Crise suicidaire et maladie d’Alzheimer débutante : intérêt d’une analyse neuropsychologique détaillée

RésuméIntroduction Le risque de développer une maladie d’Alzheimer augmente avec l’âge. Le rôle de celle-ci comme un facteur de risque indépendant de suicide n’est pas bien compris et demeure complexe et mal élucidé. L’objectif de cet article est d’envisager une compréhension neuropsychologique de la crise suicidaire dans le cas d’une maladie d’Alzheimer débutante. Méthode Une évaluation cognitive globale (Mini-Mental State Examination, Batterie Rapide d’Évaluation Frontale) complétée de l’exploration de l’inhibition cognitive selon ses fonctions d’accès (tâche de lecture en présence de distracteurs), de suppression (Trail Making Test), et de freinage (Stroop, Hayling, Go/No-Go) a été réalisée chez une femme souffrant d’une maladie d’Alzheimer (MMSE à 21/30) avant et après réalisation d’une tentative de suicide dans un contexte de dépression. Résultats L’échelle d’Hamilton était cotée à 24/52, l’échelle de dépression de Cornell à 21/38. L’intentionnalité suicidaire était modérée avec un score à 15/25 à l’échelle d’intentionnalité suicidaire de Beck. Initialement préservées, le déclin des fonctions exécutives a coïncidé avec l’émergence d’une crise suicidaire dans un contexte de dépression chez une patiente souffrant de maladie d’Alzheimer. Les fonctions de l’inhibition cognitive étaient altérées dans ses trois composantes, après ajustement des facteurs de confusion. Conclusion Une évaluation détaillée des fonctions exécutives et singulièrement de l’inhibition cognitive dans la population des patients atteints d’une maladie d’Alzheimer permettrait de détecter les personnes les plus à risque de passage à l’acte et de proposer une surveillance plus étroite dans le cadre des soins généraux de leur maladie. AbstractIntroduction The role of Alzheimer\u27s disease as a risk factor for suicide is unclear. The aim of this study was to understand neuropsychological component of the suicidal crisis in Alzheimer\u27s disease. Method Using an extensive neuropsychological battery, different aspects of cognitive inhibition were particularly examined: Access to relevant information (using the Reading with distraction task), suppression of no longer relevant information (Trail Making Test, Rule Shift Cards), and restraint of cognitive resources to relevant information (Stroop test, Hayling Sentence Completion test, Go/No-Go). One female Alzheimer depressed case was assessed before and after a suicide attempt. Results Ten days after the patient\u27s suicide attempt, dementia was still moderate with a MMSE score at 21/30 but with a worsening of executive functions (FAB at 8/18) in the context of depression and suicide. The Hamilton-Depression Rating Scale was at 24 (maximal score at 52), and the Cornell Scale for Depression was at 21 (maximal score at 38). Suicidal intent was moderate with a score of 9 on the Beck Suicide Intent Scale (maximal score at 25). The patient did not present a delirium, psychotic symptoms, or anosognosia. Her episodic memory was altered as shown by her semantic performance on verbal fluency (naming 12 animals in 120 seconds) and on lexical fluency (naming 8 words beginning with the letter P). Initially preserved, executive function declined during a suicidal crisis in a context of depression in Alzheimer\u27s disease case. Neuropsychological testing confirmed a dysexecutive syndrome (FAS at 8/18), with an impairment in her conceptualization capacity (MCST) and a deficit in cognitive inhibition and its access (reading task in the presence of distractors), deletion (TMT) and restraint (Stroop, Go/No-Go, Hayling) functions. Computed tomography has shown no signs of intracranial expansive process. Conclusion Assessing predictors of suicide and means of completion in patients with dementia may help the development of interventions to reduce risk of suicide among the growing population of individuals with dementia. Because of Alzheimer\u27s-related cognitive inhibition impairment, identification and intervention addressing the complex issues of depression, executive dysfunction and dementia may help clinicians to mitigate the risk of suicide in patients with Alzheimer\u27s disease

Npn-1 Contributes to Axon-Axon Interactions That Differentially Control Sensory and Motor Innervation of the Limb

The initiation, execution, and completion of complex locomotor behaviors are depending on precisely integrated neural circuitries consisting of motor pathways that activate muscles in the extremities and sensory afferents that deliver feedback to motoneurons. These projections form in tight temporal and spatial vicinities during development, yet the molecular mechanisms and cues coordinating these processes are not well understood. Using cell-type specific ablation of the axon guidance receptor Neuropilin-1 (Npn-1) in spinal motoneurons or in sensory neurons in the dorsal root ganglia (DRG), we have explored the contribution of this signaling pathway to correct innervation of the limb. We show that Npn-1 controls the fasciculation of both projections and mediates inter-axonal communication. Removal of Npn-1 from sensory neurons results in defasciculation of sensory axons and, surprisingly, also of motor axons. In addition, the tight coupling between these two heterotypic axonal populations is lifted with sensory fibers now leading the spinal nerve projection. These findings are corroborated by partial genetic elimination of sensory neurons, which causes defasciculation of motor projections to the limb. Deletion of Npn-1 from motoneurons leads to severe defasciculation of motor axons in the distal limb and dorsal-ventral pathfinding errors, while outgrowth and fasciculation of sensory trajectories into the limb remain unaffected. Genetic elimination of motoneurons, however, revealed that sensory axons need only minimal scaffolding by motor axons to establish their projections in the distal limb. Thus, motor and sensory axons are mutually dependent on each other for the generation of their trajectories and interact in part through Npn-1-mediated fasciculation before and within the plexus region of the limbs

Copying and Evolution of Neuronal Topology

We propose a mechanism for copying of neuronal networks that is of considerable interest for neuroscience for it suggests a neuronal basis for causal inference, function copying, and natural selection within the human brain. To date, no model of neuronal topology copying exists. We present three increasingly sophisticated mechanisms to demonstrate how topographic map formation coupled with Spike-Time Dependent Plasticity (STDP) can copy neuronal topology motifs. Fidelity is improved by error correction and activity-reverberation limitation. The high-fidelity topology-copying operator is used to evolve neuronal topologies. Possible roles for neuronal natural selection are discussed