RESUMEN
Platelet-derived growth factor receptor beta (PDGFRB) is one of the genes associated with primary familial brain calcification (PFBC), an inherited neurological disease (OMIM:173410). Genetic analysis of patients and families revealed at least 13 PDGFRB heterozygous missense variants, including two novel ones described in the present report. Limited experimental data published on five of these variants had suggested that they decrease the receptor activity. No functional information was available on the impact of variants located within the receptor extracellular domains. Here, we performed a comprehensive molecular analysis of PDGFRB variants linked to PFBC. Mutated receptors were transfected in various cell lines to monitor receptor expression, signaling, mitogenic activity and ligand binding. Four mutants caused a complete loss of tyrosine kinase activity in multiple assays. One of the novel variants, p.Pro154Ser, decreased the receptor expression and abolished binding of platelet-derived growth factor (PDGF-BB). Others showed a partial loss of function related to reduced expression or signaling. Combining clinical, genetic and molecular data, we consider nine variants as pathogenic or likely pathogenic, three as benign or likely benign and one as a variant of unknown significance. We discuss the possible relationship between the variant residual activity, incomplete penetrance, brain calcification and neurological symptoms. In conclusion, we identified distinct molecular mechanisms whereby PDGFRB variants may result in a receptor loss of function. This work will facilitate genetic counseling in PFBC.
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Encefalopatías , Calcinosis , Enfermedades Neurodegenerativas , Encéfalo/metabolismo , Encefalopatías/patología , Calcinosis/genética , Calcinosis/metabolismo , Heterocigoto , Humanos , Mutación , Enfermedades Neurodegenerativas/metabolismo , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/genética , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismoRESUMEN
PURPOSE: To assess the likely pathogenic/pathogenic (LP/P) variants rates in Mendelian dementia genes and the moderate-to-strong risk factors rates in patients with Alzheimer disease (AD). METHODS: We included 700 patients in a prospective study and performed exome sequencing. A panel of 28 Mendelian and 6 risk-factor genes was interpreted and returned to patients. We built a framework for risk variant interpretation and risk gradation and assessed the detection rates among early-onset AD (EOAD, age of onset (AOO) ≤65 years, n = 608) depending on AOO and pedigree structure and late-onset AD (66 < AOO < 75, n = 92). RESULTS: Twenty-one patients carried a LP/P variant in a Mendelian gene (all with EOAD, 3.4%), 20 of 21 affected APP, PSEN1, or PSEN2. LP/P variant detection rates in EOAD ranged from 1.7% to 11.6% based on AOO and pedigree structure. Risk factors were found in 69.5% of the remaining 679 patients, including 83 (12.2%) being heterozygotes for rare risk variants, in decreasing order of frequency, in TREM2, ABCA7, ATP8B4, SORL1, and ABCA1, including 5 heterozygotes for multiple rare risk variants, suggesting non-monogenic inheritance, even in some autosomal-dominant-like pedigrees. CONCLUSION: We suggest that genetic screening should be proposed to all EOAD patients and should no longer be prioritized based on pedigree structure.
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Enfermedad de Alzheimer , Secuenciación del Exoma , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Glicoproteínas de Membrana , Presenilina-2 , Receptores Inmunológicos , Humanos , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/diagnóstico , Pruebas Genéticas/métodos , Femenino , Masculino , Anciano , Factores de Riesgo , Estudios Prospectivos , Persona de Mediana Edad , Presenilina-2/genética , Presenilina-1/genética , Linaje , Edad de Inicio , Precursor de Proteína beta-Amiloide/genética , Anciano de 80 o más AñosRESUMEN
GRN mutations are among the main genetic causes of frontotemporal dementia (FTD). Considering the progranulin involvement in lysosomal homeostasis, we aimed to evaluate if plasma lysosphingolipids (lysoSPL) are increased in GRN mutation carriers, and whether they might represent relevant fluid-based biomarkers in GRN-related diseases. We analyzed four lysoSPL levels in plasmas of 131 GRN carriers and 142 non-carriers, including healthy controls and patients with frontotemporal dementias (FTD) carrying a C9orf72 expansion or without any mutation. GRN carriers consisted of 102 heterozygous FTD patients (FTD-GRN), three homozygous patients with neuronal ceroid lipofuscinosis-11 (CLN-11) and 26 presymptomatic carriers (PS-GRN), the latter with longitudinal assessments. Glucosylsphingosin d18:1 (LGL1), lysosphingomyelins d18:1 and isoform 509 (LSM18:1, LSM509) and lysoglobotriaosylceramide (LGB3) were measured by electrospray ionization-tandem mass spectrometry coupled to ultraperformance liquid chromatography. Levels of LGL1, LSM18:1 and LSM509 were increased in GRN carriers compared to non-carriers (p < 0.0001). No lysoSPL increases were detected in FTD patients without GRN mutations. LGL1 and LSM18:1 progressively increased with age at sampling, and LGL1 with disease duration, in FTD-GRN. Among PS-GRN carriers, LSM18:1 and LGL1 significantly increased over 3.4-year follow-up. LGL1 levels were associated with increasing neurofilaments in presymptomatic carriers. This study evidences an age-dependent increase of ß-glucocerebrosidase and acid sphingomyelinase substrates in GRN patients, with progressive changes as early as the presymptomatic phase. Among FTD patients, plasma lysoSPL appear to be uniquely elevated in GRN carriers, and thus might serve as suitable non-invasive disease-tracking biomarkers of progression, specific to the pathophysiological process. Finally, this study might add lysoSPL to the portfolio of fluid-based biomarkers, and pave the way to disease-modifying approaches based on lysosomal function rescue in GRN diseases.
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Demencia Frontotemporal , Enfermedad de Pick , Humanos , Demencia Frontotemporal/genética , Esfingolípidos , Mutación , Lisosomas , Biomarcadores , Progresión de la Enfermedad , Progranulinas/genéticaRESUMEN
BACKGROUND: While affective disturbances are a key symptomatic indicator of behavioural variant frontotemporal dementia (bvFTD), little is known about how patients process the emotional load of their autobiographical (i.e. personal) memories. METHODS: We assessed the interplay of emotional regulation and autobiographical memory by inviting 18 bvFTD and 20 control participants to remember past personal events. For each memory, participants rated its emotional valence "then" (i.e. when the event has occurred) vs "now" (i.e. when retrieving the event). RESULTS: Patients with bvFTD described their memories as neutral at both times (p = .85), while control participants rated their memories as more positive during "then" than during "now" (p = .013). Autobiographical retrieval triggered fewer emotional words (p < .001) and less specificity (p < .001) in bvFTD patients compared to control participants. CONCLUSIONS: The lack of significant differences between the emotional characteristics during "then" than "now" in patients with bvFTD (and the flattening of both) may mirror their hampered ability for emotional generation, which may be associated with difficulties in reframing their past experiences to modify and adapt their meaning. The hampered emotional regulation in bvFTD may also be associated with an avoidance strategy and a passive attitude toward the past.
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Demencia Frontotemporal , Memoria Episódica , Humanos , Demencia Frontotemporal/psicología , Emociones , Recuerdo Mental/fisiologíaRESUMEN
BACKGROUND: Diagnosis of Alzheimer disease (AD) can cause substantial psychological distress in patients. We thus assessed how patients with AD remember the announcement of diagnosis. METHODS: We recruited 47 participants with mild AD (26 women; M age=68.89 y, SD=7.37; M years of formal education=9.74, SD=3.00). We invited the participants to remember the moment when their clinicians announced their diagnosis, within 6 months of the event, as well as a control memory, over the same period. We analyzed memory retrieval regarding specificity, as well as the subjective experience of retrieval (ie, regarding mental time travel, visual imagery, emotion and importance). RESULTS: No significant differences were observed between memory of diagnosis and control memory regarding specificity, mental time travel and visual imagery. However, memory of diagnosis triggered a more intense emotional experience and feeling of importance than control memory. DISCUSSION: Retrieval of the diagnosis announcement can activate a strong emotional and personally important experience in patients with AD. When remembering the diagnosis announcement, patients with AD may re-experience some features of that turning point in which they shift from "person" to "patient."
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Enfermedad de Alzheimer , Memoria Episódica , Humanos , Femenino , Anciano , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/psicología , Recuerdo Mental/fisiología , Memoria/fisiología , Emociones/fisiologíaRESUMEN
We investigated whether pupil size can variate with the intensity of cognitive processing in patients with behavioral-variant-Frontotemporal-Dementia (bvFTD). We invited five bvFTD participants and 21 controls to perform forward spans and backward spans, and, in a control condition, to count aloud. We recorded pupil activity using eye-tracking-glasses during the spans and control condition. Analysis demonstrated larger pupil sizes during backward spans than during forward spans, and larger pupil sizes during forward spans than during counting in both bvFTD and control participants. These findings demonstrate how increased cognitive load triggers increased pupil size and how this connection is maintained in bvFTD.
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Enfermedad de Alzheimer , Demencia Frontotemporal , Enfermedad de Alzheimer/psicología , Cognición , Demencia Frontotemporal/complicaciones , Demencia Frontotemporal/diagnóstico , Demencia Frontotemporal/psicología , Humanos , Pruebas NeuropsicológicasRESUMEN
We evaluated the relationship between eye movements and future thinking. More specifically, we evaluated whether maintained fixation could influence cognitive characteristics of future thinking. We invited participants to imagine future events in two conditions: while freely exploring a white wall and while fixating a cross on the wall. Results demonstrated fewer and longer fixations, as well as fewer and shorter saccades during maintained fixation condition than in the free gaze condition. Shorter total amplitude of saccades was also observed during the maintained fixation condition than during the free-gaze condition. Regarding the cognitive characteristics of future thinking, fewer spatiotemporal details and less visual imagery, slower retrieval time, and shorter descriptions were observed for future thinking during maintained fixation than during free-gaze condition. These results demonstrate that maintaining fixation results in an effortful construction of future scenarios. We suggest that maintained fixation limits the cognitive resources that are required for future thinking.
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Fijación Ocular , Movimientos Sacádicos , Movimientos Oculares , Predicción , Humanos , Imágenes en PsicoterapiaRESUMEN
BACKGROUND AND AIMS: Autobiographical memory serves to recall past personal experiences and share them with others, promoting social bonding and communication. In this study, we investigated whether encouraging patients with Alzheimer's disease (AD) to share autobiographical memories during formal neuropsychological testing may boost the patient-clinician relationship, and more specifically, the neuropsychologist's level of sympathy as perceived by patients. METHODS: We invited patients with mild AD to perform neuropsychological testing in two conditions. In one condition, we invited patients to retrieve and share two autobiographical memories after testing, while in a control condition, the testing session ended without asking patients to retrieve and share any autobiographical memories. After the two conditions, patients were invited to rate the neuropsychologist's level of sympathy towards them. RESULTS: Analysis demonstrated that patients perceived a higher level of sympathy when their neuropsychologist invited them to retrieve and share past personal experiences. DISCUSSION: By inviting patients with AD to retrieve past personal experiences, clinicians can promote a sense of sharing, create a social bond and, consequently, enhance the therapeutic relationship. In other words, by inviting patients with AD to share autobiographical memories, clinicians can promote a "social glue" with their patients, boosting mutual sympathy and patients' well-being.
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Enfermedad de Alzheimer , Memoria Episódica , Enfermedad de Alzheimer/psicología , Humanos , Recuerdo Mental , Pruebas Neuropsicológicas , PercepciónRESUMEN
We assessed how Alzheimer's disease (AD) patients would imagine their self in the future. AD patients and healthy controls were asked to generate statements beginning with "I-will-be" to describe how they saw themselves or how they wished to be in the future. These statements were analyzed in terms of four self-dimensions, i.e., physical self, social self, psychological self and self-cessation. The latter was investigated to assess how AD patients processed the idea of their own mortality. Findings demonstrated fewer total "I-will-be" statements in AD participants than in controls, suggesting that the construction of future self-concepts becomes weaker in the disease. Our results also demonstrated fewer statements related to the physical-self, the social-self and the psychological-self, and more statements related to self-cessation in AD participants than in controls. These findings suggest that AD patients are highly preoccupied by the idea of death when thinking about the future of their self.
Asunto(s)
Enfermedad de Alzheimer , Memoria Episódica , Enfermedad de Alzheimer/psicología , Predicción , Humanos , AutoimagenRESUMEN
OBJECTIVE: Neurofilament light chain (NfL) is a promising biomarker in genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). We evaluated plasma neurofilament light chain (pNfL) levels in controls, and their longitudinal trajectories in C9orf72 and GRN cohorts from presymptomatic to clinical stages. METHODS: We analysed pNfL using Single Molecule Array (SiMoA) in 668 samples (352 baseline and 316 follow-up) of C9orf72 and GRN patients, presymptomatic carriers (PS) and controls aged between 21 and 83. They were longitudinally evaluated over a period of >2 years, during which four PS became prodromal/symptomatic. Associations between pNfL and clinical-genetic variables, and longitudinal NfL changes, were investigated using generalised and linear mixed-effects models. Optimal cut-offs were determined using the Youden Index. RESULTS: pNfL levels increased with age in controls, from ~5 to~18 pg/mL (p<0.0001), progressing over time (mean annualised rate of change (ARC): +3.9%/year, p<0.0001). Patients displayed higher levels and greater longitudinal progression (ARC: +26.7%, p<0.0001), with gene-specific trajectories. GRN patients had higher levels than C9orf72 (86.21 vs 39.49 pg/mL, p=0.014), and greater progression rates (ARC:+29.3% vs +24.7%; p=0.016). In C9orf72 patients, levels were associated with the phenotype (ALS: 71.76 pg/mL, FTD: 37.16, psychiatric: 15.3; p=0.003) and remarkably lower in slowly progressive patients (24.11, ARC: +2.5%; p=0.05). Mean ARC was +3.2% in PS and +7.3% in prodromal carriers. We proposed gene-specific cut-offs differentiating patients from controls by decades. CONCLUSIONS: This study highlights the importance of gene-specific and age-specific references for clinical and therapeutic trials in genetic FTD/ALS. It supports the usefulness of repeating pNfL measurements and considering ARC as a prognostic marker of disease progression. TRIAL REGISTRATION NUMBERS: NCT02590276 and NCT04014673.
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Esclerosis Amiotrófica Lateral/diagnóstico , Proteína C9orf72/genética , Demencia Frontotemporal/diagnóstico , Proteínas de Neurofilamentos/sangre , Progranulinas/genética , Adulto , Anciano , Anciano de 80 o más Años , Esclerosis Amiotrófica Lateral/sangre , Esclerosis Amiotrófica Lateral/genética , Progresión de la Enfermedad , Femenino , Demencia Frontotemporal/sangre , Demencia Frontotemporal/genética , Humanos , Masculino , Persona de Mediana EdadRESUMEN
We investigate whether retrograde-amnesia can be indexed with pupil activity. We present the case of L, 19-year-old, without neurological or psychiatric disorders except for retrograde-amnesia. We invited L to retrieve retrograde and anterograde memories while his pupil size was monitering with eye-tracking glasses. Results demonstrated impaired retrograde retrieval but successful anterograde retrieval in L. He also attributed lower emotional value and visual imagery to his retrograde compared to his anterograde memories. Critically, smaller pupils were observed during retrograde than during anterograde retrieval. Our study provides the first evidence on the value of pupillometry as a potential physiological marker of amnesia.
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Amnesia Retrógrada , Amnesia , Adulto , Humanos , Masculino , Adulto JovenRESUMEN
There is an increased interest in the study of eye movements during the retrieval of autobiographical memories. Following this trend, the aim of the current study was to evaluate eye movements during the retrieval of remote and recent autobiographical memories. We instructed 71 participants to retrieve memories of personal events from early childhood (6-10 years), late childhood/early adolescence (11-14 years), late adolescence (15-18 years), and the last month. During the retrieval of these memories, participants wore eye-tracking glasses. Analyses showed that early childhood memories triggered fewer fixations and fixations with longer durations than memories from the last month. However, no significant differences were observed for the number of saccades, saccade durations, or total amplitude of the saccades. The fewer and longer lasting fixations during the retrieval of early childhood memories can be attributed either to the visual system reconstructing remote memories from an observer perspective or to difficulties when reconstructing remote memories.
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Memoria Episódica , Adolescente , Niño , Preescolar , Movimientos Oculares , Humanos , Memoria a Largo Plazo , Recuerdo Mental , Movimientos SacádicosRESUMEN
BACKGROUND: Although there is a large body of research demonstrating the negative effects of Alzheimer disease (AD) on autobiographical memory (ie, memory of personal information), little is known about sex differences in autobiographical retrieval in AD. METHODS: We addressed this issue by inviting patients with AD and healthy control participants to retrieve autobiographical memories and analyzed them with regard to specificity, subjective experience (ie, time travel, emotion, and visual imagery), and retrieval time. RESULTS: Analyses demonstrated no significant differences between women and men with AD with regard to autobiographical specificity, time travel, visual imagery, or retrieval time. However, the higher emotional value was attributed to memories by women with AD than by men with AD. DISCUSSION: AD seems to equally affect the ability of women and men with AD to construct specific autobiographical memories, to mentally travel in time to relive these memories, to construct mental visual images during memory retrieval, and to organize and monitor search processes, as the latter are mirrored by retrieval time. However, women with AD seem to attribute greater emotional value to autobiographical memories than men with AD.
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Enfermedad de Alzheimer/psicología , Emociones , Memoria Episódica , Recuerdo Mental , Femenino , Humanos , Masculino , Factores SexualesRESUMEN
A 63-year-old woman was referred for visuospatial difficulties. The clinical and neuropsychological examination in association with imaging and biomarkers led to a diagnosis of posterior cortical atrophy (PCA). The patient, an amateur watercolor artist, continued to paint throughout her disease and her paintings illustrate in an original way the progression of her disorders. At an advanced stage, the evolution of neurovisual disorders is difficult to evaluate in patients. While studies have shown changes in artistic style in neurodegenerative diseases, none of them concerned PCA. Artistic production enables a different approach to trying to understand the progression of disorders.
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Arte , Enfermedades Neurodegenerativas , Lóbulo Occipital , Lóbulo Parietal , Desempeño Psicomotor/fisiología , Percepción Espacial/fisiología , Percepción Visual/fisiología , Progresión de la Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Enfermedades Neurodegenerativas/patología , Enfermedades Neurodegenerativas/fisiopatología , Lóbulo Occipital/patología , Lóbulo Occipital/fisiopatología , Lóbulo Parietal/fisiología , Lóbulo Parietal/fisiopatologíaRESUMEN
BACKGROUND: Amyloid protein precursor (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) mutations cause autosomal dominant forms of early-onset Alzheimer disease (AD-EOAD). Although these genes were identified in the 1990s, variant classification remains a challenge, highlighting the need to colligate mutations from large series. METHODS AND FINDINGS: We report here a novel update (2012-2016) of the genetic screening of the large AD-EOAD series ascertained across 28 French hospitals from 1993 onwards, bringing the total number of families with identified mutations to n = 170. Families were included when at least two first-degree relatives suffered from early-onset Alzheimer disease (EOAD) with an age of onset (AOO) ≤65 y in two generations. Furthermore, we also screened 129 sporadic cases of Alzheimer disease with an AOO below age 51 (44% males, mean AOO = 45 ± 2 y). APP, PSEN1, or PSEN2 mutations were identified in 53 novel AD-EOAD families. Of the 129 sporadic cases screened, 17 carried a PSEN1 mutation and 1 carried an APP duplication (13%). Parental DNA was available for 10 sporadic mutation carriers, allowing us to show that the mutation had occurred de novo in each case. Thirteen mutations (12 in PSEN1 and 1 in PSEN2) identified either in familial or in sporadic cases were previously unreported. Of the 53 mutation carriers with available cerebrospinal fluid (CSF) biomarkers, 46 (87%) had all three CSF biomarkers-total tau protein (Tau), phospho-tau protein (P-Tau), and amyloid ß (Aß)42-in abnormal ranges. No mutation carrier had the three biomarkers in normal ranges. One limitation of this study is the absence of functional assessment of the possibly and probably pathogenic variants, which should help their classification. CONCLUSIONS: Our findings suggest that a nonnegligible fraction of PSEN1 mutations occurs de novo, which is of high importance for genetic counseling, as PSEN1 mutational screening is currently performed in familial cases only. Among the 90 distinct mutations found in the whole sample of families and isolated cases, definite pathogenicity is currently established for only 77%, emphasizing the need to pursue the effort to classify variants.
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Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Presenilina-1/genética , Presenilina-2/genética , Adulto , Edad de Inicio , Femenino , Francia , Pruebas Genéticas , Humanos , Masculino , Persona de Mediana Edad , MutaciónRESUMEN
OBJECTIVE: The goal of this study is to evaluate brain metabolism in mild cognitive impairment (MCI) patients with and without apathy (as determined by the Neuropsychiatric Inventory Questionnaire). METHODS: Baseline data from 65 MCI participants (11 with apathy and 54 without) from the Alzheimer's Disease (AD) Neuroimaging Initiative study were analyzed. All participants underwent a comprehensive cognitive and neuropsychiatric assessment, volumetric MRI and measures of cerebral glucose metabolism applying (18)F-fluorodeoxyglucose positron emission tomography at baseline. The presence of apathy at baseline was determined by the Neuropsychiatric Inventory Questionnaire. RESULTS: There was no difference between apathy and apathy-free MCI patients regarding cognitive assessment and neuropsychiatric measures when apathy-specific items were removed. Cerebrovascular disease load and cerebral atrophy were equivalent in both groups. Compared with the apathy-free MCI patients, MCI patients with apathy had significantly decreased metabolism in the posterior cingulate cortex. CONCLUSION: The presence of apathy in MCI patients is associated with AD-specific pattern of brain metabolic defect. These results could suggest that apathy belongs to the spectrum of prodromal AD symptoms.
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Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/fisiopatología , Apatía/fisiología , Encéfalo/metabolismo , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/fisiopatología , Neuroimagen/métodos , Anciano , Enfermedad de Alzheimer/diagnóstico por imagen , Atrofia/patología , Disfunción Cognitiva/diagnóstico por imagen , Progresión de la Enfermedad , Femenino , Fluorodesoxiglucosa F18/metabolismo , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones/métodosRESUMEN
Financial decision-making requires trading off between guaranteed and probabilistic outcomes and between immediate and delayed ones. While research has demonstrated that patients with behavioural-variant frontotemporal dementia (bvFTD) prefer immediate rewards at the expense of future ones (i.e. temporal discounting), little is known about how patients choose between smaller, guaranteed and larger, but probabilistic, outcomes (i.e. probabilistic discounting). We thus investigated probabilistic discounting by inviting 18 patients with bvFTD and 20 control participants to choose between fixed smaller monetary amounts and a fixed larger monetary amount with a variated probability of occurrence (e.g. 'Would you rather have 40 for sure or a 20% chance of winning 100?'). Results demonstrated lower scores, indicating higher risk tolerance, on the probabilistic discounting task in patients with bvFTD (while impulsively choosing more immediate rewards on the temporal discounting task) compared to control participants. Probabilistic discounting was significantly correlated with a decline in general cognitive performance in patients with bvFTD. When dealing between smaller, guaranteed, and larger, but probabilistic, rewards, patients with bvFTD tend to prefer guaranteed rewards and discount the uncertain ones.
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Descuento por Demora , Demencia Frontotemporal , Recompensa , Humanos , Demencia Frontotemporal/psicología , Masculino , Femenino , Descuento por Demora/fisiología , Persona de Mediana Edad , Anciano , Pruebas Neuropsicológicas , Probabilidad , Conducta ImpulsivaRESUMEN
In this study, we offer a comprehensive assessment of the phenomenological experience of patients with behavioral-variant frontotemporal dementia (bvFTD) upon retrieval of autobiographical memory. We invited patients with bvFTD and control participants to retrieve autobiographical memories and rate, for each memory, its phenomenological characteristics. We also analyzed the retrieved memories regarding specificity (i.e., whether the memory described a general or a detailed event). Results demonstrated that, compared to control participants, patients with bvFTD attributed lower levels of reliving, back in time (feeling as if going back in time), remembering, realness, visual imagery, auditory imagery, language, emotion, rehearsal, importance, spatial recall and temporal recall to their memories. Lower autobiographical specificity was also observed in patients with bvFTD compared to control participants. Autobiographical specificity in patients with bvFTD was associated with verbal fluency and verbal episodic memory, but not with phenomenological experience. Although autobiographical memories of patients with bvFTD show low ratings of phenomenological experience, the patients may still enjoy some limited subjective experience during autobiographical retrieval.
RESUMEN
We assessed the aesthetic experience of patients with behavioral variant frontotemporal dementia (bvFTD) to understand their ability to experience feelings of the sublime and to be moved when viewing paintings. We exposed patients with bvFTD and control participants to concrete and abstract paintings and asked them how moved they were by these paintings and whether the latter were beautiful or ugly. Patients with bvFTD declared being less moved than control participants by both abstract and concrete paintings. No significant differences were observed between abstract and concrete paintings in both patients with bvFTD and control participants. Patients with bvFTD provided fewer "beautiful" and more "ugly" responses than controls for both abstract and concrete paintings. No significant differences in terms of "beautiful" and "ugly" responses were observed between abstract and concrete paintings in both patients with bvFTD and control participants. These findings suggest disturbances in the basic affective experience of patients with bvFTD when they are exposed to paintings, as well as a bias in their ability to judge the aesthetic quality of paintings.
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Background: The potential of ChatGPT in medical diagnosis has been explored in various medical conditions. Objective: We assessed whether ChatGPT can contribute to the diagnosis of Alzheimer's disease (AD). Methods: We provided ChatGPT with four generated cases (mild, moderate, or advanced stage AD dementia, or mild cognitive impairment), including descriptions of their complaints, physical examinations, as well as biomarker, neuroimaging, and neuropsychological data. Results: ChatGPT accurately diagnosed the test cases similarly to two blinded specialists. Conclusions: While the use of generated cases can be a limitation to our study, our findings demonstrate that ChatGPT can be a useful tool for symptom assessment and the diagnosis of AD. However, while the use of ChatGPT in AD diagnosis is promising, it should be seen as an adjunct to clinical judgment rather than a replacement.