Direct communication between radiologists and patients improves the quality of imaging reports.

OBJECTIVES: We investigate in what percentage of cases and to what extent radiological reports change when radiologists directly communicate with patients after imaging examinations. METHODS: One hundred twenty-two consecutive outpatients undergoing MRI examinations at a single center were prospectively included. Radiological reports of the patients were drafted by two radiologists in consensus using only the clinical information that was made available by the referring physicians. Thereafter, one radiologist talked directly with the patient and recorded the duration of the conversation. Afterwards, the additional information from the patient was used to reevaluate the imaging studies in consensus. The radiologists determined whether the radiological report changed based on additional information and, if yes, to what extent. The degree of change was graded on a 4-point Likert scale (1, non-relevant findings, to 4, highly relevant findings). RESULTS: Following direct communication (duration 170.9 ± 53.9 s), the radiological reports of 52 patients (42.6%) were changed. Of the 52 patients, the degree of change was classified as grade 1 for 8 patients (15.4 %), grade 2 for 27 patients (51.9%), grade 3 for 13 patients (25%), and grade 4 for 4 patients (7.7%). The reasons leading to changes were missing clinical information in 50 cases (96.2%) and the lack of additional external imaging in 2 cases (3.8%). CONCLUSIONS: Radiologists should be aware that a lack of accurate information from the clinician can lead to incorrect radiological reports or diagnosis. Radiologists should communicate directly with patients, especially when the provided information is unclear, as it may significantly alter the radiological report. KEY POINTS: • Direct communication between radiologists and patients for an average of 170's resulted in a change in the radiological reports of 52 patients (42.6%). • Of the 42.6% of cases where the reports were changed, the alterations were highly relevant (grades 3 and 4) in 32.7%, indicating major changes with significant impact towards patient management.

The European DTI Study on Dementia - A multicenter DTI and MRI study on Alzheimer's disease and Mild Cognitive Impairment.

The European DTI Study on Dementia (EDSD) is a multicenter framework created to study the diagnostic accuracy and inter-site variability of DTI-derived markers in patients with manifest and prodromal Alzheimer's disease (AD). The dynamically growing database presently includes 493 DTI, 512 T1-weighted MRI, and 300 FLAIR scans from patients with AD dementia, patients with Mild Cognitive Impairment (MCI) and matched Healthy Controls, acquired on 13 different scanner platforms. The imaging data is publicly available, along with the subjects' demographic and clinical characterization. Detailed neuropsychological information, cerebrospinal fluid information on biomarkers and clinical follow-up diagnoses are included for a subset of subjects. This paper describes the rationale and structure of the EDSD, summarizes the available data, and explains how to gain access to the database. The EDSD is a useful database for researchers seeking to investigate the contribution of DTI to dementia diagnostics.

Reference region selection and the association between the rate of amyloid accumulation over time and the baseline amyloid burden.

Relative quantitative analysis of amyloid plaque burden in Alzheimer's disease (AD) patients can be reported as standardized uptake value ratio (SUVR) from positron emission tomography (PET). Here, the SUVR is the ratio of the mean amyloid radioligand retention in a composite (COMP) neocortical volume of interest (VOI) to that in a reference VOI, such as the cerebellum, brainstem (BST)/pons, or white matter (WM). Some longitudinal PET investigations show that the rate of amyloid accumulation to follow-up has an inverted U relationship with baseline amyloid SUVR relative to cerebellar or brainstem/pons reference VOIs. The corresponding association with SUVR relative to WM is unknown. To test the possible benefits of WM normalization, we analyzed [18F]-AV45 PET data from 404 subjects in the AD Neuroimaging Initiative (ADNI) database at baseline and 2-year follow-up (144 cognitively normal controls, 225 patients with mild cognitive impairment, and 35 AD patients). Reference regions included subcortical WM as well as conventional cerebellar gray matter (CBL), and BST. We tested associations between each subject's inter-session change (∆) of SUVR and their baseline SUVR by applying linear, logarithmic, and quadratic regression analyses. Unscaled standardized uptake values (SUVs) were correlated between VOIs at baseline and follow-up, and within VOIs in the longitudinal run. The association between ∆SUVR and baseline SUVR relative to WM reference was best described by an inverted U-shaped function. Correlation analyses demonstrated a high regional and temporal correlation between COMP and WM VOI SUVs. For WM normalization, we confirm that the rate of amyloid accumulation over time follows an inverted U-shaped function of baseline amyloid burden. Reference region selection, however, has substantial effects on SUVR results. This reflects the extent of covariance between SUVs in the COMP VOI and those in the various reference VOIs. We speculate that PET labeling of amyloid deposition within target regions is partially confounded by effects of longitudinal changes of cerebral blood flow (CBF) on tracer delivery. Indeed, CBF may be the leading factor influencing longitudinal SUV changes. We suggest that SUVR relative to WM may be more robust to changes in CBF, and thus fitter for sensitive detection of amyloid accumulation in intervention studies.

Resting-state networks in healthy adult subjects: a comparison between a 32-element and an 8-element phased array head coil at 3.0 Tesla.

BACKGROUND: Little research exists on the influence of a magnetic resonance imaging (MRI) head coil's channel count on measured resting-state functional connectivity. PURPOSE: To compare a 32-element (32ch) and an 8-element (8ch) phased array head coil with respect to their potential to detect functional connectivity within resting-state networks. MATERIAL AND METHODS: Twenty-six healthy adults (mean age, 21.7 years; SD, 2.1 years) underwent resting-state functional MRI at 3.0 Tesla with both coils using equal standard imaging parameters and a counterbalanced design. Independent component analysis (ICA) at different model orders and a dual regression approach were performed. Voxel-wise non-parametric statistical between-group contrasts were determined using permutation-based non-parametric inference. RESULTS: Phantom measurements demonstrated a generally higher image signal-to-noise ratio using the 32ch head coil. However, the results showed no significant differences between corresponding resting-state networks derived from both coils (p < 0.05, FWE-corrected). CONCLUSION: Using the identical standard acquisition parameters, the 32ch head coil does not offer any significant advantages in detecting ICA-based functional connectivity within RSNs.

Neural correlates of moral judgments in first- and third-person perspectives: implications for neuroethics and beyond.

BACKGROUND: There appears to be an inconsistency in experimental paradigms used in fMRI research on moral judgments. As stimuli, moral dilemmas or moral statements/ pictures that induce emotional reactions are usually employed; a main difference between these stimuli is the perspective of the participants reflecting first-person (moral dilemmas) or third-person perspective (moral reactions). The present study employed functional magnetic resonance imaging (fMRI) in order to investigate the neural correlates of moral judgments in either first- or third-person perspective. RESULTS: Our results indicate that different neural mechanisms appear to be involved in these perspectives. Although conjunction analysis revealed common activation in the anterior medial prefrontal cortex, third person-perspective elicited unique activations in hippocampus and visual cortex. The common activation can be explained by the role the anterior medial prefrontal cortex may play in integrating different information types and also by its involvement in theory of mind. Our results also indicate that the so-called "actor-observer bias" affects moral evaluation in the third-person perspective, possibly due to the involvement of the hippocampus. We suggest two possible ways in which the hippocampus may support the process of moral judgment: by the engagement of episodic memory and its role in understanding the behaviors and emotions of others. CONCLUSION: We posit that these findings demonstrate that first or third person perspectives in moral cognition involve distinct neural processes, that are important to different aspects of moral judgments. These results are important to a deepened understanding of neural correlates of moral cognition-the so-called "first tradition" of neuroethics, with the caveat that any results must be interpreted and employed with prudence, so as to heed neuroethics "second tradition" that sustains the pragmatic evaluation of outcomes, capabilities and limitations of neuroscientific techniques and technologies.

Activated protein C protects against diabetic nephropathy by inhibiting endothelial and podocyte apoptosis.

Data providing direct evidence for a causative link between endothelial dysfunction, microvascular disease and diabetic end-organ damage are scarce. Here we show that activated protein C (APC) formation, which is regulated by endothelial thrombomodulin, is reduced in diabetic mice and causally linked to nephropathy. Thrombomodulin-dependent APC formation mediates cytoprotection in diabetic nephropathy by inhibiting glomerular apoptosis. APC prevents glucose-induced apoptosis in endothelial cells and podocytes, the cellular components of the glomerular filtration barrier. APC modulates the mitochondrial apoptosis pathway via the protease-activated receptor PAR-1 and the endothelial protein C receptor EPCR in glucose-stressed cells. These experiments establish a new pathway, in which hyperglycemia impairs endothelial thrombomodulin-dependent APC formation. Loss of thrombomodulin-dependent APC formation interrupts cross-talk between the vascular compartment and podocytes, causing glomerular apoptosis and diabetic nephropathy. Conversely, maintaining high APC levels during long-term diabetes protects against diabetic nephropathy.

Self processing in the brain: a paradigmatic fMRI case study with a professional singer.

Understanding the mechanisms involved in perception and conception of oneself is a fundamental psychological topic with high relevance for psychiatric and neurological issues, and it is one of the great challenges in neuroscientific research. The paradigmatic single-case study presented here aimed to investigate different components of self- and other-processes and to elucidate corresponding neurobiological underpinnings. An eminent professional opera singer with profound performance experience has undergone functional magnetic resonance imaging and was exposed to excerpts of Mozart arias, sung by herself or another singer. The results indicate a distinction between self- and other conditions in cortical midline structures, differentially involved in self-related and self-referential processing. This lends further support to the assumption of cortical midline structures being involved in the neural processing of self-specific stimuli and also confirms the power of single case studies as a research tool.

Two Sides of the Same Coin in Female Borderline Personality Disorder: Self-Reported Guilt and Shame and Their Neurofunctional Correlates.

OBJECTIVE: Patients with borderline personality disorder (BPD) report to be especially prone to social emotions like shame and guilt. At the same time, these emotions seem to play an important role in BPD pathology. The present study aimed to deepen the knowledge about the processes behind shame and guilt in patients with BPD. METHODS: Twenty patients with BPD and twenty healthy controls (HCs) took part in an experiment that induced shame and guilt by imagining scenarios during scanning using functional brain imaging. Participants also filled out self-report questionnaires and took part in diagnostic interviews. RESULTS: BPD patients reported more proneness to guilt but not to shame than the HCs. There was no difference in the self-reported intensity rating of experimentally induced emotions between the groups. Between-group contrast of neural signals in the shame condition revealed a stronger activation of cingulate and fusiform gyrus for the BPD patients compared to the controls, and a more pronounced activation in the lingual gyrus and cuneus for the HCs. In the guilt condition, activation in the caudate nucleus, the fusiform gyrus, and the posterior cingulate cortex was stronger in BPD patients, while HC showed stronger activations in cuneus, lingual gyrus, and fronto-temporal regions. CONCLUSIONS: Differences in the neuro-functional processes between BPD patients and HC were found, even though the two groups did not differ in their self-report of subjective proneness to guilt and emotional intensity of shame and guilt during the experiment. While the HCs may be engaged more by the emotional scenarios themselves, the BPD patients may be more occupied with cognitive regulatory and self-referential processing.

Classifying fMRI-derived resting-state connectivity patterns according to their daily rhythmicity.

The vast majority of biological functions express rhythmic fluctuations across the 24-hour day. We investigated the degree of daily modulation across fMRI (functional Magnetic Resonance Imaging) derived resting-state data in 15 subjects by evaluating the time courses of 20 connectivity patterns over 8h (4 sessions). For each subject, we determined the chronotype, which describes the relationship between the individual circadian rhythm and the local time. We could therefore analyze the daily time course of the connectivity patterns controlling for internal time. Furthermore, as the participants' scan times were staggered as a function of their chronotype, we prevented sleep deprivation and kept time awake constant across subjects. Individual functional connectivity within each connectivity pattern was defined at each session as connectivity strength measured by a mean z-value and, in addition, as the spatial extent expressed by the number of activated voxels. Highly rhythmic connectivity patterns included two sub-systems of the Default-Mode Network (DMN) and a network extending over sensori-motor regions. The network characterized as the most stable across the day is mainly associated with processing of executive control. We conclude that the degree of daily modulation largely varies across fMRI derived resting-state connectivity patterns, ranging from highly rhythmic to stable. This finding should be considered when interpreting results from fMRI studies.

The Interplay of Oxytocin and Attachment in Schizophrenic Patients: An fMRI Study.

BACKGROUND: Attachment theory offers an important framework for understanding interpersonal interaction experiences. In the present study, we examined the neural correlates of attachment patterns and oxytocin in schizophrenic patients (SZP) compared to healthy controls (HC) using fMRI. We assumed that male SZP shows a higher proportion of insecure attachment and an altered level of oxytocin compared to HC. On a neural level, we hypothesized that SZP shows increased neural activation in memory and self-related brain regions during the activation of the attachment system compared to HC. METHODS: We used an event-related design for the fMRI study based on stimuli that were derived from the Adult Attachment Projective Picture System to examine attachment representations and their neural and hormonal correlates in 20 male schizophrenic patients compared to 20 male healthy controls. RESULTS: A higher proportion of insecure attachment in schizophrenic patients compared to HC could be confirmed. In line with our hypothesis, Oxytocin (OXT) levels in SZP were significantly lower than in HC. We found increasing brain activations in SZP when confronted with personal relevant sentences before attachment relevant pictures in the precuneus, TPJ, insula, and frontal areas compared to HC. Moreover, we found positive correlations between OXT and bilateral dlPFC, precuneus, and left ACC in SZP only. CONCLUSION: Despite the small sample sizes, the patients' response might be considered as a mode of dysregulation when confronted with this kind of personalized attachment-related material. In the patient group, we found positive correlations between OXT and three brain areas (bilateral dlPFC, precuneus, left ACC) and may conclude that OXT might modulate within this neural network in SZP.

Correlations Between the DMN and the Smoking Cessation Outcome of a Real-Time fMRI Neurofeedback Supported Exploratory Therapy Approach: Descriptive Statistics on Tobacco-Dependent Patients.

The aim of this study was to explore the potential of default mode network (DMN) functional connectivity for predicting the success of smoking cessation in patients with tobacco dependence in the context of a real-time function al MRI (RT-fMRI) neurofeedback (NF) supported therapy.Fifty-four tobacco-dependent patients underwent three RT-fMRI-NF sessions including resting-state functional connectivity (RSFC) runs over a period of 4 weeks during professionally assisted smoking cessation. Patients were randomized into two groups that performed either active NF of an addiction-related brain region or sham NF. After preprocessing, the RSFC baseline data were statistically evaluated using seed-based ROI (SBA) approaches taking into account the smoking status of patients after 3 months (abstinence/relapse).The results of the real study group showed a widespread functional connectivity in the relapse subgroup (n = 10) exceeding the DMN template and mainly low correlations and anticorrelations in the within-seed analysis. In contrast, the connectivity pattern of the abstinence subgroup (n = 8) primarily contained the core DMN in the seed-to-whole-brain analysis and a left lateralized correlation pattern in the within-seed analysis. Calculated Multi-Subject Dictionary Learning (MSDL) matrices showed anticorrelations between DMN regions and salience regions in the abstinence group. Concerning the sham group, results of the relapse subgroup (n = 4) and the abstinence subgroup (n = 6) showed similar trends only in the within-seed analysis.In the setting of a RT-fMRI-NF-assisted therapy, a widespread intrinsic DMN connectivity and a low negative coupling between the DMN and the salience network (SN) in patients with tobacco dependency during early withdrawal may be useful as an early indicator of later therapy nonresponse.

Cognitive subtypes in recent onset psychosis: distinct neurobiological fingerprints?

In schizophrenia, neurocognitive subtypes can be distinguished based on cognitive performance and they are associated with neuroanatomical alterations. We investigated the existence of cognitive subtypes in shortly medicated recent onset psychosis patients, their underlying gray matter volume patterns and clinical characteristics. We used a K-means algorithm to cluster 108 psychosis patients from the multi-site EU PRONIA (Prognostic tools for early psychosis management) study based on cognitive performance and validated the solution independently (N = 53). Cognitive subgroups and healthy controls (HC; n = 195) were classified based on gray matter volume (GMV) using Support Vector Machine classification. A cognitively spared (N = 67) and impaired (N = 41) subgroup were revealed and partially independently validated (Nspared = 40, Nimpaired = 13). Impaired patients showed significantly increased negative symptomatology (pfdr = 0.003), reduced cognitive performance (pfdr < 0.001) and general functioning (pfdr < 0.035) in comparison to spared patients. Neurocognitive deficits of the impaired subgroup persist in both discovery and validation sample across several domains, including verbal memory and processing speed. A GMV pattern (balanced accuracy = 60.1%, p = 0.01) separating impaired patients from HC revealed increases and decreases across several fronto-temporal-parietal brain areas, including basal ganglia and cerebellum. Cognitive and functional disturbances alongside brain morphological changes in the impaired subgroup are consistent with a neurodevelopmental origin of psychosis. Our findings emphasize the relevance of tailored intervention early in the course of psychosis for patients suffering from the likely stronger neurodevelopmental character of the disease.

FDG PET Data is Associated with Cognitive Performance in Patients from a Memory Clinic.

BACKGROUND: Various reasons may lead to cognitive symptoms in elderly, including the development of cognitive decline and dementia. Often, mixed pathologies such as neurodegeneration and cerebrovascular disease co-exist in these patients. Diagnostic work-up commonly includes imaging modalities such as FDG PET, MRI, and CT, each delivering specific information. OBJECTIVE: To study the informative value of neuroimaging-based data supposed to reflect neurodegeneration (FDG PET), cerebral small vessel disease (MRI), and cerebral large vessel atherosclerosis (CT) with regard to cognitive performance in patients presenting to our memory clinic. METHODS: Non-parametric partial correlations and an ordinal logistic regression model were run to determine relationships between scores for cortical hypometabolism, white matter hyperintensities, calcified plaque burden, and results from Mini-Mental State Examination (MMSE). The final study group consisted of 162 patients (female: 94; MMSE: 6-30). RESULTS: Only FDG PET data was linked to and predicted cognitive performance (r(157) = -0.388, p < 0.001). Overall, parameters linked to cerebral small and large vessel disease showed no significant association with cognition. Further findings demonstrated a relationship between white matter hyperintensities and FDG PET data (r(157) = 0.230, p = 0.004). CONCLUSION: Only FDG PET imaging mirrors cognitive performance, presumably due to the examination's ability to reflect neurodegeneration and vascular dysfunction, thus capturing a broader spectrum of pathologies. This makes the examination a useful imaging-based diagnostic tool in the work-up of patients presenting to a memory clinic. Parameters of vascular dysfunction alone as depicted by conventional MRI and CT are less adequate in such a situation, most likely because they reflect one pathology complex only.

"I was seen by a radiologist, but unfortunately I can't remember the name and I still have questions. What should I do?" Radiologists should give thoughts to improve service professionalism and patient esteem.

BACKGROUND: The aim of the study is to investigate how well patients remember the radiologist's name after a radiological examination, and whether giving the patient a business card improves the patient's perception of the radiologist's professionalism and esteem. METHODS: In this prospective and randomized two-centre study, a total of 141 patients with BI-RADS 1 and 2 scores were included. After screening examination comprising mammography and ultrasound by a radiologist, 71 patients received a business card (group 1), while 70 received no business card (group 2). Following the examination, patients were questioned about their experiences. RESULTS: The patients in group 1 could remember the name of the radiologist in 85% of cases. The patients in group 2, in contrast, could only remember the name in 7% of cases (p < 0.001). 90% of the patients in group 1 believed it was very important that they are able to contact the radiologist at a later time, whereas only 76% of patients in group 2 felt that this was a very important service (p < 0.025). A total of 87% of the patients in group 1 indicated that they would contact the radiologist if they had any questions whereas 73% of the patients in group 2 would like to contact the radiologist but were not able to do so, because they could not remember the name (p < 0.001). All questions were analysed with a Cochran-Mantel-Haenszel (CMH) test that took study centre as stratification into account. In some cases, two categories were collapsed to avoid zero cell counts. CONCLUSIONS: Using business cards significantly increased the recall of the radiologist's name and could be an important tool in improving the relationships between patients and radiologists and enhancing service professionalism. TRIAL REGISTRATION: We have a general approval from our ethics committee. The patients have given their consent to this study.

What and how should we measure in paediatric oncology FDG-PET/CT? Comparison of commonly used SUV metrics for differentiation between paediatric tumours.

BACKGROUND: In clinical routine, SUVmax and SUVpeak are most often used to determine the glucose metabolism in tumours by 18F-FDG PET/CT. Both metrics can be further normalised to SUVs in reference regions resulting in a SUV ratio (SUVratio). The aim of the study was to directly compare several widely used SUVs/SUVratios with regard to differentiation between common tumours in paediatric patients; a special focus was put on characteristics of reference region SUVs. METHODS: The final study population consisted of 61 children and adolescents with diagnoses of non-Hodgkin lymphoma (NHL, n = 25), Hodgkin lymphoma (HL, n = 14), and sarcoma (n = 22). SUV metrics included SUVmax and SUVpeak as well as both parameters normalised to liver and mediastinal blood pool, respectively, yielding the SUVratios SUVmax/liver, SUVmax/mediastinum, SUVpeak/liver, and SUVpeak/mediastinum. RESULTS: The metrics SUVmax, SUVpeak, SUVmax/liver, and SUVpeak/liver all proved to be sensitive for tumour differentiation (p ≤ 0.008); in contrast, SUVmax/mediastinum and SUVpeak/mediastinum revealed to be non-sensitive approaches. Correlation analyses showed inverse associations between reference region SUVs and SUVratios (p < 0.05). Multiple regression analyses demonstrated significant effects of factors as bodyweight and uptake time on reference region SUVs (p < 0.01), and thus indirectly on the corresponding SUVratios. CONCLUSIONS: In the paediatric population, the ability to differentiate between common tumours remarkably varies between SUV metrics. When using SUVratios, the choice of reference region is crucial. Factors potentially influencing reference region SUVs (and thus SUVratios) should be taken into account in order to avoid erroneous conclusions. When not possible, SUVmax and SUVpeak represent less complex, more robust alternatives.

Relationship Between Body Mass Index, ApoE4 Status, and PET-Based Amyloid and Neurodegeneration Markers in Amyloid-Positive Subjects with Normal Cognition or Mild Cognitive Impairment.

Body weight loss in late-life is known to occur at a very early stage of Alzheimer's disease (AD). Apolipoprotein E4 (ApoE4) represents a major genetic risk factor for AD and is linked to an increased cortical amyloid-ß (Aß) accumulation. Since the relationship between body weight, ApoE4, and AD pathology is poorly investigated, we aimed to evaluate whether ApoE4 allelic status modifies the association of body mass index (BMI) with markers of AD pathology. A total of 368 Aß-positive cognitively healthy or mild cognitive impaired subjects had undergone [18F]-AV45-PET, [18F]-FDG-PET, and T1w-MRI examinations. Composite cortical [18F]-AV45 uptake and [18F]-FDG uptake in posterior cingulate cortex were calculated as surrogates of cortical Aß load and glucose metabolism, respectively. Multiple linear regressions were performed to assess the relationships between these PET biomarkers with BMI, present cognitive performance, and cognitive changes over time. Multivariate analysis of covariance was conducted to test for statistical differences between ApoE4/BMI categories on the PET markers and cognitive scores. In carriers of the ApoE4 allele only, BMI was inversely associated with cortical amlyoid load (ß= -0.193, p < 0.005) and recent cognitive decline (ß= -0.209, p < 0.05), and positively associated with cortical glucose metabolism in an AD-vulnerable region (ß= 0.145, p < 0.05). ApoE4/BMI category analyses demonstrated lower Aß load, higher posterior cingulate glucose metabolism, improved cognitive performance, and lower progression of cognitive decline in obese ApoE4 carriers. The effect of ApoE4 in promoting the accumulation of cortical amyoid, which may itself be a driver for weight loss, may be moderated by altering leptin signaling in the hypothalamus.

Serotonin Selective Reuptake Inhibitor Treatment Improves Cognition and Grey Matter Atrophy but not Amyloid Burden During Two-Year Follow-Up in Mild Cognitive Impairment and Alzheimer's Disease Patients with Depressive Symptoms.

Late-life depression, even when of subsyndromal severity, has shown strong associations with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Preclinical studies have suggested that serotonin selective reuptake inhibitors (SSRIs) can attenuate amyloidogenesis. Therefore, we aimed to investigate the effect of SSRI medication on amyloidosis and grey matter volume in subsyndromal depressed subjects with MCI and AD during an interval of two years. 256 cognitively affected subjects (225 MCI/ 31 AD) undergoing [18F]-AV45-PET and MRI at baseline and 2-year follow-up were selected from the ADNI database. Subjects with a positive depression item (DEP(+); n = 73) in the Neuropsychiatric Inventory Questionnaire were subdivided to those receiving SSRI medication (SSRI(+); n = 24) and those without SSRI treatment (SSRI(-); n = 49). Longitudinal cognition (Δ-ADAS), amyloid deposition rate (standardized uptake value, using white matter as reference region (SUVRWM), and changes in grey matter volume were compared using common covariates. Analyses were performed separately in all subjects and in the subgroup of amyloid-positive subjects. Cognitive performance in DEP(+)/SSRI(+) subjects (Δ-ADAS: -5.0%) showed less deterioration with 2-year follow-up when compared to DEP(+)/SSRI(-) subjects (Δ-ADAS: +18.6%, p < 0.05), independent of amyloid SUVRWM at baseline. With SSRI treatment, the progression of grey matter atrophy was reduced (-0.9% versus -2.7%, p < 0.05), notably in fronto-temporal cortex. A slight trend towards lower amyloid deposition rate was observed in DEP(+)/SSRI(+) subjects versus DEP(+)/SSRI(-). Despite the lack of effect to amyloid PET, SSRI medication distinctly rescued the declining cognitive performance in cognitively affected patients with depressive symptoms, and likewise attenuated grey matter atrophy.

Disrupted white matter structural networks in healthy older adult APOE ε4 carriers - An international multicenter DTI study.

The ε4 allelic variant of the Apolipoprotein E gene (APOE ε4) is the best-established genetic risk factor for late-onset Alzheimer's disease (AD). White matter (WM) microstructural damages measured with Diffusion Tensor Imaging (DTI) represent an early sign of fiber tract disconnection in AD. We examined the impact of APOE ε4 on WM microstructure in elderly individuals from the multicenter European DTI Study on Dementia. Voxelwise statistical analysis of fractional anisotropy (FA), mean diffusivity, radial and axial diffusivity (MD, radD and axD respectively) was carried out using Tract-Based Spatial Statistics. Seventy-four healthy elderly individuals - 31 APOE ε4 carriers (APOE ε4+) and 43 APOE ε4 non-carriers (APOE ε4-) -were considered for data analysis. All the results were corrected for scanner acquisition protocols, age, gender and for multiple comparisons. APOE ε4+ and APOE ε4- subjects were comparable regarding sociodemographic features and global cognition. A significant reduction of FA and increased radD was found in the APOE ε4+ compared to the APOE ε4- in the cingulum, in the corpus callosum, in the inferior fronto-occipital and in the inferior longitudinal fasciculi, internal and external capsule. APOE ε4+, compared to APOE ε4- showed higher MD in the genu, right internal capsule, superior longitudinal fasciculus and corona radiate. Comparisons stratified by center supported the results obtained on the whole sample. These findings support previous evidence in monocentric studies indicating a modulatory role of APOE ɛ4 allele on WM microstructure in elderly individuals at risk for AD suggesting early vulnerability and/or reduced resilience of WM tracts involved in AD.

[18F]-THK5351 PET Correlates with Topology and Symptom Severity in Progressive Supranuclear Palsy.

Progressive supranuclear palsy (PSP) is a neurodegenerative movement disorder characterized by deposition of fibrillar aggregates of 4R tau-protein in neurons and glial cells of the brain. These deposits are a key neuropathological finding, allowing a diagnosis of "definite PSP," which is usually established post mortem. To date criteria for clinical diagnosis of PSP in vivo do not include biomarkers of tau pathology. For intervention trials, it is increasingly important to (i) establish biomarkers for an early diagnosis and (ii) to develop biomarkers that correlate with disease progression of PSP. [18F]-THK5351 is a novel PET-ligand that may afford in vivo visualization and quantification of tau-related alterations. We investigated binding characteristics of [18F]-THK5351 in patients with clinically diagnosed PSP and correlate tracer uptake with clinical findings. Eleven patients (68.4 ± 7.4 year; N = 6 female) with probable PSP according to current clinical criteria and nine healthy controls (71.7 ± 7.2 year; N = 4 female) underwent [18F]-THK5351 PET scanning. Voxel-wise statistical parametric comparison and volume-of-interest based quantification of standardized-uptake-values (SUV) were conducted using the cerebellar cortex as reference region. We correlated disease severity as measured with the help of the PSP Rating Scale (PSPRS) as well as several other clinical parameters with the individual PET findings. By voxel-wise mapping of [18F]-THK5351 uptake in the patient group we delineated typical distribution patterns that fit to known tau topology for PSP post mortem. Quantitative analysis indicated the strongest discrimination between PSP patients and healthy controls based on tracer uptake in the midbrain (+35%; p = 3.01E-7; Cohen's d: 4.0), followed by the globus pallidus, frontal cortex, and medulla oblongata. Midbrain [18F]-THK5351 uptake correlated well with clinical severity as measured by PSPRS (R = 0.66; p = 0.026). OCT and MRI delineated PSP patients from healthy controls by use of established discrimination thresholds but only OCT did as well correlate with clinical severity (R = 0.79; p = 0.024). Regional [18F]-THK5351 binding patterns correlated well with the established post mortem distribution of lesions in PSP and with clinical severity. The contribution of possible MAO-B binding to the [18F]-THK5351 signal needs to be further evaluated, but nevertheless [18F]-THK5351 PET may still serve as valuable biomarker for diagnosis of PSP.

Prefrontal Transcranial Direct Current Stimulation for Treatment of Schizophrenia With Predominant Negative Symptoms: A Double-Blind, Sham-Controlled Proof-of-Concept Study.

Negative symptoms are highly relevant in the long-term course of schizophrenia and are an important target domain for the development of novel interventions. Recently, transcranial direct current stimulation (tDCS) of the prefrontal cortex has been investigated as a treatment option in schizophrenia. In this proof-of-concept study, 20 schizophrenia patients with predominantly negative symptoms were randomized to either 10 sessions of add-on active (2 mA, 20min) or sham tDCS (anode: left DLPFC/F3; cathode: right supraorbital/F4). Primary outcome measure was the change in the Scale for the Assessment of Negative Symptoms (SANS) sum score; secondary outcomes included reduction in Positive and Negative Syndrome Scale (PANSS) scores and improvement of depressive symptoms, cognitive processing speed, and executive functioning. Sixteen patients underwent 4 functional connectivity magnetic resonance imaging (fcMRI) scans (pre and post 1st and pre and post 10th tDCS) to investigate changes in resting state network connectivity after tDCS. Per-protocol analysis showed a significantly greater decrease in SANS score after active (-36.1%) than after sham tDCS (-0.7%). PANSS sum scores decreased significantly more with active (-23.4%) than with sham stimulation (-2.2%). Explorative analysis of fcMRI data indicated changes in subgenual cortex and dorsolateral prefrontal cortex (DLPFC) connectivity within frontal-thalamic-temporo-parietal networks. The results of this first proof-of-concept study indicate that prefrontal tDCS may be a promising intervention for treatment of schizophrenia with predominant negative symptoms. Large-scale randomized controlled studies are needed to further establish prefrontal tDCS as novel treatment for negative symptoms in schizophrenia.