Can a failure in the error-monitoring system explain unawareness of memory deficits in Alzheimer's disease? 2023

Solofo Razafimahatratra, and Thomas Guieysse, and François-Xavier Lejeune, and Marion Houot, and Takfarinas Medani, and Gérard Dreyfus, and André Klarsfeld, and Nicolas Villain, and Filipa Raposo Pereira, and Valentina La Corte, and Nathalie George, and Dimitrios Pantazis, and Katia Andrade
Institute of Memory and Alzheimer's Disease (IM2A), Department of Neurology, AP-HP, Pitié-Salpêtrière Hospital, Paris, France.

Unawareness of memory deficits is an early manifestation in patients with Alzheimer's disease (AD), which often delays diagnosis. This intriguing behavior constitutes a form of anosognosia, whose neural mechanisms remain largely unknown. We hypothesized that anosognosia may depend on a critical synaptic failure in the error-monitoring system, which would prevent AD patients from being aware of their own memory impairment. To investigate, we measured event-related potentials (ERPs) evoked by erroneous responses during a word memory recognition task in two groups of amyloid positive individuals with only subjective memory complaints at study entry: those who progressed to AD within the five-year study period (PROG group), and those who remained cognitively normal (CTRL group). A significant reduction in the amplitude of the positivity error (Pe), an ERP related to error awareness, was observed in the PROG group at the time of AD diagnosis (vs study entry) in intra-group analysis, as well as when compared with the CTRL group in inter-group analysis, based on the last EEG acquisition for all subjects. Importantly, at the time of AD diagnosis, the PROG group exhibited clinical signs of anosognosia, overestimating their cognitive abilities, as evidenced by the discrepancy scores obtained from caregiver/informant vs participant reports on the cognitive subscale of the Healthy Aging Brain Care Monitor. To our knowledge, this is the first study to reveal the emergence of a failure in the error-monitoring system during a word memory recognition task at the early stages of AD. This finding, along with the decline of awareness for cognitive impairment observed in the PROG group, strongly suggests that a synaptic dysfunction in the error-monitoring system may be the critical neural mechanism at the origin of unawareness of deficits in AD.

UI MeSH Term Description Entries
D008297 Male Males
D008569 Memory Disorders Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions. Memory Loss,Age-Related Memory Disorders,Memory Deficits,Memory Disorder, Semantic,Memory Disorder, Spatial,Memory Disorders, Age-Related,Retention Disorders, Cognitive,Semantic Memory Disorder,Spatial Memory Disorder,Age Related Memory Disorders,Age-Related Memory Disorder,Cognitive Retention Disorder,Cognitive Retention Disorders,Deficit, Memory,Deficits, Memory,Memory Deficit,Memory Disorder,Memory Disorder, Age-Related,Memory Disorders, Age Related,Memory Disorders, Semantic,Memory Disorders, Spatial,Memory Losses,Retention Disorder, Cognitive,Semantic Memory Disorders,Spatial Memory Disorders
D009483 Neuropsychological Tests Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury. Aphasia Tests,Cognitive Test,Cognitive Testing,Cognitive Tests,Memory for Designs Test,Neuropsychological Testing,AX-CPT,Behavioral Assessment of Dysexecutive Syndrome,CANTAB,Cambridge Neuropsychological Test Automated Battery,Clock Test,Cognitive Function Scanner,Continuous Performance Task,Controlled Oral Word Association Test,Delis-Kaplan Executive Function System,Developmental Neuropsychological Assessment,Hooper Visual Organization Test,NEPSY,Neuropsychologic Tests,Neuropsychological Test,Paced Auditory Serial Addition Test,Repeatable Battery for the Assessment of Neuropsychological Status,Rey-Osterrieth Complex Figure,Symbol Digit Modalities Test,Test of Everyday Attention,Test, Neuropsychological,Tests, Neuropsychological,Tower of London Test,Neuropsychologic Test,Test, Cognitive,Testing, Cognitive,Testing, Neuropsychological,Tests, Cognitive
D004569 Electroencephalography Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain. EEG,Electroencephalogram,Electroencephalograms
D005071 Evoked Potentials Electrical responses recorded from nerve, muscle, SENSORY RECEPTOR, or area of the CENTRAL NERVOUS SYSTEM following stimulation. They range from less than a microvolt to several microvolts. The evoked potential can be auditory (EVOKED POTENTIALS, AUDITORY), somatosensory (EVOKED POTENTIALS, SOMATOSENSORY), visual (EVOKED POTENTIALS, VISUAL), or motor (EVOKED POTENTIALS, MOTOR), or other modalities that have been reported. Event Related Potential,Event-Related Potentials,Evoked Potential,N100 Evoked Potential,P50 Evoked Potential,N1 Wave,N100 Evoked Potentials,N2 Wave,N200 Evoked Potentials,N3 Wave,N300 Evoked Potentials,N4 Wave,N400 Evoked Potentials,P2 Wave,P200 Evoked Potentials,P50 Evoked Potentials,P50 Wave,P600 Evoked Potentials,Potentials, Event-Related,Event Related Potentials,Event-Related Potential,Evoked Potential, N100,Evoked Potential, N200,Evoked Potential, N300,Evoked Potential, N400,Evoked Potential, P200,Evoked Potential, P50,Evoked Potential, P600,Evoked Potentials, N100,Evoked Potentials, N200,Evoked Potentials, N300,Evoked Potentials, N400,Evoked Potentials, P200,Evoked Potentials, P50,Evoked Potentials, P600,N1 Waves,N2 Waves,N200 Evoked Potential,N3 Waves,N300 Evoked Potential,N4 Waves,N400 Evoked Potential,P2 Waves,P200 Evoked Potential,P50 Waves,P600 Evoked Potential,Potential, Event Related,Potential, Event-Related,Potential, Evoked,Potentials, Event Related,Potentials, Evoked,Potentials, N400 Evoked,Related Potential, Event,Related Potentials, Event,Wave, N1,Wave, N2,Wave, N3,Wave, N4,Wave, P2,Wave, P50,Waves, N1,Waves, N2,Waves, N3,Waves, N4,Waves, P2,Waves, P50
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D000369 Aged, 80 and over Persons 80 years of age and older. Oldest Old
D000377 Agnosia Loss of the ability to comprehend the meaning or recognize the importance of various forms of stimulation that cannot be attributed to impairment of a primary sensory modality. Tactile agnosia is characterized by an inability to perceive the shape and nature of an object by touch alone, despite unimpaired sensation to light touch, position, and other primary sensory modalities. Auditory Agnosia,Finger Agnosia,Sensory Agnosia,Tactile Agnosia,Visual Agnosia,Agnosia for Pain,Agnosia for Smell,Agnosia for Taste,Agnosia for Temperature,Anosognosia,Auditory Agnosia, Congenital,Body-Image Agnosia,Congenital Auditory Agnosia,Developmental Agnosia,Gustatory Agnosia,Ideational Agnosia,Olfactory Agnosia,Position Agnosia,Somatosensory Agnosia,Time Agnosia,Topographical Agnosia,Visual Agnosia for Objects,Visual Disorientation Syndrome,Visuospatial Agnosia,Agnosia for Tastes,Agnosia, Auditory,Agnosia, Body-Image,Agnosia, Congenital Auditory,Agnosia, Developmental,Agnosia, Finger,Agnosia, Gustatory,Agnosia, Ideational,Agnosia, Olfactory,Agnosia, Position,Agnosia, Sensory,Agnosia, Somatosensory,Agnosia, Tactile,Agnosia, Time,Agnosia, Topographical,Agnosia, Visual,Agnosia, Visuospatial,Agnosias,Agnosias, Auditory,Agnosias, Body-Image,Agnosias, Congenital Auditory,Agnosias, Developmental,Agnosias, Finger,Agnosias, Ideational,Agnosias, Olfactory,Agnosias, Position,Agnosias, Sensory,Agnosias, Somatosensory,Agnosias, Tactile,Agnosias, Time,Agnosias, Topographical,Agnosias, Visual,Agnosias, Visuospatial,Anosognosias,Auditory Agnosias,Auditory Agnosias, Congenital,Body Image Agnosia,Body-Image Agnosias,Congenital Auditory Agnosias,Developmental Agnosias,Finger Agnosias,Ideational Agnosias,Olfactory Agnosias,Position Agnosias,Sensory Agnosias,Somatosensory Agnosias,Syndrome, Visual Disorientation,Syndromes, Visual Disorientation,Tactile Agnosias,Time Agnosias,Topographical Agnosias,Visual Agnosias,Visual Disorientation Syndromes,Visuospatial Agnosias

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