Predeath grief conceptualizes complex feelings of loss experienced for someone who is still living and is linked to poor emotional well-being. The Road Less Travelled program aimed to help carers of people with rarer dementias identify and process predeath grief. This study evaluated the feasibility, acceptability, and preliminary effectiveness of this program.

Pre–post interventional mixed methods study.

Online videoconference group program for carers across the UK held in 2021.

Nine family carers of someone living with a rare form of dementia. Eight were female and one male (mean age 58) with two facilitators.

The Road Less Travelled is an online, facilitated, group-based program that aims to help carers of people with rarer dementias to explore and accept feelings of grief and loss. It involved six fortnightly 2-hour sessions.

We collected measures for a range of well-being outcomes at baseline (T1), post-intervention (T2), and 3 months post-intervention (T3). We conducted interviews with participants and facilitators at T2.

Participant attendance was 98% across all sessions. Findings from the semistructured interviews supported the acceptability of the program and identified improvements in carer well-being. Trends in the outcome measures suggested an improvement in quality of life and a reduction in depression.

The program was feasible to conduct and acceptable to participants. Qualitative reports and high attendance suggest perceived benefits to carers, including increased acceptance of grief, and support the need for a larger-scale pilot study to determine effectiveness.

Neurological involvement associated with SARS-CoV-2 infection is increasingly recognized. However, the specific characteristics and prevalence in pediatric patients remain unclear. The objective of this study was to describe the neurological involvement in a multinational cohort of hospitalized pediatric patients with SARS-CoV-2.

This was a multicenter observational study of children <18 years of age with confirmed SARS-CoV-2 infection or multisystemic inflammatory syndrome (MIS-C) and laboratory evidence of SARS-CoV-2 infection in children, admitted to 15 tertiary hospitals/healthcare centers in Canada, Costa Rica, and Iran February 2020–May 2021. Descriptive statistical analyses were performed and logistic regression was used to identify factors associated with neurological involvement.

One-hundred forty-seven (21%) of 697 hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Headache (n = 103), encephalopathy (n = 28), and seizures (n = 30) were the most reported. Neurological signs/symptoms were significantly associated with ICU admission (OR: 1.71, 95% CI: 1.15–2.55; p = 0.008), satisfaction of MIS-C criteria (OR: 3.71, 95% CI: 2.46–5.59; p < 0.001), fever during hospitalization (OR: 2.15, 95% CI: 1.46–3.15; p < 0.001), and gastrointestinal involvement (OR: 2.31, 95% CI: 1.58–3.40; p < 0.001). Non-headache neurological manifestations were significantly associated with ICU admission (OR: 1.92, 95% CI: 1.08–3.42; p = 0.026), underlying neurological disorders (OR: 2.98, 95% CI: 1.49–5.97, p = 0.002), and a history of fever prior to hospital admission (OR: 2.76, 95% CI: 1.58–4.82; p < 0.001).

In this study, approximately 21% of hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Future studies should focus on pathogenesis and long-term outcomes in these children.

Attention Deficit / Hyperactivity Disorder (ADHD) is a highly prevalent neurodevelopmental condition characterized by inattention, motor hyperactivity and impulsivity. ADHD cognitive and behavioral presentation is characterized by a high heterogeneity (APA, 2013). Indeed, a complex diagnostic process, that considers several validated tools, is, to date, necessary.

The main aim is to develop supervised machine learning (ML) algorithms that could be used to support the diagnostic process for ADHD, by identifying the most relevant features in discriminating between the presence or absence of the ADHD diagnosis in children.

We analyzed data from 342 children (Mean age: 8y 8m ± 1y; 61 F) referred for possible ADHD symptomatology. Assessments were performed by an expert clinician and through questionnaires: Social Responsiveness Scale (SRS), Child Behavior Checklist (CBCL), Conners Rating Scale for Parents (CPRS) and for Teachers (CTRS). Data were analyzed using a decision tree classifier and random forest algorithms.

The decision tree model performed an accuracy of 0.71. The random forest model that was identified as the best tested, performed an accuracy of 0.77 (Figure 1) and it identified as most informative parent- and teacher-rated DSM-oriented ADHD symptoms (Figure 2).

Figure 1: Random forest confusion matrix and statistics.

Figure 2: Ranking of variables importance.

A random forest classifier could represent an effective algorithm to support the identification of ADHD children and to simplify the diagnostic process as an initial step. The use of supervised machine learning algorithms could be useful in helping the diagnostic process, highlighting the importance of a personalized medicine approach.

No significant relationships.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by lack of self-regulation and deficits in organizing behaviors in response to emotional stimuli. Methylphenidate (MPH) is one of the most effective psychostimulant drugs for ADHD, however, a possible predictive utility of brain hemodynamic data related to MPH administration and its relation to clinical symptomatology is still not clear. To address these questions, we used Near Infrared Spectroscopy (NIRS) technology, a non-invasive optical technique that allows to investigate the effect of psychopharmacological treatment on cortical hemodynamics.

Twenty children with ADHD underwent a three-waves study and 25 healthy controls were recruited at W1. At W2 children with ADHD received first MPH administration and at W3 they reached the titration phase. At each phase children performed - during NIRS recording - an emotional continuous performance task with visual stimuli of different emotional content. Clinical data were also collected at W1 and W3. We investigated the relationship among the difference between NIRS activation at W2 and W1 (Delta1) and W3 and W2 (Delta2), for each subject, task condition and brain region. Lastly, we investigated correlations between the Delta1 and clinical symptomatology indexes at W1 and between Delta2 and clinical data at W3.

Our study results suggest that hemodynamic changes in right prefrontal region probably induced by first MPH administration could predict hemodynamic changes related to MPH titration phase. These biological indexes could be associated to clinical evidences related not only to core ADHD symptoms but also to affective correlates.

No significant relationships.

Epigenetics hypothesizes a crucial link between postnatal risk factors, individual response to stress, DNA methylation and psychiatric symptomatology changes during life.

We analyzed methylation within two gene exons: NR3C1 and SLC6A4, which are involved in responses to environmental stressors. We investigated the relationship between methylation, postnatal risk factors and psychopathology assessed by Child Behavior Checklist (CBCL) in our help-seeking sample evaluated in infancy (W1), preadolescence (W2) and adult life (W3).

Postnatal risk factors data were collected at W1 in 205 clinical subjects (156 M, 49 F; age=9,13±1,95). The CBCL scores were collected at W1 and W2 (W2 age=14,52±2,12). Data regarding methylation were collected at W2. At W3 we are also collecting clinical scores. A Spearman correlation coefficient was calculated between methylation percentage and clinical data at W2. The externalizing and internalizing trajectories were evaluated through repeated measure ANOVA with postnatal risk factors (presence/absence) as between-groups factor.

Significant associations were found between methylation and internalizing and total clinical scores (Table 1). The rm-ANOVA results showed a significant interaction between the CBCL internalizing score and presence/absence of postnatal risk, with higher internalizing problems in subjects that were exposed to postnatal risk factors. This effect was significant at W2 but not at W1 (Figure 1).

Psychopathological symptoms trajectories could depend on epigenetics and early environmental risk factors. Further analyses will address a Linear Discriminant Analysis to proceed to a machine learning oriented approach.

No significant relationships.

Our 15-years follow-up ReMIND project aims to re-assess an epidemiological and a clinical sample of adults (Wave 3), who were assessed in preadolescence (Wave 1) and adolescence (Wave 2), to evaluate symptoms trajectories and their relationship with genetic/epigenetic data, environmental risk factors and neuroimaging measures.

Here, we depict preliminary results regarding the epidemiological sample.

We assessed internalizing and externalizing symptoms in 40 italian subjects (25 F) from general population at three waves (W1 mean age: 12±0,82; W2 mean age: 17±0,88, W3 mean age: 28±1), through the Child Behavior Checklist (W1 and W2) or the Adult Self Report (W3), and perinatal risk factors through a socio-anamnestic questionnaire, by a new online platform (MedicalBit). We analyzed symptoms trajectories and their relation with perinatal risk factors through a repeated measures multivariate analysis of variance (rm-MANOVA).

rm-MANOVA results show that high number of perinatal risks was significantly associated with higher internalizing symptomatology in preadolescence but not in adolescence and adult life. The mean difference was 8 T-points. The same trend is evident in adolescence but not in adult age (Graph 1). Perinatal risk factors did not have a significant effect on externalizing symptoms at any time point, despite a non-significant trend is evident (Graph 2).

Our preliminary results suggest a trend of increased internalizing symptoms from childhood to adulthood and a significant role of perinatal risk factors in pre-adolescence. Further investigations are necessary to better understand symptoms trajectories and the role of biological and environmental factors.

No significant relationships.

To examine the direct and indirect effects of age, APOE ϵ4 genotype, amyloid positivity, and volumetric reductions in AD-prone brain regions as it relates to semantic intrusion errors reflecting proactive semantic interference (PSI) and the failure to recover from proactive semantic interference (frPSI) on the Loewenstein-Acevedo Scales of Semantic Interference and Learning (LASSI-L), a cognitive stress test that has been consistently more predictive of preclinical and prodromal Alzheimer’s disease (AD) than traditional list-learning tests.

Cross-sectional study.

1Florida Alzheimer’s Disease Research Center baseline study.

Two-hundred and twelve participants with Mini-Mental State Examination (MMSE) score above 16 and a broad array of cognitive diagnoses ranging from cognitively normal (CN) to dementia, of whom 58% were female, mean age of 72.1 (SD 7.9).

Participants underwent extensive clinical and neuropsychological evaluations, MR and amyloid Positron Emission Tomography/Computer/Computer Tomography (PET/CT) imaging, and analyses of APOE ϵ4 genotype. Confirmatory path analyses were conducted in the structural equation modeling framework that estimated multiple equations simultaneously while controlling for important covariates such as sex, education, language of evaluation, and global cognitive impairment.

Both amyloid positivity and decreased brain volumes in AD-prone regions were directly related to LASSI-L Cued B1 and Cued B2 intrusions (sensitive to PSI and frPSI effects) even after controlling for covariates. APOE ϵ4 status did not evidence direct effects on these LASSI-L cognitive markers, but rather exerted their effects on amyloid positivity, which in turn related to PSI and frPSI. Similarly, age did not have a direct relationship with LASSI-L scores, but exerted its effects indirectly through amyloid positivity and volumes of AD-prone brain regions.

Our study provides insight into the relationships among age, APOE ϵ4, amyloid, and brain volumetric reductions as it relates to semantic intrusion errors. The investigation expands our understanding of the underpinnings of PSI and frPSI intrusions in a large cohort.

Late life suicide is an international public health crisis, yet the mechanisms underlying late life suicide risk are far less understood compared to younger age groups. Executive dysfunction is widely documented in late life depression (LLD), and cognitive flexibility and inhibition are specifically hypothesized as vulnerabilities for suicide risk. There is some evidence that LLD patients with suicidal ideation or attempt suicide have worse executive dysfunction than LLD patients that do not; however, it is unknown whether these differences exist in Passive Suicidal Ideation (PSI), which may be an important early stage of suicide risk. Delineating the mechanisms of risk for PSI in LLD is a crucial direction for late life suicide research. The purpose of our study was to examine whether cognitive flexibility and inhibitory ability are neurocognitive markers of PSI. The secondary purpose of our study was to determine if neurocognitive differences due to PSI are mediated by volumetric differences in the prefrontal cortex.

Forty community-dwelling middle- and older-aged adults with LLD (18 with PSI, 22 without) completed a neurocognitive battery that assessed cognitive flexibility, inhibitory ability, as well as other neurocognitive domains, and underwent structural neuroimaging.

The PSI group performed significantly worse on cognitive flexibility and inhibitory ability, but not on other neurocognitive tasks which included other measures of executive function. The PSI group had a larger left mid-frontal gyrus (LMFG) than those without PSI, but there was no association between LMFG and cognitive flexibility or inhibitory ability, nor was there statistical evidence of mediation.

Our findings implicate a unique neurocognitive signature in LLD with PSI: poorer cognitive flexibility and poorer inhibitory ability not better accounted for by other domains of cognitive dysfunction and not mediated by volumetric differences in the prefrontal cortex. Volumetric brain differences in the LMFG appear unrelated to differences in cognitive flexibility and inhibitory ability, which suggests two specific but independent risk factors for PSI in middle- and older-aged adults.

(1) To delineate whether cognitive flexibility and inhibitory ability are neurocognitive markers of passive suicidal ideation (PSI), an early stage of suicide risk in depression and (2) to determine whether PSI is associated with volumetric differences in regions of the prefrontal cortex (PFC) in middle-aged and older adults with depression.

Cross-sectional study.

University medical school.

Forty community-dwelling middle-aged and older adults with depression from a larger study of depression and anxiety (NIMH R01 MH091342-05 PI: O’Hara).

Psychiatric measures were assessed for the presence of a DSM-5 depressive disorder and PSI. A neurocognitive battery assessed cognitive flexibility, inhibitory ability, as well as other neurocognitive domains.

The PSI group (n = 18) performed significantly worse on cognitive flexibility and inhibitory ability, but not on other neurocognitive tasks, compared to the group without PSI (n = 22). The group with PSI had larger left mid-frontal gyri (MFG) than the no-PSI group. There was no association between cognitive flexibility/inhibitory ability and left MFG volume.

Findings implicate a neurocognitive signature of PSI: poorer cognitive flexibility and poor inhibitory ability not better accounted for by other domains of cognitive dysfunction and not associated with volumetric differences in the left MFG. This suggests that there are two specific but independent risk factors of PSI in middle- and older-aged adults.