Purpose
In 2017, the Geneva Alzheimer’s disease (AD) strategic biomarker roadmap initiative proposed a framework of the systematic validation AD biomarkers to harmonize and accelerate their ...development and implementation in clinical practice. Here, we use this framework to examine the translatability of the second-generation tau PET tracers into the clinical context.
Methods
All available literature was systematically searched based on a set of search terms that related independently to analytic validity (phases 1–2), clinical validity (phase 3–4), and clinical utility (phase 5). The progress on each of the phases was determined based on scientific criteria applied for each phase and coded as fully, partially, preliminary achieved or not achieved at all.
Results
The validation of the second-generation tau PET tracers has successfully passed the analytical phase 1 of the strategic biomarker roadmap. Assay definition studies showed evidence on the superiority over first-generation tau PET tracers in terms of off-target binding. Studies have partially achieved the primary aim of the analytical validity stage (phase 2), and preliminary evidence has been provided for the assessment of covariates on PET signal retention. Studies investigating of the clinical validity in phases 3, 4, and 5 are still underway.
Conclusion
The current literature provides overall preliminary evidence on the establishment of the second-generation tau PET tracers into the clinical context, thereby successfully addressing some methodological issues from the tau PET tracer of the first generation. Nevertheless, bigger cohort studies, longitudinal follow-up, and examination of diverse disease population are still needed to gauge their clinical validity.
The Covid-19 pandemic is burning all over the world. National healthcare systems are facing the contagion with incredible strength, but concern regarding the psychosocial and economic effects is ...growing quickly. The PsyCovid Study assessed the influence of psychosocial variables on individual differences from the perceived impact of the Covid-19 outbreak on the issues of health and economy in the Italian population. Italian volunteers from different regions completed an online anonymous survey. The main outcomes were the perceived impact of the Covid-19 outbreak on health and the economy. A two-way MANOVA evaluated differences in the main outcomes, with geographical area (northern, central, and southern regions) and professional status (healthcare workers or not) as factors. We then tested the relationship linking psychosocial variables (i.e. perceived distress and social isolation, empathy, and coping style) to the main outcomes through two different mediation models. 1163 responders completed the survey (835 females; mean age: 42 ± 13.5 y.o.; age range: 18-81 y.o.) between March 14 and 21, 2020. Healthcare workers and people living in northern Italy reported a significantly worse outbreak impact on health, but not on the economy. In the whole sample, distress and loneliness were key variables influencing the perceived impact of the Covid-19 outbreak on health, while empathy and coping style affected the perceived impact on the economy. The Covid-19 pandemic is a worldwide emergency in terms of psychological, social, and economic consequences. Our data suggests that in the Italian population, actual differences in individual perception of the Covid-19 outbreak severity for health are dramatically modulated by psychosocial frailty (i.e., distress and loneliness). At the same time, problem-oriented coping strategies and enhanced empathic abilities increase people's awareness of the severity of the impact of the Covid-19 emergency on economics. There is an immediate need for consensus guidelines and healthcare policies to support interventions aimed to manage psychosocial distress and increase population resilience towards the imminent crisis.
The use of social tasks in the neuropsychological assessment of the behavioral variant of frontotemporal dementia (bvFTD) is at present not required by diagnostic guidelines, despite extensive ...literature shows relevant social cognitive dysfunctions in such patients. In this systematic review, we explored the clinical maturity of social cognition measures in the diagnosis of bvFTD. Papers were selected according to the PRISMA guidelines by searching the PubMed and Medline databases. Only papers reporting indices of diagnostic accuracy and/or sensitivity/specificity in classifying bvFTD from controls or from other relevant diseases were considered. Quality of evidence was assessed through QUADAS-2. Among the 663 articles entered in the paper selection only 14 papers were eligible for the scope of the present review and showed an overall moderate-to-low quality. The major risk of bias was the lack of pathological confirmation. The evaluation of the accuracy of social cognition tasks in bvFTD detection compared to normal controls, as well as in the discrimination with Alzheimer’s disease and psychiatric patients, is mainly focused on emotion recognition and theory of mind. However, the use of different cognitive measures, variable task formats and the limited normative data hamper study comparability. Although literature seems to suggest that emotion recognition and ToM tasks could be the best choice to ensure a high diagnostic accuracy in clinical settings, further comparative studies are required and no recommendation concerning the use of a specific social task in bvFTD diagnosis can be currently provided.
Covid-19 pandemic is exerting a tragic impact all around the world. First-person experience of life-threatening and stressful events can modify individuals' risk perception, and, consequently, ...risk-taking behaviours. Here we investigated risk-taking profiles in 130 Italian residents, and compared healthcare to non-healthcare workers, during the lockdown phase. We ad hoc developed the "Covid-19 Risk Task", including the classic monetary Holt-Laury Paired Lottery Task (Monetary Condition, MC) and two new ecological conditions exploring Covid-19 related risk-taking aptitudes in relation to different health (Health Status Condition, HsC) and employment (Employment Status Condition, EsC) outcomes. Results showed that, in the whole sample, individuals were more risk-averse in MC than in HsC and EsC. Moreover, a payoff increase produced a shift toward more risk-averse behaviours in MC, but not in HsC and EsC, where we found an opposite trend suggesting a more risk-loving behaviour. Finally, we found that healthcare workers were significantly less risk-averse compared to non-healthcare workers in EsC, but not in MC and HsC. These findings provided evidence of the possible effects of Covid-19 outbreak on risk-taking aptitudes. The negative impact on human choices and, consequently, on the whole world economy of this catastrophic life event must not be underestimated.
Purpose
Assess the individual and combined diagnostic value of amyloid-PET and tau-PET in a memory clinic population.
Methods
Clinical reports of 136 patients were randomly assigned to two diagnostic ...pathways: AMY-TAU, amyloid-PET is presented before tau-PET; and TAU-AMY, tau-PET is presented before amyloid-PET. Two neurologists independently assessed all reports with a balanced randomized design, and expressed etiological diagnosis and diagnostic confidence (50–100%) three times: (i) at baseline based on the routine diagnostic workup, (ii) after the first exam (amyloid-PET for the AMY-TAU pathway, and tau-PET for the TAU-AMY pathway), and (iii) after the remaining exam. The main outcomes were changes in diagnosis (from AD to non-AD or vice versa) and in diagnostic confidence.
Results
Amyloid-PET and tau-PET, when presented as the first exam, resulted in a change of etiological diagnosis in 28% (
p
= 0.006) and 28% (
p
< 0.001) of cases, and diagnostic confidence increased by 18% (
p
< 0.001) and 19% (
p
< 0.001) respectively, with no differences between exams (
p
> 0.05). We observed a stronger impact of a negative amyloid-PET versus a negative tau-PET (
p
= 0.014). When added as the second exam, amyloid-PET and tau-PET resulted in a further change in etiological diagnosis in 6% (
p
= 0.077) and 9% (
p
= 0.149) of cases, and diagnostic confidence increased by 4% (
p
< 0.001) and 5% (
p
< 0.001) respectively, with no differences between exams (
p
> 0.05).
Conclusion
Amyloid-PET and tau-PET significantly impacted diagnosis and diagnostic confidence in a similar way, although a negative amyloid-PET has a stronger impact on diagnosis than a negative tau-PET. Adding either of the two as second exam further improved diagnostic confidence.
Trial number
PB 2016-01346.
Neural responses in striatal, limbic and somatosensory brain regions track individual differences in loss aversion, i.e. the higher sensitivity to potential losses compared with equivalent gains in ...decision-making under risk. The engagement of structures involved in the processing of aversive stimuli and experiences raises a further question, i.e. whether the tendency to avoid losses rather than acquire gains represents a transient fearful overreaction elicited by choice-related information, or rather a stable component of one's own preference function, reflecting a specific pattern of neural activity. We tested the latter hypothesis by assessing in 57 healthy human subjects whether the relationship between behavioral and neural loss aversion holds at rest, i.e. when the BOLD signal is collected during 5minutes of cross-fixation in the absence of an explicit task. Within the resting-state networks highlighted by a spatial group Independent Component Analysis (gICA), we found a significant correlation between strength of activity and behavioral loss aversion in the left ventral striatum and right posterior insula/supramarginal gyrus, i.e. the very same regions displaying a pattern of neural loss aversion during explicit choices. Cross-study analyses confirmed that this correlation holds when voxels identified by gICA are used as regions of interest in task-related activity and vice versa. These results suggest that the individual degree of (neural) loss aversion represents a stable dimension of decision-making, which reflects in specific metrics of intrinsic brain activity at rest possibly modulating cortical excitability at choice.
•Loss aversion correlates with striatal and insular intrinsic brain activity.•Striatal and insular intrinsic brain activity predicts the degree of loss aversion.•Neural loss aversion occurs in the voxels correlating with loss aversion at rest.•Neural loss aversion is a stable feature of brain reward and interoceptive systems.•Behavioral loss aversion likely represents a stable dimension of decision-making.
Purpose
The research community has focused on defining reliable biomarkers for the early detection of the pathological hallmarks of Alzheimer’s disease (AD). In 2017, the Geneva AD Biomarker Roadmap ...initiative adapted the framework for the systematic validation of oncological biomarkers to AD, with the aim to accelerate their development and implementation in clinical practice. The aim of this work was to assess the validation status of tau PET ligands of the THK family and PBB3 as imaging biomarkers for AD, based on the Biomarker Roadmap methodology.
Methods
A panel of experts in AD biomarkers convened in November 2019 at a 2-day workshop in Geneva. The level of clinical validity of tau PET ligands of the THK family and PBB3 was assessed based on the 5-phase development framework before the meeting and discussed during the workshop.
Results
PET radioligands of the THK family discriminate well between healthy controls and patients with AD dementia (phase 2; partly achieved) and recent evidence suggests an accurate diagnostic accuracy at the mild cognitive impairment (MCI) stage of the disease (phase 3; partly achieved). The phases 2 and 3 were considered not achieved for PBB3 since no evidence exists about the ligand’s diagnostic accuracy. Preliminary evidence exists about the secondary aims of each phase for all ligands.
Conclusion
Much work remains for completing the aims of phases 2 and 3 and replicating the available evidence. However, it is unlikely that the validation process for these tracers will be completed, given the presence of off-target binding and the development of second-generation tracers with improved binding and pharmacokinetic properties.
Pharmacological treatments in Parkinson's disease (PD), albeit effective in alleviating many motor symptoms, have limited effects in non-motor signatures as cognitive impairment, as well as in other ...aspects included postural instability. Consequently, complementary interventions are nowadays a prerogative of clinical practice managing PD symptomatology. In this pilot longitudinal study, we recruited twenty-four PD patients participating in one of two interventions: adapted Argentine Tango or group-based physiotherapy. Participants underwent a motor and neuropsychological evaluation before and after four months of activities, carried out twice a week. We found a general stabilization of motor and cognitive abilities, with significant improvements in several motor skills, mainly pertaining to static and dynamic balance, similarly in both groups. At cognitive level, we measured a significant improvement in both groups in the Action Naming task. Interestingly, only PD patients in the Tango group improved their performance in the test measuring facial emotion recognition. These findings highlight the crucial role that physical activities have in the stabilization and slowdown of disease's progression in PD. They further highlight the beneficial effects of a group-based physical intervention, which, especially in the case of Tango, could lead to behavioral ameliorations in domains other than the motor, such as emotion recognition.
Purpose
The A/T/N model is a research framework proposed to investigate Alzheimer’s disease (AD) pathological bases (i.e., amyloidosis A, neurofibrillary tangles T, and neurodegeneration N). The ...application of this system on clinical populations is still limited. The aim of the study is to evaluate the topography of T distribution by 18F-flortaucipir PET in relation to A and N and to describe the A/T/N status through imaging biomarkers in memory clinic patients.
Methods
Eighty-one patients with subjective and objective cognitive impairment were classified as A+/A− and N+/N− through amyloid PET and structural MRI. Tau deposition was compared across A/N subgroups at voxel level. T status was defined through a global cut point based on A/N subgroups and subjects were categorized following the A/T/N model.
Results
A+N+ and A+N− subgroups showed higher tau burden compared to A−N− group, with A+N− showing significant deposition limited to the medial and lateral temporal regions. Global cut point discriminated A+N+ and A+N− from A−N− subjects. On A/T/N classification, 23% of patients showed a negative biomarker profile, 58% fell within the Alzheimer’s continuum, and 19% of the sample was characterized by non-AD pathologic change.
Conclusion
Medial and lateral temporal regions represent a site of significant tau accumulation in A+ subjects and possibly a useful marker of early clinical changes. This is the first study in which the A/T/N model is applied using 18F-flortaucipir PET in a memory clinic population. The majority of patients showed a profile consistent with the Alzheimer’s continuum, while a minor percentage showed a profile suggestive of possible other neurodegenerative diseases. These results support the applicability of the A/T/N model in clinical practice.
First-person experience of stressful life events can change individuals' risk attitudes, driving to increased or decreased risk perception. This shift to more risk-averse or risk-loving behaviors may ...find a correlate in the individual psycho-socio-emotional profile. To this purpose, we aimed to estimate the relationship between differences in risk-taking attitudes toward possible negative health outcomes and psycho-socio-emotional dimensions modulating the experience of life-threatening situations, in the context of the Covid-19 pandemic. In March 2020, we launched the PsyCovid Study (
https://wprn.org/item/428452
) to assess psycho-socio-emotional changes due to Covid-19 pandemic in the Italian population. Additionally, we distributed to 130 participants the Covid-19 Risk Task, including monetary and health-related stimuli, estimating a measure of risk-aversion toward health and classifying participants on the basis of their risk-attitude profiles. The set of psycho-socio-emotional variables was reduced to three PCA components:
Proactivity, Isolation, Inactivity
. The individual degree of risk-aversion toward negative health outcomes was directly related to
Proactivity
, encasing empathic, social support and positive coping strategies, which may prompt individuals to put in place self-protection strategies toward possible negative health consequences. These findings indicate that a risk-averse profile toward possible negative health outcomes may be associated to higher levels of individual prosocial and proactive dispositions, possibly making individuals' more compliant with the social and hygienic guidelines and, thus, reducing their exposure to the SARS-CoV-2 infection.
PDF
