The Revised Self-Monitoring Scale detects early impairment of social cognition in genetic frontotemporal dementia within the GENFI cohort

Abstract Background Although social cognitive dysfunction is a major feature of frontotemporal dementia (FTD), it has been poorly studied in familial forms. A key goal of studies is to detect early cognitive impairment using validated measures in large patient cohorts. Methods We used the Revised Self-Monitoring Scale (RSMS) as a measure of socioemotional sensitivity in 730 participants from the genetic FTD initiative (GENFI) observational study: 269 mutation-negative healthy controls, 193 C9orf72 expansion carriers, 193 GRN mutation carriers and 75 MAPT mutation carriers. All participants underwent the standardised GENFI clinical assessment including the ‘CDR® plus NACC FTLD’ scale and RSMS. The RSMS total score and its two subscores, socioemotional expressiveness (EX score) and modification of self-presentation (SP score) were measured. Volumetric T1-weighted magnetic resonance imaging was available from 377 mutation carriers for voxel-based morphometry (VBM) analysis. Results The RSMS was decreased in symptomatic mutation carriers in all genetic groups but at a prodromal stage only in the C9orf72 (for the total score and both subscores) and GRN (for the modification of self-presentation subscore) groups. RSMS score correlated with disease severity in all groups. The VBM analysis implicated an overlapping network of regions including the orbitofrontal cortex, insula, temporal pole, medial temporal lobe and striatum. Conclusions The RSMS indexes socioemotional impairment at an early stage of genetic FTD and may be a suitable outcome measure in forthcoming trials.

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The Revised Self-monitoring Scale Detects Early Impairment of Social Cognition in Genetic Frontotemporal Dementia Within the GENFI Cohort

10.21203/rs.3.rs-230933/v1 ◽

2021 ◽

Author(s):

Hannah Daisy Franklin ◽

Lucy L Russell ◽

Georgia Peakman ◽

Caroline V Greaves ◽

Martina Bocchetta ◽

...

Keyword(s):

Frontotemporal Dementia ◽

Medial Temporal Lobe ◽

Social Cognitive ◽

Early Stage ◽

Self Monitoring ◽

Self Presentation ◽

Genetic Groups ◽

Mutation Carriers ◽

Large Patient ◽

Weighted Magnetic Resonance Imaging

Abstract BackgroundAlthough social cognitive dysfunction is a major feature of frontotemporal dementia (FTD) it has been poorly studied in familial forms. A key goal of studies is to detect early cognitive impairment using validated measures in large patient cohorts. MethodsWe used the Revised Self-Monitoring Scale (RSMS) as a measure of socioemotional sensitivity in 730 participants from the Genetic FTD initiative (GENFI) observational study: 269 mutation-negative healthy controls, 193 C9orf72 expansion carriers, 193 GRN mutation carriers and 75 MAPT mutation carriers. All participants underwent the standardised GENFI clinical assessment including the ‘CDR® plus NACC FTLD’ scale and RSMS. The RSMS Total score and its two subscores, socioemotional expressiveness (EX score), and modification of self-presentation (SP score) were measured. Volumetric T1-weighted magnetic resonance imaging was available from 377 mutation carriers for voxel-based morphometry (VBM) analysis. ResultsThe RSMS was decreased in symptomatic mutation carriers in all genetic groups but at a prodromal stage only in the C9orf72 (for the total score and both subscores), and GRN (for the modification of self-presentation subscore) groups. RSMS score correlated with disease severity in all groups. The VBM analysis implicated an overlapping network of regions including the orbitofrontal cortex, insula, temporal pole, medial temporal lobe and striatum. ConclusionsThe RSMS indexes socioemotional impairment at an early stage of genetic FTD, and may be a suitable outcome measure in forthcoming trials.

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Comparison of clinical rating scales in genetic frontotemporal dementia within the GENFI cohort

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2021-326868 ◽

2021 ◽

pp. jnnp-2021-326868

Author(s):

Georgia Peakman ◽

Lucy L Russell ◽

Rhian S Convery ◽

Jennifer M Nicholas ◽

John C Van Swieten ◽

...

Keyword(s):

Frontotemporal Dementia ◽

Disease Severity ◽

Outcome Measures ◽

Severe Disease ◽

Genetic Group ◽

Control Group ◽

Sample Sizes ◽

Genetic Groups ◽

Mutation Carriers ◽

The Mean

BackgroundTherapeutic trials are now underway in genetic forms of frontotemporal dementia (FTD) but clinical outcome measures are limited. The two most commonly used measures, the Clinical Dementia Rating (CDR)+National Alzheimer’s Disease Coordinating Center (NACC) Frontotemporal Lobar Degeneration (FTLD) and the FTD Rating Scale (FRS), have yet to be compared in detail in the genetic forms of FTD.MethodsThe CDR+NACC FTLD and FRS were assessed cross-sectionally in 725 consecutively recruited participants from the Genetic FTD Initiative: 457 mutation carriers (77 microtubule-associated protein tau (MAPT), 187 GRN, 193 C9orf72) and 268 family members without mutations (non-carrier control group). 231 mutation carriers (51 MAPT, 92 GRN, 88 C9orf72) and 145 non-carriers had available longitudinal data at a follow-up time point.ResultsCross-sectionally, the mean FRS score was lower in all genetic groups compared with controls: GRN mutation carriers mean 83.4 (SD 27.0), MAPT mutation carriers 78.2 (28.8), C9orf72 mutation carriers 71.0 (34.0), controls 96.2 (7.7), p<0.001 for all comparisons, while the mean CDR+NACC FTLD Sum of Boxes was significantly higher in all genetic groups: GRN mutation carriers mean 2.6 (5.2), MAPT mutation carriers 3.2 (5.6), C9orf72 mutation carriers 4.2 (6.2), controls 0.2 (0.6), p<0.001 for all comparisons. Mean FRS score decreased and CDR+NACC FTLD Sum of Boxes increased with increasing disease severity within each individual genetic group. FRS and CDR+NACC FTLD Sum of Boxes scores were strongly negatively correlated across all mutation carriers (rs=−0.77, p<0.001) and within each genetic group (rs=−0.67 to −0.81, p<0.001 in each group). Nonetheless, discrepancies in disease staging were seen between the scales, and with each scale and clinician-judged symptomatic status. Longitudinally, annualised change in both FRS and CDR+NACC FTLD Sum of Boxes scores initially increased with disease severity level before decreasing in those with the most severe disease: controls −0.1 (6.0) for FRS, −0.1 (0.4) for CDR+NACC FTLD Sum of Boxes, asymptomatic mutation carriers −0.5 (8.2), 0.2 (0.9), prodromal disease −2.3 (9.9), 0.6 (2.7), mild disease −10.2 (18.6), 3.0 (4.1), moderate disease −9.6 (16.6), 4.4 (4.0), severe disease −2.7 (8.3), 1.7 (3.3). Sample sizes were calculated for a trial of prodromal mutation carriers: over 180 participants per arm would be needed to detect a moderate sized effect (30%) for both outcome measures, with sample sizes lower for the FRS.ConclusionsBoth the FRS and CDR+NACC FTLD measure disease severity in genetic FTD mutation carriers throughout the timeline of their disease, although the FRS may be preferable as an outcome measure. However, neither address a number of key symptoms in the FTD spectrum, for example, motor and neuropsychiatric deficits, which future scales will need to incorporate.

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Modelling the cascade of biomarker changes in GRN-related frontotemporal dementia

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2020-323541 ◽

2021 ◽

pp. jnnp-2020-323541

Author(s):

Jessica L Panman ◽

Vikram Venkatraghavan ◽

Emma L van der Ende ◽

Rebecca M E Steketee ◽

Lize C Jiskoot ◽

...

Keyword(s):

White Matter ◽

Frontotemporal Dementia ◽

Disease Severity ◽

Grey Matter ◽

Clinical Stage ◽

Data Driven ◽

Grey Matter Volume ◽

Matter Volume ◽

Mutation Carriers ◽

Individual Disease

ObjectiveProgranulin-related frontotemporal dementia (FTD-GRN) is a fast progressive disease. Modelling the cascade of multimodal biomarker changes aids in understanding the aetiology of this disease and enables monitoring of individual mutation carriers. In this cross-sectional study, we estimated the temporal cascade of biomarker changes for FTD-GRN, in a data-driven way.MethodsWe included 56 presymptomatic and 35 symptomatic GRN mutation carriers, and 35 healthy non-carriers. Selected biomarkers were neurofilament light chain (NfL), grey matter volume, white matter microstructure and cognitive domains. We used discriminative event-based modelling to infer the cascade of biomarker changes in FTD-GRN and estimated individual disease severity through cross-validation. We derived the biomarker cascades in non-fluent variant primary progressive aphasia (nfvPPA) and behavioural variant FTD (bvFTD) to understand the differences between these phenotypes.ResultsLanguage functioning and NfL were the earliest abnormal biomarkers in FTD-GRN. White matter tracts were affected before grey matter volume, and the left hemisphere degenerated before the right. Based on individual disease severities, presymptomatic carriers could be delineated from symptomatic carriers with a sensitivity of 100% and specificity of 96.1%. The estimated disease severity strongly correlated with functional severity in nfvPPA, but not in bvFTD. In addition, the biomarker cascade in bvFTD showed more uncertainty than nfvPPA.ConclusionDegeneration of axons and language deficits are indicated to be the earliest biomarkers in FTD-GRN, with bvFTD being more heterogeneous in disease progression than nfvPPA. Our data-driven model could help identify presymptomatic GRN mutation carriers at risk of conversion to the clinical stage.

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Analysis of brain atrophy and local gene expression in genetic frontotemporal dementia

Brain Communications ◽

10.1093/braincomms/fcaa122 ◽

2020 ◽

Vol 2 (2) ◽

Cited By ~ 1

Author(s):

Andre Altmann ◽

David M Cash ◽

Martina Bocchetta ◽

Carolin Heller ◽

Regina Reynolds ◽

...

Keyword(s):

Gene Expression ◽

Frontotemporal Dementia ◽

Cell Function ◽

Neurodegenerative Disorder ◽

Positive Association ◽

Negative Association ◽

Marker Genes ◽

Gene Set ◽

Genetic Groups ◽

Cortical Regions

Abstract Frontotemporal dementia is a heterogeneous neurodegenerative disorder characterized by neuronal loss in the frontal and temporal lobes. Despite progress in understanding which genes are associated with the aetiology of frontotemporal dementia, the biological basis of how mutations in these genes lead to cell loss in specific cortical regions remains unclear. In this work, we combined gene expression data for 16 772 genes from the Allen Institute for Brain Science atlas with brain maps of grey matter atrophy in symptomatic C9orf72, GRN and MAPT mutation carriers obtained from the Genetic Frontotemporal dementia Initiative study. No significant association was seen between C9orf72, GRN and MAPT expression and the atrophy patterns in the respective genetic groups. After adjusting for spatial autocorrelation, between 1000 and 5000 genes showed a negative or positive association with the atrophy pattern within each individual genetic group, with the most significantly associated genes being TREM2, SSBP3 and GPR158 (negative association in C9Orf72, GRN and MAPT respectively) and RELN, MXRA8 and LPA (positive association in C9Orf72, GRN and MAPT respectively). An overrepresentation analysis identified a negative association with genes involved in mitochondrial function, and a positive association with genes involved in vascular and glial cell function in each of the genetic groups. A set of 423 and 700 genes showed significant positive and negative association, respectively, with atrophy patterns in all three maps. The gene set with increased expression in spared cortical regions was enriched for neuronal and microglial genes, while the gene set with increased expression in atrophied regions was enriched for astrocyte and endothelial cell genes. Our analysis suggests that these cell types may play a more active role in the onset of neurodegeneration in frontotemporal dementia than previously assumed, and in the case of the positively associated cell marker genes, potentially through emergence of neurotoxic astrocytes and alteration in the blood–brain barrier, respectively.

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Prophylactic irradiation to the contralateral breast for BRCA mutation carriers with early-stage breast cancer

Annals of Oncology ◽

10.1093/annonc/mdy515 ◽

2019 ◽

Vol 30 (3) ◽

pp. 412-417 ◽

Cited By ~ 8

Author(s):

E. Evron ◽

A.M. Ben-David ◽

H. Goldberg ◽

G. Fried ◽

B. Kaufman ◽

...

Keyword(s):

Breast Cancer ◽

Early Stage ◽

Brca Mutation ◽

Contralateral Breast ◽

Early Stage Breast Cancer ◽

Mutation Carriers ◽

Brca Mutation Carriers ◽

Prophylactic Irradiation

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The Dark Triad and the self-presentation variables of socially desirable responding and self-monitoring

Personality and Individual Differences ◽

10.1016/j.paid.2017.09.007 ◽

2018 ◽

Vol 120 ◽

pp. 234-237 ◽

Cited By ~ 22

Author(s):

Christopher Marcin Kowalski ◽

Radosław Rogoza ◽

Philip A. Vernon ◽

Julie Aitken Schermer

Keyword(s):

Dark Triad ◽

The Self ◽

Socially Desirable Responding ◽

Self Monitoring ◽

Self Presentation

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Nascent entrepreneur characteristic predictors of early-stage entrepreneurship outcomes

Journal of Small Business and Enterprise Development ◽

10.1108/jsbed-08-2019-0283 ◽

2021 ◽

Vol ahead-of-print (ahead-of-print) ◽

Author(s):

Stephen E. Lanivich ◽

Laci M. Lyons ◽

Anthony R. Wheeler

Keyword(s):

Social Cognitive ◽

Cognitive Theory ◽

Early Stage ◽

Fear Of Failure ◽

Nascent Entrepreneurs ◽

Nascent Entrepreneurship ◽

Content Type ◽

Assistance Programs ◽

Perceived Success ◽

Core Self

PurposeSocial cognitive theory suggests that entrepreneurs' characteristics affect entrepreneurial outcomes through interaction with their environment. This study examines the relationship between entrepreneurs' characteristics and performance in the context of entrepreneurial nascence.Design/methodology/approachThis study investigated lagged-panel responses from a sample of 100 confirmed nascent entrepreneurs. Data collected on three separate occasions included core self-evaluations, commitment, fear of failure and success. PLS analysis was used to assess mediation of commitment on the self-evaluation – success relationship.FindingsCore self-evaluations are an important predictor of entrepreneurial success in nascent-stage entrepreneurs participating in pre-venture assistance programs; positively affecting success and commitment, while negatively affecting fear of failure.Research limitations/implicationsThis investigation contributes to a fuller understanding of social cognitive theory as it pertains to nascent entrepreneurship. Furthermore, contrary to general expectations found in the entrepreneurship literature, the authors uncover a context where entrepreneurs' characteristics are relevant predictors of early entrepreneurial outcomes.Practical implicationsResults showed core self-evaluations as a robust predictor of perceived success in nascent entrepreneurs. Administrators of pre-venture assistance programs should consider screening applicants to programs designed to assist nascent entrepreneurial opportunity development for signs of high core self-evaluations.Originality/valueThis study advances theory by (1) demonstrating the value of assessing nascent entrepreneurs' core self-evaluations as a specific predictor of early-stage entrepreneurial outcomes, (2) suggesting social interaction amidst participation in pre-venture assistance programs makes commitment a salient part of perceived success and (3) providing evidence that entrepreneur-level characteristics need consideration in the context of nascent entrepreneurship and pre-venture assistance programs.

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What Types of Leaders Fight for “Face”?

Who Fights for Reputation ◽

10.23943/princeton/9780691181288.003.0002 ◽

2018 ◽

pp. 19-43

Author(s):

Keren Yarhi-Milo

Keyword(s):

Use Of Force ◽

Large Body ◽

Military Force ◽

Social Situations ◽

Self Monitoring ◽

Self Presentation ◽

Ideal Types ◽

International Reputation ◽

Willingness To Use ◽

And Control

This chapter discusses what self-monitoring is, and how and why individuals differ in their self-monitoring dispositions. Self-monitoring concerns the extent to which individuals strategically cultivate their public appearances. A very large body of scholarship reviews how individuals differ in the extent to which they monitor and control their self-presentation in social situations. The literature distinguishes between two ideal-types of individuals: high self-monitors and low self-monitors. On average, high self-monitors are more likely to be concerned about reputation for resolve compared to low self-monitor individuals, and those tendencies could be moderated by overall dispositions about use of force. The chapter then explains how individuals’ beliefs about the efficacy of military force have an important intervening effect on whether a given leader will fight for reputation. It classifies leaders with regard to their willingness to use military instruments for international reputation into four ideal-types: reputation crusaders, reputation believers, reputation skeptics, and reputation critics.

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