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Diminished basal parasympathetic nervous system activity is a feature of frontotemporal dementia that relates to left frontoinsula dysfunction and empathy impairment. Individuals with a pathogenic expansion of the hexanucleotide repeat in chromosome 9 open reading frame 72 (C9orf72), the most common genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis, provide a unique opportunity to examine whether parasympathetic activity is disrupted in genetic forms of frontotemporal dementia and to investigate when parasympathetic deficits manifest in the pathophysiological cascade. We measured baseline respiratory sinus arrhythmia, a parasympathetic measure of heart rate variability, over two minutes in a sample of 102 participants that included 19 asymptomatic expansion carriers (C9+ asymp), 14 expansion carriers with mild cognitive impairment (C9+ MCI), 16 symptomatic expansion carriers with frontotemporal dementia (C9+ FTD), and 53 expansion-negative healthy controls (C9- HC) who also underwent structural magnetic resonance imaging. In follow-up analyses, we compared baseline respiratory sinus arrhythmia in the C9+ FTD group with an independent age-, sex-, and clinical severity-matched group of 26 people with sporadic behavioral variant frontotemporal dementia. The Frontotemporal Lobar Degeneration-modified Clinical Dementia Rating-Sum of Boxes score was used to quantify behavioral symptom severity, and informant ratings on the Interpersonal Reactivity Index provided measures of participants’ current emotional (empathic concern) and cognitive (perspective-taking) empathy. Results indicated that the C9+ FTD group had lower baseline respiratory sinus arrhythmia than the C9+ MCI, C9+ asymp, and C9- HC groups, a deficit that was comparable to that of sporadic behavioral variant frontotemporal dementia. Linear regression analyses indicated that lower baseline respiratory sinus arrhythmia was associated with worse behavioral symptom severity and lower empathic concern and perspective-taking across the C9orf72 expansion carrier clinical spectrum. Whole-brain voxel-based morphometry analyses in participants with C9orf72 pathogenic expansions found that lower baseline respiratory sinus arrhythmia correlated with smaller gray matter volume in the left frontoinsula and bilateral thalamus, key structures that support parasympathetic function, and in the bilateral parietal lobes, occipital lobes, and cerebellum, regions that are also vulnerable in individuals with C9orf72 expansions. This study provides novel evidence that basal parasympathetic functioning is diminished in FTD due to C9orf72 expansions and suggests that baseline respiratory sinus arrhythmia may be a potential non-invasive biomarker that is sensitive to behavioral symptoms in the early stages of disease.

Purpose: Frontotemporal lobar degeneration (FTLD) is a common cause of early onset dementia. Behavioral variant frontotemporal dementia (bvFTD), its most common subtype, is characterized by deep alterations in behavior and personality. In 2011, new diagnostic criteria were suggested that incorporate imaging criteria into diagnostic algorithms. The study aimed at validating the potential of imaging criteria to individually predict diagnosis with machine learning algorithms. Materials & methods: Brain atrophy was measured with structural magnetic resonance imaging (MRI) at 3 Tesla in a multi-centric cohort of 52 bvFTD patients and 52 healthy control subjects from the German FTLD Consortium's Study. Beside group comparisons, diagnosis bvFTD vs. controls was individually predicted in each subject with support vector machine classification in MRI data across the whole brain or in frontotemporal, insular regions, and basal ganglia known to be mainly affected based on recent meta-analyses. Multi-center effects were controlled for with a new method, “leave one center out” conjunction analyses, i.e. repeatedly excluding subjects from each center from the analysis. Results: Group comparisons revealed atrophy in, most consistently, the frontal lobe in bvFTD beside alterations in the insula, basal ganglia and temporal lobe. Most remarkably, support vector machine classification enabled predicting diagnosis in single patients with a high accuracy of up to 84.6%, where accuracy was highest in a region-of-interest approach focusing on frontotemporal, insular regions, and basal ganglia in comparison with the whole brain approach. Conclusion: Our study demonstrates that MRI, a widespread imaging technology, can individually identify bvFTD with high accuracy in multi-center imaging data, paving the road to personalized diagnostic approaches in the future.

Purpose: ‘Phenocopy’ frontotemporal dementia (phFTD) patients may clinically mimic the behavioral variant of FTD (bvFTD), but do not show functional decline or abnormalities upon visual inspection of routine neuroimaging. We aimed to identify abnormalities in gray matter (GM) volume and perfusion in phFTD and to assess whether phFTD belongs to the FTD spectrum. We compared phFTD patients with both healthy controls and bvFTD patients. Materials & methods: Seven phFTD and 11 bvFTD patients, and 20 age-matched controls underwent structural T1-weighted magnetic resonance imaging (MRI) and 3D pseudo-continuous arterial spin labeling (pCASL) at 3T. Normalized GM (nGM) volumes and perfusion, corrected for partial volume effects, were quantified regionally as well as in the entire supratentorial cortex, and compared between groups taking into account potential confounding effects of gender and scanner. Results: PhFTD patients showed cortical atrophy, most prominently in the right temporal lobe. Apart from this regional atrophy, GM volume was generally not different from either controls or from bvFTD. BvFTD however showed extensive frontotemporal atrophy. Perfusion was increased in the left prefrontal cortex compared to bvFTD and to a lesser extent to controls. Conclusion: PhFTD and bvFTD show overlapping cortical structural abnormalities indicating a continuum of changes especially in the frontotemporal regions. Together with functional changes suggestive of a compensatory response to incipient pathology in the left prefrontal regions, these findings are the first to support a possible neuropathological etiology of phFTD and suggest that phFTD may be a neurodegenerative disease on the FTD spectrum.

Graph theory is a novel approach used to examine the balance of brain connectomes. However, the clinical relevance of white matter (WM) connectome changes in the behavioral variant frontotemporal dementia (bvFTD) is not well understood. We aimed to investigate the clinical relevance of WM topological alterations in bvFTD. Thirty patients with probable bvFTD and 30 healthy controls underwent diffusion tensor imaging, structural MRI, and neuropsychological assessment. WM connectivity between 90 brain regions was calculated and the graph approach was applied to capture the individual characteristics of the anatomical network. Voxel-based morphometry and tract-based spatial statistics were used to present the gray matter atrophy and disrupted WM integrity. The topological organization was disrupted in patients with bvFTD both globally and locally. Compared to controls, bvFTD data showed a different pattern of hub region distributions. Notably, the nodal efficiency of the right superior orbital frontal gyrus was associated with apathy and disinhibition. Topological measures may be potential image markers for early diagnosis and disease severity monitoring of bvFTD., Competing Interests: Disclosure statement The authors report no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Behavioral variant frontotemporal dementia (bvFTD) is a neurodegenerative syndrome whose clinical diagnosis remains a challenging task especially in the early stage of the disease. Currently, the presence of frontal and anterior temporal lobe atrophies on magnetic resonance imaging (MRI) is part of the diagnostic criteria for bvFTD. However, MRI data processing is usually dependent on the acquisition device and mostly require human-assisted crafting of feature extraction. Following the impressive improvements of deep architectures, in this study we report on bvFTD identification using various classes of artificial neural networks, and present the results we achieved on classification accuracy and obliviousness on acquisition devices using extensive hyperparameter search. In particular, we will demonstrate the stability and generalization of different deep networks based on the attention mechanism, where data intra-mixing confers models the ability to identify the disorder even on MRI data in inter-device settings, i.e., on data produced by different acquisition devices and without model fine tuning, as shown from the very encouraging performance evaluations that dramatically reach and overcome the 90% value on the AuROC and balanced accuracy metrics., (Copyright © 2022. Published by Elsevier Ltd.)

There is an urgent need for a better understanding of the pathophysiology of cognitive impairment in syndromes associated with frontotemporal lobar degeneration. Here, we used magnetic resonance spectroscopy to quantify metabolite deficits in sixty patients with a clinical syndrome associated with frontotemporal lobar degeneration (behavioral variant frontotemporal dementia n = 11, progressive supranuclear palsy n = 26, corticobasal syndrome n = 11, primary progressive aphasias n = 12), and 38 age- and sex-matched healthy controls. We measured nine metabolites in the right inferior frontal gyrus, superior temporal gyrus and right primary visual cortex. Metabolite concentrations were corrected for age, sex, and partial volume then compared with cognitive and behavioral measures using canonical correlation analysis. Metabolite concentrations varied significantly by brain region and diagnosis (region x metabolite x diagnosis interaction F (64)  = 1.73, p < 0.001, corrected for age, sex, and atrophy within the voxel). N-acetyl aspartate and glutamate concentrations were reduced in the right prefrontal cortex in behavioral variant frontotemporal dementia and progressive supranuclear palsy, even after partial volume correction. The reduction of these metabolites was associated with executive dysfunction and behavioral impairment (canonical correlation analysis R = 0.85, p < 0.001)., (Copyright © 2021. Published by Elsevier Inc.)

Frontotemporal dementia (FTD) is an umbrella term covering a plethora of progressive changes in executive functions, motor abilities, behavior, and/or language. Different clinical syndromes have been described in relation to localized atrophy, informing on the functional networks that underlie these specific cognitive, emotional, and behavioral processes. These functional declines are linked with the underlying neurodegeneration of frontal and/or temporal lobes due to diverse molecular pathologies. Initially, the accumulation of misfolded proteins targets specifically susceptible cell assemblies, leading to relatively focal neurodegeneration that later spreads throughout large-scale cortical networks. Here, we discuss the most recent clinical, neuropathological, imaging, and genetics findings in FTD-spectrum syndromes affecting the temporal lobe. We focus on the semantic variant of primary progressive aphasia and its mirror image, the right temporal variant of FTD. Incipient focal atrophy of the left anterior temporal lobe (ATL) manifests with predominant naming, word comprehension, reading, and object semantic deficits, while cases of predominantly right ATL atrophy present with impairments of socioemotional, nonverbal semantic, and person-specific knowledge. Overall, the observations in FTD allow for crucial clinical-anatomic inferences, shedding light on the role of the temporal lobes in both cognition and complex behaviors. The concerted activity of both ATLs is critical to ensure that percepts are translated into concepts, yet important hemispheric differences should be acknowledged. On one hand, the left ATL attributes meaning to linguistic, external stimuli, thus supporting goal-oriented, action-related behaviors (e.g., integrating sounds and letters into words). On the other hand, the right ATL assigns meaning to emotional, visceral stimuli, thus guiding socially relevant behaviors (e.g., integrating body sensations into feelings of familiarity)., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Apathy is one of the core symptoms in behavioral variant of frontotemporal dementia (bvFTD), and increases patient's morbidity and caregiver's distress. In this study, we applied a graph theoretical analysis (GTA) to analyze the topological properties of cerebral blood flow (CBF) network in 64 bvFTD patients with and without apathy (47 bvFTD-apathy and 17 bvFTD-woapathy, respectively), and 20 normal controls (NCs) based on single photon emission tomography (SPECT). Compared with the NCs, both the bvFTD groups preserved global function and typical features of small-worldness, but exhibited the loss of hubs mainly distributed in the prefrontal cortex (PFC). Compared with bvFTD-woapathy, the bvFTD-apathy group exhibited additional loss of hubs in the ventral PFC areas, middle cingulate cortex, limbic and paralimbic system, and subcortical regions, but recruited hubs in the areas of angular gyrus, precuneus and posterior cingulate cortex. Overall, our findings support the hypothesis that the disruption of frontostriatal circuit is associated with apathy in bvFTD., (Copyright © 2020. Published by Elsevier B.V.)

Loss of warmth is well-documented in behavioral variant frontotemporal dementia (bvFTD) and semantic variant primary progressive aphasia (svPPA) at a group level, and has been linked to salience (SN) and semantic-appraisal (SAN) network atrophy. However, clinical observations of individual patients show much greater heterogeneity, thus measuring this clinical variability and identifying the underlying neurologic mechanisms is a critical step for understanding the symptom profile of any one patient. We used reliable change indexes with premorbid and current informant-based evaluations to characterize patterns of change on the warmth subscale of the Interpersonal Adjective Scale (IAS) questionnaire in 132 patients (21 bvFTD, 19 svPPA, 22 nonfluent variant primary progressive aphasia [nfvPPA], 37 Alzheimer's disease [AD]) and 33 healthy older adults. We investigated whether individual differences in warmth change were reflected in SN or SAN functional connectivity, or structural volume of individual brain regions in these two networks. Though one subset of patients showed significant drop in warmth to abnormally low levels (bvFTD: 38%; svPPA: 21%; nfvPPA: 5%; AD: 11%), a second subset significantly dropped but remained within the clinically normal range (bvFTD: 33%; svPPA: 21%; nfvPPA: 9%; AD: 5%), and a third subset did not drop and stayed in the clinically normal range (bvFTD: 29%; svPPA: 58%; nfvPPA: 86%; AD: 84%). Furthermore, interpersonal warmth score was strongly predicted by SN functional connectivity (p < .01), but not by SAN functional connectivity or by structural volume in these networks. Our results extend earlier group-level findings by showing wide individual variability in degree of disease-related reduction of interpersonal warmth and SN functional connectivity in bvFTD and svPPA, and highlight new approaches to revealing how brain connectivity predicts behavior on an individual patient level. Our findings suggest that measures of interpersonal warmth can provide important clinical information about changes in underlying brain networks, and help clinicians and clinical researchers better identify which bvFTD and svPPA patients are at greater risk for interpersonal disruption., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

The frontal lobes play an integral role in human socioemotional and cognitive function. Sense of self, moral decisions, empathy, and behavioral monitoring of goal-states all depend on key nodes within frontal cortex. While several neurodegenerative diseases can affect frontal function, frontotemporal dementia (FTD) has particularly serious and specific effects, which thus provide insights into the role of frontal circuits in homeostasis and adaptive behavior. FTD represents a collection of disorders with specific clinical-pathologic correlates, imaging, and genetics. Patients with FTD and initial prefrontal degeneration often present with neuropsychiatric symptoms such as loss of social decorum, new obsessions, or lack of empathy. In those patients with early anterior temporal degeneration, language (particularly in patients with left-predominant disease) and socioemotional changes (particularly in patients with right-predominant disease) precede eventual frontal dysregulation. Herein, we review a brief history of FTD, initial clinical descriptions, and the evolution of nomenclature. Next, we consider clinical features, neuropathology, imaging, and genetics in FTD-spectrum disorders in relation to the integrity of frontal circuits. In particular, we focus our discussion on behavioral variant FTD given its profound impact on cortical and subcortical frontal structures. This review highlights the clinical heterogeneity of behavioral phenotypes as well as the clinical-anatomic convergence of varying proteinopathies at the neuronal, regional, and network level. Recent neuroimaging and modeling approaches in FTD reveal varying network dysfunction centered on frontal-insular cortices, which underscores the role of the human frontal lobes in complex behaviors. We conclude the chapter reviewing the cognitive and behavioral neuroscience findings furnished from studies in FTD related to executive and socioemotional function, reward-processing, decision-making, and sense of self., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Frontotemporal dementia (FTD) is the second commonest cause of young onset dementia. Our understanding of FTD and its related syndromes has advanced significantly in recent years. Among the most prominent areas of progress is the overlap between FTD, MND, and other neurodegenerative conditions at a clinicopathologic and genetic level. In parallel major advances in neuroimaging techniques, the discovery of new genetic mutations as well as the development of potential biomarkers may serve to further expand knowledge of the biologic processes at play in FTD and may in turn propel research toward identifying curative and preventative pharmacologic therapies. The aim of this chapter is to discuss the clinical, pathologic, and genetic complexities of FTD and related disorders., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Diagnosing frontotemporal dementia may be challenging. New methods for analysis of regional brain atrophy patterns on magnetic resonance imaging (MRI) could add to the diagnostic assessment. Therefore, we aimed to develop automated imaging biomarkers for differentiating frontotemporal dementia subtypes from other diagnostic groups, and from one another., Methods: In this retrospective multicenter cohort study, we included 1213 patients (age 67 ± 9, 48% females) from two memory clinic cohorts: 116 frontotemporal dementia, 341 Alzheimer's disease, 66 Dementia with Lewy bodies, 40 vascular dementia, 104 other dementias, 229 mild cognitive impairment, and 317 subjective cognitive decline. Three MRI atrophy biomarkers were derived from the normalized volumes of automatically segmented cortical regions: 1) the anterior vs. posterior index, 2) the asymmetry index, and 3) the temporal pole left index. We used the following performance metrics: area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. To account for the low prevalence of frontotemporal dementia we pursued a high specificity of 95%. Cross-validation was used in assessing the performance. The generalizability was assessed in an independent cohort (n = 200)., Results: The anterior vs. posterior index performed with an AUC of 83% for differentiation of frontotemporal dementia from all other diagnostic groups (Sensitivity = 59%, Specificity = 95%, positive likelihood ratio = 11.8, negative likelihood ratio = 0.4). The asymmetry index showed highest performance for separation of primary progressive aphasia and behavioral variant frontotemporal dementia (AUC = 85%, Sensitivity = 79%, Specificity = 92%, positive likelihood ratio = 9.9, negative likelihood ratio = 0.2), whereas the temporal pole left index was specific for detection of semantic variant primary progressive aphasia (AUC = 85%, Sensitivity = 82%, Specificity = 80%, positive likelihood ratio = 4.1, negative likelihood ratio = 0.2). The validation cohort provided corresponding results for the anterior vs. posterior index and temporal pole left index., Conclusion: This study presents three quantitative MRI biomarkers, which could provide additional information to the diagnostic assessment and assist clinicians in diagnosing frontotemporal dementia., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Behavioral variant frontotemporal dementia (bvFTD) is the most common form of frontotemporal dementia, and tau pathology can be found in 40%-50% of bvFTD patients. In this study, we sought to investigate 18 F-flortaucipir-binding patterns and their correlates in clinically diagnosed bvFTD patients by comparing with results for Alzheimer's disease (AD) patients. We enrolled 20 bvFTD, 20 AD, and 20 age-matched healthy subjects who underwent neuropsychological tests, magnetic resonance imaging, and tau positron emission tomography scans with 18 F-flortaucipir. Regional standardized uptake value ratios for the cerebral cortex and underlying white matter were compared between the 2 groups. The bvFTD patients showed increased 18 F-flortaucipir binding in the putamen and globus pallidus when compared to the healthy controls. In addition, bvFTD was associated with increased binding in the white matter regions underlying the frontal, anterior cingulate, and insula cortices. The bvFTD patients may exhibit predominantly subcortical 18 F-flortaucipir-binding pattern that is distinct from the patterns seen in AD patients. We hypothesize that the clinical characteristics of bvFTD patients may be attributable to the dysfunctional frontal-subcortical networks. However, concerns remain regarding unknown "off-target" binding in the white matter and the basal ganglia., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Although deficits in social cognition are established as core features in behavioral variant frontotemporal dementia (bvFTD), it remains unresolved if impaired social cognition distinguishes bvFTD from the broad differential diagnoses in clinical practice. Our aim was to study whether social cognition discriminates bvFTD from other neurodegenerative diseases and psychiatric disorders in patients presenting with late-onset frontal symptoms. Next, we studied the association of social cognition with frontal symptoms and cognitive functioning., Methods: In this longitudinal multicenter study, besides clinical rating scales for frontal symptoms, social cognition was determined by Ekman 60 Faces test and Faux Pas in addition to neuropsychological tests for other cognitive domains in patients with probable and definite bvFTD (N = 22), other neurodegenerative diseases (N = 24), and psychiatric disorders (N = 33). Median symptom duration was 2.8 years, and patients were prospectively followed over 2 years., Results: Total scores from Ekman 60 Faces test were significantly lower in bvFTD than in other neurodegenerative diseases and psychiatric disorders. Ekman 60 Faces test explained 91.2% of the variance of psychiatric disorders and other neurodegenerative diseases versus bvFTD (χ 2  = 11.02, df = 1, p = 0.001) and was associated with all other cognitive domains. Faux Pas and the other cognitive domains did not differ between these diagnostic groups., Conclusion: In this clinical sample Ekman 60 Faces test distinguished bvFTD successfully from other neurodegenerative diseases and psychiatric disorders. Although associated with social cognition, other cognitive domains were not discriminative. This study provides arguments to add the Ekman 60 Faces test to the neuropsychological examination in the diagnostic procedure of bvFTD., (Copyright © 2018 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

We set out to study whether single-subject gray matter (GM) networks show disturbances that are specific for Alzheimer's disease (AD; n = 90) or behavioral variant frontotemporal dementia (bvFTD; n = 59), and whether such disturbances would be related to cognitive deficits measured with mini-mental state examination and a neuropsychological battery, using subjective cognitive decline subjects as reference. AD and bvFTD patients had a lower degree, connectivity density, clustering, path length, betweenness centrality, and small world values compared with subjective cognitive decline. AD patients had a lower connectivity density than bvFTD patients (F = 5.79, p = 0.02; mean ± standard deviation bvFTD 16.10 ± 1.19%; mean ± standard deviation AD 15.64 ± 1.02%). Lasso logistic regression showed that connectivity differences between bvFTD and AD were specific to 23 anatomical areas, in terms of local GM volume, degree, and clustering. Lower clustering values and lower degree values were specifically associated with worse mini-mental state examination scores and lower performance on the neuropsychological tests. GM showed disease-specific alterations, when comparing bvFTD with AD patients, and these alterations were associated with cognitive deficits., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 American Association for Geriatric Psychiatry. All rights reserved.)

The hypoglossal nucleus was recently identified as a key brain region in which the presence of TDP-43 pathology could accurately discriminate TDP-43 proteinopathy cases with clinical amyotrophic lateral sclerosis (ALS). The objective of the present study was to assess the hypoglossal nucleus in behavioral variant frontotemporal dementia (bvFTD), and determine whether TDP-43 in this region is associated with clinical ALS. Twenty-nine cases with neuropathological FTLD-TDP and clinical bvFTD that had not been previously assessed for hypoglossal TDP-43 pathology were included in this study. Of these 29 cases, 41% (n=12) had a dual diagnosis of bvFTD-ALS at presentation, all 100% (n=12) of which demonstrated hypoglossal TDP-43 pathology. Of the 59% (n=17) cohort that presented with pure bvFTD, 35% (n=6) were identified with hypoglossal TDP-43 pathology. Review of the case files of all pure bvFTD cases revealed evidence of possible or probable ALS in 5 of the 6 hypoglossal-positive cases (83%) towards the end of disease, and this was absent from all cases without such pathology. In conclusion, the present study validates grading the presence of TDP-43 in the hypoglossal nucleus for the pathological identification of bvFTD cases with clinical ALS, and extends this to include the identification of cases with possible ALS at end-stage., (Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.)

This study investigates regional coherence between white matter (WM) microstructure and gray matter (GM) volume and perfusion measures in Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) using a correlational approach. WM-GM coherence, compared with controls, was stronger between cingulum WM and frontotemporal GM in AD, and temporoparietal GM in bvFTD. In addition, in AD compared with controls, coherence was stronger between inferior fronto-occipital fasciculus WM microstructure and occipital GM perfusion. In this first study assessing regional WM-GM coherence in AD and bvFTD, we show that WM microstructure and GM volume and perfusion measures are coherent, particularly in regions implicated in AD and bvFTD pathology. This indicates concurrent degeneration in disease-specific networks. Our methodology allows for the detection of incipient abnormalities that go undetected in conventional between-group analyses., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We examined patterns of cortical thickness loss and cognitive decline over time in 19 patients with Alzheimer's disease (AD), 10 with behavioral variant frontotemporal dementia (bvFTD), and 34 controls with a mean interval of 2.1 ± 0.4 years. We measured vertexwise and regional cortical thickness changes of 6 lobar regions of interest between groups with the longitudinal FreeSurfer pipeline. Compared with controls, AD and bvFTD had a steeper rate of cognitive decline and showed faster cortical thinning per year. Decrease of thickness over time was highest in AD and generalized throughout the whole brain, most pronounced posteriorly, whereas bvFTD patients had a more selective loss in frontal cortex and in anterior parts of the temporal lobes. In a direct comparison, AD patients showed faster cortical thinning in the insula, temporal, and parietal regions, whereas bvFTD patients only showed faster cortical thinning in the orbitofrontal gyrus. Decline of cognitive performances was in line with cortical thinning and deteriorated the most in AD patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The aim of the present study was to evaluate changes in event-related evoked potentials (ERPs) in patients with Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD)., Methods: A total of 42AD patients, 29 behavioral variant frontotemporal dementia (bvFTD) patients, and 30 healthy controls were examined. The subjects underwent neuropsychological tests and cognitive (N200 and P300) ERP examination. The amplitudes and latencies of the cortical potentials were compared among AD and bvFTD patients and control subjects., Results: No differences in the ERP latencies and amplitudes for the N200 component were observed among the groups. AD patients exhibited significantly longer latencies of P300 at both Pz (p=0.002) and Cz (p=0.007) compared with the controls. Patients with bvFTD displayed longer P300 latencies at Pz (p=0.046) and a smaller amplitude at both Pz (p=0.000) and Cz (p=0.23) than the controls., Conclusions: The results of the present study confirm the relevance of ERPs in evaluating cognitive disorders. These non-invasive examinations have the potential to contribute to the diagnosis of AD and bvFTD., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Amyotrophic lateral sclerosis (ALS) and behavioral variant frontotemporal dementia (bvFTD) lie on a clinical, pathologic, and genetic continuum. Neuroimaging techniques have proven to be potentially useful to unravel the shared features of these syndromes. Using resting-state functional magnetic resonance imaging (RS-fMRI), we investigated functional connectivity of brain networks in 15 ALS and 15 bvFTD patients in early stages of disease and 15 healthy controls, looking expressly for connectivity pattern divergence or overlap between the 2 disorders. Compared with controls, we found decreased RS-fMRI signals within sensorimotor, right frontoparietal, salience, and executive networks in both patient groups. Within the default mode network (DMN), divergent connectivity patterns were observed, with RS-fMRI signals in the posterior cingulate cortex enhanced in bvFTD patients and suppressed in ALS patients. Our findings confirm that ALS and bvFTD not only broadly share common RS-fMRI connectivity patterns, probably representing different phenotypical expressions of the same neurodegenerative process, but also differ in the DMN, probably reflecting a different stage of neurodegeneration., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Frontotemporal dementia was documented over a century ago. The last decade, however, has seen substantial changes in our conceptions of this increasingly recognized disorder. Different clinical variants have been delineated, the most common of which is the behavioral variant (bvFTD). Updated diagnostic criteria have been established. New histopathological findings and genetic etiologies have been discovered. Research continues to uncover molecular mechanisms by which abnormal proteins accumulate in degenerating brain tissue. Novel neuroimaging techniques suggest that functional networks are diminished in bvFTD that might be relevant to empathy and social behavior. Despite rapid advances in our understanding of bvFTD, the disease is still under-recognized and commonly misdiagnosed. The result is inappropriate patient care. Recognizing the various presentations of bvFTD and its histological and genetic subtypes might further diagnosis, treatment, and research., (© 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.)