Cognitive profile in cerebral small vessel disease: comparison between cerebral amyloid angiopathy and hypertension-related microangiopathy.

Cerebral amyloid angiopathy (CAA) is recognized as a cause of cognitive impairment, but its cognitive profile needs to be characterized, also respect to hypertension-related microangiopathy (HA). We aimed at comparing difference or similarity of CAA and HA patients' cognitive profiles, and their associated factors. Participants underwent an extensive clinical, neuropsychological, and neuroimaging protocol. HA patients (n = 39) were more frequently males, with history of vascular risk factors than CAA (n = 32). Compared to HA, CAA patients presented worse performance at MoCA (p = 0.001) and semantic fluency (p = 0.043), and a higher prevalence of amnestic MCI (46% vs. 68%). In univariate analyses, multi-domain MCI was associated with worse performance at MoCA, Rey Auditory Verbal Learning Test (RAVLT), and semantic fluency in CAA patients, and with worse performance at Symbol Digit Modalities Test (SDMT) and phonemic fluency in HA ones. In multivariate models, multi-domain deficit remained as the only factor associated with RAVLT (ß = - 0.574) in CAA, while with SDMT (ß = - 0.364) and phonemic fluency (ß = - 0.351) in HA. Our results highlight different patterns of cognitive deficits in CAA or HA patients. While HA patients' cognitive profile was confirmed as mainly attentional/executive, a complex cognitive profile, characterized also by deficit in semantic memory, seems the hallmark of CAA patients.

Comorbidities and Disease Duration in Tourette Syndrome: Impact on Cognition and Quality of Life of Children.

BACKGROUND: Cognitive functions represent foundational factors for mental health and quality of life (QoL). In Tourette syndrome (TS), psychiatric comorbidities are common and have been inconsistently reported to affect the cognition and QoL of patients, while the role of tic disorder duration has not been yet explored. METHODS: To examine how comorbidities and TS duration may influence cognition and QoL, N = 80 children with TS (6-16 years) were evaluated using the Wechsler Intelligence Scale for Children (WISC-IV). Standardized questionnaires were used to assess the presence and severity of TS main comorbidities and QoL. Data were interpreted using linear correlations, regression, and mediation analysis. RESULTS: Depression and attention-deficit/hyperactivity disorder (ADHD) symptoms accounted for poorer cognitive performance. Anxiety oppositely predicted better cognitive performance, while no significant role for obsessive compulsive disorder (OCD) was observed. Disease duration was associated with lower total IQ, verbal reasoning, and working memory abilities. Depression, anxiety, and TS duration also deeply influenced QoL measures. CONCLUSIONS: TS common comorbidities have a differential impact on the cognitive abilities of children and adolescents, which translates into a complex influence on their perceived QoL. A longer clinical history of tics was related to worse cognitive outcomes, which prompts further consideration of disease duration in both clinical and research settings involving children and adolescents.

The cognitive profile of essential tremor on the Repeatable Battery for the Assessment of Neuropsychological Status.

Objective: Essential tremor (ET), while defined by progressive motor symptoms, is increasingly associated with cognitive impairments (e.g. attention, memory, and executive functions). This study characterizes the cognitive profile of individuals with ET on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), a commonly-used neuropsychological screening measure. Method: Seventy-seven individuals (mean age: 70.6, 34% female) diagnosed with ET and being considered for surgical/procedural intervention were recruited from a Movement Disorders Clinic. All participants completed the RBANS, Grooved Pegboard Test (GPB), and Fahn, Tolosa, Marin Tremor Scale (FTMTS) in the clinical evaluation of their tremor. Results: One-sample t-tests found Immediate Memory, Language, Attention, and Total Scale Index scores to be significantly lower than the expected population mean (p < .05). List Learning, Semantic Fluency, Coding, and List Recall subtests were significantly lower and Picture Naming was significantly higher than the expected population mean (p < .05). GPB scores were correlated with the Attention Index as well as List Learning and Coding subtests. FTMTS Severity was correlated with the Coding subtest and FTMTS Disability was correlated with the Figure Recall subtest. Conclusions: Results support prior literature indicating cognitive weaknesses in those with ET. Individuals with ET had poorer global cognitive abilities, with specific decrements in Immediate Memory, Attention, and Language. Notably, the Attention Index and Coding subtest were most affected by motor functioning. Cognitive screening measures, like the RBANS, can efficiently identify strengths and weaknesses in individuals with ET seeking surgical/procedural interventions.

Characterization of neurocognitive deficits in patients with post-COVID-19 syndrome: persistence, patients' complaints, and clinical predictors.

Introduction: Cognitive symptoms persisting beyond 3 months following COVID-19 present a considerable disease burden. We aimed to establish a domain-specific cognitive profile of post-COVID-19 syndrome (PCS). We examined the deficits' persistence, relationships with subjective cognitive complaints, and clinical variables, to identify the most relevant cognitive deficits and their predictors. Methods: This cross-sectional study examined cognitive performance and patient-reported and clinical predictors of cognitive deficits in PCS patients (n = 282) and socio-demographically comparable healthy controls (n = 52). Results: On the Oxford Cognitive Screen-Plus, the patient group scored significantly lower in delayed verbal memory, attention, and executive functioning than the healthy group. In each affected domain, 10 to 20% of patients performed more than 1.5 SD below the control mean. Delayed memory was particularly affected, with a small effect of hospitalization and age. Attention scores were predicted by hospitalization and fatigue. Discussion: Thus, PCS is associated with long-term cognitive dysfunction, particularly in delayed memory, attention, and executive functioning. Memory deficits seem to be of particular relevance to patients' experience of subjective impairment. Hospitalization, fatigue, and age seem to predict cognitive deficits, while time since infection, depression, and pre-existing conditions do not.

Cognitive Profile Discrepancies among Typical University Students and Those with Dyslexia and Mixed-Type Learning Disorder.

BACKGROUND: Previous studies have identified areas of cognitive weakness in children diagnosed with Specific Learning Disorder (SLD), in the areas of working memory and processing speed in particular. In adulthood, this literature is still scant, and no studies have compared the cognitive profile of university students with dyslexia (DD) with that of students with Mixed-type SLD. METHOD: Thus, in this study, the WAIS-IV was used to examine the cognitive functioning of three groups of university students: students with DD, with Mixed-type SLD, and typical students. Statistical analyses were performed to examine differences in WAIS-IV FSIQ, main, and additional indexes and subtests. RESULTS: The results showed strengths in perceptual reasoning and good verbal comprehension abilities in both the DD and Mixed-type SLD group, with weaknesses in working memory and processing speed, leading to a pattern of a better General Ability Index (GAI) than Cognitive Proficiency Index (CPI) in both clinical groups. Thus, discrepancies between GAI and CPI, well documented in children with SLD, still manifest in adulthood in university students. Our findings also revealed worse cognitive performance in university students with mixed learning disorder relative to students with only a reading deficit. CONCLUSIONS: The cognitive features and distinctive subtest profiles that emerged should guide the assessment and the definitions of intervention programs, special educational needs, and strategies of compensation.

Cognitive profile in functional disorders.

INTRODUCTION: Patients with functional disorders (FD) often experience cognitive problems such as forgetfulness and distractibility alongside physical symptoms that cannot be attributed to a known somatic disease. METHOD: Test scores of cognitive tests and psychiatric rating scales of 100 outpatients diagnosed with a functional disorder were compared to a control group (n = 300) of patients with other diagnoses and to test norms for the general population. RESULTS: Out of the 100 patients with functional disorders, 59 reported significant subjective cognitive symptoms. A moderate difference (d = 0.5-0.7) was found between the FD group mean and the population mean in processing speed tests, as well as in four psychiatric rating scales (depression, anxiety, phobias, somatisation) but there were no statistically significant differences in verbal and nonverbal reasoning or in logical memory. Somatisation and logical verbal memory scores were higher in the FD group compared to the control group. CONCLUSION: The findings of the study suggest that a decline in processing speed is a central feature in the cognitive profile of patients with functional disorders.

Cognitive Profile in Autism and ADHD: A Meta-Analysis of Performance on the WAIS-IV and WISC-V.

OBJECTIVE: Previous research has suggested that neurodevelopmental conditions may be associated with distinctive cognitive profiles on the Wechsler intelligence tests (of which the most recent editions are the WAIS-IV and WISC-V). However, the extent to which a cognitive profile can be reliably identified for individuals meeting criteria for autism or ADHD remains unclear. The present review investigated this issue. METHOD: A search was conducted in PsycInfo, Embase, and Medline in October 2022 for papers reporting the performance of children or adults diagnosed with autism or ADHD on the WAIS-IV or the WISC-V. Test scores were aggregated using meta-analysis. RESULTS: Scores were analyzed from over 1,800 neurodivergent people reported across 18 data sources. Autistic children and adults performed in the typical range for verbal and nonverbal reasoning, but scored ~1 SD below the mean for processing speed and had slightly reduced scores on working memory. This provides evidence for a "spiky" cognitive profile in autism. Performance of children and adults with ADHD was mostly at age-expected levels, with slightly reduced scores for working memory. CONCLUSION: Although the pattern of performance on the Wechsler tests is not sufficiently sensitive or specific to use for diagnostic purposes, autism appears to be associated with a cognitive profile of relative strengths in verbal and nonverbal reasoning and a weakness in processing speed. Attention deficit hyperactivity disorder appears less associated with a particular cognitive profile. Autistic individuals may especially benefit from a cognitive assessment to identify and support with their strengths and difficulties.

Specific Learning Disorders (SLD) and Behavior Impairment: Comorbidity or Specific Profile?

INTRODUCTION: Specific Learning Disorder (SLD) is a neurodevelopmental disorder characterized by difficulties in perceiving and processing verbal and non-verbal information. It is usually accompanied by impaired academic skills leading to school dropout and emotional disturbances, resulting in significant distress and behavioral problems. METHODS: A cognitive, academic, and emotional-behavioral assessment was performed at T0 and T1 in children and adolescents with SLD. Participants received psychotherapy and speech therapy treatment from T0 to T1. RESULTS: In SLD, the most compromised cognitive functions were working memory and writing skills. An impact on academic abilities was found. Children and adolescents with SLD experience greater anxiety and depression levels compared to their control peers. CONCLUSIONS: SLD may adversely influence psychological well-being. To counteract such a consequence, more specific cognitive and academic skill-oriented strategies should be taken into consideration.

Neuropsychological profile of CSF1R-related leukoencephalopathy.

Introduction: The neuropsychological profile of CSF1R-related leukoencephalopathy (CRL) is undefined. This study defines the profile, contrasts it with that of other dementia syndromes, and highlights measures sensitive to cognitive impairment. Methods: We administered a standardized battery of neuropsychological tests to five consecutive CRL cases. Results: The neuropsychological profile of CRL reflects impaired general cognitive function, processing speed, executive function, speeded visual problem solving, verbal fluency, and self-reported depression and anxiety. Confrontation naming and memory are preserved. Within cognitive domains, certain measures more frequently identified impairment than others. Discussion: CRL impairs general cognitive function, processing speed, executive function. Language and visual problem solving may be impaired if processing speed is required. Confrontation naming and memory are uniquely preserved, contrasting CRL to other dementia syndromes. Cognitive screens excluding processing speed and executive function may not detect CRL cognitive manifestations. Findings sharply define cognitive impairment of CRL and inform cognitive test selection.

Cognitive profile in adult women with turner syndrome: IQ split and associations with ADHD and ASD.

INTRODUCTION: The behavioural phenotype in Turner syndrome (TS) is associated with an uneven cognitive profile and social and executive difficulties. Still, studies in adult populations of TS are scarce, and the interactions between different behavioural domains are unclear. The aim of this study was to examine the cognitive profile in relation to measures of ADHD and ASD in a Swedish sample of 30 adult women with TS. METHODS: Standardized psychological tests and questionnaires were used for behavioural assessments in a sample of adult women with a diagnosis of TS (n = 30). Both frequentist and Bayesian statistics were applied. RESULTS: The cognitive profile was characterized by a verbal > non-verbal intelligence quotient (IQ) split, and 77% of the sample displayed a split exceeding cut-off for clinical significance. Symptoms on screening measures reaching thresholds for ADHD were reported in two of the 30 participants (7%) and thresholds for autism spectrum disorders (ASD) in one participant (3%). Bayesian statistics gave substantial evidence for no association between the IQ split and symptoms of ADHD/ASD. CONCLUSIONS: These results show that the TS phenotype in adulthood is associated with a clinically significant uneven cognitive profile, and particular impairments in integrative executive functions.

Timing of Ketogenic Dietary Therapy (KDT) Introduction and Its Impact on Cognitive Profiles in Children with Glut1-DS-A Preliminary Study.

The aim of this research was to characterize cognitive abilities in patients with Glut1-Deficiency syndrome (Glut1DS) following ketogenic diet therapy (KDT). METHODS: The cognitive profiles of eight children were assessed using the Wechsler Intelligence Scale (WISC-IV). The effect of ketogenic diet therapy (KDT) on individual subareas of intelligence was analyzed considering the potential influence of speech motor impairments. RESULTS: Patients with Glut1DS showed a wide range of cognitive performance levels. Some participants showed statistically and clinically significant discrepancies between individual subdomains of intelligence. Both variables, KDT initiation as well as duration, had a positive effect on the overall IQ score. Significant correlations were partially found between the time of KDT initiation and the level of IQ scores, depending on the presence of expressive language test demands of the respective subtests of the WISC-IV. Accordingly, the participants benefited les in the linguistic cognitive domain. The discrepancies in cognitive performance profiles of patients with Glut1DS can be attributed to the possibility of a negative distortion of the results due to the influence of speech motor impairments. CONCLUSIONS: The individual access skills of test persons should be more strongly considered in test procedures for the assessment of intelligence to reduce the negative influence of motor deficits on test performance. Specific characterization and systematization of the speech disorder are indispensable for determining the severity of speech motor impairment in Glut1DS. Therefore, a stronger focus on dysarthria during diagnosis and therapy is necessary.

Patient-specific cognitive profiles in the detection of dementia subtypes: A proposal.

Many physicians rely on sum score cognitive screening tests to evaluate patients for cognitive decline. Because the vast majority of cognitively impaired patients never receive more extensive testing, the results of these screening tests impact patients and their family members profoundly. No previous study has examined whether the metrics used by the popular Mini-Mental State Examination, Montreal Cognitive Assessment, and Saint Louis University Mental Status tests reliably identify single-domain deficits or allow clinicians to adequately track disease progression. We compare side by side the metrics used by these three tests to highlight the differences in the ways they measure domain impairments. We then contrast the sum score approach to cognitive screening with brief domain-specific tests that use extended metrics in each domain examined. Last, we suggest that moderate-to-severe domain-specific deficits on these tests should lead physicians to anticipate specific functional problems and alert family members.

Specific Learning Disabilities and Emotional-Behavioral Difficulties: Phenotypes and Role of the Cognitive Profile.

Specific Learning Disabilities (SLD) are often associated with emotional-behavioral problems. Many studies highlighted a greater psychopathological risk in SLD, describing both internalizing and externalizing problems. The aims of this study were to investigate the emotional-behavioral phenotype through the Child Behavior Checklist (CBCL), and evaluate the mediating role of background and cognitive characteristics on the relationship between CBCL profile and learning impairment in children and adolescents with SLD. One hundred and twenty-one SLD subjects (7-18 years) were recruited. Cognitive and academic skills were assessed, and parents completed the questionnaire CBCL 6-18. The results showed that about half of the subjects manifested emotional-behavioral problems with a prevalence of internalizing symptoms, such as anxiety and depression, over externalizing ones. Older children showed greater internalizing problems than younger ones. Males have greater externalizing problems compared to females. A mediation model analysis revealed that learning impairment is directly predicted by age and familiarity for neurodevelopmental disorders and indirectly via the mediation of the WISC-IV/WAIS-IV Working Memory Index (WMI) by the CBCL Rule-Breaking Behavior scale. This study stresses the need to combine the learning and neuropsychological assessment with a psychopathological evaluation of children and adolescents with SLD and provides new interpretative insights on the complex interaction between cognitive, learning, and emotional-behavioral phenotypes.

Neurocognitive profile of a cohort of SMA type 1 pediatric patients and emotional aspects, resilience and coping strategies of their caregivers.

Spinal muscular atrophy (SMA) type 1 represents the most severe condition of the spectrum of SMA 5q. In the absence of therapeutic interventions, patients do not achieve any motor milestone and their life expectancy does not exceed two years of age. To date, three disease-modifying drugs have been approved for SMA type I. These treatments have radically changed the natural history of the disease, improving motor, respiratory and bulbar functions. In recent years huge amount of data have been collected worldwide related to motor, respiratory and swallowing function outcome in treated patients, whereas the neurocognitive profile of treated patients has been poorly explored. Here we report the neurocognitive development profile of a cohort of SMA type I children treated with a disease modifying therapy. We also describe the burden and resilience as well as the coping strategies of their caregivers. Our finding show a global developmental delay in most patients and defects in gross motor functions contribute most to lower the general development quotient of Griffiths III, whereas the scores obtained on evaluating learning and language abilities scales suggest a positive trend in the developmental trajectory of general neurocognitive abilities. Some parents reported anxiety and stress but overall they were resilient (and had good coping strategies towards the burden of care for their child. These results reinforce the importance of routinely assessing the neurocognitive aspects in SMA type I patients and to offer an early intervention to favor the psychosocial development of these children.

ASIS Cognitive Profiles of Children with Learning Disabilities / Perfiles cognitivos de ASIS enniños con problemas de aprendizaje

Las escalas de inteligencia se utilizan ampliamente para el análisis de perfiles cognitivos en el diagnóstico de problemas de aprendizaje. El propósito de este estudio fue explorar los perfiles cognitivos de los niños con problemas de aprendizaje en una nueva prueba de inteligencia, la Escala de Inteligencia Anadolu-Sak. La prueba de inteligencia se administró a 89 niños diagnosticados con discapacidades generales de aprendizaje. Se seleccionó aleatoriamente un grupo de control emparejado (N = 92) de la muestra estándar. Los análisis de datos incluyeron análisis de perfil latente y comparaciones de puntuaciones entre grupos y comparaciones dentro de los grupos. Los hallazgos mostraron que la inteligencia general media y los medios de la capacidad verbal y visual de los niños con problemas de aprendizaje estaban en el rango promedio pero más cerca del límite inferior. La media de la memoria de trabajo estaba ligeramente por debajo del rango medio y significativamente más baja que la media del grupo de control emparejado. Los análisis de perfil latente mostraron tres perfiles distintos: el perfil en zigzag, el perfil ondulado y el perfil en cascada. La única debilidad compartida por los tres perfiles es la memoria de procesamiento secuencial visual. Los resultados implican que la memoria de procesamiento secuencial débil puede contribuir a las discapacidades de aprendizaje.(AU)

Intelligence scales are widely used for cognitive profile analyses in the diagnosis of learning disabilities. The purpose of this study was to explore the cognitive profiles of children with learning disabilities on a new test of intelligence, the Anadolu-Sak Intelligence Scale. The intelligence test was administered to 89 children diagnosed with general learning disabili-ties. A matched control group (N = 92) was randomly selected from the norm sample. Data analyses included latent profile analyses and compari-sons of scores across groups and within-group comparisons. The findings showed that the mean general intelligence and means of the verbal and visual ability of children with learning disabilities were in the average range but closer to the lower boundary. The mean of working memory was slightly below the average range and significantly lower than the mean of the matched control group. Latent profile analyses showed three distinct profiles: the zigzag profile, the wavy profile, the and waterfall profile. The only weakness shared by the three profiles is visual sequential processing memory. The results imply that weak sequential processing memory may contribute to learning disabilities.(AU)

Comparison of WPPSI-IV and WISC-V cognitive profiles in 6-7-year-old Finland-Swedish children - findings from the FinSwed study.

The Wechsler scales are among the most widely used tests in cognitive and neuropsychological assessments. When assessing children aged 6:0-7:7 years the clinician can choose between Wechsler Preschool and Primary Scale of Intelligence - Fourth Edition (WPPSI-IV) and Wechsler Intelligence Scale for Children - Fifth Edition (WISC-V). Information about how the tests function and differ in this overlapping age range is limited. Using a between-subjects design, the present study compared the cognitive profiles of typically developing Swedish-speaking children in Finland in this overlapping age range (6:1 - 7:2 years), assessed with the Swedish versions of either WPPSI-IV (n = 38) or WISC-V (n = 24). Profile analyses and one-way ANCOVA were performed to investigate differences in the comparable subtests, indexes and Full Scale IQ. On the subtest level, children assessed with WISC-V had significantly lower scores on the subtests Vocabulary, Matrix Reasoning, and Bug/Symbol Search compared to children assessed with WPPSI-IV. On the index level, scores for the Verbal Comprehension Index and the Fluid Reasoning Index were significantly lower for children assessed with WISC-V. The Full Scale IQ was significantly lower on WISC-V. Taken together, the findings indicate that WPPSI-IV and WISC-V produce partly different cognitive profiles. These differences are important to recognize when choosing which test to use and when interpreting the results of clinical assessments of children in this age group.

The Cognitive Profile of Atypical Parkinsonism: A Meta-Analysis.

Atypical Parkinsonism (AP) syndromes are characterized by a wide spectrum of non-motor symptoms including prominent attentional and executive deficits. However, the cognitive profile of AP and its differences and similarities with that of Parkinson's Disease (PD) are still a matter of debate. The present meta-analysis aimed at identifying patterns of cognitive impairment in AP by comparing global cognitive functioning, memory, executive functions, visuospatial abilities, language, non-verbal reasoning, and processing speed test performances of patients with AP relative to healthy controls and patients with PD. All investigated cognitive domains showed a substantial impairment in patients with AP compared to healthy controls. When AP syndromes were considered separately, their cognitive functioning was distributed along a continuum from Multiple Systemic Atrophy at one extreme, with the least impaired cognitive profile (similar to that observed in PD) to Progressive Supranuclear Palsy, with the greatest decline in global cognitive and executive functioning (similar to Corticobasal Syndrome). These findings indicate that widespread cognitive impairment could represent an important clinical indicator to distinguish AP from other movement disorders.

Event-related potential and lexical decision task in dyslexic adults: Lexical and lateralization effects.

Developmental dyslexia is a specific learning disorder that presents cognitive and neurobiological impairments related to different patterns of brain activation throughout development, continuing in adulthood. Lexical decision tasks, together with electroencephalography (EEG) measures that have great temporal precision, allow the capture of cognitive processes during the task, and can assist in the understanding of altered brain activation processes in adult dyslexics. High-density EEG allows the use of temporal analyses through event-related potentials (ERPs). The aim of this study was to compare and measure the pattern of ERPs in adults with developmental dyslexia and good readers, and to characterize and compare reading patterns between groups. Twenty university adults diagnosed with developmental dyslexia and 23 healthy adult readers paired with dyslexics participated in the study. The groups were assessed in tests of intelligence, phonological awareness, reading, and writing, as well as through the lexical decision test (LDT). During LDT, ERPs were recorded using a 128-channel EEG device. The ERPs P100 occipital, N170 occipito-temporal, N400 centro-parietal, and LPC centro-parietal were analyzed. The results showed a different cognitive profile between the groups in the reading, phonological awareness, and writing tests but not in the intelligence test. In addition, the brain activation pattern of the ERPs was different between the groups in terms of hemispheric lateralization, with higher amplitude of N170 in the dyslexia group in the right hemisphere and opposite pattern in the control group and specificities in relation to the items of the LDT, as the N400 were more negative in the Dyslexia group for words, while in the control group, this ERP was more pronounced in the pseudowords. These results are important for understanding different brain patterns in developmental dyslexia and can better guide future interventions according to the changes found in the profile.

Are Executive Dysfunctions Relevant for the Autism-Specific Cognitive Profile?

Executive functions (EF) have been shown to be important for the understanding of Autism Spectrum Disorder (ASD), but dysfunctions of EF are not autism-specific. The specific role of EF in ASD, its relationship to core autism characteristics, such as mentalizing, needs to be explored. Medline- and PsychINFO databases were searched for studies published between 1990 and 2020 that included measures of EF in ASD and typically developing control persons (TD) in combination with either Theory of Mind (ToM) or Weak Central Coherence (WCC) tasks. A pre-registered meta-analysis and cross-study regression was performed including a total of 42 studies (ASD n = 1,546, TD n = 1,206). Results were reported according to PRISMA guidelines. In all cognitive domains, the ASD group showed significantly reduced performance. Importantly, EF subdomains and ToM were not significantly correlated. This finding rules out a significant association between EF subdomains and ToM and questions the relevance of EF dysfunctions for the autism-specific feature of reduced mentalizing.

Inbred Mice Again at Stake: How the Cognitive Profile of the Wild-Type Mouse Background Discloses Pathogenic Effects of APP Mutations.

Increasing efforts have been made in the last decades to increase the face validity of Alzheimer's disease (AD) mouse models. Main advancements have consisted in generating AD mutations closer to those identified in humans, enhancing genetic diversity of wild-type backgrounds, and choosing protocols much apt to reveal AD-like cognitive dysfunctions. Nevertheless, two aspects remain less considered: the cognitive specialization of inbred strains used as recipient backgrounds of mutations and the heuristic importance of studying destabilization of memory circuits in pre-symptomatic mice facing cognitive challenges. This article underscores the relevance of these behavioral/experimental aspects by reviewing data which show that (i) inbred mice differ in their innate predisposition to rely on episodic vs. procedural memory, which implicates differential sensitivity to mutations aimed at disrupting temporal lobe-dependent memory, and that (ii) investigating training-driven neural alterations in asymptomatic mutants unveils early synaptic damage, which considerably anticipates detection of AD first signs.