Objective: The frontal variant of frontotemporal degeneration (fvFTD) is characterized by a predominant behavioral syndrome, which is mostly attributable to an orbital-medial prefrontal dysfunction. ...The orbital and ventral medial prefrontal functions in humans are difficult to assess in clinical practice. Here, we propose a new tool, the SEA (Social cognition and Emotional Assessment), for use in evaluating the functions of the orbital and ventral-medial portions of the prefrontal cortex. Method: The SEA is composed of five subtests, each assessing a specific orbitofrontal-related function: a test of identification of facial emotions, a reversal/extinction task, a behavioral control task, a theory of mind test, and an apathy scale. The maximum score is 55. Three groups have been tested: 22 fvFTD patients, 22 patients with Alzheimer's disease (AD) or amnesic mild cognitive impairment (aMCI), and 30 healthy control subjects, all matched for age and educational level. Results: FvFTD patients showed significantly lower performances in all subtests of the SEA. A cut-off score of 39.4/55 was proposed to separate normal controls from fvFTD patients, with a maximum sensitivity and specificity of 100%. A very high specificity (88.5%) was obtained using the same cut-off with AD/aMCI patients and normal controls versus fvFTD patients. FvFTD patients' performance in the SEA did not correlate with any other neuropsychological scores, particularly the classical cognitive executive tests. Conclusions: The SEA is a new and useful tool for diagnosing fvFTD and, more generally, all of the diseases affecting the orbital and medial prefrontal functions.
Full text
Available for:
CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
Behavioural variant of frontotemporal dementia (bvFTD) is a neurodegenerative disease that is clinically characterised by progressive behavioural changes and social interpersonal dysfunctions. Its ...diagnosis remains a clinical challenge, and depression is one of the main causes of misdiagnoses due to the prevalence of apathy in bvFTD.
To evaluate the sensitivity and specificity of the Social Cognition and Emotional Assessment (SEA) and the mini-SEA for differentiating bvFTD from major depressive disorder (MDD).
Scores for the SEA and mini-SEA for 37 patients with bvFTD (divided into subgroups of 17 with early bvFTD and 20 with moderate bvFTD according to the normal range of the Mattis Dementia Rating Scale), 19 MDD patients and 30 control subjects were compared to define the discrimination power of these tools compared with other standard neuropsychological tests.
SEA and mini-SEA scores were significantly lower for both the early and moderate bvFTD groups compared with control subjects and the MDD group, and very few scores overlapped between patients in the bvFTD subgroups and patients in the MDD and control subgroups. SEA and mini-SEA scores distinguished early bvFTD from MDD with sensitivity and specificity rates above 94%.
Unlike standard executive neuropsychological tests, SEA and the mini-SEA can differentiate MDD from bvFTD in the early stages of the disease. The mini-SEA is an easy tool that can be utilised in neurological or psychiatric departments.
The aim of this study was to explore the cerebral correlates of functional deficits that occur in behavioral variant frontotemporal dementia (bvFTD). A specific neuropsychological battery, the Social ...cognition & Emotional Assessment (SEA; Funkiewiez et al., 2012), was used to assess impaired social and emotional functions in 20 bvFTD patients who also underwent structural MRI scanning. The SEA subscores of theory of mind, reversal-learning tests, facial emotion identification, and apathy evaluation were entered as covariates in a voxel-based morphometry analysis. The results revealed that the gray matter volume in the rostral part of the medial prefrontal cortex mPFC, Brodmann area (BA) 10 was associated with scores on the theory of mind subtest, while gray matter volume within the orbitofrontal (OFC) and ventral mPFC (BA 11 and 47) was related to the scores observed in the reversal-learning subtest. Gray matter volume within BA 9 in the mPFC was correlated with scores on the emotion recognition subtest, and the severity of apathetic symptoms in the Apathy scale covaried with gray matter volume in the lateral PFC (BA 44/45). Among these regions, the mPFC and OFC cortices have been shown to be atrophied in the early stages of bvFTD. In addition, SEA and its abbreviated version (mini-SEA) have been demonstrated to be sensitive to early impairments in bvFTD (Bertoux et al., 2012). Taken together, these results suggest a differential involvement of orbital and medial prefrontal subregions in SEA subscores and support the use of the SEA to evaluate the integrity of these regions in the early stages of bvFTD.
Patients with neurodegenerative diseases affecting the frontal lobes have difficulties in categorization tasks, such as the similarity tasks. They give two types of unusual response to the question: ...“In what way are an orange and a banana alike?”, either a differentiation (“one is yellow, the other is orange”) or a concrete similarity (“they are sweet”).
To characterize the categorization deficit of frontal patients and develop a short diagnostic tool to assess the nature of these difficulties.
We analyzed the responses provided by frontal and non-frontal neurodegenerative patients in a novel verbal similarity task (SimiCat). We included 40 frontal patients with behavioral variant fronto-temporal dementia (bvFTD) and progressive supranuclear palsy (PSP), 23 patients with Alzheimer's disease (AD) and 41 healthy matched controls. Responses that did not correspond to the expected taxonomic category (e.g.: fruits) were considered as errors.
All patients groups were impaired at the SimiCat test compared to controls. Differentiation errors were specific to frontal patients. Receiver operating characteristic analyses showed that a cut-off of two differentiation errors or more achieved 85% sensitivity of 100% specificity to discriminate bvFTD from AD. A short version of the test (<5 min) showed similar discriminative validity as the full version.
Differentiation responses were specific to frontal patients. The SimiCat demonstrates good discriminative validity to differentiate between bvFTD and AD. The short version of the test is a promising diagnostic tool that will need validation in future studies.
•Neurodegenerative patients provide unexpected responses at the similarities task.•Both frontal and non-frontal patients provide concrete similarities.•Only frontal patients provide differences when asked for similarities.•The SimiCat Task accurately discriminates AD from bvFTD patients.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
OBJECTIVETo determine relative frequencies and linguistic profiles of primary progressive aphasia (PPA) variants associated with GRN (progranulin) mutations and to study their neuroanatomic ...correlates. METHODSPatients with PPA carrying GRN mutations (PPA-GRN) were selected among a national prospective research cohort of 1,696 patients with frontotemporal dementia, including 235 patients with PPA. All patients with amyloid-positive CSF biomarkers were excluded. In this cross-sectional study, speech/language and cognitive profiles were characterized with standardized evaluations, and gray matter (GM) atrophy patterns using voxel-based morphometry. Comparisons were performed with controls and patients with sporadic PPA. RESULTSAmong the 235 patients with PPA, 45 (19%) carried GRN mutations, and we studied 32 of these. We showed that logopenic PPA (lvPPA) was the most frequent linguistic variant (n = 13, 41%), followed by nonfluent/agrammatic (nfvPPA; n = 9, 28%) and mixed forms (n = 8, 25%). Semantic variant was rather rare (n = 2, 6%). Patients with lvPPA, qualified as nonamyloid lvPPA, presented canonical logopenic deficit. Seven of 13 had a pure form; 6 showed subtle additional linguistic deficits not fitting criteria for mixed PPA and hence were labeled as logopenic-spectrum variant. GM atrophy involved primarily left posterior temporal gyrus, mirroring neuroanatomic changes of amyloid-positive-lvPPA. Patients with nfvPPA presented agrammatism (89%) rather than apraxia of speech (11%). CONCLUSIONSThis study shows that the most frequent PPA variant associated with GRN mutations is nonamyloid lvPPA, preceding nfvPPA and mixed forms, and illustrates that the language network may be affected at different levels. GRN testing is indicated for patients with PPA, whether familial or sporadic. This finding is important for upcoming GRN gene-specific therapies.
C9orf72 repeat expansions are rarely associated with primary progressive aphasias (PPA). In-depth characterization of the linguistic deficits, and the underlying patterns of grey-matter atrophy in ...PPA associated with the C9orf72 expansions (PPA-C9orf72) are currently lacking. In this study, we comprehensively analyzed a unique series of 16 patients affected by PPA-C9orf72. Eleven patients were issued from two independent French and Finnish cohorts, and five were identified by means of literature review. Voxel-based morphometry (VBM) studies were performed on three of them.
This study depicts the spectrum of C9orf72–related aphasic phenotypes, and illustrates their linguistic presentation. The non-fluent/agrammatic variant was the most frequent phenotype in our series (9/16 patients, 56%), with apraxia of speech being the main defining feature. Left frontal lobe atrophy was present in these subjects, peaking in inferior frontal gyrus. Three patients (19%) showed the semantic variant, with progression of atrophy in temporo-polar regions, later involving orbitofrontal cortex. Anterior temporal lobe dysfunction was also particularly relevant in two patients (12.5%) with mixed forms of PPA. Lastly, two patients (12.5%) had unclassifiable PPA with predominating word-finding difficulties. No PPA-C9orf72 patients in our series fulfilled the criteria of the logopenic variant.
Importantly, this study underlines the role of C9orf72 mutation in the disruption of the most anterior parts of the language network, including prefrontal and temporo-polar areas. It provides guidelines for C9orf72 testing in PPA patients, with important clinical impact as gene-specific therapies are upcoming.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
variants are a frequent cause of familial frontotemporal dementia (FTD). Monitoring disease progression in asymptomatic carriers of genetic variants is a major challenge in delivering preventative ...therapies before clinical onset. This study aimed to assess the usefulness of fluorodeoxyglucose (FDG)-PET in identifying metabolic changes in presymptomatic
carriers (PS-
+) and to trace their longitudinal progression.
Participants were longitudinally evaluated over 5 years in a prospective cohort study focused on
disease (Predict-PGRN). They underwent cognitive/behavioral assessment, plasma neurofilament measurement, brain MRI, and FDG-PET. Voxel-wise comparisons of structural and metabolic imaging data between 2 groups were performed for each time point. Longitudinal PET changes were evaluated with voxel-wise comparisons and the metabolic percent annual changes method. The association of regional brain metabolism with plasma neurofilament and cognitive changes was analyzed.
Among the 80 individuals enrolled in the study, 58 (27 PS-
+ and 31 noncarriers) were included in the analyses. Cross-sectional comparisons between PS-
+ and controls found a significant hypometabolism in the left superior temporal sulcus (STS) region (encompassing the middle and superior temporal gyri), approximately 15 years before the expected disease onset, without significant cortical atrophy. The longitudinal metabolic decline over the following 5 years peaked around the right STS in carriers (
< 0.001), without significantly greater volume loss compared with that in controls. Their estimated annualized metabolic decrease (-1.37%) was higher than that in controls (-0.21%,
= 0.004). Lower glucose uptake was associated with higher neurofilament increase (
= 0.003) and lower frontal cognitive scores (
= 0.014) in PS-
+.
This study detected brain metabolic changes in the STS region, preceding structural and cognitive alterations, thus contributing to the characterization of the pathochronology of preclinical
disease. Owing to the STS involvement in the perception of facially communicated cues, it is likely that its dysfunction contributes to social cognition deficits characterizing FTD. Overall, our study highlights brain metabolic changes as an early disease-tracking biomarker and proposes annualized percent decrease as a metric to monitor therapeutic response in forthcoming trials.
Impulse control disorders (ICD), including pathological gambling, are common in Parkinson's disease (PD) and tend to improve after subthalamic (STN) stimulation after a marked reduction of ...dopaminergic medication. In order to investigate the effect of STN stimulation on impulsive decision making, we used the Iowa Gambling task (IGT).
We investigated IGT performance in 20 patients with PD before STN surgery with and without dopaminergic treatment and in 24 age-matched controls. All patients underwent an extensive neuropsychological interview screening for behavioural disorders. Assessment in patients was repeated 3 months after surgery without dopaminergic treatment with and without stimulation.
Chronic antiparkinsonian treatment was drastically reduced after surgery (-74%). At baseline, on high chronic dopaminergic treatment 8/20 patients with PD presented with pathological hyperdopaminergic behaviours, which had resolved in 7/8 patients 3 months after surgery on low chronic dopaminergic treatment. Preoperative performance on the IGT was significantly impaired compared to after surgery.
Dopaminergic medication likely contributes to the impairment in decision making underlying ICDs. Deep brain stimulation allows drastic reduction of dopaminergic medication and, thus, concomitant remediation of medication-induced impairment in decision making.
▶ Creativity is decreased in frontotemporal dementia (FTD). ▶ Disinhibited and perseverative responses lead to “pseudo-creative” productions. ▶ In FTD, rostral prefrontal hypoperfusion correlates ...with poor creative thinking.
The prefrontal cortex (PFC) supports functions critical for creative thinking. Damage to the PFC is expected to impair creativity. Yet, previous works suggested the emergence of artistic talent in patients with frontotemporal lobar degeneration (FTLD), which was interpreted as increased creativity.
We designed a study in patients with frontal variant (fv) of FTLD in order to verify whether: (1) creativity is impaired after frontal degeneration, (2) poor creativity is associated with frontal dysfunctions, and (3) poor creativity is related to hypoperfusion in specific PFC regions.
Three groups of subjects were enrolled in the study: fvFTLD patients (n=17), non-demented Parkinson's disease (PD) patients (n=12) and healthy controls (n=17). Participants performed a standardized test of creativity, the Torrance Test of Creative Thinking (TTCT) and tests assessing frontal functions. Brain perfusion was correlated to fvFTLD patients’ performance in the TTCT.
Patients with fvFTLD were strongly impaired in all dimensions of the TTCT, compared to PD patients and controls. Disinhibited and perseverative responses were observed only in fvFTLD patients, leading to “pseudo-creative” responses. Poor creativity was positively correlated with several frontal tests. Poor creativity was also correlated with prefrontal hypoperfusion, particularly in the frontal pole.
Poor creativity is associated with fvFTLD. The results also suggest that the integrity of the PFC (in particular frontopolar) is strongly associated with creative thinking. The emergence of artistic talent in patients with fvFTLD is explained by the release of involuntary behaviors, rather than by the development of creative thinking.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
PDF
