Disrupting Pre-SMA Activity Impairs Facial Happiness Recognition: An Event-Related TMS Study

It has been suggested that the left pre-supplementary motor area (pre-SMA) could be implicated in facial emotion expression and recognition, especially for laughter/happiness. To test this hypothesis, in a single-blind, randomized crossover study, we investigated the impact of transcranial magnetic stimulation (TMS) on performances of 18 healthy participants during a facial emotion recognition task. Using a neuronavigation system based on T1-weighted magnetic resonance imaging of each participant, TMS (5 pulses, 10 Hz) was delivered over the pre-SMA or the vertex (control condition) in an event-related fashion after the presentation of happy, fear, and angry faces. Compared with performances during vertex stimulation, we observed that TMS applied over the left pre-SMA specifically disrupted facial happiness recognition (FHR). No difference was observed between the 2 conditions neither for fear and anger recognition nor for reaction times (RT). Thus, interfering with pre-SMA activity with event-related TMS after stimulus presentation produced a selective impairment in the recognition of happy faces. These findings provide new insights into the functional implication of the pre-SMA in FHR, which may rely on the mirror properties of pre-SMA neuron

An innovative therapeutic educational program to support older drivers with cognitive disorders: Description of a randomized controlled trial study protocol

Older drivers face the prospect of having to adjust their driving habits because of health problems, which can include neurocognitive disorders. Self-awareness of driving difficulties and the interaction between individual with neurocognitive disorders and natural caregiver seem to be important levers for the implementation of adaptation strategies and for the subsequent voluntary cessation of driving when the cognitive disorders become too severe. This study aims to evaluate an educational program for patient/natural caregiver dyads who wish to implement self-regulation strategies in driving activity, and to improve self-awareness of driving ability. The ACCOMPAGNE program is based on seven group workshops, which target the dyad. The workshops deal with the impact of cognitive, sensory and iatrogenic disorders on driving. They tackle questions about responsibility, and about autonomy and social life. They also provide alternative solutions aimed at maintaining outward-looking activities even if driving is reduced or stopped. A randomized controlled trial is planned to evaluate the effectiveness of the program 2 months and 6 months after inclusion, and to compare this to the effectiveness of conventional approaches. The main outcome of this trial (i.e., the implementation of self-regulated driving strategies), will be measured based on scores on the “Current Self-Regulatory Practices” subscale of the Driver Perception and Practices Questionnaire. The Driving Habits Questionnaire will be used to measure secondary outcomes (indicators of driving changes; indicators of changes in mood, quality of life and caregiver burden; and self-awareness of driving abilities). Indicators will be collected for both patients and natural caregivers. This cognitive, social and psychological program should allow older individuals with cognitive disorders to drive more safely, and help to maintain the quality of life and mood of both patient and natural caregiver despite driving limitations. The patient's care path would be optimized, as he/she would become an actor in the process of giving up driving, which will, most certainly, be needed at some point in the progress of neurocognitive disorders. This process ranges from becoming aware of driving difficulties, to implementing self-regulation strategies, through to complete cessation of driving when necessary.Clinical trial registration numberNCT04493957

Correlations between soluble alpha/beta forms of amyloid precursor protein and Abeta38, 40 and 42 in human cerebrospinal fluid

International audienceCerebrospinal fluid (CSF) biomarkers are now widely used for diagnosis of Alzheimer disease (AD) in atypical clinical forms, for differential and early diagnosis, or for stratification of patients in clinical trials. Among these biomarkers, different forms of amyloid peptides (Aβ) produced by the cleavage of a transmembrane precursor protein called APP (amyloid precursor protein) have a major role. Aβ peptides exist in different length the most common ones having 40 (Aβ40), 42 (Aβ42), or 38 (Aβ38) amino acids in length. APP processing by gamma-secretase releases also an amino-terminal secreted fragment called sAβPP-beta while an alternative nonamyloidogenic cleavage of APP, through an alpha-secretase, liberates another fragment called sAβPP-alpha. To decipher the molecular and pathological mechanisms leading to the production and the detection of these entities is essential for the comprehension and the prevention of AD. In this report, we present the results of the Keywords: Biomarkers CSF Soluble amyloid precursor proteins Aβ fragment peptides Alzheimer disease Dementi

Personality, Alzheimer's disease and behavioural and cognitive symptoms of dementia: the PACO prospective cohort study protocol

International audienceBACKGROUND: Alzheimer's disease is characterised by a loss of cognitive function and behavioural problems as set out in the term "Behavioural and Psychological Symptoms of Dementia". These behavioural symptoms have heavy consequences for the patients and their families. A greater understanding of behavioural symptoms risk factors would allow better detection of those patients, a better understanding of crisis situations and better management of these patients. Some retrospective studies or simple observations suggested that personality could play a role in the occurrence of behavioural symptoms. Finally, performance in social cognition like facial recognition and perspective taking could be linked to certain personality traits and the subsequent risks of behavioural symptoms. We propose to clarify this through a prospective, multicentre, multidisciplinary study. Main Objective: -To assess the effect of personality and life events on the risk of developing behavioural symptoms. Secondary Objectives: -To evaluate, at the time of inclusion, the connection between personality and performance in social cognition tests; -To evaluate the correlation between performance in social cognition at inclusion and the risks of occurrence of behavioural symptoms; -To evaluate the correlation between regional cerebral atrophy, using brain Magnetic Resonance Imaging at baseline, and the risk of behavioural symptoms.METHODS/DESIGN: Study type and Population: Prospective multicentre cohort study with 252 patients with Alzheimer's disease at prodromal or mild dementia stage. The inclusion period will be of 18 months and the patients will be followed during 18 months. The initial evaluation will include: a clinical and neuropsychological examination, collection of behavioural symptoms data (Neuropsychiatric-Inventory scale) and their risk factors, a personality study using both a dimensional (personality traits) and categorical approach, an inventory of life events, social cognition tests and an Magnetic Resonance Imaging. Patients will be followed every 6 months (clinical examination and collection of behavioural symptoms data and risk factors) during 18 months.DISCUSSION: This study aims at better identifying the patients with Alzheimer's disease at high risk of developing behavioural symptoms, to anticipate, detect and quickly treat these disorders and so, prevent serious consequences for the patient and his caregivers.TRIAL REGISTRATION: ClincalTrials.gov: NCT01297140

White matter hyperintensities in Alzheimer’s disease: Topography of lesions and association with cognition: Neuroimaging/differential diagnosis

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Decreased sAβPPβ, Aβ38, and Aβ40 Cerebrospinal Fluid Levels in Frontotemporal Dementia.

International audienceTo improve the etiological diagnosis of neurodegenerative dementias like Alzheimer's disease (AD) or frontotemporal dementia (FTD), we evaluated the value of individual and combined measurements of the following relevant cerebrospinal fluid (CSF) biomarkers: Tau, 181p-Tau, Aβ38, Aβ40, Aβ42, sAβPPα, and sAβPPβ. This study conducted in two centers included patients with FTD (n = 34), AD (n = 52), as well as a control group of persons without dementia (CTRL, n = 42). Identical clinical criteria and pre-analytical conditions were used while CSF biomarkers were measured using commercial single and multiplex quantitative immunoassays. Thorough statistical analyses, including ROC curves, logistic regressions, and decision trees, were performed. We validated in AD the specific increase of p-Tau levels and the decrease of Aβ42 levels, two biological hallmarks of this disease. Tau concentrations were highest in AD and intermediate in FTD when compared to CTRL. The most interesting results were obtained by focusing on amyloid biomarkers as we found out in FTD a significant decrease of sAβPPβ, Aβ38, and Aβ40 levels. Aβ38 in particular was the most useful biomarker to differentiate FTD subjects from the CTRL population. Combining p-Tau and Aβ38 led us to correctly classifying FTD patients with sensitivity at 85% and specificity at 82%. Significant changes in amyloid biomarkers, particularly for Aβ38, are therefore seen in FTD. This could be quite useful for diagnosis purposes and it might provide additional evidence on the interrelationship between Tau and AβPP biology which understanding is essential to progress towards optimal therapeutic and diagnostic approaches of dementia

Emotional Facial Expression Detection in the Peripheral Visual Field

BACKGROUND: In everyday life, signals of danger, such as aversive facial expressions, usually appear in the peripheral visual field. Although facial expression processing in central vision has been extensively studied, this processing in peripheral vision has been poorly studied. METHODOLOGY/PRINCIPAL FINDINGS: Using behavioral measures, we explored the human ability to detect fear and disgust vs. neutral expressions and compared it to the ability to discriminate between genders at eccentricities up to 40°. Responses were faster for the detection of emotion compared to gender. Emotion was detected from fearful faces up to 40° of eccentricity. CONCLUSIONS: Our results demonstrate the human ability to detect facial expressions presented in the far periphery up to 40° of eccentricity. The increasing advantage of emotion compared to gender processing with increasing eccentricity might reflect a major implication of the magnocellular visual pathway in facial expression processing. This advantage may suggest that emotion detection, relative to gender identification, is less impacted by visual acuity and within-face crowding in the periphery. These results are consistent with specific and automatic processing of danger-related information, which may drive attention to those messages and allow for a fast behavioral reaction

Diabetes Mellitus and Cognition: A Pathway Analysis in the MEMENTO Cohort

OBJECTIVE: To assess the role of biomarkers of Alzheimer's Disease (AD), neurodegeneration and small vessel disease (SVD) as mediators in the association between diabetes mellitus and cognition. METHODS: The study sample was derived from MEMENTO, a cohort of French adults recruited in memory clinics and screened for either isolated subjective cognitive complaints or mild cognitive impairment. Diabetes was defined based on blood glucose assessment, use of antidiabetic agent or self-report. We used structural equation modelling to assess whether latent variables of AD pathology (PET mean amyloid uptake, Aβ(42)/Aβ(40) ratio and CSF phosphorylated tau), SVD (white matter hyperintensities volume and visual grading), and neurodegeneration (mean cortical thickness, brain parenchymal fraction, hippocampal volume, and mean fluorodeoxyglucose uptake) mediate the association between diabetes and a latent variable of cognition (five neuropsychological tests), adjusting for potential confounders. RESULTS: There were 254 (11.1%) participants with diabetes among 2,288 participants (median age 71.6 years; 61.8% women). The association between diabetes and lower cognition was significantly mediated by higher neurodegeneration (standardized indirect effect: -0.061, 95% confidence interval: -0.089; -0.032), but not mediated by SVD and AD markers. Results were similar when considering latent variables of memory or executive functioning. CONCLUSION: In a large clinical cohort in the elderly, diabetes is associated with lower cognition through neurodegeneration, independently of SVD and AD biomarkers

Associations among hypertension, dementia biomarkers, and cognition: The MEMENTO cohort

Introduction Approximately 40% of dementia cases could be delayed or prevented acting on modifiable risk factors including hypertension. However, the mechanisms underlying the hypertension–dementia association are still poorly understood. Methods We conducted a cross-sectional analysis in 2048 patients from the MEMENTO cohort, a French multicenter clinic-based study of outpatients with either isolated cognitive complaints or mild cognitive impairment. Exposure to hypertension was defined as a combination of high blood pressure (BP) status and antihypertensive treatment intake. Pathway associations were examined through structural equation modeling integrating extensive collection of neuroimaging biomarkers and clinical data. Results Participants treated with high BP had significantly lower cognition compared to the others. This association was mediated by higher neurodegeneration and higher white matter hyperintensities load but not by Alzheimer's disease (AD) biomarkers. Discussion These results highlight the importance of controlling hypertension for prevention of cognitive decline and offer new insights on mechanisms underlying the hypertension–dementia association. Highlights Paths of hypertension–cognition association were assessed by structural equation models. The hypertension–cognition association is not mediated by Alzheimer's disease biomarkers. The hypertension–cognition association is mediated by neurodegeneration and leukoaraiosis. Lower cognition was limited to participants treated with uncontrolled blood pressure. Blood pressure control could contribute to promote healthier brain aging.Stopping cognitive decline and dementia by fighting covert cerebral small vessel diseas

Alzheimers Dement

Introduction: The free and cued selective reminding test is used to identify memory deficits in mild cognitive impairment and demented patients. It allows assessing three processes: encoding, storage, and recollection of verbal episodic memory. Methods: We investigated the neural correlates of these three memory processes in a large cohort study. The Memento cohort enrolled 2323 outpatients presenting either with subjective cognitive decline or mild cognitive impairment who underwent cognitive, structural MRI and, for a subset, fluorodeoxyglucose-positron emission tomography evaluations. Results: Encoding was associated with a network including parietal and temporal cortices; storage was mainly associated with entorhinal and parahippocampal regions, bilaterally; retrieval was associated with a widespread network encompassing frontal regions. Discussion: The neural correlates of episodic memory processes can be assessed in large and standardized cohorts of patients at risk for Alzheimer's disease. Their relation to pathophysiological markers of Alzheimer's disease remains to be studied