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Data in social and behavioral sciences typically possess heavy tails. Structural equation modeling is commonly used in analyzing interrelations among variables of such data. Classical methods for structural equation modeling fit a proposed model to the sample covariance matrix, which can lead to very inefficient parameter estimates. By fitting a structural model to a robust covariance matrix for data with heavy tails, one generally gets more efficient parameter estimates. Because many robust procedures are available, we propose using the empirical efficiency of a set of invariant parameter estimates in identifying an optimal robust procedure. Within the class of elliptical distributions, analytical results show that the robust procedure leading to the most efficient parameter estimates also yields a most powerful test statistic. Examples illustrate the merit of the proposed procedure. The relevance of this procedure to data analysis in a broader context is noted.
Data are ipsative if they are subject to a constant-sum constraint for each individual. In the present study, ordinal ipsative data (OID) are defined as the ordinal rankings across a vector of variables. It is assumed that OID are the manifestations of their underlying nonipsative vector y, which are difficult to observe directly. A two-stage estimation procedure is suggested for the analysis of structural equation models with OID. In the first stage, the partition maximum likelihood (PML) method and the generalized least squares (GLS) method are proposed for estimating the means and the covariance matrix of Acy, where Ac is a known contrast matrix. Based on the joint asymptotic distribution of the first stage estimator and an appropriate weight matrix, the generalized least squares method is used to estimate the structural parameters in the second stage. A goodness-of-fit statistic is given for testing the hypothesized covariance structure. Simulation results show that the proposed method works properly when a sufficiently large sample is available.
Inappropriate diagnosis and treatment of urinary tract infections (UTIs) contribute to antibiotic overuse. The Inappropriate Diagnosis of UTI (ID-UTI) measure uses a standard definition of asymptomatic bacteriuria (ASB) and was validated in large hospitals. Critical access hospitals (CAHs) have different resources which may make ASB stewardship challenging. To address this inequity, we adapted the ID-UTI metric for use in CAHs and assessed the adapted measure’s feasibility, validity, and reliability.
Design:
Retrospective observational study
Participants:
10 CAHs
Methods:
From October 2022 to July 2023, CAHs submitted clinical information for adults admitted or discharged from the emergency department who received antibiotics for a positive urine culture. Feasibility of case submission was assessed as the number of CAHs achieving the goal of 59 cases. Validity (sensitivity/specificity) and reliability of the ID-UTI definition were assessed by dual-physician review of a random sample of submitted cases.
Results:
Among 10 CAHs able to participate throughout the study period, only 40% (4/10) submitted >59 cases (goal); an additional 3 submitted >35 cases (secondary goal). Per the ID-UTI metric, 28% (16/58) of cases were ASB. Compared to physician review, the ID-UTI metric had 100% specificity (ie all cases called ASB were ASB on clinical review) but poor sensitivity (48.5%; ie did not identify all ASB cases). Measure reliability was high (93% [54/58] agreement).
Conclusions:
Similar to measure performance in non-CAHs, the ID-UTI measure had high reliability and specificity—all cases identified as ASB were considered ASB—but poor sensitivity. Though feasible for a subset of CAHs, barriers remain.
Asymptomatic bacteriuria (ASB) treatment is a common form of antibiotic overuse and diagnostic error. Antibiotic stewardship using the inappropriate diagnosis of urinary tract infection (ID-UTI) measure has reduced ASB treatment in diverse hospitals. However, critical access hospitals (CAHs) have differing resources that could impede stewardship. We aimed to determine if stewardship including the ID-UTI measure could reduce ASB treatment in CAHs.
Methods:
From October 2022 to July 2023, ten CAHs participated in an Intensive Quality Improvement Cohort (IQIC) program including 3 interventions to reduce ASB treatment: 1) learning labs (ie, didactics with shared learning), 2) mentoring, and 3) data-driven performance reports including hospital peer comparison based on the ID-UTI measure. To assess effectiveness of the IQIC program, change in the ID-UTI measure (ie, percentage of patients treated for a UTI who had ASB) was compared to two non-equivalent control outcomes (antibiotic duration and unjustified fluoroquinolone use).
Results:
Ten CAHs abstracted a total of 608 positive urine culture cases. Over the cohort period, the percentage of patients treated for a UTI who had ASB declined (aOR per month = 0.935, 95% CI: 0.873, 1.001, P = 0.055) from 28.4% (range across hospitals, 0%-63%) in the first to 18.6% (range, 0%-33%) in the final month. In contrast, antibiotic duration and unjustified fluoroquinolone use were unchanged (P = 0.768 and 0.567, respectively).
Conclusions:
The IQIC intervention, including learning labs, mentoring, and performance reports using the ID-UTI measure, was associated with a non-significant decrease in treatment of ASB, while control outcomes (duration and unjustified fluoroquinolone use) did not change.
Previous studies in rodents suggest that mismatch between fetal and postnatal nutrition predisposes individuals to metabolic diseases. We hypothesized that in nonhuman primates (NHP), fetal programming of maternal undernutrition (MUN) persists postnatally with a dietary mismatch altering metabolic molecular systems that precede standard clinical measures. We used unbiased molecular approaches to examine response to a high fat, high-carbohydrate diet plus sugar drink (HFCS) challenge in NHP juvenile offspring of MUN pregnancies compared with controls (CON). Pregnant baboons were fed ad libitum (CON) or 30% calorie reduction from 0.16 gestation through lactation; weaned offspring were fed chow ad libitum. MUN offspring were growth restricted at birth. Liver, omental fat, and skeletal muscle gene expression, and liver glycogen, muscle mitochondria, and fat cell size were quantified. Before challenge, MUN offspring had lower body mass index (BMI) and liver glycogen, and consumed more sugar drink than CON. After HFCS challenge, MUN and CON BMIs were similar. Molecular analyses showed HFCS response differences between CON and MUN for muscle and liver, including hepatic splicing and unfolded protein response. Altered liver signaling pathways and glycogen content between MUN and CON at baseline indicate in utero programming persists in MUN juveniles. MUN catchup growth during consumption of HFCS suggests increased risk of obesity, diabetes, and cardiovascular disease. Greater sugar drink consumption in MUN demonstrates altered appetitive drive due to programming. Differences in blood leptin, liver glycogen, and tissue-specific molecular response to HFCS suggest MUN significantly impacts juvenile offspring ability to manage an energy rich diet.
Awareness of health disparities’ impact on clinical outcomes is increasing. However, public health’s ability to highlight these trends can be limited by data missingness, such as on race and ethnicity. To better understand race and ethnicity’s impact, we compared all-cause 30-day mortality rates between non-Hispanic (NH) Black, NH White, and Hispanic/NH other racial and ethnic patients among cases of carbapenem-resistant Enterobacterales (CRE).
Methods:
We performed data linkage using CRE statewide surveillance, Hospital Discharge Data System, and vital records data to obtain demographics and clinical outcomes on CRE cases in TN. We evaluated the association between race and ethnicity with all-cause 30-day mortality among CRE cases.
Results:
Among 2,804 reported CRE cases from 2015 to 2019, 65% (n = 1,832) were missing race and ethnicity; data linkage methods reduced missingness to 10% (n = 285). 22%, 74%, and 3% of cases were among NH Black, NH White, and Hispanic/NH other patients, respectively. Thirty-day all-cause mortality among NH Black patients was 5.7 per 100,000 population, 1.9 and 5.7 times higher than NH White and Hispanic/NH other patients. We observed that the risk of dying within 30 days of CRE diagnosis was 35% higher for NH Black compared to NH White patients; unmeasured confounders may be present (adjusted risk ratio 1.35; 95% CI 1.00, 1.83).
Conclusion:
Data linkage effectively reduced missingness of race and ethnicity. Among those with CRE, NH Blacks may have an increased risk of all-cause 30-day mortality. Data missingness creates barriers in identifying health disparities; data linkage is one approach to overcome this challenge.
Future events can spring to mind unbidden in the form of involuntary mental images also known as ‘flashforwards’, which are deemed important for understanding and treating emotional distress. However, there has been little exploration of this form of imagery in youth, and even less so in those with high psychopathology vulnerabilities (e.g. due to developmental differences associated with neurodiversity or maltreatment).
Aims:
We aimed to test whether flashforwards are heightened (e.g. more frequent and emotional) in autistic and maltreatment-exposed adolescents relative to typically developing adolescents. We also explored their associations with anxiety/depression symptoms.
Method:
A survey including measures of flashforward imagery and mental health was completed by a group of adolescents (n=87) aged 10–16 (and one of their caregivers) who met one of the following criteria: (i) had a diagnosis of autism spectrum disorder; (ii) a history of maltreatment; or (ii) no autism/maltreatment.
Results:
Flashforwards (i) were often of positive events and related to career, education and/or learning; with phenomenological properties (e.g. frequency and emotionality) that were (ii) not significantly different between groups; but nevertheless (iii) associated with symptoms of anxiety across groups (particularly for imagery emotionality), even after accounting for general trait (non-future) imagery vividness.
Conclusions:
As a modifiable cognitive risk factor, flashforward imagery warrants further consideration for understanding and improving mental health in young people. This implication may extend to range of developmental backgrounds, including autism and maltreatment.
Auditory verbal hallucinations (AVHs) in schizophrenia have been suggested to arise from failure of corollary discharge mechanisms to correctly predict and suppress self-initiated inner speech. However, it is unclear whether such dysfunction is related to motor preparation of inner speech during which sensorimotor predictions are formed. The contingent negative variation (CNV) is a slow-going negative event-related potential that occurs prior to executing an action. A recent meta-analysis has revealed a large effect for CNV blunting in schizophrenia. Given that inner speech, similar to overt speech, has been shown to be preceded by a CNV, the present study tested the notion that AVHs are associated with inner speech-specific motor preparation deficits.
Objectives
The present study aimed to provide a useful framework for directly testing the long-held idea that AVHs may be related to inner speech-specific CNV blunting in patients with schizophrenia. This may hold promise for a reliable biomarker of AVHs.
Methods
Hallucinating (n=52) and non-hallucinating (n=45) patients with schizophrenia, along with matched healthy controls (n=42), participated in a novel electroencephalographic (EEG) paradigm. In the Active condition, they were asked to imagine a single phoneme at a cue moment while, precisely at the same time, being presented with an auditory probe. In the Passive condition, they were asked to passively listen to the auditory probes. The amplitude of the CNV preceding the production of inner speech was examined.
Results
Healthy controls showed a larger CNV amplitude (p = .002, d = .50) in the Active compared to the Passive condition, replicating previous results of a CNV preceding inner speech. However, both patient groups did not show a difference between the two conditions (p > .05). Importantly, a repeated measure ANOVA revealed a significant interaction effect (p = .007, ηp2 = .05). Follow-up contrasts showed that healthy controls exhibited a larger CNV amplitude in the Active condition than both the hallucinating (p = .013, d = .52) and non-hallucinating patients (p < .001, d = .88). No difference was found between the two patient groups (p = .320, d = .20).
Conclusions
The results indicated that motor preparation of inner speech in schizophrenia was disrupted. While the production of inner speech resulted in a larger CNV than passive listening in healthy controls, which was indicative of the involvement of motor planning, patients exhibited markedly blunted motor preparatory activity to inner speech. This may reflect dysfunction in the formation of corollary discharges. Interestingly, the deficits did not differ between hallucinating and non-hallucinating patients. Future work is needed to elucidate the specificity of inner speech-specific motor preparation deficits with AVHs. Overall, this study provides evidence in support of atypical inner speech monitoring in schizophrenia.
Adolescents with depression have distinct affective reactions to daily events, but current research is controversial. The emotional context insensitivity theory suggests blunted reactivity in depression, whereas the hypotheses of negative potentiation and mood brightening effect suggest otherwise. While nonlinear associations between depression severity and affective reactivity have been observed, studies with a separate subclinical group remain rare. Subthreshold depression (SD), defined by two to four symptoms lasting for two weeks or more, provides a dimensional view to the underpinnings of affective reactivity. In this study, we compared positive affect (PA) and negative affect (NA) reactivity to positive and negative daily events (uplifts and stress) among adolescents with Major Depressive Disorder (MDD), SD and healthy controls (HC) using experience sampling methods (ESM).
Objectives
We hypothesized a stepped difference in affective reactivity along the depression spectrum: the MDD group will have the strongest reactivity of PA and NA to uplifts and stress, followed by SD and HC.
Methods
Three groups (MDD, SD, and HC) of adolescents were recruited from an epidemiologic sample entitled ‘Hong Kong Child and Adolescent Psychiatric Epidemiologic Survey: Age 6 to 17’. Group status was determined by the Diagnostic Interview Schedule for Children Version 5. They completed an experience sampling diary on smartphone for 14 consecutive days, with 5-10 entries per day. Momentary levels of PA (happy, relaxed, contented), NA (irritated, low, nervous), uplifts and stress experienced before the entry were measured on a 1-7 Likert scale.
Results
The sample consisted of 19 adolescents with MDD, 30 with SD, and 59 HC. The M:F ratio was 17:19. The age range was 12-18 with a mean of 14.8. The overall ESM completion rate was 46%. The MDD group had the highest levels of stress and NA, and the lowest levels of uplifts and PA, followed by the SD and HC groups respectively (p<0.01). Across groups, levels of PA were positively associated with uplifts and negatively associated with stress, whereas levels of NA were positively associated with stress and negatively associated with uplifts. The Group x Uplift interaction effect on PA was significant, with greater PA reactivity in SD (p<0.01) and MDD (p=0.07) when compared with HC. The Group x Uplift interaction effect on NA was significant, with greater NA reactivity in SD than HC (p<0.01). The Group x Stress interaction effect on PA was significant, with greater PA reactivity in SD than HC (p<0.01) and MDD (p<0.01). The Group x Stress interaction effect with NA is non-significant.
Conclusions
Contrary to our hypothesis, adolescents with SD experienced strongest PA and NA reactivity in uplifts and PA reactivity in stress. It provides evidence towards a nonlinear relationship between severity of depression and affective reactivity.
Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.
Methods
Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11–36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.
Results
Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).
Conclusions
Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.
The prevalence of childhood obesity is increasing globally(1). While BMI is commonly used to define obesity, it is unable to differentiate between fat and muscle mass, leading to calls to measure body composition specifically(2). While several tools are available to assess body composition in infancy, it is unclear if they are directly comparable. Among a subset of healthy infants born to mothers participating in a randomised controlled trial of a preconception and antenatal nutritional supplement(3), measurements were made at ages 6 weeks (n = 58) and 6 months (n = 70) using air displacement plethysmography (ADP), whole-body dual-energy X-ray absorptiometry (DXA), and bioelectrical impedance spectroscopy (BIS). Estimates of percentage fat mass (%FM) were compared using Cohen’s kappa statistic (κ) and Bland-Altman analysis (4,5). There was none to weak agreement when comparing tertiles of %FM (κ = 0.15–0.59). When comparing absolute values, the bias (i.e., mean difference) was smallest when comparing BIS to ADP at 6 weeks (+1.7%). A similar bias was observed at 6 months when comparing DXA to ADP (+1.8%). However, when comparing BIA to DXA at both ages, biases were much larger (+7.6% and +4.7% at 6 weeks and 6 months, respectively). Furthermore, there was wide interindividual variance (limits of agreement [LOA] i.e., ± 1.96 SD) for each comparison. At 6 weeks, LOA ranged from ± 4.8 to ± 6.5% for BIA vs. DXA and BIA vs. ADP, respectively. At 6 months, LOA were even wider, ranging from ± 7.3 to ± 8.1% (DXA vs. ADP and BIA vs. DXA, respectively). Proportional biases were apparent when comparing BIS to the other tools at both ages, with BIS generally overestimating %FM more among infants with low adiposity. In addition to differences according to tool type, within-tool factors impacted body composition estimation. For ADP measurements, the choice of FFM density reference (Fomon vs. Butte) had minimal impact; however, choice of DXA software version (GE Lunar enCORE basic vs. enhanced) and BIS analysis approach (empirical equation vs. mixture theory prediction) led to very different estimates of body composition. In conclusion, when comparing body composition assessment tools in infancy, there was limited agreement between three commonly used tools. Therefore, researchers and clinicians must be cautious when conducting longitudinal analyses or when comparing findings across studies, as estimates are not comparable across tools.
Previous studies suggest that influenza virus infection may provide temporary non-specific immunity and hence lower the risk of non-influenza respiratory virus infection. In a randomized controlled trial of influenza vaccination, 1 330 children were followed-up in 2009–2011. Respiratory swabs were collected when they reported acute respiratory illness and tested against influenza and other respiratory viruses. We used Poisson regression to compare the incidence of non-influenza respiratory virus infection before and after influenza virus infection. Based on 52 children with influenza B virus infection, the incidence rate ratio (IRR) of non-influenza respiratory virus infection after influenza virus infection was 0.47 (95% confidence interval: 0.27–0.82) compared with before infection. Simulation suggested that this IRR was 0.87 if the temporary protection did not exist. We identified a decreased risk of non-influenza respiratory virus infection after influenza B virus infection in children. Further investigation is needed to determine if this decreased risk could be attributed to temporary non-specific immunity acquired from influenza virus infection.
Simple equations are presented which allow double-layer potentials of clays to be derived from co-ion exclusion measurements in monovalent and divalent electrolyte solutions. These equations have been used to re-interpret earlier results for illite and montmorillonite. The potentials derived follow the lyotropic series for the various homoionic modification of each clay. We have demonstrated that the Schofield equation, which assumes high double-layer potentials, cannot be applied to co-ion exclusion in clay systems. Re-analysis of earlier measurements has shown that for a given homoionic clay the potentials are almost independent of concentration over the range 0.3 to 0.003 molar. Thus, clay surfaces appear to behave more like constant-potential than constant-charge surfaces.
Population-wide restrictions during the COVID-19 pandemic may create barriers to mental health diagnosis. This study aims to examine changes in the number of incident cases and the incidence rates of mental health diagnoses during the COVID-19 pandemic.
Methods
By using electronic health records from France, Germany, Italy, South Korea and the UK and claims data from the US, this study conducted interrupted time-series analyses to compare the monthly incident cases and the incidence of depressive disorders, anxiety disorders, alcohol misuse or dependence, substance misuse or dependence, bipolar disorders, personality disorders and psychoses diagnoses before (January 2017 to February 2020) and after (April 2020 to the latest available date of each database [up to November 2021]) the introduction of COVID-related restrictions.
Results
A total of 629,712,954 individuals were enrolled across nine databases. Following the introduction of restrictions, an immediate decline was observed in the number of incident cases of all mental health diagnoses in the US (rate ratios (RRs) ranged from 0.005 to 0.677) and in the incidence of all conditions in France, Germany, Italy and the US (RRs ranged from 0.002 to 0.422). In the UK, significant reductions were only observed in common mental illnesses. The number of incident cases and the incidence began to return to or exceed pre-pandemic levels in most countries from mid-2020 through 2021.
Conclusions
Healthcare providers should be prepared to deliver service adaptations to mitigate burdens directly or indirectly caused by delays in the diagnosis and treatment of mental health conditions.
Persons newly diagnosed with dementia and their family member is imperative often experience uncertainty and inadequate support. This study aims to evaluate a post-diagnostic support programme guided by the 5 Pillars Model proposed by Alzheimer Scotland on the self-efficacy among persons with early dementia and their family members.
Methods:
A prospective cohort study design was conducted between 2019 and 2022. Subject recruitment was conducted in four non-government organizations. A multi-domain empowerment programme, covering various aspects about dementia knowledge, management skills, peer support, future decision-making and community resources, was developed. The programme was provided to people newly diagnosed of early dementia in small group format over 2 months and to family members individually through an eLearning platform over 9 months. Self efficacy in dementia management of people with dementia and their family members were measured using Chronic Disease Self-efficacy Scale and Caregiver Self-efficacy Scale (CSES), respectively, whereas caregiving burden was measured using Zarit Burden Interview (ZBI). Study outcomes were measured at baseline, immediate and 6-month post-intervention. Paired t-tests were performed to detect within-subject changes over time.
Results:
A total of 151 persons with early dementia and 294 family caregivers completed assessment at baseline and follow up. Self-efficacy in dementia management reported by persons with dementia at 6-month post-intervention was significantly higher than that reported at baseline (p = .021) and immediate post-intervention (i.e. 2-month follow up) (p = .006). Family members reported a significantly higher CSES score (p < .001) and subscale scores in thoughts (p = .001) and disruptive behaviour management (p = .001) at 9-month follow up, but significant reduction in caregiving burden (p < .001) was only noted among those who perceived higher burden than the local norms at baseline (ZBI score ≥ 25, n = 110).
Discussion:
This study provides empirical evidence that post-diagnostic support would empower persons with early dementia and their family members on adapting the impacts brought by dementia. Further study on examining the longer term effects on care outcomes and health service utilisation would be valuable.
People with dementia are more prone to premature nursing home placement after hospitalization due to physical and mental deconditioning which makes care-at- home more difficult. This study aimed to evaluate the effect of a post hospital discharge transitional care program on reduction of nursing home placement in people with dementia.
Methods:
A matched case-control study was conducted between 2018 and 2021. A transitional care program using case management approach was developed. Participants enrolled the program by self-enrolment or referral from hospitals or NGOs. Community-dwelling people with dementia discharged from hospitals received a four- week residential care at a dementia care centre with intensive nursing care, physiotherapy and group activities promoting social engagement, followed by eight- week day care rehabilitation activities to improve their mobility and cognitive functioning. They were matched on a 1:5 ratio by age and sex to people with dementia discharged from a convalescent hospital who did not participate in this program for comparison. The study outcome was nursing home admission, measured three months (i.e. post-intervention), six months, and nine months after hospital discharge. Multinomial logistic regression was conducted to investigate factors associated with nursing home placement at each measurement time-point.
Results:
361 hospital admission episodes (n=67 interevntion, n=294 control) were examined. The regression results showed that participants in the intervention group were significantly less likely to be admitted to nursing home three months (OR = 0.023, 95% CI: 0.003-0.201, p = .001) and six months (OR = 0.094, 95% CI: 0.025-0.353, p = .001) than the controls after hospital discharge, but the intervention effect did not sustain nine months after hospital discharge. Longer hospital length of stay, and hospital admission due to dementia, mental disturbances such as delirium, or mental disorders IPA_Abstract_PDP_20230119_clean 2 such as schizophrenia significantly predicted nursing home admission three months and six months after hospital discharge.
Conclusion:
The transitional care program could help reduce nursing home placement in people with dementia after hospital discharge. To sustain the intervention effect, more continual support after the intervention as well as family caregiver training would be required.
Attention-deficit/hyperactivity disorder (ADHD) symptoms are associated with myriad adverse outcomes, including interpersonal difficulties, but factors that moderate the developmental course and functional impact of ADHD over time are not well understood. The present study evaluated developmental contributions of the triarchic neurobehavioral traits (boldness, meanness, and disinhibition) to ADHD symptomatology and its subdimensions from adolescence to young adulthood. Participants were twins and triplets assessed at ages 14, 17, and 19 (initial N = 1,185, 51.2% female). Path analyses using negative binomial regression revealed that boldness at age 14 was associated with more ADHD symptoms cross-sectionally (especially hyperactivity/impulsivity), but fewer symptoms (especially inattention) at age 19 in the prospective analysis. Notably, inclusion of interpersonal problems at ages 14 and 17 as covariates reduced the latter effect to nonsignificant. Disinhibition concurrently and prospectively predicted higher levels of ADHD symptoms, including both subdimensions, and the prospective effects were partially mediated by greater social impairment at age 17. Meanness prospectively (but not concurrently) predicted higher levels of hyperactivity/impulsivity symptoms. Sex moderated certain associations of meanness and disinhibition with ADHD symptoms. These findings highlight how fundamental neurobehavioral traits shape both psychopathology and adaptive outcomes in the developmental course of ADHD.
The current research framework recommends using biomarkers to further understand Alzheimer’s disease (AD) pathogenesis, including other contributing factors like cerebrovascular disease. In longitudinal studies of people with neuropathological examination after death, baseline loneliness was associated with lower cognition, faster cognitive decline, and future AD risk, independent of AD pathology. Examination of memory impairment along with AD and cerebrovascular biomarkers, could aid risk reduction efforts earlier in the lifecourse and among populations with more exposure to loneliness. We hypothesized that loneliness is associated with amyloid, vascular, and neurodegeneration biomarkers; with worse memory; and that loneliness increases the susceptibility to biomarker-related memory impairment.
Participants and Methods:
A subset of cognitively unimpaired older adults with available amyloid PET, vascular MRI (white matter hyperintensity volume, WMH), structural MRI (cortical thickness in AD signature regions), neuropsychological testing (memory factor score), dichotomized loneliness data (one item from CES-D), and relevant medical data were drawn from the community-based Washington Heights-Inwood Columbia Aging Project (WHICAP; n=169; covariates included age=81±6 years; 63% women; 49/31/20% Non-Hispanic Black/Non-Hispanic White/Hispanic; education=13±4 years; 32% APOE-e4 carriers). General linear models in the overall sample and stratified by race and ethnicity tested the association between loneliness and AD and cerebrovascular biomarkers, loneliness and memory, and the interaction of loneliness and biomarkers on memory, adjusting for covariates.
Results:
Loneliness was endorsed in 18% of participants, marginally associated with older age (2.1 [-0.2, 4.4], p=0.08), was more likely in those with untreated diabetes (13/0.1% lonely/not lonely, p=0.001), associated with lower cortical thickness (-0.05 [-0.09, -0.02], p=0.01), and associated with lower memory (0.3 [-0.6, -0.001], p=0.05). In Non-Hispanic White participants, loneliness was associated with greater WMH volume (0.5 [0.07, 0.82], p=0.03), while in Hispanic participants, loneliness was associated with lower cortical thickness (-0.16 [-0.24, -0.08], p=0.0006). In Non-Hispanic Black participants, loneliness was associated with lower memory (-13 [-26, -0.5], p=0.05), and the association between lower cortical thickness and lower memory was stronger in those that endorse loneliness (5 [0.2, 10], p=0.05). In Hispanic participants, loneliness was associated with higher memory (13 [4, 22], p=0.009), but the association between higher amyloid burden and lower memory was stronger in those that endorse loneliness (-12 [-20, -4], p=0.006); further, loneliness was marginally associated with lower memory (-0.7 [-1.4, 0.1], p=0.09), independently of WMH.
Conclusions:
Associations between loneliness and biomarkers may relate to health seeking behavior, reported as treatment status for diabetes, for cerebrovascular burden and general neurodegeneration, but might be more complex for amyloid. The degree to which loneliness increased the susceptibility to amyloid and neurodegeneration-related, but not cerebrovascular-related, memory impairment, specifically, may suggest that domains beyond memory should be considered. Future work should be longitudinal to disentangle the effects of loneliness from related constructs like depression and anxiety, incorporate other AD biomarkers such as hyperphosphorylated tau, and incorporate biological mechanisms (e.g., stress, inflammation) into models of loneliness and AD pathogenesis. Older adults from all backgrounds may be more susceptible to loneliness, which was associated with lower memory; culturally-humble, social support-based interventions may reduce the risk of cognitive impairment.
Early identification of individuals at risk for dementia provides an opportunity for risk reduction strategies. Many older adults (30-60%) report specific subjective cognitive complaints, which has also been shown to increase risk for dementia. The purpose of this study is to identify whether there are particular types of complaints that are associated with future: 1) progression from a clinical diagnosis of normal to impairment (either Mild Cognitive impairment or dementia) and 2) longitudinal cognitive decline.
Participants and Methods:
415 cognitively normal older adults were monitored annually for an average of 5 years. Subjective cognitive complaints were measured using the Everyday Cognition Scales (ECog) across multiple cognitive domains (memory, language, visuospatial abilities, planning, organization and divided attention). Cox proportional hazards models were used to assess associations between self-reported ECog items at baseline and progression to impairment. A total of 114 individuals progressed to impairment over an average of 4.9 years (SD=3.4 years, range=0.8-13.8). A subset of individuals (n=352) underwent repeat cognitive assessments for an average of 5.3 years. Mixed effects models with random intercepts and slopes were used to assess associations between baseline ECog items and change in episodic memory or executive function on the Spanish and English Neuropsychological Assessment Scales. Time in years since baseline, the ECog items, and the interaction were key terms of interest in the models. Separate models for both the progression analyses and mixed effects models were fit for each ECog item that included age at the baseline visit, gender, and years of education as covariates.
Results:
More complaints on five of the eight memory items, three of the nine language items, one of the seven visuospatial items, two of the five planning items, and one of the six organization items were associated with progression to impairment (HR=1.25 to 1.59, ps=0.003 to 0.03). No items from the divided attention domain were significantly associated with progression to impairment. In individuals reporting no difficulty on ECog items at the baseline visit there was no significant change over time in episodic memory(p>0.4). More complaints on seven of the eight memory items, two of the nine language items, and three of the seven visuospatial items were associated with more decline in episodic memory (ps=0.003 to 0.04). No items from the planning, organization, or divided attention domains were significantly associated with episodic memory decline. Among those reporting no difficulty on ECog items at the baseline visit there was slight decline in executive function (ps=<0.001 to 0.06). More complaints on three of the eight memory items and three of the nine language items were associated with decline in executive function (ps=0.002 to 0.047). No items from the visuospatial, planning, organization, or divided attention domains were significantly associated with decline in executive function.
Conclusions:
These findings suggest that, among cognitively normal older adults at baseline, specific complaints across several cognitive domains are associated with progression to impairment. Complaints in the domains of memory and language are associated with decline in both episodic memory and executive function.