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BACKGROUND: Cholinergic degeneration is strongly associated with cognitive decline in patients with Parkinson's disease (PD) but may also cause motor symptoms and olfactory dysfunction. Regional differences are striking and may reflect different PD related symptoms and disease progression patterns.OBJECTIVE: To map and quantify the regional cerebral cholinergic alterations in non-demented PD patients.METHODS: We included 15 non-demented PD patients in early-moderate disease stage and 15 age- and sex-matched healthy controls for [18F]FEOBV positron emission tomography imaging. We quantitated regional variations using VOI-based analyses which were supported by a vertex-wise cluster analysis. Correlations between imaging data and clinical and neuropsychological data were explored.RESULTS: We found significantly decreased [18F]FEOBV uptake in global neocortex (38%, p = 0.0002). The most severe reductions were seen in occipital and posterior temporo-parietal regions (p < 0.0001). The vertex-wise cluster analysis corroborated these findings. All subcortical structures showed modest non-significant reductions. Motor symptoms (postural instability and gait difficulty) and cognition (executive function and composite z-score) correlated with regional [18F]FEOBV uptake (thalamus and cingulate cortex/insula/hippocampus, respectively), but the correlations were not statistically significant after multiple comparison correction. A strong correlation was found between interhemispheric [18F]FEOBV asymmetry, and motor symptom asymmetry of the extremities (r = 0.84, p = 0.0001).CONCLUSION: Cortical cholinergic degeneration is prominent in non-demented PD patients, but more subtle in subcortical structures. Regional differences suggest uneven involvement of cholinergic nuclei in the brain and may represent a window to follow disease progression. The correlation between asymmetric motor symptoms and neocortical [18F]FEOBV asymmetry indicates that unilateral cholinergic degeneration parallels ipsilateral dopaminergic degeneration.

Background: The average human lifespan has increased dramatically over the past century. However, molecular and physiological alterations of the healthy brain during aging remain incompletely understood. Generalized synaptic restructuring may contribute to healthy aging and the reduced metabolism observed in the aged brain. The aim of this study was to assess healthy brain aging using [18F]FDG as a measure of cerebral glucose consumption and [11C]UCB-J PET as an indicator of synaptic density. Method: Using in vivo PET imaging and the novel synaptic-vesicle-glycoprotein 2A (SV2A) radioligand [11C]UCB-J alongside with the fluorodeoxyglucose radioligand [18F]FDG, we obtained SUVR-1 values for 14 pre-defined volume-of-interest brain regions defined on MRI T1 scans. Regional differences in relative [18F]FDG and [11C]UCB-J uptake were investigated using a voxel-wise approach. Finally, correlations between [11C]UCB-J, [18F]FDG PET, and age were examined. Results: We found widespread cortical reduction of synaptic density in a cohort of older HC subjects (N = 15) compared with young HC subjects (N = 11). However, no reduction persisted after partial volume correction and corrections for multiple comparison. Our study confirms previously reported synaptic stability during aging. Regional differences in relative [18F]FDG and [11C]UCB-J uptake were observed with up to 20 % higher [11C]UCB-J uptake in the amygdala and temporal lobe and up to 34 % higher glucose metabolism in thalamus, striatum, occipital, parietal and frontal cortex. Conclusion: In vivo PET using [11C]UCB-J does not support declining synaptic density levels during aging. Thus, loss of synaptic density may be unrelated to aging and does not seem to be a sufficient explanation for the recognized reduction in brain metabolism during aging. Our study also demonstrates that the relationship between glucose consumption and synaptic density is not uniform throughout the human brain with implications for our understanding of neuroenergetics.

Background: Sleep disturbances are common in women treated for breast cancer. We have previously shown that internet-delivered cognitive-behavioral therapy for insomnia (e-CBT-I) is an efficacious, low-cost treatment approach. Furthermore, research has shown that e-CBT-I can result in sustained improvements at 12 months post-treatment. However, given the complexity and long duration of post-treatment symptomatology in breast cancer patients, as well as the recommended use of antihormonal therapy for up to 10 years, it is relevant to investigate long-term (>12 months) changes in sleep following e-CBT-I in this population. In the present study, we report data from a 3-year long-term follow-up assessment after e-CBT-I. Methods: Women treated for breast cancer with sleep disturbances (Pittsburg Sleep Quality Index [PSQI] global score >5) who had previously been enrolled in a randomized-controlled trial investigating the efficacy of e-CBT-I (n = 255), were invited to participate in a 3-year follow-up study. All women in the initial control group had also been granted access to e-CBT-I. Assessment included self-reported sleep quality (PSQI), insomnia severity (Insomnia Severity Index, ISI), cancer-related fatigue and symptoms of depression. Within-group changes in these outcomes from baseline to the 3-year long-term follow-up assessment were analyzed. Results: A total of 131 women (51%) participated in the 3-year follow-up study of which 77 (59%) were from the initial intervention group and 54 (41%) from the initial control group. For the pooled sample, within-group improvements from baseline to the 3-year follow-up assessment corresponding to large effect sizes were observed in sleep quality (Cohen's d = 1.0 95% CI [0.78, 1.21]) and insomnia severity (Cohen's d = 1.36 CI 95% [1.12, 1.59]). Similar changes were observed in cancer-related fatigue (Cohen's d = 0.48 CI 95% [0.30, 0.66]) and symptoms of depression (Cohen's d = 0.80 CI 95%. [0.60, 0.99]). The proportion of patients with scores above established cut-offs on the PSQI and the ISI were 56.1% and 29.8%, respectively. Within the initial intervention group, 15.6% evidenced relapse at the 3-year assessment. Conclusion: Overall, these results indicate that long-term sleep quality and insomnia severity following the use of e-CBT-in women treated for breast cancer is significantly lower than the pre-treatment levels. However, a substantial proportion of participants still evidence sleep disturbances.

The average human lifespan has increased dramatically over the past century. However, molecular and physiological alterations of the healthy brain during aging remain incompletely understood. Generalized synaptic restructuring may contribute to healthy aging and the reduced metabolism observed in the aged brain. The aim of this study was to assess healthy brain aging using [Using in vivo PET imaging and the novel synaptic-vesicle-glycoprotein 2A (SV2A) radioligand [We found widespread cortical reduction of synaptic density in a cohort of older HC subjects (N = 15) compared with young HC subjects (N = 11). However, no reduction persisted after partial volume correction and corrections for multiple comparison. Our study confirms previously reported synaptic stability during aging. Regional differences in relative [In vivo PET using [

This research examines the perceived fairness of two types of job interviews: robot-mediated and face-to-face interviews. The robot-mediated interview tests the concept of a fair proxy in the shape of a teleoperated social robot. In Study 1, a mini-public (n=53) revealed four factors that influence fairness perceptions of the robot-mediated interview and showed how HR professionals’ perception of fair personnel selection is influenced by moral pragmatism despite clear moral awareness of discriminative biases in interviews. In Study 2, an experimental survey (n=242) conducted at an unemployment center showed that the respondents perceived the robot-mediated interview as fairer than the face-to-face interview. Overall, the studies suggest that HR professionals and jobseekers exhibit diverging fairness perceptions and that the business case for the robot-mediated interview undermines its social case (i.e., reducing discrimination). The paper concludes by addressing key implications and avenues for future research.