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Zusammenfassung: Die Untersuchung sozial-kognitiver Fähigkeiten kann zur Diagnostik kognitiver Störungen beitragen. In diesem Zusammenhang stellt sich die Frage, inwieweit sozial-kognitive Fähigkeiten in deutschsprachigen Memory-Kliniken (MK) untersucht werden. Wir führten dazu eine Befragung in 87 deutschsprachigen MK in Deutschland, österreich und der Schweiz durch. Es zeigte sich, dass die Untersuchung sozial-kognitiver Fähigkeiten mehrheitlich befürwortet wird, jedoch nur selten erfolgt. Die Mehrheit der MK könnte sich jedoch vorstellen, in Zukunft sozial-kognitive Diagnostik durchzuführen, vorausgesetzt, dass hierfür adäquate psychometrische Testverfahren vorliegen. Die Forderung der MK nach psychometrischen sozial-kognitiven Tests gewinnt an Bedeutung angesichts der Tatsache, dass die kürzlich publizierten ICD-11-Kriterien (International Statistical Classification of Diseases and Related Health Problems) die Untersuchung sozial-kognitiver Fähigkeiten bei der Abklärung einer kognitiven Störung empfehlen.

Background and objectives Early-stage behavioural variant frontotemporal dementia (bvFTD) is often misdiagnosed, highlighting the need for new diagnostic instruments. Based on the revised diagnostic criteria for bvFTD, we developed the Behavioural Dysfunction Questionnaire (BDQ). In this explorative study, we aimed to determine the best scoring and analytical method for the BDQ to discriminate between bvFTD and non-bvFTD patients. Materials and methods 34 patients with early-stage bvFTD, 56 with early-stage Alzheimer's disease dementia (ADD) and 41 with major depressive disorder (MDD) were recruited. We calculated BDQ-items with or without inclusion of a time criterion: (a) without time criterion, (b) with 10 years’ time criterion (symptom presence less than 10 years), and (c) with 3 years’ time criterion (symptom presentation within the first 3 years). Using these three differently calculated items, we generated six variables, i.e. 3*2 [BDQ-Global Score (BDQ-GS; domains average score); BDQ-Global Domain Score (BDQ-GDS; domains categorical score)]. Then, we performed univariate and bivariate (BDQ-GS and BDQ-GDS combined) ROC analyses. Results Models including BDQ-GS, BDQ-GDS or both variables combined discriminated similarly between groups. In contrast, models without time criterion or with 10 years’ time criterion discriminated better than models including variables with 3 years’ time criterion. These models discriminated highly (AUC = 85.98–87.78) between bvFTD and MDD and bvFTD and ADD, respectively. Conclusion BDQ-scores without any time criterion discriminated highly between early-stage bvFTD and non-bvFTD groups, which could improve the early diagnosis of bvFTD. With its standardised procedure, the BDQ is also appropriate for repeated assessments.

Emotion recognition (ER) is commonly impaired in many brain disorders. Therefore, its reliable and ecologically valid examination is a crucial part of any comprehensive neuropsychological assessment. In this regard, an established English-language test identifying deficits in ER is "The Awareness of Social Inference Test-Emotion Evaluation Test" (TASIT-EET). However, no comparable German-language ER test currently exists. In this study, we aimed to develop and preliminarily validate the first German-language adaption of TASIT-EET in healthy adults.We selected 22 scenes [three scenes per emotion (i.e., anger, disgust, fear, happiness, sadness, surprise, and neutral) and one practice scene] out of the 56 TASIT-EET scenes. In collaboration with a film institute and professional actors, we filmed each scene (except neutral) at three different emotional intensities. Then, we administered these intensity version scenes to 240 cognitively and mentally healthy participants, equally distributed in sex and age, ranging from 35 to 92 years.By applying Rasch analysis, the one intensity version per scene was selected that showed neither floor nor ceiling effects in participants whose ability in ER was in the medium range.We have conducted a preliminary validation of the first German-language adaption of TASIT-EET, i.e., the "Basel Version of the Awareness of Social Inference Test-Emotion Recognition" (BASIT-ER). The BASIT-ER comprises the strengths of the TASIT-EET, while it overcomes its limitations such as ceiling effects in healthy participants and the simple response format. Next, the BASIT-ER needs to be validated in clinical populations. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

We characterize the whole-brain N-acetyl-aspartate (WBNAA) and brain tissue fractions across the adult lifespan and test the hypothesis that, despite age-related atrophy, neuronal integrity (reflected by WBNAA) is preserved in normal aging. Two-hundred-and-seven participants: 133 cognitively intact older adults (73.6 ± 7.4 mean ± standard deviation, range: 60–90 year old) and 84 young (37.9 ± 11, range: 21–59 year old) were scanned with proton magnetic resonance spectroscopy and T1-weighted MRI. Their WBNAA, fractional brain parenchyma, and gray and white matter volumes (fBPV, fGM, and fWM) were compared and modeled as functions of age and sex. Compared with young, older-adults’ WBNAA was lower by ~35%, and fBPV, fGM and fWM were lower by ~10%. Linear regressions found 0.5%/year WBNAA and 0.2%/year fBPV and fGM declines, whereas fWM rose to age ~40 years, and declined thereafter. fBPV and fGM were 1.8% and 4% higher in women, with no sex decline rates difference. We conclude that contrary to our hypothesis, atrophy was accompanied by WBNAA decline. Across the entire age range, women's brains showed less atrophy than men's. Formulas to estimate WBNAA and brain tissue fractions in healthy adults are provided to help differentiate normal from abnormal aging.

The Memory Centres of several Swiss hospitals have set up a national online registry for Alzheimer's research, called www.BHR-suisse.org. This type of registry already exists in the United States (www.brainhealthregistry.org/) and the Netherlands (https://hersenonderzoek.nl/). It contributes, as do these initiating sites, to the creation of a global database of research partnersLes centres de la mémoire de plusieurs hôpitaux suisses ont créé un Registre national suisse en ligne pour la recherche sur Alzheimer, intitulé www.bhr-suisse.org. Ce type de registre existe déjà aux États-Unis (www.brainhealthregistry.org/) et aux Pays-Bas (hersenonderzoek.nl/). Il contribue, au même titre que ces sites initiateurs, à constituer une base de données globale de partenaires de recherche

Impairments of Theory of Mind (ToM) abilities occur in a wide range of brain disorders. Therefore, reliable and ecologically valid examination of these abilities is a crucial part of any comprehensive neuropsychological assessment. An established and ecologically valid, English-language test identifying deficits in ToM abilities is "The Awareness of Social Inference Test - Social Inference Minimal (TASIT-SIM)". However, no comparable German-language ToM test currently exists. In this study, we aimed to develop the first German-language adaption of TASIT-SIM in healthy adults. We selected 13 scenes [four scenes per message type (i.e., honesty, simple sarcasm, paradoxical sarcasm) and one practice scene] out of the 30 TASIT-SIM scenes. In collaboration with a film institute, we filmed each scene at three different intensities. These intensity version scenes were then administered to 240 healthy adults, equally distributed in sex and age, ranging from 35 to 92 years. By applying Rasch analysis, we selected intensity versions that showed neither floor nor ceiling effects in the majority of ToM questions in participants whose ToM abilities were in the medium range. In conclusion, we have developed the first German-language adaption of TASIT-SIM, i.e., the "Basel Version of the Awareness of Social Inference Test - Theory of Mind (BASIT-ToM)". The BASIT-ToM incorporates the strengths of TASIT-SIM, while overcoming its limitations such as inconsistencies in cinematic realization and ceiling effects in healthy participants. Next, the BASIT-ToM needs to be validated in healthy people and clinical populations.

In October 2019, a Swiss panel of experts met for the Dementia Summit in Brunnen, Switzerland, to discuss the latest scientific findings on basic and clinical research, as well as practical and political approaches to the challenges of dementia disorders in Switzerland. Here, we present the conference summary. To study pathophysiological changes, as well as the underlying mechanism of fluid biomarker changes, excellent experimental approaches, including transgenic mouse models, are available. Current knowledge about presymptomatic disease progression is largely derived from the longitudinal study of individuals with autosomal dominant mutations (Dominantly Inherited Alzheimer Network). Importantly, more than one third of identified dementia risk factors can be modified. For example, sleep disturbances are not only associated with dementia and neurodegeneration in specific brain regions, but also precede cognitive decline and contribute to the development of brain pathology. Regarding the neuropsychological examination of dementia disorders, standardised tests of social cognition, one of the six cognitive domains that must be assessed according to the fifth edition of the Diagnostic and Statistical Manual for Mental Disorders, are missing, but now under development. The most important new therapeutic approach in the treatment of Alzheimer’s disease is the current attempt to prevent β-amyloid accumulation. While until now clinical studies have failed because of side effects or insufficient clinical effectiveness, Biogen recently announced positive results of high doses of aducanumab, a monoclonal antibody against β-amyloid. Other approaches also show promise. In China, sodium oligomannate has been approved to treat Alzheimer's disease. The substance suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression. Assistive technologies for dementia patients can help identify relevant information for care and nursing, as well as measurements for clinical interventions. Dementia patients have a high risk of developing delirium, even in the home environment. Therefore, it is necessary to use and further develop multi-disciplinary and systematic detection and prevention strategies. Homecare models for dementia patients with multidisciplinary teams have been established and evaluated and should be expanded. Dementia is the third-leading cause of death in Switzerland. In palliative care for severe dementia, the improvement of quality of life is of primary importance. The goals of the National Dementia Strategy, to increase the quality of life in those affected and to reduce taboos surrounding the disease, are still unrealised. The need for further national and regional engagement in order to implement the different findings of the strategy has largely been acknowledged, and these implementations have become the core tasks of a national dementia platform.

Serial Position Effects (SPE) in wordlist learning provide a rich set of metrics of cognitive functioning. In this study, we systematically mapped the neuroanatomical correlates of SPEs across delays in Major and Minor Neurocognitive disorders. Primacy, middle, and recency SPE scores of the California Verbal Learning Test at Learning, Short delay, and Long delay in healthy controls and patients with neurodegenerative disease were correlated with MRI gray matter signal intensities (voxel-based morphometry, VBM). The VBM analyses revealed distinct patterns of brain-behavioral correlations depending on both the SPE and the time-point. Unlike patients, the healthy controls’ performance incrementally improved recall of primacy items from Learning to Short and to Long delay, i.e., primacy progression. Moreover, the proportion of correct primacy items recalled at long delay compared to Learning correlated with bilateral medial temporal lobe regions, which commonly bear the brunt of pathology of Alzheimer’s disease. The results implicate the primacy progression score as an accessible and sensitive measure for disease detection, progression, and therapeutic response in Major and Minor Neurocognitive disorders.

Tau is a microtubule stabilizing protein that forms aggregates in Alzheimer’s disease (AD). Tau derived from AD patients’ brains induces tau aggregation in a prion-like manner when injected into susceptible mouse models. Here we investigated whether cerebrospinal fluid (CSF) collected from patients diagnosed with probable AD or mild cognitive impairment (MCI) likely due to AD harbors a prion-like tau seeding potential. CSF was injected intrahippocampally into young P301S tau transgenic mice. CSF obtained from AD or MCI patients increased hippocampal tau hyperphosphorylation and tau tangle formation in these mice at 4 months post-seeding. Tau pathology was also accentuated in the contralateral hippocampus, and in anterior and posterior directions, indicative of spreading. We provide first evidence for in vivo prion-like properties of AD patients’ CSF, accelerating tau pathology in susceptible tau transgenic mice. This demonstrates that biologically active tau seeds reach the CSF compartment in AD. Further studies may help to evaluate strain specific properties of CSF derived tau bioseeds, and to assess their diagnostic potential. Electronic supplementary material The online version of this article (10.1186/s40478-019-0725-3) contains supplementary material, which is available to authorized users.

Objective Features of behavioral variant frontotemporal dementia (bvFTD) such as executive dysfunction, apathy, and impaired empathic abilities are also observed in major depressive disorder (MDD). This may contribute to the reason why early stage bvFTD is often misdiagnosed as MDD. New assessment tools are thus needed to improve early diagnosis of bvFTD. Although emotion processing is affected in bvFTD and MDD, growing evidence indicates that the pattern of emotion processing deficits varies between the two disorders. As such, emotion processing paradigms have substantial potentials to distinguish bvFTD from MDD. Design and Participants The current study compared 25 patients with bvFTD, 21 patients with MDD, 21 patients with Alzheimer disease (AD) dementia, and 31 healthy participants on a novel facial emotion intensity rating task. Stimuli comprised morphed faces from the Ekman and Friesen stimulus set containing faces of each sex with two different degrees of emotion intensity for each of the six basic emotions. Measurements and Results Analyses of covariance uncovered a significant dissociation between bvFTD and MDD patients in rating the intensity of negative emotions overall (i.e., bvFTD patients underrated negative emotions overall, whereas MDD patients overrated negative emotions overall compared with healthy participants). In contrast, AD dementia patients rated negative emotions similarly to healthy participants, suggesting no impact of cognitive deficits on rating facial emotions. Conclusions By strongly differentiating bvFTD and MDDpatients through negative facial emotions, this sensitive and short rating task might help improve the early diagnosis of bvFTD.

Connectivity in intrinsically connected networks (ICNs) may predict individual differences in cognition and behavior. The drastic alterations in socioemotional awareness of patients with behavioral variant frontotemporal dementia (bvFTD) are presumed to arise from changes in one such ICN, the salience network (SN). We examined how individual differences in SN connectivity are reflected in overt social behavior in healthy individuals and patients, both to provide neuroscientific insight into this key brain-behavior relationship, and to provide a practical tool to diagnose patients with early bvFTD. We measured SN functional connectivity and socioemotional sensitivity in 65 healthy older adults and 103 patients in the earliest stage [Clinical Dementia Rating (CDR) Scale score ≤1] of five neurodegenerative diseases [14 bvFTD, 29 Alzheimer's disease (AD), 20 progressive supranuclear palsy (PSP), 21 semantic variant primary progressive aphasia (svPPA), and 19 non-fluent variant primary progressive aphasia (nfvPPA)]. All participants underwent resting-state functional imaging and an informant described their responsiveness to subtle emotional expressions using the Revised Self-Monitoring Scale (RSMS). Higher functional connectivity in the SN, predominantly between the right anterior insula (AI) and both "hub" cortical and "interoceptive" subcortical nodes, predicted socioemotional sensitivity among healthy individuals, showing that socioemotional sensitivity is a behavioral marker of SN function, and particularly of right AI functional connectivity. The continuity of this relationship in both healthy and neurologically affected individuals highlights the role of socioemotional sensitivity as an early diagnostic marker of SN connectivity. Clinically, this is particularly important for identification of patients in the earliest stage of bvFTD, where the SN is selectively vulnerable.

The importance of including measures of emotion processing, such as tests of facial emotion recognition (FER), as part of a comprehensive neuropsychological assessment is being increasingly recognized. In clinical settings, FER tests need to be sensitive, short, and easy to administer, given the limited time available and patient limitations. Current tests, however, commonly use stimuli that either display prototypical emotions, bearing the risk of ceiling effects and unequal task difficulty, or are cognitively too demanding and time-consuming. To overcome these limitations in FER testing in patient populations, we aimed to define FER threshold levels for the six basic emotions in healthy individuals. Forty-nine healthy individuals between 52 and 79 years of age were asked to identify the six basic emotions at different intensity levels (25%, 50%, 75%, 100%, and 125% of the prototypical emotion). Analyses uncovered differing threshold levels across emotions and sex of facial stimuli, ranging from 50% up to 100% intensities. Using these findings as “healthy population benchmarks”, we propose to apply these threshold levels to clinical populations either as facial emotion recognition or intensity rating tasks. As part of any comprehensive social cognition test battery, this approach should allow for a rapid and sensitive assessment of potential FER deficits. (JINS, 2015, 21, 568–572)

Background Several cognitive, neuroimaging, and cerebrospinal fluid (CSF) markers predict conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia. However, predictors might be more or less powerful depending on the characteristics of the MCI sample. Objective To investigate which cognitive markers and biomarkers predict conversion to AD dementia and course of cognitive functioning in a MCI sample with a high proportion of early-stage MCI patients. Methods Variables known to predict progression in MCI patients and hypothesized to predict progression in early-stage MCI patients were selected. Cognitive (long-delay free recall, regional primacy score), imaging (hippocampal and entorhinal cortex volumes, fornix fractional anisotropy), and CSF (Aβ1-42/t-tau, Aβ1-42) variables from 36 MCI patients were analyzed with Cox regression and mixed-effect models to determine their individual and combined abilities to predict time to conversion to AD dementia and course of global cognitive functioning, respectively. Results Those variables hypothesized to predict the course of early-stage MCI patients were most predictive for MCI progression. Specifically, regional primacy score (a measure of word-list position learning) most consistently predicted conversion to AD dementia and course of cognitive functioning. Both the prediction of conversion and course of cognitive functioning were maximized by including CSF Aβ1-42 and fornix integrity biomarkers, respectively, indicating the complementary information carried by cognitive variables and biomarkers. Conclusion Predictors of MCI progression need to be interpreted in light of the characteristics of the respective MCI sample. Future studies should aim to compare predictive strengths of markers between early-stage and late-stage MCI patients.

Background: Mild cognitive impairment (MCI) is an intermediary state on the way to Alzheimer’s disease (AD). Little is known about whole brain concentration of the neuronal marker, N-acetylaspartate (NAA) in MCI patients. Objective: To test the hypothesis that since MCI and AD are both neurodegenerative, quantification of the NAA in their whole brain (WBNAA) could differentiate them from cognitively-intact matched controls. Methods: Proton MR spectroscopy to quantify the WBNAA was applied to 197 subjects (86 females) 72.6 ± 8.4 years old (mean ± standard deviation). Of these, 102 were cognitively intact, 42 diagnosed as MCI, and 53 as probable AD. Their WBNAA amounts were converted into absolute concentration by dividing with the brain volume segmented from the MRI that also yielded the fractional brain volume (fBPV), an atrophy metric. Results: WBNAA concentration of MCI and AD patients (10.5 ± 3.0 and 10.1 ± 2.9 mM) were not significantly different (p = 0.85). They were, however, highly significantly 25–29% lower than the 14.1 ± 2.4 mM of normal matched controls (p

Accurate self-awareness is essential for adapting one's tasks and goals to one's actual abilities. Patients with neurodegenerative diseases, particularly those with right frontal involvement, often present with poor self-awareness of their functional limitations that may exacerbate their already jeopardized decision-making and behaviour. We studied the structural neuroanatomical basis for impaired self-awareness among patients with neurodegenerative disease and healthy older adults. One hundred and twenty-four participants (78 patients with neurodegenerative diseases including Alzheimer's disease, behavioural variant frontotemporal dementia, right-temporal frontotemporal dementia, semantic variant and non-fluent variant primary progressive aphasia, and 46 healthy controls) described themselves on the Patient Competency Rating Scale, rating observable functioning across four domains (daily living activities, cognitive, emotional control, interpersonal). All participants underwent structural magnetic resonance imaging. Informants also described subjects' functioning on the same scale. Self-awareness was measured by comparing self and informant ratings. Group differences in discrepancy scores were analysed using general linear models, controlling for age, sex and disease severity. Compared with controls, patients with behavioural variant frontotemporal dementia overestimated their functioning in all domains, patients with Alzheimer's disease overestimated cognitive and emotional functioning, patients with right-temporal frontotemporal dementia overestimated interpersonal functioning, and patients with non-fluent aphasia overestimated emotional and interpersonal functioning. Patients with semantic variant aphasia did not overestimate functioning on any domain. To examine the neuroanatomic correlates of impaired self-awareness, discrepancy scores were correlated with brain volume using voxel-based morphometry. To identify the unique neural correlates of overlooking versus exaggerating deficits, overestimation and underestimation scores were analysed separately, controlling for age, sex, total intracranial volume and extent of actual functional decline. Atrophy related to overestimating one's functioning included bilateral, right greater than left frontal and subcortical regions, including dorsal superior and middle frontal gyri, lateral and medial orbitofrontal gyri, right anterior insula, putamen, thalamus, and caudate, and midbrain and pons. Thus, our patients' tendency to under-represent their functional decline was related to degeneration of domain-general dorsal frontal regions involved in attention, as well as orbitofrontal and subcortical regions likely involved in assigning a reward value to self-related processing and maintaining accurate self-knowledge. The anatomic correlates of underestimation (right rostral anterior cingulate cortex, uncorrected significance level) were distinct from overestimation and had a substantially smaller effect size. This suggests that underestimation or 'tarnishing' may be influenced by non-structural neurobiological and sociocultural factors, and should not be considered to be on a continuum with overestimation or 'polishing' of functional capacity, which appears to be more directly mediated by neural circuit dysfunction.

Background Neuroimaging studies examining neural substrates of impaired self-awareness in patients with neurodegenerative diseases have shown divergent results depending on the modality (cognitive, emotional, behavioral) of awareness. Evidence is accumulating to suggest that self-awareness arises from a combination of modality-specific and large-scale supramodal neural networks. Methods We investigated the structural substrates of patients' tendency to overestimate or underestimate their own capacity to demonstrate empathic concern for others. Subjects' level of empathic concern was measured using the Interpersonal Reactivity Index, and subject-informant discrepancy scores were used to predict regional atrophy pattern, using voxel-based morphometry analysis. Of the 102 subjects, 83 were patients with neurodegenerative diseases such as behavioral variant frontotemporal dementia (bvFTD) or semantic variant primary progressive aphasia (svPPA); the other 19 were healthy older adults. Results bvFTD and svPPA patients typically overestimated their level of empathic concern compared to controls, and overestimating one's empathic concern predicted damage to predominantly right-hemispheric anterior infero-lateral temporal regions, whereas underestimating one's empathic concern showed no neuroanatomical basis. Conclusions These findings suggest that overestimation and underestimation of one's capacity for empathic concern cannot be interpreted as varying degrees of the same phenomenon, but may arise from different pathophysiological processes. Damage to anterior infero-lateral temporal regions has been associated with semantic self-knowledge, emotion processing, and social perspective taking; neuropsychological functions partly associated with empathic concern itself. These findings support the hypothesis that—at least in the socioemotional domain—neural substrates of self-awareness are partly modality-specific.

Introduction Changes in personality differ qualitatively and quantitatively among patients with different neurodegenerative diseases, likely due to divergent patterns of regional neurodegeneration. Regional damage to circuits underlying various cognitive and emotional functions have been associated with interpersonal traits like dominance, extraversion, and warmth in patients with neurodegenerative diseases, suggesting that personality may in part be mediated by these more basic neuropsychological functions. In this study, we hypothesized that different combinations of cognitive, neuropsychiatric, and emotional measures would predict different interpersonal traits in patients with neurodegenerative diseases. Methods A battery of cognitive, neuropsychiatric, and emotional measures was administered to 286 patients with various neurodegenerative diseases such as Alzheimer’s disease, behavioral variant frontotemporal dementia, semantic dementia, and progressive supranuclear palsy, and informants described patients’ dominance, extraversion, and warmth using the Interpersonal Adjective Scales (IAS) personality questionnaire. Regression modeling was performed to identify which neuropsychological factors uniquely predicted current personality, controlling for age, gender, and premorbid personality. Results Social dominance covaried with patients’ capacity for cognitive control and verbal fluency. Conversely, warmth did not rely on these executive or verbal skills, but covaried primarily with patients’ capacity for emotional responsiveness. Extraversion, representing a blend of dominance and warmth, demonstrated an intermediate degree of relationship to both executive/verbal and emotional functions. Conclusions These findings suggest that different personality traits are partly subserved by specific cognitive and emotional functions in neurodegenerative disease patients. While this study was performed in the context of brain damage, the results raise the question of whether individual differences in these neuropsychological abilities may also underlie variability in normal personality.

Self-conscious emotions such as embarrassment arise when one's actions fail to meet salient social expectations and are accompanied by marked physiological and behavioral activation. We investigated the neural correlates of self-conscious emotional reactivity in 27 patients with behavioral variant frontotemporal dementia (bvFTD), a neurodegenerative disease that disrupts self-conscious emotion and targets brain regions critical for emotional functioning early in the disease course, and in 33 healthy older controls. Subjects participated in an embarrassing karaoke task in which they watched a video clip of themselves singing. They also watched a sad film clip; these data were used to control for non-self-conscious emotional reactivity in response to audiovisual stimuli. Using Freesurfer to quantify regional brain volumes from structural magnetic resonance imaging, right pregenual anterior cingulate cortex (pACC) gray matter volume was the only brain region that was a significant predictor of self-conscious emotion. Smaller pACC volume was associated with attenuated physiological and behavioral self-conscious emotional reactivity, and this relationship was not specific to diagnosis. We argue that these results reflect the significant role that right pACC plays in the visceromotor responding that accompanies self-conscious emotion and that neurodegeneration in this region may underlie the self-conscious emotional decline seen in bvFTD.

Social cognitive neuroscience is a novel field of interdisciplinary research that examines socio-emotional cognition and behavior by emphasizing the neural substrates of these processes. Insights from this biological perspective have established that socio-emotional processing does not happen in a sequential, but in a recursive and interlinked fashion; that individual brain regions are not associated with one, but multiple distinct social functions; and that brain regions are organized into dynamically interacting networks. These factors explain why it is difficult to pinpoint the neural substrates of particular social deficits in patients with brain diseases. With that said, there are specific brain regions that are highly specialized for the perception, regulation and modulation of emotion and behavior. This chapter will review key aspects of social processing beginning with their underlying neural substrates, including 1) perception of social signals, 2) social and emotional evaluation, and 3) behavioral response generation and selection. Case studies will be used to illustrate the real-life social deficits resulting from distinct patterns of neuroanatomic damage, highlighting the brain regions most critical for adequate social behavior.

Objective: Our purpose was to measure Aβ1–42, T-tau and P-tau181 in the cerebrospinal fluid (CSF) of patients with posterior cortical atrophy (PCA), a presenile dementia likely to represent a variant of Alzheimer’s disease (AD). Methods: CSF samples from 34 subjects including 9 patients with PCA, 11 age-matched patients with AD and 14 age-matched cognitively healthy controls were analyzed using commercially available ELISA kits. Results: The Aβ1–42, T-tau and P-tau181 levels in PCA patients differed significantly (p < 0.02) from those in healthy controls but were indistinguishable from subjects with a clinical diagnosis of AD. Conclusion: High T-tau and P-tau181 and low Aβ1–42 levels in PCA – typically observed in AD – indicate that the underlying pathology of PCA is usually AD. If these findings are replicated in PCA patients with autopsy-confirmed AD neuropathology, PCA patients may be eligible for disease-modifying AD treatments.

The functional importance of the basal lamina in Schwann cell development and in adult peripheral nerve fibers is well known. We have demonstrated previously by confocal microscopy that IgM deposits are present on the basal lamina of myelinating Schwann cells of nerve biopsies from patients with an anti-MAG IgM neuropathy. Therefore, the basal lamina was postulated to represent an early target for the uptake of autoantibodies on the surface of myelinated nerve fibers. In this study, the preparation of cell- and myelin-free basal lamina from human peripheral nerves, using a detergent-dependent method is described and characterized by immunohistochemical and biochemical analysis. Using these methods we demonstrated that an enrichment of basal lamina components of Schwann cells with extraction of myelin could be achieved. Western blot analysis and immunohistochemical characterization showed that anti-MAG IgM antibodies did not recognize an epitope on the basal lamina of normal nerves. The established method will allow in situ investigations of basal lamina components from human peripheral nerves in health and in disease, e.g. peripheral neuropathies of infectious or inflammatory origin.

Background It is unclear whether the predictive strength of established cognitive variables for progression to Alzheimer's disease (AD) dementia from mild cognitive impairment (MCI) varies depending on time to conversion. We investigated which cognitive variables were best predictors, and which of these variables remained predictive for patients with longer times to conversion. Methods Seventy-five participants with MCI were assessed on measures of learning, memory, language, and executive function. Relative predictive strengths of these measures were analyzed using Cox regression models. Results Measures of word-list position—namely, serial position scores—together with Short Delay Free Recall of word-list learning best predicted conversion to AD dementia. However, only serial position scores predicted those participants with longer time to conversion. Conclusions Results emphasize that the predictive strength of cognitive variables varies depending on time to conversion to dementia. Moreover, finer measures of learning captured by serial position scores were the most sensitive predictors of AD dementia.

Diffusion imaging is a promising marker of microstructural damage in neurodegenerative disorders, but interpretation of its relationship with underlying neuropathology can be complex. Here, we examined both volumetric and brain microstructure abnormalities in 13 amnestic patients with mild cognitive impairment (MCI), who progressed to probable Alzheimer's disease (AD) no earlier than 2 years after baseline scanning, in order to focus on early, and hence more sensitive, imaging markers. We compared them to 22 stable amnestic MCI patients with similar cognitive performance and episodic memory impairment but who did not show progression of symptoms for at least 3 years. Significant group differences were mainly found in the volume and microstructure of the left hippocampus, while white matter group differences were also found in the body of the fornix, left fimbria, and superior longitudinal fasciculus (SLF). Diffusion index abnormalities in the SLF were the sign of a subtle microstructural injury not detected by standard atrophy measures in the corresponding gray matter regions. The microstructural measure obtained in the left hippocampus using diffusion imaging showed the most substantial differences between the two groups and was the best single predictor of future progression to AD. An optimal prediction model (91% accuracy, 85% sensitivity, 96% specificity) was obtained by combining MRI measures and CSF protein biomarkers. These results highlight the benefit of using the information of brain microstructural damage, in addition to traditional gray matter volume, to detect early, subtle abnormalities in MCI prior to clinical progression to probable AD and, in combination with CSF markers, to accurately predict such progression.

We hypothesize that normal aging implies neuronal durability, reflected by age-independent concentrations of their marker—the amino acid derivative N-acetylaspartate (NAA). To test this, we obtained the whole-brain and whole-head N-acetylaspartate concentrations (WBNAA and WHNAA) with proton magnetic resonance (MR) spectroscopy; and the fractional brain parenchyma volume (fBPV)—a metric of atrophy, by segmenting the magnetic resonance image (MRI) from 42 (18 male) healthy young (31.9 ± 5.8 years old) and 100 (64 male, 72.6 ± 7.3 years old) cognitively normal elderly. The 12.8 ± 1.9 mM WBNAA of the young was not significantly different from the 13.1 ± 3.1 mM in the elderly (p > 0.05). In contrast, both fBPV (87.3 ± 4.7% vs. 74.8 ± 4.8%) and WHNAA (11.1 ± 1.7 mM vs. 9.8 ± 2.4 mM) were significantly higher in the young (approximately 14%; p < 0.0001 for both). The similarity in mean WBNAA between 2 cohorts 4 decades of normal aging apart suggests that neuronal integrity is maintained across the lifespan. Clinically, WBNAA could be used as a marker for normal (hence, also abnormal) brain aging. In contrast, WHNAA and fBPV seem age-related suggesting that brain atrophy may occur without compromising the remaining tissue.

We compared the performance of the Meso Scale Diagnostics electrochemiluminescence (MSD) multiplex assay for t-tau and p-tau(231), originally developed for measurement of brain cell extract and tissue cultures, with the established standard method, the Innogenetics ELISA for total and p-tau(181). The methods were also clinically evaluated with 120 samples from our mono center population. The established Innogenetics ELISA procedures have been well optimized to measure patient samples in the normal and pathological range. Compared to the MSD they were superior in the limit of detection for total as well as p-tau. The obtained reference values for our normal controls were in the upper third of the published studies. Innogenetics tau, Innogenetics p-tau(181) and MSD t-tau differentiated the Alzheimer's (n=44) and minimal impairment group (MCI, n=39) from normal controls (n=37), but the MCI group was not statistically different from the normal controls. The MSD multiplex assay measured t-tau adequately but p-tau(231) could not differentiate normal from pathological results in CSF due to the high limit of detection. Both procedures however, have to be further standardized and complemented by adequate internal and external quality control schemes to qualify for routine analysis in a medical laboratory.

Background Different degenerative brain diseases result in distinct personality changes as a result of divergent patterns of brain damage; however, little is known about the natural history of these personality changes throughout the course of each disease. Objective To investigate how interpersonal traits change as a function of degenerative brain disease type and severity. Methods Using the Interpersonal Adjective Scales, informant ratings of retrospective premorbid and current scores for dominance, extraversion, warmth and ingenuousness were collected annually for 1 to 4 years on 188 patients (67 behavioural variant frontotemporal dementia (bvFTD), 40 semantic dementia (SemD), 81 Alzheimer9s disease (AD)) and 65 older healthy controls. Using random coefficient models, interpersonal behaviour scores at very mild, mild or moderate-to-severe disease stages were compared within and between patient groups. Results Group-level changes from premorbid personality occurred as a function of disease type and severity, and were apparent even at a very mild disease stage (Clinical Dementia Rating=0.5) for all three diseases. Decreases in interpersonal traits were associated with emotional affiliation (ie, extraversion, warmth and ingenuousness) and more rigid interpersonal behaviour differentiated bvFTD and SemD patients from AD patients. Conclusions Specific changes in affiliative interpersonal traits differentiate degenerative brain diseases even at a very mild disease stage, and patterns of personality change differ across bvFTD, SemD and AD with advancing disease. This study describes the typical progression of change of interpersonal traits in each disease, improving the ability of clinicians and caregivers to predict and plan for symptom progression.

Successful navigation of the social world requires the ability to recognize and track emotions as they unfold and change dynamically. Neuroimaging and neurological studies of emotion recognition have primarily focused on the ability to identify the emotion shown in static photographs of facial expressions, showing correlations with the amygdala as well as temporal and frontal brain regions. In the current study we examined the neural correlates of continuously tracking dynamically-changing emotions. Fifty-nine patients with diverse neurodegenerative diseases used a rating dial to track continuously how positive or how negative the character in a film clip felt. Tracking accuracy was determined by comparing participants’ ratings with the ratings of 10 normal control participants. The relationship between tracking accuracy and regional brain tissue content was examined using voxel-based morphometry. Low tracking accuracy was primarily associated with gray matter loss in the right lateral orbitofrontal cortex (OFC). Our finding that the right OFC is critical to the ability to track dynamically-changing emotions is consistent with previous research showing right OFC involvement in both socioemotional understanding and modifying responding in changing situations.

Our purpose was to measure Abeta(1-42), T-tau and P-tau(181) in the cerebrospinal fluid (CSF) of patients with posterior cortical atrophy (PCA), a presenile dementia likely to represent a variant of Alzheimer's disease (AD).CSF samples from 34 subjects including 9 patients with PCA, 11 age-matched patients with AD and 14 age-matched cognitively healthy controls were analyzed using commercially available ELISA kits.The Abeta(1-42), T-tau and P-tau(181) levels in PCA patients differed significantly (p0.02) from those in healthy controls but were indistinguishable from subjects with a clinical diagnosis of AD.High T-tau and P-tau(181) and low Abeta(1-42) levels in PCA - typically observed in AD - indicate that the underlying pathology of PCA is usually AD. If these findings are replicated in PCA patients with autopsy-confirmed AD neuropathology, PCA patients may be eligible for disease-modifying AD treatments.

Several functional and structural imaging studies have investigated the neural basis of personality in healthy adults, but human lesions studies are scarce. Personality changes are a common symptom in patients with neurodegenerative diseases like frontotemporal dementia (FTD) and semantic dementia (SD), allowing a unique window into the neural basis of personality. In this study, we used the Interpersonal Adjective Scales to investigate the structural basis of eight interpersonal traits (dominance, arrogance, coldness, introversion, submissiveness, ingenuousness, warmth, and extraversion) in 257 subjects: 214 patients with neurodegenerative diseases such as FTD, SD, progressive non-fluent aphasia, Alzheimer’s disease, amnestic mild cognitive impairment, corticobasal degeneration, and progressive supranuclear palsy and 43 healthy elderly people. Measures of interpersonal traits were correlated with regional atrophy pattern using voxel-based morphometry (VBM) analysis of structural MR images. Interpersonal traits mapped onto distinct brain regions depending on the degree to which they involved agency and affiliation. Interpersonal traits high in agency related to left dorsolateral prefrontal and left lateral frontopolar regions, whereas interpersonal traits high in affiliation related to right ventromedial prefrontal and right anteromedial temporal regions. Consistent with the existing literature on neural networks underlying social cognition, these results indicate that brain regions related to externally-focused, executive control-related processes underlie agentic interpersonal traits such as dominance, whereas brain regions related to internally-focused, emotion- and reward-related processes underlie affiliative interpersonal traits such as warmth. In addition, these findings indicate that interpersonal traits are subserved by complex neural networks rather than discrete anatomic areas.

While sarcasm can be conveyed solely through contextual cues such as counterfactual or echoic statements, face-to-face sarcastic speech may be characterized by specific paralinguistic features that alert the listener to interpret the utterance as ironic or critical, even in the absence of contextual information. We investigated the neuroanatomy underlying failure to understand sarcasm from dynamic vocal and facial paralinguistic cues. Ninety subjects (20 frontotemporal dementia, 11 semantic dementia [SemD], 4 progressive non-fluent aphasia, 27 Alzheimer's disease, 6 corticobasal degeneration, 9 progressive supranuclear palsy, 13 healthy older controls) were tested using the Social Inference - Minimal subtest of The Awareness of Social Inference Test (TASIT). Subjects watched brief videos depicting sincere or sarcastic communication and answered yes-no questions about the speaker's intended meaning. All groups interpreted Sincere (SIN) items normally, and only the SemD group was impaired on the Simple Sarcasm (SSR) condition. Patients failing the SSR performed more poorly on dynamic emotion recognition tasks and had more neuropsychiatric disturbances, but had better verbal and visuospatial working memory than patients who comprehended sarcasm. Voxel-based morphometry analysis of SSR scores in SPM5 demonstrated that poorer sarcasm comprehension was predicted by smaller volume in bilateral posterior parahippocampi (PHc), temporal poles, and R medial frontal pole (pFWE