Biological age captures physiological deterioration better than chronological age and is amenable to interventions. Blood-based biomarkers have been identified as suitable candidates for biological ...age estimation. This study aims to improve biological age estimation using machine learning models and a feature-set of 60 circulating biomarkers available from the UK Biobank (n = 306,116). We implement an Elastic-Net derived Cox model with 25 selected biomarkers to predict mortality risk (C-Index = 0.778; 95% CI 0.767-0.788), which outperforms the well-known blood-biomarker based PhenoAge model (C-Index = 0.750; 95% CI 0.739-0.761), providing a C-Index lift of 0.028 representing an 11% relative increase in predictive value. Importantly, we then show that using common clinical assay panels, with few biomarkers, alongside imputation and the model derived on the full set of biomarkers, does not substantially degrade predictive accuracy from the theoretical maximum achievable for the available biomarkers. Biological age is estimated as the equivalent age within the same-sex population which corresponds to an individual's mortality risk. Values ranged between 20-years younger and 20-years older than individuals' chronological age, exposing the magnitude of ageing signals contained in blood markers. Thus, we demonstrate a practical and cost-efficient method of estimating an improved measure of Biological Age, available to the general population.
The present study has two-fold aims: to investigate whether gender differences persist even when more time is given to acquire spatial information; to assess the gender effect when the retrieval ...phase requires recalling the pathway from the same or a different reference perspective (egocentric or allocentric). Specifically, we analyse the performance of men and women while learning a path from a map or by observing an experimenter in a real environment. We then asked them to reproduce the learned path using the same reference system (map learning vs. map retrieval or real environment learning vs. real environment retrieval) or using a different reference system (map learning vs. real environment retrieval or vice versa). The results showed that gender differences were not present in the retrieval phase when women have the necessary time to acquire spatial information. Moreover, using the egocentric coordinates (both in the learning and retrieval phase) proved easier than the other conditions, whereas learning through allocentric coordinates and then retrieving the environmental information using egocentric coordinates proved to be the most difficult. Results showed that by manipulating familiarity, gender differences disappear, or are attenuated in all conditions.
The triadic taxonomy posits that three distinct types of body representations do exist, namely the body schema (BS), which corresponds to the representation derived from multiple sensory and motor ...inputs, the body structural representation (BSR), which corresponds to the structural description of spatial relations among the body parts, and the body semantics (SEM), which corresponds to the lexical-semantic representation of the body. Although several studies have assessed neural correlates of these representations, no study has compared them in brain-damaged patients, controlling for deficits in other cognitive domains. Also, little is known about the contribution of the right hemisphere to different body representations. Here we used a computerized battery to test these three body representations in twenty-six right brain damaged patients, controlling for other cognitive deficits by means of tests tapping similar spatial and lexical processes on non-body related stimuli. Residual scores corresponding to the BS, the BSR and the SEM were used to test neural correlates, which were assessed by integrating topological and hodological approaches to lesion-deficit analyses. We found that the BSR was associated with lesion of the superior temporal gyrus, the insula, the supramarginal gyrus and the temporo-parietal junction, extending also to the Rolandic operculum and the inferior frontal gyrus. Also, it was associated with the disconnection probability of the posterior arcuate segment. The BS was associated with a small cluster of voxels in the precentral and postcentral gyri, whereas the SEM was associated with white matter lesion at the boundary between the parietal and temporal lobes. Overall, these results provide strong support to the regional and connectional contribution of the right hemisphere to body representation, and more specifically to the BSR.
•BSR was associated with regions spanning from temporal and parietal lobe.•BSR was associated with disconnection of posterior arcuate segment.•BS was associated with voxels at the boundary between pre and postcentral gyri.•Different regions and pathways contribute to different body representations.
Abstract Visual hallucinations in Lewy body disease (LBD) can be differentiated based on phenomenology into minor phenomena (MVH) and complex hallucinations (CVH). MVH include a variety of phenomena, ...such as illusions, presence and passage hallucinations occurring at early stages of LBD. The neural mechanisms of visual hallucinations are largely unknown. The hodotopic model posits that the hallucination state is due to abnormal activity in specialized visual areas, that occurs in the context of wider network connectivity alterations and that phenomenology of VH, including content and temporal characteristics, may help identify brain regions underpinning these phenomena. Here we investigated both the topological and hodological neural basis of visual hallucinations integrating grey and white matter imaging analyses. We studied LBD patients with VH and age matched healthy controls (HC). VH were assessed using a North-East-Visual-Hallucinations-Interview that captures phenomenological detail. Then we applied voxel-based morphometry and tract based spatial statistics approaches to identify grey and white matter changes. First, we compared LBD patients and HC. We found a reduced grey matter volume and a widespread damage of white tracts in LBD compared to HC. Then we tested the association between CVH and MVH and grey and white matter indices. We found that CVH duration was associated with decreased grey matter volume in the fusiform gyrus suggesting that LBD neurodegeneration-related abnormal activity in this area is responsible for CVH. An unexpected finding was that MVH severity was associated with a greater integrity of white matter tracts, specifically those connecting dorsal, ventral attention networks and visual areas. Our results suggest that networks underlying MVH need to be partly intact and functional for MVH experiences to occur, while CVH occur when cortical areas are damaged. The findings support the hodotopic view and the hypothesis that MVH and CVH relate to different neural mechanisms, with wider implications for the treatment of these symptoms in a clinical context.
Adult acute lymphoblastic leukemia (ALL) with BCR-ABL1 rearrangement (Philadelphia chromosome, Ph) is a hematological aggressive disease with a fatal outcome in more than 50% of cases. Tyrosine ...kinase inhibitors (TKIs) targeting the activity of BCR-ABL1 protein have improved the prognosis; however, relapses are frequent because of acquired somatic mutations in the BCR-ABL1 kinase domain causing resistance to first, second and third generation TKIs. Axitinib has shown in vitro and ex vivo activity in blocking ABL1; however, clinical trials exploring its efficacy in ALL are missing. Here, we presented a 77-year-old male with a diagnosis of Ph positive ALL resistant to ponatinib and carrying a rare threonine to leucine (T315L) mutation on
gene. The patient was treated with axitinib at 5 mg/twice daily as salvage therapy showing an immediate although transient benefit with an overall survival of 9.3 months. Further dose-finding and randomized clinical trials are required to assess the real efficacy of axitinib for adult Ph positive ALL resistant to third generation TKIs.
Several studies have shown that the working memory is sensitive to temporal variations. We used a new visuospatial working memory task, the "Time Squares Sequences," to investigate whether implicit ...variations in stimuli presentation time affect task performance.
A total of 50 healthy participants saw two sequences (S1 and S2) of seven white squares presented in a matrix of gray squares and assessed whether S2 matched S1. There were four conditions depending on the spatial position and the presentation time (i.e., timing) of the white squares in S1 and S2: two with the same (S1 fixed/S2 fixed and S1 variable/S2 variable) and two with different (S1 fixed/S2 variable and S1 variable/S2 fixed) presentation times.
Findings showed impaired performance when S1 had a fixed presentation time and S2 had a variable presentation time.
These findings are attributed to increased cognitive load due to S2 timing difference, pointing to a monitoring process, sensitive to temporal variations.
Visual hallucinations (VH) in Lewy body disease (LBD) have a heterogenous phenomenology classified into minor phenomena (MVH) and complex hallucinations (CVH). Mechanisms underpinning VH and their ...temporal aspects are largely unknown. According to the hodotopic model, we investigated whether changes in distinct cognitive domains and neural networks in the hallucination trait underpin temporal aspects of MVH and CVH in the hallucination state. 35 LBD patients with VH underwent a complete neuropsychological evaluation and resting-state fMRI. North-East-Visual-Hallucinations-Interview was used to assess their typical VH content, duration, and frequency. We found that MVH was not associated with cognitive impairment, while CVH was associated with impairments in visuoperceptual processes, attention and visual abstract reasoning. In seed-to-seed functional connectivity (FC) analysis we identified functional couplings associated with MVH and CVH temporal severity (duration x frequency), duration and frequency. MVH severity was negatively associated with FC between early visual areas (EVA) and ventral-visual-stream regions, and negatively associated with FC between brainstem and EVA, which may be linked to LBD brainstem neuropathology. CVH duration was positively associated with FC between ventral-visual stream and salience network (SN). CVH frequency was negatively associated with FC between DMN and SN. Functional alterations in distinct visual and attentional networks and their dynamic interaction in trait LBD hallucinators are linked to both the phenomenology of state content and its temporal characteristics. Within a network, VH frequency and duration may be linked to different types of functional alterations: increased connectivity leading to sustained activity prolonging VH (duration) and decreased connectivity increasing dysregulated, spontaneous activity (frequency). These findings support the hodotopic hypothesis of VH and may reflect a link between VH phenomenology, LBD neuropathological progression and the involvement of specific neurotransmitter systems.
Background:
Patients with glioma have a poor prognosis and, in a short period of time, have to deal with severe forms of disability, which compromise their psychological distress and quality of life. ...The caregivers of these patients consequently carry a heavy burden in terms of emotional and patient care. The study aims to evaluate the coping strategies of patients and their caregivers during the course of the disease in order to frame the adaptation process in a rapidly progressing pathology.
Methods:
A prospective study on 24 dyads of patients affected by malignant glioma and their caregivers was conducted between May 2016 and July 2018. Questionnaires designed to identify the coping style (MINI-MaC Scale) and psychological distress (HADS scores) and assess QOL (EQ-5D) were administered at two time points: at first lines of treatment and at disease recurrence.
Results:
Patients and their caregiver structure adaptive coping strategies during the disease: a coping style oriented toward a fighting spirit prevails at baseline (Mini-Mac Mean 3.23); fatalism prevails at recurrence (Mini-Mac Mean 3.03). Psychological distress affects the coping style expressed: high levels of anxiety symptoms were found to be significantly associated with a coping style oriented toward anxious preoccupation, helpless–hopeless, and fatalism; low depressive symptoms were inversely correlated with fighting spirit coping style. Patients' and caregivers' perceptions of quality of life were correlated between them and with performance status assessed by clinicians. In a dyadic perspective, the adaptation of a member of the couple varies as a function of the other partner's coping style.
Conclusions:
Our data are in line with previous literature on cancer patients, demonstrating that coping style is not a persistent dimension of personality, but can change depending on the situation. Despite the disease rapid course, patients and their caregivers can structure adaptive and functional defenses to manage the disease.
Abstract
Background
Visual hallucinations (VH) phenomenology in Lewy Body Disease (LBD) is heterogenous, including minor phenomena (passage, presence, illusions) and complex hallucinations. Neural ...substrates and mechanisms involved are still unclear. Here we investigated grey matter (GM) alterations associated with minor (MVH) and complex VH (CVH).
Method
LBD patients (n = 28) with VH and Healthy controls (HC‐n = 20) underwent MRI. We administered the North East Visual Hallucinations Interview (NEVHI), a semi‐structured interview assessing the phenomenology of VH, their duration and frequency. VH were clustered in MVH and CVH and treated as a patient’s trait. First we compared GM volume of LBD and HC. Then, multiple regressions were performed to disclose alterations associated with the duration, frequency and severity of MVH and CVH, including the opposite VH domain, total intracranial volume (TIV) and MMSE as nuisance regressors.
Result
We found a decreased GM volume in the bilateral fusiform gyrus (FG), in the left posterior cingulate and in the right inferior frontal gyrus in LBD compared to HC. We also found that CVH duration was negatively associated with GM volume in the left FG. We did not find any association with MVH phenomenology.
Conclusion
LBD patients showed GM alterations in ventral‐visual‐stream, default‐mode‐network and inhibitory regions compared to HC. Although the LBD versus HC comparison is not specific to VH, the regions identified have been implicated in VH in previous studies suggesting they may represent structural hallmarks of functional alterations in networks contributing to VH. When the association with VH phenomenology was tested, we did not find GM alterations associated with MVH. It is likely that these phenomena might be not associated with structural alterations but with functional alterations within visual networks. CVH were instead associated with decreased GM in FG. The atrophy in the FG may lead to a spontaneous activation of this region that sustain CVH duration, accounting for VH content (D’Antonio et al., 2022). These alterations may represent the predisposing condition to VH in LBD. According to the hodotopic model, VH phenomenology may help identify brain regions implicated and might reveal the substrates for cortical region/network dysfunctions occurring during VH state (ffytche et al., 2008).
PDF
