Criteria For bvFTD Research Articles

The Pitfall of Behavioral Variant Frontotemporal Dementia Mimics Despite Multidisciplinary Application of the FTDC Criteria

The behavioral variant of frontotemporal dementia (bvFTD) has a broad differential diagnosis including other neurological and psychiatric disorders. Psychiatric misdiagnoses occur in up to 50% of bvFTD patients. Numbers on misdiagnosis of bvFTD in psychiatric disorders are lacking. The aim of our study was to investigate the frequency and characteristics of bvFTD misdiagnoses in psychiatric disorders and other neurologic disorders. Thirty-five patients with a (possible or probable) bvFTD diagnosis made by specialized memory clinic neurologists were included. Change in diagnosis after consulting a psychiatrist at baseline was recorded as well as change in diagnosis after two years of multidisciplinary neuropsychiatric follow-up. Differences in cognitive and behavioral profiles were investigated per diagnostic group after follow-up (bvFTD, psychiatry, other neurologic disorders). Clinical profiles are described in detail. In 17 patients (48.5%), the bvFTD baseline diagnosis changed: Two at baseline after psychiatric consultation, and 15 after two years of multidisciplinary follow-up. Eleven (64.5%) of these 17 patients (31.5% of total) were reclassified with a psychiatric diagnosis. We found no differences for cognitive baseline profiles between patients with bvFTD versus psychiatric diagnoses. In almost half of cases, the initial bvFTD diagnosis was changed after follow-up, most often into a psychiatric disorder. A multidisciplinary neuropsychiatric approach in the diagnostic process of bvFTD results in the identification of treatable disorders. Our findings illustrate a limited specificity of the [18F]FDG-PET-scan and the bvFTD criteria in a neuropsychiatric cohort, especially combined with certain clinical symptoms, like disinhibition, apathy, or loss of empathy.

GENETIC MUTATIONS IN EARLY-ONSET DEMENTIA: REPORT FROM THE MEMORY CLINIC FROM SERBIA

Monogenetic forms of early onset Alzheimer disease (EAOD) are very rare approximately 2.5 % of all dementia cases with three well known mutations in APP gene, Presenilin 1(PSEN1), and Presenilin 2 (PSEN2). Fronto-temporal dementia (FTD) is the second most common cause of early onset dementia (EOD), characterized by behavioral changes (behavioral variant; bvFTD) or language deficits. Frontotemporal dementia is a highly heritable neurodegenerative disorder. In about a third of patients, the disease is caused by autosomal dominant genetic mutations usually in one of three genes: progranulin (GRN), microtubule-associated protein tau (MAPT), or chromosome 9 open reading frame 72 (C9orf72). The aim of this study was to assess the genetic mutations in a cohort of 322 Serbian patients with EOD and to report phenotypic features of identified carriers. PSEN1 was recorded in 2.42%, APP in 1.2 %, and PSEN2 in 1.21%. A family history of dementia is found in 30% of cases of FTD and about 10% have a clear autosomal-dominant inheritance. Some patients have an associated movement disorder, either parkinsonism, as in progressive supranuclear palsy and corticobasal syndrome, or motor neuron disease (FTD–MND). There was no MAPT mutation in our cohort. Four patients have been diagnosed with mutation in progranulin gene (GRN). Three patients were classified in the FTD spectrum and one with possible Alzheimer disease. We identified 4 patients with EOD to have C9orf72 hexanucleotide expansions. All patients were classified in the FTD disease spectrum group (8.2%): 3 patients fulfilled the criteria for bvFTD, and 1 patient had FTD-MND. None of the patients with the C9orf72 hexanucleotide expansion fulfilled the diagnostic criteria for language variants of FTD, FTD-progressive supranuclear palsy overlap syndrome, dementia with Lewy bodies or Alzheimer's dementia. Mutations in valosin-containing protein (VCP) was found in 3 patients with isolated bvFTD, and no inclusion body myopathy or Paget disease. Patients often present with an extensive phenotypic variability, even among different members of the same kindred carrying an identical disease mutation.

BEHAVIORAL VARIANT FRONTOTEMPORAL DEMENTIA AS A SERIOUS COMPLICATION OF SPONTANEOUS INTRACRANIAL HYPOTENSION

Behavioral variant frontotemporal dementia (bvFTD) is a devastating early onset dementia. Symptoms of bvFTD also may be caused by spontaneous intracranial hypotension (SIH), a treatable disorder, but no comprehensive study of such patients has been reported. We therefore reviewed our extensive experience with patients with SIH and bvFTD. Using a prospectively maintained registry, we identified all patients with SIH (based on the criteria of the International Classification of Headache Disorders, third edition [ICHD-III]) who met clinical criteria for bvFTD (International Behavioral Variant FTD Criteria Consortium [FTDC]). Patients or their caregivers/family were contacted for follow-up. A modified Migraine Disability Assessment Score (MIDAS) questionnaire was used to assess the severity of the symptoms (Grade I or II: good outcome; grade III or IV: poor outcome). The patients were compared to a cohort of SIH patients without bvFTD. The mean age at onset of SIH symptoms for the 21 men and eight women was 50.6 years (range, 34–65 years) and it was 52.9 years (range, 37–65 years) at the time of onset of bvFTD symptoms. All patients had hypersomnolence. MRI showed brain sagging in all patients, CSF opening pressure was low in about half of patients, but a spinal CSF leak could not be detected in any patient. Three patients only underwent epidural blood patching, with a good outcome in one patient. After unsuccessful directed percutaneous treatments, the remaining 26 patients underwent one or more surgical procedures with a good outcome in 20 patients (77%). Overall, a good outcome was obtained in 21 patients (72%); 20 (91%) of 22 patients who had not undergone prior Chiari surgery compared to one (14%) of seven patients who did undergo Chiari surgery (p<0.003). Compared to SIH patients without symptoms of bvFTD (n=547), those with bvFTD symptoms were older, more often male, less often demonstrated a CSF leak on spinal imaging, and more often underwent surgery (p<0.02).

So Close Yet So Far: Executive Contribution to Memory Processing in Behavioral Variant Frontotemporal Dementia.

Memory impairment in behavioral variant frontotemporal dementia (bvFTD) is traditionally considered to be mild and attributed to prefrontal cortex dysfunction. Recent studies, however, indicated that some patients can present with a memory impairment of the hippocampal type, showing storage and consolidation deficits in addition to the more executive/prefrontal related encoding and strategic difficulties. This study aimed to study the relationship between executive functions (EF) and memory processes in bvFTD via a data-driven approach. Participants consisted of 71 bvFTD (among which 60.6% had a lumbar puncture showing non-Alzheimer biomarker profile) and 60 controls (among which 45% had amyloid imaging showing a normal profile). EF were assessed by the Frontal Assessment Battery, semantic/lexical verbal fluency tests, and forward/backward digit spans. Patients were split into amnestic (n = 33) and non-amnestic (n = 38) subgroups based on normative data (total recall score) from the Free and Cued Selective Reminding Test (FCSRT). Relationships between FCSRT subscores and EF measures were explored through hierarchical clustering analysis, partial correlation analysis with an EF component, and automated linear modeling. Convergent findings across the statistical approaches show that, overall, memory performance was independent from EF in bvFTD whereas the relationship was stronger in controls. Indeed, in bvFTD, memory performance did not cluster with EF, was not correlated with the EF component, and was only partially (4% - 12.7%) predicted by EF. These findings show that executive dysfunctions cannot solely explain the memory deficits occurring in bvFTD. Indeed, some patients present with a genuine amnesia affecting storage and consolidation abilities, which are independent from executive dysfunctions. On the clinical level, this study highlights the importance of revising the neuropsychological diagnosis criteria for bvFTD.

Distinct Subtypes of Behavioral Variant Frontotemporal Dementia Based on Patterns of Network Degeneration.

Clearer delineation of the phenotypic heterogeneity within behavioral variant frontotemporal dementia (bvFTD) will help uncover underlying biological mechanisms and improve clinicians' ability to predict disease course and to design targeted management strategies. To identify subtypes of bvFTD syndrome based on distinctive patterns of atrophy defined by selective vulnerability of specific functional networks targeted in bvFTD using statistical classification approaches. In this retrospective observational study, 90 patients meeting the Frontotemporal Dementia Consortium consensus criteria for bvFTD underwent evaluation at the Memory and Aging Center of the Department of Neurology at University of California, San Francisco. Patients underwent a multidisciplinary clinical evaluation, including clinical demographics, genetic testing, symptom evaluation, neurologic examination, neuropsychological bedside testing, and socioemotional assessments. All patients underwent structural magnetic resonance imaging at their earliest evaluation at the memory clinic. From each patient's structural imaging scans, the mean volumes of 18 regions of interest (ROI) constituting the functional networks specifically vulnerable in bvFTD, including the salience network (SN), with key nodes in the frontoinsula and pregenual anterior cingulate, and the semantic appraisal network (SAN), anchored in the anterior temporal lobe and subgenual cingulate, were estimated. Principal component and cluster analyses of ROI volumes were used to identify patient clusters with anatomically distinct atrophy patterns. Data were collected from from June 19, 2002, to January 13, 2015. Evaluation of brain morphology and other clinical features, including presenting symptoms, neurologic examination signs, neuropsychological performance, rate of dementia progression, and socioemotional function, in each patient cluster. Ninety patients (54 men [60%]; 36 women [40%]; mean [SD] age at evaluation, 55.1 [9.7] years) were included in the analysis. Four subgroups of patients with bvFTD with distinct anatomic patterns of network degeneration were identified, including 2 salience network-predominant subgroups (frontal/temporal [SN-FT] and frontal [SN-F]), a semantic appraisal network-predominant group (SAN), and a subcortical-predominant group. Subgroups demonstrated distinct patterns of cognitive, socioemotional, and motor symptoms, as well as genetic compositions and estimated rates of disease progression. Divergent patterns of vulnerability in specific functional network components make an important contribution to the clinical heterogeneity of bvFTD. The data-driven anatomic classification identifies biologically meaningful anatomic phenotypes and provides a replicable approach to disambiguate the bvFTD syndrome.

Screening for C9orf72 Expansion Mutation in Serbian Patients with Early-Onset Dementia

Background: Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia (EOD), characterized by behavioral changes (behavioral variant; bvFTD) or language deficits. A hexanucleotide repeat expansion in a noncoding region of chromosome 9 open reading frame 72 (C9orf72) has been proved to be a major cause of both familial and sporadic amyotrophic lateral sclerosis or FTD, with or without concomitant motor neuron disease (MND). Methods: The aim of this study was to assess the frequency of the C9orf72 hexanucleotide expansion in a cohort of 117 Serbian patients with EOD and to report phenotypic features of identified carriers. Results: We identified 4 of 117 (3.4%) patients with EOD to have C9orf72 hexanucleotide expansions. All patients were classified in the FTD disease spectrum group (8.2%): 3 patients fulfilled the criteria for bvFTD, and 1 patient had FTD-MND. None of the patients with the C9orf72 hexanucleotide expansion fulfilled the diagnostic criteria for language variants of FTD, FTD-progressive supranuclear palsy overlap syndrome, dementia with Lewy bodies or Alzheimer's dementia. Conclusion: In a cohort of consecutive patients with EOD, 3.4% had the C9orf72 hexanucleotide expansion with clinical phenotypes of bvFTD or an overlap of bvFTD and MND.

Key emerging issues in frontotemporal dementia.

Frontotemporal dementia (FTD) encompasses the syndromes of behavioural variant FTD (bvFTD) and primary progressive aphasia (PPA) and refers to those neurodegenerative diseases characterised by predominant pathological involvement of the frontal and temporal lobes. Recent years have witnessed major advances in the clinical characterisation of FTD, reflected in the publication of updated diagnostic criteria for bvFTD and PPA, and the discovery of new pathogenic mutations has added to the understanding of genotype-phenotype interactions and of disease mechanisms. Emerging results from longitudinal studies of familial FTD show that imaging and cognitive changes occur years before symptom onset and such studies may yield biomarkers of early disease that in turn will facilitate earlier diagnosis. The hope and (guarded) expectation is that these advances may together herald the beginning of the end of the chapter in which FTD is considered an inexorably progressive and untreatable condition.

The behavioural variant frontotemporal dementia (bvFTD) syndrome in psychiatry

The primary goal of this article is to critically discuss the syndromic overlap that exists between early behavioural variant frontotemporal dementia (bvFTD)—the most common clinical syndrome associated with frontotemporal lobar...

Early stage of behavioral variant frontotemporal dementia: clinical and neuroimaging correlates

The early stages of behavioral variant frontotemporal dementia (bvFTD) are still not completely characterized. In a consecutive series of patients with probable bvFTD diagnosis confirmed by follow-up, we retrospectively evaluated the features at onset. Patients were reclassified according to presenting features and current diagnostic criteria into probable and possible bvFTD. The term “pre-bvFTD” was adopted for patients with cognitive and/or behavioral impairment not fulfilling bvFTD criteria and no deficits in activities of daily living. One hundred ninety-four subjects were included; at first visit, 70% (n = 136) patients were already classified as probable bvFTD. Of the remaining 30% (n = 58), 60% fulfilled criteria for possible bvFTD, while 40% did not, and were classified as pre-FTD. The neuropsychological pattern in possible bvFTD and pre-bvFTD was similar, although possible bvFTD showed more behavioral abnormalities. Pre-bvFTD subjects had frontotemporal gray matter atrophy, although less extensive than possible bvFTD. Conclusively, most bvFTD patients fulfill current diagnostic criteria at first admission, whereas a relatively small group is characterized by mild behavioral and/or cognitive abnormalities in spite of frontotemporal gray matter atrophy. Our preliminary findings will require a validation in prospective studies involving larger samples of patients.

The Phenotype of the C9ORF72 Expansion Carriers According to Revised Criteria for bvFTD.

BackgroundThe C9ORF72 expansion is one of the most common genetic etiologies observed with behavioural variant frontotemporal dementia (bvFTD). Revised diagnostic criteria for bvFTD (FTDC) were recently introduced but only a few studies have evaluated the accuracy of these criteria.ObjectiveThe objective of the study was to evaluate the applicability of the FTDC criteria and assess the psychiatric history of these patients.MethodsThe study examined 36 patients carrying the C9ORF72 expansion and suffering from bvFTD (N = 32) or from bvFTD with motor neuron disease (bvFTD-MND, N = 4). Neuropsychological, neuropsychiatric, structural brain imaging and PET/SPECT data were evaluated.ResultsWe found 0.75 sensitivity (SD 0.44, 95%CI 0.57–0.87) for possible bvFTD and 0.64 (SD 0.44, 95%CI 0.57–0.87) for probable bvFTD. The sensitivity was even higher in bvFTD patients without MND, i.e., 0.81 for possible bvFTD and 0.69 for probable bvFTD. PET/SPECT was normal in 17.6% of scanned patients with bvFTD. A history of psychiatric symptoms (psychotic and/or mood symptoms) was detected in 61% of cases.ConclusionsThe FTDC possible and probable bvFTD criteria seem to identify the majority of the C9ORF72 expansion carriers with bvFTD, even though they exhibit only a limited number of behavioral criteria but a significant amount of psychiatric symptoms. The presence of a normal PET/SPECT does not exclude the possibility the C9ORF72 associated bvFTD.

Diagnostic accuracy of behavioral variant frontotemporal dementia consortium criteria (FTDC) in a clinicopathological cohort.

The aims of this study were to assess the sensitivity of the International Behavioural Variant FTD Criteria Consortium (FTDC) revised criteria of behavioural variant frontotemporal dementia (bvFTD) in a pathological cohort and to determine their predictive values in a clinical context suggestive of bvFTD. In addition, the study aimed to assess the influence of the age at onset and underlying pathology in the clinicopathological correlations. Retrospective, blinded review of the clinical and neuropathological data from the Neurological Tissue Bank of the Biobank Hospital Clinic-IDIBAPS, Barcelona (Spain) was conducted, assessing the fulfilment of the diagnostic criteria on a case-by-case basis. Two separate nonexclusive cohorts were selected: Cohort 1 (n = 58) subjects with pathological diagnosis of frontotemporal lobar degeneration (FTLD) and Cohort 2 (n = 66) subjects with the premortem diagnosis of bvFTD. The FTDC criteria reached a sensitivity of 93% for possible and 80% for probable bvFTD. Early-onset cases displayed significantly more disinhibition, loss of empathy and compulsive behaviour with respect to late-onset bvFTD, leading to a slightly higher sensitivity of the diagnostic criteria (97% vs. 91%). There were no differences in the diagnostic performance between tau-positive and tau-negative cases. In subjects clinically diagnosed as bvFTD, a 'possible bvFTD' diagnosis reached a positive predictive value for FTLD pathology of 90%, irrespective of underlying proteinopathy. False-positive clinical diagnoses were mainly Alzheimer's disease. These cases were significantly older, had less family history of dementia and had a predominantly apathetic clinical picture. The revised bvFTD criteria present good sensitivity and positive predictive value in both early- and late-onset cases and regardless of the underlying FTLD pathology.

Clinical and Neuropsychological Comparisons of Early-Onset Versus Late-Onset Frontotemporal Dementia: A CREDOS-FTD Study.

Cognitive performance changes with chronological aging. Previous studies investigating clinical heterogeneity in frontotemporal dementia (FTD) according to the age of symptom onset did not consider the effect of chronological aging on cognition. We compared cognitive and behavioral symptoms in patients with early-onset (EO) and late-onset (LO) FTD with consideration of chronological aging effect. A total of 166 FTD patients were enrolled consecutively from multi-center memory clinics using a nationwide FTD register. To control for the effects of chronological aging on neuropsychological scores, seven hundred and two subjects with normal cognition were also enrolled and regression models were set up. Neuropsychological scores that were detrended with the regression models and the behavioral symptoms of the EO-FTD and LO-FTD groups were compared. Subgroup analyses were performed for three main subtypes of FTD, behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SD), and progressive non-fluent aphasia (PNFA). Among 166 FTD patients, there were 76 bvFTD, 57 SD, and 33 PNFA patients who met new diagnostic criteria for bvFTD or primary progressive aphasia, respectively. LO-FTD (48.2%) was more common than previously thought and the proportions of EO and LO groups differed across FTD subtypes. EO-FTD patients had lower memory and frontal/executive scores and more prominent frontal/behavioral symptoms than LO-FTD patients. Our study suggested that FTD could be heterogeneous with respect the age of symptom onset. After controlling for the effects of chronological aging, EO-FTD patients exhibited more profound memory and frontal/executive dysfunction and more behavioral symptoms than LO-FTD patients.

Behavioural variant frontotemporal dementia: Clinical and therapeutic approaches

IntroductionBehavioural variant frontotemporal dementia (bvFTD) is the most frequent presentation in the clinical spectrum of frontotemporal dementia (FTD) and it is characterised by progressive changes in personality and conduct. Major breakthroughs in molecular biology and genetics made during the last two decades have lent us a better understanding of this syndrome, which may be the first manifestation in many different neurodegenerative diseases. DevelopmentWe reviewed the main epidemiological, clinical, diagnostic and therapeutic aspects of bvFTD. Most cases manifest sporadically and the average age of onset is 58 years. Current criteria for bvFTD propose three levels of diagnostic certainty: possible, probable, and definite. Clinical diagnosis is based on a detailed medical history provided by family members and caregivers, in conjunction with neuropsychological testing. Treatments which have been used in bvFDT to date are all symptomatic and their effectiveness is debatable. New drugs designed for specific molecular targets that are implicated in frontotemporal lobar degeneration are being developed. ConclusionsBvFDT is a frequent cause of dementia. It is a non-specific syndrome associated with heterogeneous histopathological and biomolecular findings. The definition of clinical subtypes complemented by biomarker identification may help predict the underlying pathology. This knowledge, along with the development of drugs designed for molecular targets, will offer new treatment possibilities.

Observational themes of social behavioral disturbances in frontotemporal dementia.

ABSTRACT Background: Caregivers report early disturbances in social behavior among patients with behavioral variant frontotemporal dementia (bvFTD); however, there are few direct observational studies of these social behavioral disturbances. This study aimed to identify social behavioral themes in bvFTD by direct observation in naturalistic interactions. The identification of these themes can help caregivers and clinicians manage the social behavioral disturbances of this disease. Methods: Researchers observed 13 bvFTD patients in their homes and community-based settings and recorded field notes on their interpersonal interactions. A qualitative analysis of their social behavior was then conducted using ATLAS.ti application and a constant comparison method. Results: Qualitative analysis revealed the following themes: (1) diminished relational interest and initiation, indicating failure to seek social interactions; (2) lack of social synchrony/intersubjectivity, indicating an inability to establish and maintain interpersonal relationships; and (3) poor awareness and adherence to social boundaries and norms. These themes corresponded with changes from caregiver reports and behavioral scales. Conclusion: This analysis indicates that real-world observation validates the diagnostic criteria for bvFTD and increases understanding of social behavioral disturbances in this disorder. The results of this and future observational studies can highlight key areas for clinical assessment, caregiver education, and targeted interventions that enhance the management of social behavioral disturbances in bvFTD.

Frontotemporal Dementia Associated With theC9ORF72Mutation

While advances have been made in characterizing the C9ORF72 clinical phenotype, the hallmark features that discriminate between carriers and noncarriers remain unclear. To determine the frequency of the C9ORF72 mutation in a frontotemporal dementia (FTD) cohort and to define the clinical, neuropsychological, behavioral, and imaging features of C9ORF72 mutation carriers in comparison with noncarriers in a well-defined behavioral-variant (bv)-FTD cohort. A prospective cohort study of patients assessed during a 5-year period from January 1, 2008, to December 31, 2012, at an FTD specialist referral center (FRONTIER). A total of 114 consecutive patients with FTD, FTD-amyotrophic lateral sclerosis (ALS), and corticobasal syndrome were assessed at FRONTIER. Patients with bvFTD who carried the C9ORF72 mutation (n = 10) were compared with noncarriers (n = 19) and a healthy control group (n = 35). These were matched for age, sex, and education history. Blood sampling for gene analysis was performed after informed consent was obtained. Clinical, behavioral, cognitive, and neuropsychological deficits, cortical atrophy on a magnetic resonance imaging visual rating scale, and family history as quantified by the Goldman Scale. In a cohort of 114 FTD cases, 14 patients expressed the C9ORF72 mutation, representing a frequency rate of 34% in bvFTD and 17% in FTD-ALS. Family histories of ALS (P = .001) and psychiatric disorders (P = .02) were significantly more common in mutation carriers. The C9ORF72 carriers were also more likely to experience psychotic symptoms (P = .03). The degree of brain atrophy was significantly less in the C9ORF72 cohort, and in many the progression was slow. Presenting features of C9ORF72 carriers were compared against International Consensus Diagnostic Criteria for bvFTD, and most cases failed to satisfy criteria for probable bvFTD. The C9ORF72 mutation appears to be a common cause of bvFTD. Many of the C9ORF72 carriers have a family history of ALS or psychiatric illness. Psychotic features emerged as the most discriminating clinical feature between mutation carriers and noncarriers. Progression is often slow and brain atrophy is less pronounced than in nonmutation cases of bvFTD. These findings have clinical relevance for both diagnosis and selection of patients for genetic testing.

Two Distinct Amnesic Profiles in Behavioral Variant Frontotemporal Dementia

Whether or not episodic memory deficit is a characteristic of behavioral variant frontotemporal dementia (bvFTD) is a crucial question for its diagnosis and management. We compared the episodic memory performance profile of bvFTD patients with healthy control subjects and patients with Alzheimer's disease (AD) as defined by clinical and biological criteria. Episodic memory was assessed with the Free and Cued Selective Reminding Test, which controls for effective encoding and identifies memory storage ability resulting from consolidation processing. One hundred thirty-four participants were evaluated: 56 patients with typical clinical presentation of AD and pathophysiological evidence as defined by cerebrospinal fluid AD biomarker profile and/or significant amyloid retention on Pittsburgh Compound B positron emission tomography; 56 patients diagnosed with bvFTD with no evidence of AD-cerebrospinal fluid biomarkers when a profile was available (28/56), including 44 progressive (bvFTD) and 12 nonprogressive (phenocopies) patients; and 22 control subjects with negative amyloid imaging. Memory scores could not differentiate bvFTD from AD patients (sensitivity and specificity <50%). Taking into account the individual distribution of Free and Cued Selective Reminding Test scores, half of bvFTD patients had a deficit of free recall, total (free + cued) recall, and delayed recall as severe as AD patients. The other half had subnormal scores similar to phenocopies and a delayed recall score similar to control subjects. We observed two distinct amnesic profiles in bvFTD patients that could reflect two types of hippocampal structure and Papez circuit involvement. These findings on episodic memory profiles could contribute to discussions on the recent international consensus criteria for bvFTD.

Demencia frontotemporal variante conductual: aproximación clínica y terapéutica

IntroductionBehavioural variant frontotemporal dementia (bvFTD) is the most frequent presentation in the clinical spectrum of frontotemporal dementia (FTD) and it is characterised by progressive changes in personality and conduct. Major breakthroughs in molecular biology and genetics made during the last two decades have lent us a better understanding of this syndrome, which may be the first manifestation in many different neurodegenerative diseases. DevelopmentWe reviewed the main epidemiological, clinical, diagnostic and therapeutic aspects of bvFTD. Most cases manifest sporadically and the average age of onset is 58 years. Current criteria for bvFTD propose three levels of diagnostic certainty: possible, probable, and definite. Clinical diagnosis is based on a detailed medical history provided by family members and caregivers, in conjunction with neuropsychological testing. Treatments which have been used in bvFDT to date are all symptomatic and their effectiveness is debatable. New drugs designed for specific molecular targets that are implicated in frontotemporal lobar degeneration are being developed. ConclusionsBvFDT is a frequent cause of dementia. It is a non-specific syndrome associated with heterogeneous histopathological and biomolecular findings. The definition of clinical subtypes complemented by biomarker identification may help predict the underlying pathology. This knowledge, along with the development of drugs designed for molecular targets, will offer new treatment possibilities.

Sensitivity and specificity of FTDC criteria for behavioral variant frontotemporal dementia

We aimed to assess sensitivity and specificity of the updated criteria for behavioral variant frontotemporal dementia (bvFTD) based on a large autopsy-confirmed cohort of patients with dementia. Two hundred thirty-nine consecutive pathologically confirmed dementia patients, clinically assessed in a specialist cognitive unit were identified. Patients with predominant aphasia, motor disorders, or insufficient clinical information were excluded. Frontotemporal Dementia Consensus criteria were applied to anonymized clinical data taken from patients' initial assessment by raters who were blinded to clinical and pathologic diagnosis. The final study cohort comprised 156 patients with predominantly early-onset dementia. The updated criteria for possible bvFTD had a sensitivity of 95% and specificity of 82%. Probable bvFTD criteria had a sensitivity of 85% and specificity of 95%. False positives were predominantly patients with presenile Alzheimer disease. Revised diagnostic criteria show encouragingly high sensitivity and specificity when applied to patients with early-onset dementia. They therefore provide a useful tool both for specialist researchers and general clinicians. There is a need for further prospective studies of sensitivity and specificity involving a broader spectrum of patients with dementia.

Behavioural-variant frontotemporal dementia: an update.

Behavioural-variant frontotemporal dementia (bvFTD) is characterised by insidious changes in personality and interpersonal conduct that reflect progressive disintegration of the neural circuits involved in social cognition, emotion regulation, motivation and decision making. The underlying pathology is heterogeneous and classified according to the presence of intraneuronal inclusions of tau, TDP-43 or occasionally FUS. Biomarkers to detect these histopathological changes in life are increasingly important with the development of disease-modifying drugs. Gene mutations have been found which collectively account for around 10-20% of cases including a novel hexanucleotide repeat on chromosome 9 (C9orf72). The recently reviewed International Consensus Criteria for bvFTD propose three levels of diagnostic certainly: possible, probable and definite. Detailed history taking from family members to elicit behavioural features underpins the diagnostic process with support from neuropsychological testing designed to detect impairment in decision-making, emotion processing and social cognition. Brain imaging is important for increasing the level of diagnosis certainty. Carer education and support remain of paramount importance.

Neuroanatomical correlates of behavioural phenotypes in behavioural variant of frontotemporal dementia

BackgroundBehavioural variant of frontotemporal dementia (bvFTD) frequently presents complex behavioural changes, that rarely occur in isolation. Targeting behavioural phenotypes instead of single behavioural symptoms may potentially provide a disease model in which to investigate brain substrates of behavioural abnormalities. ObjectiveTo identify behavioural phenotypes and to assess the associated brain correlates in a cohort of patients with bvFTD. MethodsTwo hundred and seven consecutive individuals fulfilling clinical criteria for bvFTD were enrolled. Each participant's caregiver completed frontal behavioural inventory on 24 key behavioural disturbances. Confirmatory factor analysis (CFA) models were applied, and behavioural phenotypes identified. For each phenotype, a score was derived based on the “best” CFA model (Bifactor CFA). One hundred two participants underwent SPECT scan. A regression analysis between scores for each factor and regional cerebral blood flow was carried out (P<0.001). ResultsOne “general” behavioural phenotype and four factors were identified, that were termed “disinhibited”, “apathetic”, “aggressive”, and “language” phenotypes. The most robust brain correlate was identified for “disinhibited” phenotype, in the region of the anterior cingulated and anterior temporal cortex, bilaterally, and for apathetic phenotype in the left dorsolateral frontal cortex. As expected, language phenotype correlated with greater hypoperfusion in the left frontotemporal lobes. No significant correlation between aggressive phenotype and regional cerebral blood flow was found. Moreover, the “general” behavioural severity was associated with greater damage in the right frontal lobe. ConclusionsBehavioural phenotypes are associated with specific brain damage in bvFTD, involving distinct cerebral networks.