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1.
Geriatr Psychol Neuropsychiatr Vieil ; 22(1): 76-84, 2024 Mar 01.
Article in French | MEDLINE | ID: mdl-38573147

ABSTRACT

Cognitive performance of older adults is very often inferior to that of younger adults on a variety of laboratory tests assessing basic functions such as memory, inhibition, or attention. Classic hypotheses and theories share the idea that these cognitive deficits are irreversible, due to profound cerebral changes. In this review article, we develop a more positive conception of aging, according to which cognitive deficits are not all irreversible, and can even be partially if not completely reversible. To this end, we present some of the most illustrative research on the reversibility of the effects of aging on cognition. We show how subtle contextual manipulations can change older adults' motivation and strategy, which improve their cognitive performance. We also show that guidance toward the selection of the most appropriate strategy, whether explicit as in selectivity paradigms or implicit as in dual-task procedures, can increase older adults' cognitive performance. We finally describe the hypotheses and theories that both account for low cognitive performance in old age and ways to reverse the effects of cognitive aging.


Subject(s)
Cognition Disorders , Cognitive Aging , Cognitive Dysfunction , Humans , Aged , Cognition , Aging
2.
J Parkinsons Dis ; 14(1): 209-219, 2024.
Article in English | MEDLINE | ID: mdl-38217611

ABSTRACT

BACKGROUND: There are currently no recommendations on the therapeutic management of Parkinson's disease (PD) patients at the end of life. OBJECTIVE: To describe a cohort of patients with PD who benefited from continuous subcutaneous apomorphine infusion (CSAI) initiation at the end of their life as comfort care. METHODS: This real-life cohort includes 14 PD patients, who benefited from 24-h, low-dose CSAI (0.5-3 mg/h) in the context of terminal care. Patient's comfort (pain, rigidity, and/or ability to communicate) and occurrence of CSAI-related side-effects (nausea/vomiting, cutaneous and behavioral manifestations) were evaluated based on medical records. RESULTS: All patients (age 62-94 years, disease duration 2-32 years) presented with late-stage PD and a compromised oral route. Treatment lasted from a few hours to 39 days. CSAI led to substantial functional improvement, with a good safety profile. Overall clinical comfort was deemed improved by the medical team, the patient, and/or caregivers. CONCLUSIONS: CSAI might be a promising approach in PD terminal care, as it reduces motor symptoms and overall discomfort, with an apparent good safety profile. Use of the apomorphine pen, sublingual film or a classic syringe pump might be considered when apomorphine pumps are not available. Larger observational cohorts and randomized controlled trials are needed to establish the efficacy and tolerability of apomorphine in the context of terminal care and more broadly, in an advance care planning perspective.


Subject(s)
Parkinson Disease , Terminal Care , Humans , Middle Aged , Aged , Aged, 80 and over , Apomorphine , Parkinson Disease/drug therapy , Antiparkinson Agents/therapeutic use , Patient Comfort
3.
Geriatr Psychol Neuropsychiatr Vieil ; 21(3): 363-375, 2023 Sep 01.
Article in French | MEDLINE | ID: mdl-38093573

ABSTRACT

Alzheimer's disease leads to an alteration of decision-making abilities which may increase risk-taking behaviours, particularly associated anosognosia. Anticipating the progression of the disease raises a number of questions, particularly in relation to aging in place. Our qualitative study aimed to identify the arguments used by older patients with Alzheimer's disease when choosing a place to age. The study included 22 older adults, living at home, and diagnosed as mild dementia. The patients' arguments in favour of ageing in place were based mainly on the preservation of internal security, through the familiarity of places and relations as well as the maintenance of their independence and their lifestyle habits, allowing stability in their daily lives. Despite the identification of memory loss, the associated risks were minimized or hidden from the reflection on the choice of the place to age.


Subject(s)
Agnosia , Alzheimer Disease , Humans , Aged , Alzheimer Disease/diagnosis , Independent Living , Memory Disorders , Agnosia/etiology , Agnosia/diagnosis
4.
Front Neurosci ; 17: 1237734, 2023.
Article in English | MEDLINE | ID: mdl-37790591

ABSTRACT

Introduction: The Balloon Analog Risk Task (BART), a computerized behavioral paradigm, is one of the most common tools used to assess the risk-taking propensity of an individual. Since its initial behavioral version, the BART has been adapted to neuroimaging technique to explore brain networks of risk-taking behavior. However, while there are a variety of paradigms adapted to neuroimaging to date, no consensus has been reached on the best paradigm with the appropriate parameters to study the brain during risk-taking assessed by the BART. In this review of the literature, we aimed to identify the most appropriate BART parameters to adapt the initial paradigm to neuroimaging and increase the reliability of this tool. Methods: A systematic review focused on the BART versions adapted to neuroimaging was performed in accordance with PRISMA guidelines. Results: A total of 105 articles with 6,879 subjects identified from the PubMed database met the inclusion criteria. The BART was adapted in four neuroimaging techniques, mostly in functional magnetic resonance imaging or electroencephalography settings. Discussion: First, to adapt the BART to neuroimaging, a delay was included between each trial, the total number of inflations was reduced between 12 and 30 pumps, and the number of trials was increased between 80 and 100 balloons, enabling us to respect the recording constraints of neuroimaging. Second, explicit feedback about the balloon burst limited the decisions under ambiguity associated with the first trials. Third, employing an outcome index that provides more informative measures than the standard average pump score, along with a model incorporating an exponential monotonic increase in explosion probability and a maximum explosion probability between 50 and 75%, can yield a reliable estimation of risk profile. Additionally, enhancing participant motivation can be achieved by increasing the reward in line with the risk level and implementing payment based on their performance in the BART. Although there is no universal adaptation of the BART to neuroimaging, and depending on the objectives of a study, an adjustment of parameters optimizes its evaluation and clinical utility in assessing risk-taking.

5.
Cells ; 12(12)2023 06 10.
Article in English | MEDLINE | ID: mdl-37371068

ABSTRACT

Apathy is commonly defined as a loss of motivation leading to a reduction in goal-directed behaviors. This multidimensional syndrome, which includes cognitive, emotional and behavioral components, is one of the most prevalent neuropsychiatric features of Parkinson's disease (PD). It has been established that the prevalence of apathy increases as PD progresses. However, the pathophysiology and anatomic substrate of this syndrome remain unclear. Apathy seems to be underpinned by impaired anatomical structures that link the prefrontal cortex with the limbic system. It can be encountered in the prodromal stage of the disease and in fluctuating PD patients receiving bilateral chronic subthalamic nucleus stimulation. In these stages, apathy may be considered as a disorder of motivation that embodies amotivational behavioral syndrome, is underpinned by combined dopaminergic and serotonergic denervation and is dopa-responsive. In contrast, in advanced PD patients, apathy may be considered as cognitive apathy that announces cognitive decline and PD dementia, is underpinned by diffuse neurotransmitter system dysfunction and Lewy pathology spreading and is no longer dopa-responsive. In this review, we discuss the clinical patterns of apathy and their treatment, the neurobiological basis of apathy, the potential role of the anatomical structures involved and the pathways in motivational and cognitive apathy.


Subject(s)
Apathy , Parkinson Disease , Humans , Apathy/physiology , Parkinson Disease/metabolism , Depression , Limbic System , Syndrome , Dihydroxyphenylalanine
6.
Brain Sci ; 13(6)2023 Jun 19.
Article in English | MEDLINE | ID: mdl-37371445

ABSTRACT

Diseases such as Alzheimer's cause an alteration of cognitive functions, which can lead to increased daily risk-taking in older adults living at home. The assessment of decision-making abilities is primarily based on clinicians' global analysis. Usual neuropsychological tests such as the MoCA (Montreal Cognitive Assessment) cover most of the cognitive domains and include mental flexibility tasks. Specific behavioral tasks for risk-taking, such as the Balloon Analogue Risk Task (BART) or the Iowa Gambling Task (IGT), have been developed to assess risk-taking behavior, particularly in the field of addictology. Our cross-sectional study aims to determine whether the MoCA global cognitive assessment could be used as a substitute for behavioral tasks in the assessment of risky behavior. In the current study, 24 patients (age: 82.1 ± 5.9) diagnosed with mild dementia completed the cognitive assessment (MoCA and executive function assessment) and two behavioral risk-taking tasks (BART, simplified version of the IGT). Results revealed no relationship between scores obtained in the MoCA and behavioral decision-making tasks. However, the two tasks assessing risk-taking behavior resulted in concordant risk profiles. In addition, patients with a high risk-taking behavior profile on the BART had better Trail Making Test (TMT) scores and thus retained mental flexibility. These findings suggest that MoCA scores are not representative of risk-taking behavioral inclinations. Thus, additional clinical tests should be used to assess risk-taking behavior in geriatric settings. Executive function measures, such as the TMT, and behavioral laboratory measures, such as the BART, are recommended for this purpose.

7.
Alzheimers Res Ther ; 15(1): 93, 2023 05 11.
Article in English | MEDLINE | ID: mdl-37170141

ABSTRACT

BACKGROUND: APP duplication is a rare genetic cause of Alzheimer disease and cerebral amyloid angiopathy (CAA). We aimed to evaluate the phenotypes of APP duplications carriers. METHODS: Clinical, radiological, and neuropathological features of 43 APP duplication carriers from 24 French families were retrospectively analyzed, and MRI features and cerebrospinal fluid (CSF) biomarkers were compared to 40 APP-negative CAA controls. RESULTS: Major neurocognitive disorders were found in 90.2% symptomatic APP duplication carriers, with prominent behavioral impairment in 9.7%. Symptomatic intracerebral hemorrhages were reported in 29.2% and seizures in 51.2%. CSF Aß42 levels were abnormal in 18/19 patients and 14/19 patients fulfilled MRI radiological criteria for CAA, while only 5 displayed no hemorrhagic features. We found no correlation between CAA radiological signs and duplication size. Compared to CAA controls, APP duplication carriers showed less disseminated cortical superficial siderosis (0% vs 37.5%, p = 0.004 adjusted for the delay between symptoms onset and MRI). Deep microbleeds were found in two APP duplication carriers. In addition to neurofibrillary tangles and senile plaques, CAA was diffuse and severe with thickening of leptomeningeal vessels in all 9 autopsies. Lewy bodies were found in substantia nigra, locus coeruleus, and cortical structures of 2/9 patients, and one presented vascular amyloid deposits in basal ganglia. DISCUSSION: Phenotypes associated with APP duplications were heterogeneous with different clinical presentations including dementia, hemorrhage, and seizure and different radiological presentations, even within families. No apparent correlation with duplication size was found. Amyloid burden was severe and widely extended to cerebral vessels as suggested by hemorrhagic features on MRI and neuropathological data, making APP duplication an interesting model of CAA.


Subject(s)
Alzheimer Disease , Cerebral Amyloid Angiopathy , Humans , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/genetics , Alzheimer Disease/complications , Amyloid/genetics , Cerebral Amyloid Angiopathy/diagnostic imaging , Cerebral Amyloid Angiopathy/genetics , Cerebral Amyloid Angiopathy/complications , Cerebral Hemorrhage/complications , Cerebral Hemorrhage/genetics , Cerebral Hemorrhage/pathology , Magnetic Resonance Imaging , Phenotype , Retrospective Studies
8.
Brain Sci ; 12(2)2022 Jan 29.
Article in English | MEDLINE | ID: mdl-35203948

ABSTRACT

BACKGROUND: Cognitive deficits are common in multiple sclerosis (MS) and affect patients at all stages of the disease, regardless of phenotype. AIMS: This literature review focuses the cognitive deficits observed in secondary progressive MS (SPMS). It is mainly based on studies that compared the frequency and main characteristics of cognitive deficits in SPMS with other phenotypes. METHODS: A bibliographic search was carried out using the PubMed database with the following keywords: multiple sclerosis, secondary-progressive, cognition. RESULTS: Thirteen studies were initially selected that were published in English, reporting the neuropsychological data of a sample of at least 30 patients with SPMS, comparing them with patients with other phenotypes. Studies suggest that there is an association between the duration of the disease and the frequency and extent of the cognitive disorders. Studies also showed that the SP form is associated with an increased frequency of cognitive impairment and with an increased severity as compared to relapsing-remitting MS (RRMS). Compared to RRMS, progressive forms of MS are associated with more severe impairment in certain cognitive areas, such as episodic verbal memory, information processing speed, working memory, or verbal fluency. Two studies showed that cognitive performances decline overtime in SPMS. CONCLUSION: Cognitive disorders are more frequent and more severe in the SP form than in relapsing course of MS. The profile of cognitive impairment encountered in the SP form also appears to be different from those found in the other phenotypes.

9.
J Pers Med ; 11(11)2021 Nov 11.
Article in English | MEDLINE | ID: mdl-34834535

ABSTRACT

Bipolar disorder is associated with an increased risk of dementia with aging. Little is known regarding this association, limiting appropriate diagnosis and management. We aimed to describe the characteristics of bipolar patients with late cognitive impairment for whom the hypothesis of an underlying neurodegenerative disease had been raised. We performed a retrospective multicenter study, recruiting bipolar patients over 50 years old from five French tertiary memory centers who had undergone cerebrospinal fluid (CSF) biomarker assessment for Alzheimer's disease (AD). Clinical, neuropsychological, and paraclinical characteristics were analyzed and 78 patients were included. The mean age at the onset of cognitive impairment was 62.4 years (±9.2). The mean MMSE score was 22.8 (±4.5), the mean FAB was 11.7 (±3.9), and the mean FCRST was 15.8 (±7.4)/36.8 (±9.7) (free/total recall). A total of 48.6% of the patients displayed cognitive fluctuations, and 38.2% showed cognitive improvement during follow-ups; and 56.3% of the patients showed Parkinsonism, of which 12.7% had never received antipsychotics. Among patients who underwent DAT-scans, 35.3% displayed dopaminergic denervation; 10.3% of patients had CSF AD biological signature ("A+ T+" profile), while 56.4% had other abnormal CSF profiles. Thus, clinical presentation was dominated by executive dysfunction, episodic memory impairment, fluctuating cognition, and a high frequency of Parkinsonism. Specifically, high frequency of delusional episodes suggests limited tolerance of psychotropic drugs. Most patients had abnormal CSF biomarker profiles, but only a minority displayed AD's specific biomarker signature. Therefore, while our results unveil shared common neurocognitive features in bipolar patients with cognitive impairment of suspected neurodegenerative origin they suggest a participation of various underlying pathologies rather than a common degenerative mechanism in the pathophysiology of this condition.

10.
J Alzheimers Dis ; 84(4): 1439-1446, 2021.
Article in English | MEDLINE | ID: mdl-34690148

ABSTRACT

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia have a strong clinical, genetic, and pathological connection but association of ALS with Alzheimer's disease (AD) is seldom reported. We report a series of 5 cases of AD associated with ALS. Our patients presented with cognitive deterioration with episodic memory impairment meeting criteria for AD. ALS occurred subsequently in all cases and its phenotype was not homogenous. Amyloid process was confirmed in four cases with cerebrospinal fluid biomarkers. One case underwent postmortem exam, demonstrating hallmarks lesions of both diseases. This series highlights that ALS-AD phenotype could be a specific underexplored entity.


Subject(s)
Alzheimer Disease/pathology , Amyotrophic Lateral Sclerosis/pathology , Biomarkers/cerebrospinal fluid , Brain/pathology , Cognition Disorders/pathology , Aged , Aged, 80 and over , Amyloid/cerebrospinal fluid , Female , Humans , Male , Memory Disorders/pathology , Neuropsychological Tests/statistics & numerical data
11.
Front Psychol ; 12: 724731, 2021.
Article in English | MEDLINE | ID: mdl-34675839

ABSTRACT

Late-Life Depression (LLD) is often associated with cognitive impairment. However, distinction between cognitive impairment due to LLD and those due to normal aging or mild Alzheimer's Disease (AD) remain difficult. The aim of this study was to present and compare the multivariate base rates of low scores in LLD, mild AD, and healthy control groups on a battery of neuropsychological tests. Participants (ages 60-89) were 352 older healthy adults, 390 patients with LLD, and 234 patients with mild AD (i.e., MMSE ≥ 20). Multivariate base rates of low scores (i.e., ≤ 5th percentile) were calculated for each participant group within different cognitive domains (verbal episodic memory, executive skills, mental processing speed, constructional praxis, and language/semantic memory). Obtaining at least one low score was relatively common in healthy older people controls (from 9.4 to 17.6%), and may thus result in a large number of false positives. By contrast, having at least two low scores was unusual (from 0.3 to 4.6%) and seems to be a more reliable criterion for identifying cognitive impairment in LLD. Having at least three low memory scores was poorly associated with LLD (5.9%) compared to mild AD (76.1%) and may provide a useful way to differentiate between these two conditions [ χ ( 1 ) 2 = 329.8, p < 0.001; Odds Ratio = 50.7, 95% CI = 38.2-77.5]. The multivariate base rate information about low scores in healthy older people and mild AD may help clinicians to identify cognitive impairments in LLD patients, improve the clinical decision-making, and target those who require regular cognitive and clinical follow-up.

12.
BMJ Open ; 11(9): e053549, 2021 09 29.
Article in English | MEDLINE | ID: mdl-34588264

ABSTRACT

INTRODUCTION: Assessment of decision-making capacity (DMC) is essential in daily life as well as for defining a person-centred care plan. Nevertheless, in ageing, especially if signs of dementia appear, it becomes difficult to assess decision-making ability and raises ethical questions. Currently, the assessment of DMC is based on the clinician's evaluation, completed by neuropsychological tests. Functional MRI (fMRI) could bring added value to the diagnosis of DMC in difficult situations. METHODS AND ANALYSIS: IMAGISION is a prospective, monocentric, single-arm study evaluating fMRI compared with clinical assessment of DMC. The study will begin during Fall 2021 and should be completed by Spring 2023. Participants will be recruited from a memory clinic where they will come for an assessment of their cognitive abilities due to decision-making needs to support ageing in place. They will be older people over 70 years of age, living at home, presenting with a diagnosis of mild dementia, and no exclusion criteria of MRI. They will be clinically assessed by a geriatrician on their DMC, based on the neuropsychological tests usually performed. Participants will then perform a behavioural task in fMRI (Balloon Analogue Risk Task) to analyse the activation areas. Additional semistructured interviews will be conducted to explore real life implications. The main analysis will study concordance/discordance between the clinical classification and the activation of fMRI regions of interest. Reclassification as 'capable', based on fMRI, of patients for whom clinical diagnosis is 'questionable' will be considered as a diagnostic gain. ETHICS AND DISSEMINATION: IMAGISION has been authorised by a research ethics board (Comité de Protection des Personnes, Bordeaux, II) in France, in accordance with French legislation on interventional biomedical research, under the reference IDRCB number 2019-A00863-54, since 30 September 2020. Participants will sign an informed consent form. The results of the study will be presented in international peer-reviewed scientific journals, international scientific conferences and public lectures. TRIAL REGISTRATION NUMBER: NCT03931148.


Subject(s)
Dementia , Functional Neuroimaging , Aged , Aged, 80 and over , Decision Making , Dementia/diagnostic imaging , Humans , Independent Living , Prospective Studies
13.
Brain Sci ; 11(8)2021 Aug 06.
Article in English | MEDLINE | ID: mdl-34439662

ABSTRACT

Decision making is a complex cognitive phenomenon commonly used in everyday life. Studies have shown differences in behavioral strategies in risky decision-making tasks over the course of aging. The development of functional neuroimaging has gradually allowed the exploration of the neurofunctional bases of these behaviors. The purpose of our study was to carry out a meta-analysis on the neural networks underlying risky decision making in healthy older adults. Following the PRISMA guidelines, we systematically searched for fMRI studies of decision making in older adults using risky decision-making tasks. To perform the quantitative meta-analysis, we used the revised version of the activation likelihood estimation (ALE) algorithm. A total of 620 references were selected for initial screening. Among these, five studies with a total of 98 cognitively normal older participants (mean age: 69.5 years) were included. The meta-analysis yielded two clusters. Main activations were found in the right insula, bilateral dorsolateral prefrontal cortex (dlPFC) and left orbitofrontal cortex (OFC). Despite the limited number of studies included, our meta-analysis highlights the crucial involvement of circuits associated with both emotion regulation and the decision to act. However, in contrast to the literature on young adults, our results indicate a different pattern of hemispheric lateralization in older participants. These activations can be used as a minimum pattern of activation in the risky decision-making tasks of healthy older subjects.

14.
Brain Sci ; 11(6)2021 Jun 03.
Article in English | MEDLINE | ID: mdl-34204860

ABSTRACT

Alzheimer's disease (AD) is associated with progressive memory loss and decline in executive functions, as well as neuropsychiatric symptoms. Patients usually consider quality of life (QoL) and mood as more important for their health status than disease-specific physical and mental symptoms. In this open-label uncontrolled trial, 12 subjects diagnosed with AD underwent 10 sessions of repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (10 Hz, 20 min, 2000 pulses/day, 110% MT). Outcomes were measured before and 30 days after treatment. Our primary objective was to test the efficacy of rTMS as an add-on treatment for AD on the global cognitive function, assessed through the Mini-Mental State Examination (MMSE) and the Mattis Dementia Rating Scale (MDRS). As secondary objectives, the detailed effect on cognitive functions, depression and anxiety symptoms, QoL, and functionality in daily life activities were evaluated, as well as correlations between QoL and cognition, depression and anxiety scores. The treatment significantly enhanced semantic memory and reduced anxiety. Improvement of these features in AD could become an important target for treatment strategies. Although limited by its design, this trial may contribute with another perspective on the analysis and the impact of rTMS on AD.

15.
Front Neurol ; 12: 706639, 2021.
Article in English | MEDLINE | ID: mdl-34322089

ABSTRACT

Objectives: The aim of this observational study was to describe social support and patterns of attachment among patients with migraine. We hypothesized that in comparison to the general population, insecure attachment is overrepresented in migraine patients, and that these patients have less social support. We also aimed to study the specific relationship between attachment and social support. We hypothesized that patients with an insecure attachment style have less social support than patients with a secure attachment style. Methods: A total of 101 consecutive patients (88.1% women) aged between 25 and 60 (average age = 41.4) were recruited at the Specialized Center for the Consultation of Primary Headaches at the Regional University Hospital Center of Besançon (France). Migraine impact and disability were evaluated using the Headache Impact Test (HIT-6) questionnaire and Migraine Disability Assessment (MIDAS) questionnaire. Patients also completed several self-administered psychological questionnaires in their validated French versions: the Medical Outcome Survey 36-Item Short-Form Health Survey, the Cungi Scale, the State-Trait Anxiety Inventory, the Beck Depression Inventory, the Relationship Scales Questionnaire and the Sarason's Social Support Questionnaire. Results: The distribution of attachment profiles was different from that of the general population, with an overrepresentation of insecure attachment styles (p = 0.018). Our study showed that migraine patients had less social support than the general population, both in terms of the number of people providing support (p = 0.002) and the level of satisfaction concerning this social support (p = 0.000). We also found that neither the number of available persons score nor the satisfaction score were statistically different between the four attachment categories (p = 0.49). Patient's attachment style and social support influence the patient-doctor relationship, the therapeutic alliance and health behaviors such as treatment adherence. Conclusions: Based on the data we obtained, we developed applications in patient care for people with particular attachment styles and low social support. A treatment plan adapted to the patient's attachment profile should be created to develop "precision medicine" using a personalized approach to the doctor-patient relationship. We would also recommend encouraging patients to participate in support groups, in order to strengthen their attachment systems and gain social support. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03577548, identifier NCT03577548.

16.
Acta Neuropathol ; 142(2): 259-278, 2021 08.
Article in English | MEDLINE | ID: mdl-34095977

ABSTRACT

Microduplications of the 17q21.31 chromosomal region encompassing the MAPT gene, which encodes the Tau protein, were identified in patients with a progressive disorder initially characterized by severe memory impairment with or without behavioral changes that can clinically mimic Alzheimer disease. The unique neuropathological report showed a primary tauopathy, which could not be unanimously classified in a given known subtype, showing both 4R- and 3R-tau inclusions, mainly within temporal cortical subregions and basal ganglia, without amyloid deposits. Recently, two subjects harboring the same duplication were reported with an atypical extrapyramidal syndrome and gait disorder. To decipher the phenotypic spectrum associated with MAPT duplications, we studied ten carriers from nine families, including two novel unrelated probands, gathering clinical (n = 10), cerebrospinal fluid (n = 6), MRI (n = 8), dopamine transporter scan (n = 4), functional (n = 5), amyloid (n = 3) and Tau-tracer (n = 2) PET imaging data as well as neuropathological examination (n = 4). Ages at onset ranged from 37 to 57 years, with prominent episodic memory impairment in 8/10 patients, associated with behavioral changes in four, while two patients showed atypical extrapyramidal syndrome with gait disorder at presentation, including one with associated cognitive deficits. Amyloid imaging was negative but Tau imaging showed significant deposits mainly in both mesiotemporal cortex. Dopaminergic denervation was found in 4/4 patients, including three without extrapyramidal symptoms. Neuropathological examination exclusively showed Tau-immunoreactive lesions. Distribution, aspect and 4R/3R tau aggregates composition suggested a spectrum from predominantly 3R, mainly cortical deposits well correlating with cognitive and behavioral changes, to predominantly 4R deposits, mainly in the basal ganglia and midbrain, in patients with prominent extrapyramidal syndrome. Finally, we performed in vitro seeding experiments in HEK-biosensor cells. Morphological features of aggregates induced by homogenates of three MAPT duplication carriers showed dense/granular ratios graduating between those induced by homogenates of a Pick disease and a progressive supranuclear palsy cases. These results suggest that MAPT duplication causes a primary tauopathy associated with diverse clinical and neuropathological features.


Subject(s)
Brain/pathology , Tauopathies/pathology , tau Proteins/metabolism , Adult , Age of Onset , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/pathology , Female , Heterozygote , Humans , Inclusion Bodies/pathology , Male , Middle Aged , Tauopathies/metabolism , tau Proteins/genetics
17.
Geriatr Psychol Neuropsychiatr Vieil ; 19(2): 181-190, 2021 Jun 01.
Article in French | MEDLINE | ID: mdl-34106056

ABSTRACT

Neurodevelopmental disorders are frequent in the general population and are often lifelong conditions despite sometimes being masked by conscious or unconscious compensation and avoidance mechanisms. These conditions are often unknown or underestimated in adults, even when diagnosed in childhood. Neurodevelopmental disorders share similarities with and frequently interact in a complex way with neurodegenerative disorders. Considering these aspects during memory clinic assessments can provide a new perspective on lifelong neurocognitive trajectories. Assessing both neurodevelopmental and neurodegenerative dimensions is challenging but should improve diagnostic accuracy. It is therefore necessary to understand the lifelong specific neurocognitive trajectory of each patient in order to develop personalized and focused cognitive medicine and care.


Subject(s)
Neurodegenerative Diseases , Neurodevelopmental Disorders , Humans , Neurodegenerative Diseases/diagnosis
18.
J Alzheimers Dis ; 79(4): 1397-1407, 2021.
Article in English | MEDLINE | ID: mdl-33459644

ABSTRACT

Neurodevelopmental and neurodegenerative disorders are both growing major public health topics with similarities and frequent complex interactions with each other. Taking these aspects into account can provide a new point of view on lifelong neurocognitive trajectories. Assessing both neurodevelopmental and neurodegenerative dimensions during cognitive and behavioral clinical assessments is challenging but might improve diagnostic accuracy and physiopathological understanding. It is therefore necessary to understand the lifelong specific neurocognitive trajectory of each patient in order to develop personalized precision cognitive medicine.


Subject(s)
Neurodegenerative Diseases , Neurodevelopmental Disorders , Animals , Humans
19.
BMC Med Educ ; 21(1): 16, 2021 Jan 06.
Article in English | MEDLINE | ID: mdl-33407399

ABSTRACT

BACKGROUND: Some students have neurodevelopmental disorders that might affect their academic and professional careers if they are not identified and addressed by specific pedagogic adaptations. The objective of this work was to describe medical teachers' opinions of students with neurodevelopmental disorders and their management of these students. METHODS: An anonymous cross-sectional electronic survey was performed to describe medical teachers' opinions about the impact of neurodevelopmental disorders on the student's life and on the medical teachers' management. aThe survey was created, including visual analogic scales and free text, to assess teachers' opinions from identification and assessment of neurodevelopemental burden on students and teachers, to their own knowledge about neurodevelopemental disorders and the specific pedagogic management available. The survey was sent to 175 medical teachers in 2019, of whom 67 responded. Quantitative descriptive statistics and qualitative analysis of free text were reported. RESULTS: Many medical teachers report having encountered students who might have had neurodevelopmental disorders (dyspraxia 33%; dyslexia 46%; autism spectrum disorders 68%; attention deficit hyperactivity disorders 75%). Impact on students and on teachers was considered as important (mean VAS score for impact over 60/100 for all syndromes except for dyspraxia). Medical teachers' self-reported knowledge about neurodevelopmental disorders (mean VAS score 43.9/100) and available pedagogical adaptations (mean VAS score 19.0/100) was limited. The teachers were concerned about ethical issues (mean VAS score 72.2/100) but were interested in receiving specialized training (mean VAS score 64.4/100). CONCLUSION: Medical teachers feel unprepared to manage students with neurodevelopmental disorders. They would be interested in specific training and procedures about the pedagogic management of these students.


Subject(s)
Faculty , Students , Attitude , Cross-Sectional Studies , Humans , Surveys and Questionnaires
20.
Ann Phys Rehabil Med ; 64(2): 101394, 2021 Mar.
Article in English | MEDLINE | ID: mdl-32450272

ABSTRACT

BACKGROUND: Clinical symptoms of multiple sclerosis (MS) are variable and may include cognitive impairment, which can be assessed with the verbal fluency test (VFT). This test is evaluated by counting words spoken during a 2-min period, which is not a functional approach. OBJECTIVE: The objectives of this observational study were to: (1) determine new parameters that reflect communication and cognitive functions in persons with multiple sclerosis (PwMS) considering the evaluation of real-time word production in the VFT; (2) compare the results with those of a control group; and (3) evaluate the impact of including errors. METHODS: A phonological fluency test ("letter P") and a semantic fluency test ("animals") were used. The real-time word production was recorded. The main variables studied were the total number of words, first word delay, moment of inflection of the curve corresponding to the change in the cognitive process, speed of word production before inflection, and maximum delay between 2 consecutive words. These variables were studied by taking into account or not errors. RESULTS: We included 68 PwMS and 33 healthy controls. VFT results were impaired in PwMS. The total number of words, first word delay, speed before inflection, and maximum delay were relevant to the study of phonologic fluency. For studying semantic fluency, the total number of words, first word delay, speed before inflection, and inflection time of the curve seemed relevant. Taking into account errors was significant only for total number of words. CONCLUSION: Taking into account errors in evaluating real-time word production in PwMS is of interest only for the total number of words performed but has no impact on the variables studied. These variables should be used to quantitatively evaluate verbal fluency with the objective of evaluating functionally relevant parameters (communication).


Subject(s)
Multiple Sclerosis , Verbal Behavior , Humans , Linguistics , Neuropsychological Tests , Semantics
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