domain (ps>0.24). APOE4+ status was also associated with thinner entorhinal cortex (ß=-0.24, p=.02). APOE status was not significantly associated with hippocampal volume (ß=-0.08, p=0.32) or parahippocampal thickness (ß=-0.18, p=.08). Lastly, race interacted with APOE status such that the negative association between APOE4+ status and cognition was stronger in NH-White PWH as compared to AA/Black PWH in learning, delayed recall, and verbal fluency (ps<0.05). There were no APOE by race interactions for any MTL structures (ps>0.10).
Conclusions:
Findings suggest that APOE4 carrier status is associated with worse episodic memory and thinner entorhinal cortex in mid- to older-aged PWH. While APOE4+ groups were small, we found that APOE4 carrier status had a larger association with cognition in NH-White PWH as compared to AA/Black PWH, consistent with studies demonstrating an attenuated effect of APOE4 in older AA/Black HIV-negative older adults. These findings further highlight the importance of recruiting diverse samples and suggest exploring other genetic markers (e.g., ABCA7) that may be more predictive of AD in some races to better understand AD risk in diverse groups of PWH.