scholarly journals Education modulates brain maintenance in presymptomatic frontotemporal dementia

2019 ◽  
Vol 90 (10) ◽  
pp. 1124-1130 ◽  
Author(s):  
Stefano Gazzina ◽  
Mario Grassi ◽  
Enrico Premi ◽  
Maura Cosseddu ◽  
Antonella Alberici ◽  
...  
Keyword(s):  
At Risk ◽  
Frontotemporal Dementia ◽  
Grey Matter ◽  
Principal Component ◽  
Grey Matter Volume ◽  
Brain Reserve ◽  
Matter Volume ◽  
Brain Maintenance ◽  
Over Time

ObjectiveCognitively engaging lifestyles have been associated with reduced risk of conversion to dementia. Multiple mechanisms have been advocated, including increased brain volumes (ie, brain reserve) and reduced disease progression (ie, brain maintenance). In cross-sectional studies of presymptomatic frontotemporal dementia (FTD), higher education has been related to increased grey matter volume. Here, we examine the effect of education on grey matter loss over time.MethodsTwo-hundred twenty-nine subjects at-risk of carrying a pathogenic mutation leading to FTD underwent longitudinal cognitive assessment and T1-weighted MRI at baseline and at 1 year follow-up. The first principal component score of the graph-Laplacian Principal Component Analysis on 112 grey matter region-of-interest volumes was used to summarise the grey matter volume (GMV). The effects of education on cognitive performances and GMV at baseline and on the change between 1 year follow-up and baseline (slope) were tested by Structural Equation Modelling.ResultsHighly educated at-risk subjects had better cognition and higher grey matter volume at baseline; moreover, higher educational attainment was associated with slower loss of grey matter over time in mutation carriers.ConclusionsThis longitudinal study demonstrates that even in presence of ongoing pathological processes, education may facilitate both brain reserve and brain maintenance in the presymptomatic phase of genetic FTD.

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

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.

scholarly journals Neuroanatomical correlates of different vulnerability states for psychosis and their clinical outcomes

2009 ◽  
Vol 195 (3) ◽  
pp. 218-226 ◽  
Author(s):  
Nikolaos Koutsouleris ◽  
Gisela J. E. Schmitt ◽  
Christian Gaser ◽  
Ronald Bottlender ◽  
Johanna Scheuerecker ◽  
...  
Keyword(s):  
At Risk ◽  
Clinical Outcome ◽  
Mental State ◽  
Grey Matter ◽  
Mental States ◽  
Grey Matter Volume ◽  
Healthy Controls ◽  
Imaging Data ◽  
Matter Volume ◽  
At Risk Mental State

BackgroundStructural brain abnormalities have been described in individuals with an at-risk mental state for psychosis. However, the neuroanatomical underpinnings of the early and late at-risk mental state relative to clinical outcome remain unclear.AimsTo investigate grey matter volume abnormalities in participants in a putatively early or late at-risk mental state relative to their prospective clinical outcome.MethodVoxel-based morphometry of magnetic resonance imaging data from 20 people with a putatively early at-risk mental state (ARMS–E group) and 26 people with a late at-risk mental state (ARMS–L group) as well as from 15 participants with at-risk mental states with subsequent disease transition (ARMS–T group) and 18 participants without subsequent disease transition (ARMS–NT group) were compared with 75 healthy volunteers.ResultsCompared with healthy controls, ARMS–L participants had grey matter volume losses in frontotemporolimbic structures. Participants in the ARMS–E group showed bilateral temporolimbic alterations and subtle prefrontal abnormalities. Participants in the ARMS–T group had prefrontal alterations relative to those in the ARMS–NT group and in the healthy controls that overlapped with the findings in the ARMS–L group.ConclusionsBrain alterations associated with the early at-risk mental state may relate to an elevated susceptibility to psychosis, whereas alterations underlying the late at-risk mental state may indicate a subsequent transition to psychosis.

scholarly journals Structural brain abnormalities in individuals with an at-risk mental state who later develop psychosis

2007 ◽  
Vol 191 (S51) ◽  
pp. s69-s75 ◽  
Author(s):  
Stefan J. Borgwardt ◽  
Philip K. McGuire ◽  
Jacqueline Aston ◽  
Gregor Berger ◽  
Paola Dazzan ◽  
...  
Keyword(s):  
At Risk ◽  
Healthy Volunteers ◽  
Mental State ◽  
Grey Matter ◽  
First Episode ◽  
Grey Matter Volume ◽  
Psychotic Illness ◽  
Matter Volume ◽  
Structural Brain ◽  
At Risk Mental State

BackgroundNeuroanatomical abnormalities are a well-established feature of schizophrenia. However, the timing of their emergence and the extent to which they are related to vulnerability to the disorder as opposed to psychotic illness itself is unclearAimsTo assess regional grey matter volume in the at-risk individuals who subsequently developed psychosisMethodMagnetic resonance imaging data from at-risk individuals who developed psychosis (n = 12) within the following 25 months were compared with data from healthy volunteers (n=22) and people with first-episode psychosis (n=25)ResultsCompared with healthy volunteers, individuals who subsequently developed psychosis had smaller grey matter volume in the posterior cingulate gyrus, precuneus, and paracentral lobule bilaterally and in the left superior parietal lobule, and greater grey matter volume in a left parietal/posterior temporal region. Compared with first-episode patients, they had relatively greater grey matter volume in the temporal gyrus bilaterally and smaller grey matter volume in the right lentiform nucleusConclusionsSome of the structural brain abnormalities in individuals with an at-risk mental state may be related to an increased vulnerability to psychosis, while others are associated with the development of a psychotic illness

scholarly journals Baseline grey matter volume of non-transitioned “ultra high risk” for psychosis individuals with and without attenuated psychotic symptoms at long-term follow-up

2016 ◽  
Vol 173 (3) ◽  
pp. 152-158 ◽  
Author(s):  
Vanessa L. Cropley ◽  
Ashleigh Lin ◽  
Barnaby Nelson ◽  
Renate L.E.P. Reniers ◽  
Alison R. Yung ◽  
...  
Keyword(s):  
High Risk ◽  
Grey Matter ◽  
Psychotic Symptoms ◽  
Grey Matter Volume ◽  
Matter Volume ◽  
Ultra High Risk ◽  
Long Term Follow Up

scholarly journals Cortical involvement determines impairment 30 years after a clinically isolated syndrome

Brain ◽  
2021 ◽  
Author(s):  
Lukas Haider ◽  
Ferran Prados ◽  
Karen Chung ◽  
Olivia Goodkin ◽  
Baris Kanber ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Grey Matter ◽  
Disease Duration ◽  
Magnetization Transfer ◽  
Clinically Isolated Syndrome ◽  
Cervical Cord ◽  
Grey Matter Volume ◽  
Cortical Lesions ◽  
Matter Volume

Abstract Many studies report an overlap of MRI and clinical findings between patients with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), which in part is reflective of inclusion of subjects with variable disease duration and short periods of follow-up. To overcome these limitations, we examined the differences between RRMS and SPMS and the relationship between MRI measures and clinical outcomes 30 years after first presentation with clinically isolated syndrome suggestive of multiple sclerosis. Sixty-three patients were studied 30 years after their initial presentation with a clinically isolated syndrome; only 14% received a disease modifying treatment at any time point. Twenty-seven patients developed RRMS, 15 SPMS and 21 experienced no further neurological events; these groups were comparable in terms of age and disease duration. Clinical assessment included the Expanded Disability Status Scale, 9-Hole Peg Test and Timed 25-Foot Walk and the Brief International Cognitive Assessment For Multiple Sclerosis. All subjects underwent a comprehensive MRI protocol at 3 T measuring brain white and grey matter (lesions, volumes and magnetization transfer ratio) and cervical cord involvement. Linear regression models were used to estimate age- and gender-adjusted group differences between clinical phenotypes after 30 years, and stepwise selection to determine associations between a large sets of MRI predictor variables and physical and cognitive outcome measures. At the 30-year follow-up, the greatest differences in MRI measures between SPMS and RRMS were the number of cortical lesions, which were higher in SPMS (the presence of cortical lesions had 100% sensitivity and 88% specificity), and grey matter volume, which was lower in SPMS. Across all subjects, cortical lesions, grey matter volume and cervical cord volume explained 60% of the variance of the Expanded Disability Status Scale; cortical lesions alone explained 43%. Grey matter volume, cortical lesions and gender explained 43% of the variance of Timed 25-Foot Walk. Reduced cortical magnetization transfer ratios emerged as the only significant explanatory variable for the symbol digit modality test and explained 52% of its variance. Cortical involvement, both in terms of lesions and atrophy, appears to be the main correlate of progressive disease and disability in a cohort of individuals with very long follow-up and homogeneous disease duration, indicating that this should be the target of therapeutic interventions.

scholarly journals Negative symptoms and longitudinal grey matter tissue loss in adolescents at risk of psychosis: Preliminary findings from a 6-year follow-up study

2016 ◽  
Vol 208 (6) ◽  
pp. 565-570 ◽  
Author(s):  
Andrew G. McKechanie ◽  
Thomas W. J. Moorhead ◽  
Andrew C. Stanfield ◽  
Heather C. Whalley ◽  
Eve C. Johnstone ◽  
...  
Keyword(s):  
At Risk ◽  
Negative Symptoms ◽  
Grey Matter ◽  
Imaging Techniques ◽  
Tissue Loss ◽  
Psychotic Symptoms ◽  
Grey Matter Volume ◽  
Left Temporal Lobe ◽  
Left Posterior

BackgroundNegative symptoms are perhaps the most disabling feature of schizophrenia. Their pathogenesis remains poorly understood and it has been difficult to assess their development over time with imaging techniques.AimsTo examine, using tensor-based structural imaging techniques, whether there are regions of progressive grey matter volume change associated with the development of negative symptoms.MethodA total of 43 adolescents at risk of psychosis were examined using magnetic resonance imaging and whole brain tensor-based morphometry at two time points, 6 years apart.ResultsWhen comparing the individuals with significant negative symptoms with the remaining participants, we identified five regions of significant grey matter tissue loss over the 6-year period. These regions included the left temporal lobe, the left cerebellum, the left posterior cingulate and the left inferior parietal sulcus.ConclusionsNegative symptoms are associated with longitudinal grey matter tissue loss. The regions identified include areas associated with psychotic symptoms more generally but also include regions uniquely associated with negative symptoms.

scholarly journals Multimodal MRI of grey matter, white matter, and functional connectivity in cognitively healthy mutation carriers at risk for frontotemporal dementia and Alzheimer's disease

BMC Neurology ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Rogier A. Feis ◽  
Mark J. R. J. Bouts ◽  
Elise G. P. Dopper ◽  
Nicola Filippini ◽  
Verena Heise ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
White Matter ◽  
Functional Connectivity ◽  
Frontotemporal Dementia ◽  
Grey Matter ◽  
Region Of Interest ◽  
Grey Matter Volume ◽  
Matter Volume ◽  
Mutation Carriers ◽  
Healthy Carriers

Abstract Background Frontotemporal dementia (FTD) and Alzheimer’s disease (AD) are associated with divergent differences in grey matter volume, white matter diffusion, and functional connectivity. However, it is unknown at what disease stage these differences emerge. Here, we investigate whether divergent differences in grey matter volume, white matter diffusion, and functional connectivity are already apparent between cognitively healthy carriers of pathogenic FTD mutations, and cognitively healthy carriers at increased AD risk. Methods We acquired multimodal magnetic resonance imaging (MRI) brain scans in cognitively healthy subjects with (n=39) and without (n=36) microtubule-associated protein Tau (MAPT) or progranulin (GRN) mutations, and with (n=37) and without (n=38) apolipoprotein E ε4 (APOE4) allele. We evaluated grey matter volume using voxel-based morphometry, white matter diffusion using tract-based spatial statistics (TBSS), and region-to-network functional connectivity using dual regression in the default mode network and salience network. We tested for differences between the respective carriers and controls, as well as for divergence of those differences. For the divergence contrast, we additionally performed region-of-interest TBSS analyses in known areas of white matter diffusion differences between FTD and AD (i.e., uncinate fasciculus, forceps minor, and anterior thalamic radiation). Results MAPT/GRN carriers did not differ from controls in any modality. APOE4 carriers had lower fractional anisotropy than controls in the callosal splenium and right inferior fronto-occipital fasciculus, but did not show grey matter volume or functional connectivity differences. We found no divergent differences between both carrier-control contrasts in any modality, even in region-of-interest analyses. Conclusions Concluding, we could not find differences suggestive of divergent pathways of underlying FTD and AD pathology in asymptomatic risk mutation carriers. Future studies should focus on asymptomatic mutation carriers that are closer to symptom onset to capture the first specific signs that may differentiate between FTD and AD.

Social cognition and brain organization in chimpanzees (Pan troglodytes) and bonobos (Pan paniscus)

2018 ◽  
Author(s):  
William D. Hopkins ◽  
Cheryl D. Stimpson ◽  
Chet C. Sherwood
Keyword(s):  
Social Cognition ◽  
Social Behaviour ◽  
Grey Matter ◽  
Species Differences ◽  
Pan Paniscus ◽  
Grey Matter Volume ◽  
Evolutionary Models ◽  
Brain Organization ◽  
Matter Volume ◽  
Cognition Sociale

Bonobos and chimpanzees are two closely relates species of the genus Pan, yet they exhibit marked differences in anatomy, behaviour and cognition. For this reason, comparative studies on social behaviour, cognition and brain organization between these two species provide important insights into evolutionary models of human origins. This chapter summarizes studies on socio-communicative competencies and social cognition in chimpanzees and bonobos from the authors’ laboratory in comparison to previous reports. Additionally, recent data on species differences and similarities in brain organization in grey matter volume and distribution is presented. Some preliminary findings on microstructural brain organization such as neuropil space and cellular distribution in key neurotransmitters and neuropeptides involved in social behaviour and cognition is presented. Though these studies are in their infancy, the findings point to potentially important differences in brain organization that may underlie bonobo and chimpanzees’ differences in social behaviour, communication and cognition. Les bonobos et les chimpanzés sont deux espèces du genus Pan prochement liées, néanmoins ils montrent des différences anatomiques, comportementales et cognitives marquées. Pour cette raison, les études comparatives sur le comportement social, la cognition et l’organisation corticale entre ces deux espèces fournissent des idées sur les modèles évolutionnaires des origines humaines. Dans ce chapitre, nous résumons des études sur les compétences socio-communicatives et la cognition sociale chez les chimpanzés et les bonobos de notre laboratoire en comparaison avec des rapports précédents. En plus, nous présentons des données récentes sur les différences et similarités d’organisation corticale du volume et distribution de la matière grise entre espèces. Nous présentons plus de résultats préliminaires sur l’organisation corticale microstructurale comme l’espace neuropile et la division cellulaire dans des neurotransmetteurs clés et les neuropeptides impliqués dans le comportement social et la cognition. Bien que ces études sont dans leur enfance, les résultats montrent des différences d’organisation corticale importantes qui sont à la base des différences de comportement social, la communication et la cognition entre les bonobos et les chimpanzés.

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