Julia Heller

Brain imaging findings in idiopathic REM sleep behavior disorder (RBD) – A systematic review on potential biomarkers for neurodegeneration

Idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by the loss of physiological atonia of skeletal muscles with abnormal behavior during dream sleep. RBD may be the initial manifestation of neurodegenerative diseases, particularly of α-synucleinopathies such as Parkinsons disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). However, gauging the individual risk of subsequent phenoconversion and making assumptions on the type of disease that may subsequently follow RBD is challenging. Over the past years, a growing number of studies have sought to establish reliable neuroimaging markers to detect neurodegenerative brain changes in RBD subjects at the earliest possible stage. The present review summarizes recent advances in brain imaging in RBD and provides recommendations for the application of currently available structural and functional neuroimaging modalities to monitor disease progression and risk of subsequent phenoconversion. Further imaging research applying multimodal approaches is encouraged to enhance accuracy of prognoses. Additionally, more longitudinal studies are warranted to validate findings from cross-sectional studies on RBD progression and risk of subsequent phenoconversion. Aside from enabling reliable prognoses on a single-subject-level in the near future, this might give further insight into RBD pathophysiology, and finally augment the development of intervention strategies and disease-modifying therapies.

Evidence for Gender Differences in Cognition, Emotion and Quality of Life in Parkinson’s Disease?

A number of gender differences have been documented in the incidence and symptomatology of the second most common age-related neurodegenerative disorder, idiopathic Parkinsons disease (PD). Overall, previous reports suggest a less frequent incidence and a more benign phenotype in women mainly in Western populations, which is thought to be mediated by estrogens in particular in early stages of the disease. Not only motor symptoms seem to underlie gender effects, but also non-motor symptoms such as psychiatric and cognitive impairments, which can often precede motor manifestation. However, reliable results for gender differences in PD in particular of cognitive function and emotion processing, having a major impact on quality of life, are lacking. Moreover, studies investigating gender effects in PD in these areas have revealed highly heterogeneous results. The present review summarizes findings of currently available studies on gender effects on neuropsychological tests covering major cognitive domains, emotion processing as well as quality of life in patients with PD. Overall, the occurrence of cognitive impairment in PD seems to be associated with male gender, though inconsistent results were shown in cognitive screening tests. Regarding emotion recognition, men with PD were found to be less accurate than women with PD at identifying fearful expressions, whereas vice versa results appeared in healthy subjects. Lower quality of life and greater disability were reported by women compared to men with PD, which corresponds with the results in healthy subjects. Several disease-specific mediators as well as the question of a general gender and age-related effect as observed in healthy individuals are discussed. Increased knowledge on possible gender effects in PD would provide an enhanced insight in underlying pathological mechanisms, and has potential implications for the diagnosis and treatment of PD.

Functional Connectivity Differences of the Subthalamic Nucleus Related to Parkinson's Disease

A typical feature of Parkinsons disease (PD) is pathological activity in the subthalamic nucleus (STN). Here, we tested whether in patients with PD under dopaminergic treatment functional connectivity of the STN differs from healthy controls (HC) and whether some brain regions show (anti‐) correlations between functional connectivity with STN and motor symptoms. We used functional magnetic resonance imaging to investigate whole‐brain resting‐state functional connectivity with STN in 54 patients with PD and 55 HC matched for age, gender, and within‐scanner motion. Compared to HC, we found attenuated negative STN‐coupling with Crus I of the right cerebellum and with right ventromedial prefrontal regions in patients with PD. Furthermore, we observed enhanced negative STN‐coupling with bilateral intraparietal sulcus/superior parietal cortex, right sensorimotor, right premotor, and left visual cortex compared to HC. Finally, we found a decline in positive STN‐coupling with the left insula related to severity of motor symptoms and a decline of inter‐hemispheric functional connectivity between left and right STN with progression of PD‐related motor symptoms. Motor symptom related uncoupling of the insula, a key region in the saliency network and for executive function, from the STN might be associated with well‐known executive dysfunction in PD. Moreover, uncoupling between insula and STN might also induce an insufficient setting of thresholds for the discrimination between relevant and irrelevant salient environmental stimuli, explaining observations of disturbed response control in PD. In sum, motor symptoms in PD are associated with a reduced coupling between STN and a key region for executive function. Hum Brain Mapp 37:1235–1253, 2016.

Impaired Emotional Mirroring in Parkinson’s Disease—A Study on Brain Activation during Processing of Facial Expressions

Background Affective dysfunctions are common in patients with Parkinson’s disease, but the underlying neurobiological deviations have rarely been examined. Parkinson’s disease is characterized by a loss of dopamine neurons in the substantia nigra resulting in impairment of motor and non-motor basal ganglia-cortical loops. Concerning emotional deficits, some studies provide evidence for altered brain processing in limbic- and lateral-orbitofrontal gating loops. In a second line of evidence, human premotor and inferior parietal homologs of mirror neuron areas were involved in processing and understanding of emotional facial expressions. We examined deviations in brain activation during processing of facial expressions in patients and related these to emotion recognition accuracy. Methods 13 patients and 13 healthy controls underwent an emotion recognition task and a functional magnetic resonance imaging (fMRI) measurement. In the Emotion Hexagon test, participants were presented with blends of two emotions and had to indicate which emotion best described the presented picture. Blended pictures with three levels of difficulty were included. During fMRI scanning, participants observed video clips depicting emotional, non-emotional, and neutral facial expressions or were asked to produce these facial expressions themselves. Results Patients performed slightly worse in the emotion recognition task, but only when judging the most ambiguous facial expressions. Both groups activated inferior frontal and anterior inferior parietal homologs of mirror neuron areas during observation and execution of the emotional facial expressions. During observation, responses in the pars opercularis of the right inferior frontal gyrus, in the bilateral inferior parietal lobule and in the bilateral supplementary motor cortex were decreased in patients. Furthermore, in patients, activation of the right anterior inferior parietal lobule was positively related to accuracy in the emotion recognition task. Conclusion Our data provide evidence for a contribution of human homologs of monkey mirror areas to the emotion recognition deficit in Parkinson’s disease.

Impact of gender and genetics on emotion processing in Parkinson's disease - A multimodal study

Highlights • Understanding of the phenotypic heterogeneity of Parkinsons disease is needed.• Gender and genetics determine manifestation and progression of Parkinsons disease.• Altered emotion processing in Parkinsons disease is specific to male patients.• This is influenced by endocrinal and genetic factors in both genders.• This finding may impact the diagnosis and treatment of emerging clinical features.

Cognitive decline in Parkinson’s disease: the impact of the motor phenotype on cognition

Objectives Parkinson’s disease (PD) is the second most common neurodegenerative disorder and is further associated with progressive cognitive decline. In respect to motor phenotype, there is some evidence that akinetic-rigid PD is associated with a faster rate of cognitive decline in general and a greater risk of developing dementia. The objective of this study was to examine cognitive profiles among patients with PD by motor phenotypes and its relation to cognitive function. Methods Demographic, clinical and neuropsychological cross-sectional baseline data of the DEMPARK/LANDSCAPE study, a multicentre longitudinal cohort study of 538 patients with PD were analysed, stratified by motor phenotype and cognitive syndrome. Analyses were performed for all patients and for each diagnostic group separately, controlling for age, gender, education and disease duration. Results Compared with the tremor-dominant phenotype, akinetic-rigid patients performed worse in executive functions such as working memory (Wechsler Memory Scale-Revised backward; p=0.012), formal-lexical word fluency (p=0.043), card sorting (p=0.006), attention (Trail Making Test version A; p=0.024) and visuospatial abilities (Leistungsprüfungssystem test 9; p=0.006). Akinetic-rigid neuropsychological test scores for the executive and attentive domain correlated negatively with non-tremor motor scores. Covariate-adjusted binary logistic regression analyses showed significant odds for PD-mild cognitive impairment for not-determined as compared with tremor-dominant (OR=3.198) and akinetic-rigid PD (OR=2.059). The odds for PD-dementia were significant for akinetic-rigid as compared with tremor-dominant phenotype (OR=8.314). Conclusion The three motor phenotypes of PD differ in cognitive performance, showing that cognitive deficits seem to be less severe in tremor-dominant PD. While these data are cross-sectional, longitudinal data are needed to shed more light on these differential findings.