Propriétés des stimuli et fonction mnémonique de la formation hippocampique chez le rat

Le but de cette thèse est d'étudier le rôle des propriétés des stimuli dans la fonction mnémonique de la formation hippocampique chez le rat. Les neufs expériences rapportées dans ce texte comparent la performance de rats avec une lésion du fomix (FX) à celle d'animaux contrôles avec lésion simulée (SH) dans des tâches de mémoire spatiale (labyrinthe radial) et non spatiale (labyrinthe radial et épreuves de reconnaissance d'odeurs). Dans la version spatiale de la tâche du labyrinthe radial, le déficit des rats du groupe FX s'explique à la fois par l'organisation des stimuli et par le maintien des informations en mémoire de travail. Dans d'autres versions inédites et non exclusivement spatiales de la tâches du labyrinthe radial, des résultats tout à fait inattendus montrent que l'apprentissage des groupes FX dépend en partie de l'emplacement des stimuli pertinents, mais aussi de la stabilité de leurs positions relatives. Enfin, tant dans les tâches spatiales que non spatiales, des résultats indiquent que les groupes FX ont des difficultés à reconnaître des stimuli qui présentent des chevauchements avec d'autres stimuli. Donc, la fonction mnémonique de la formation hippocampique n'est pas exclusivement spatiale puisque diverses propriétés des stimuli y sont traitées

The use of executive fluency tasks to detect cognitive impairment in individuals with subjective cognitive decline

Objective: Although evidence has indicated that subjective cognitive decline (SCD) may be an early sign of Alzheimer’s disease (AD), the objectification of cognitive impairment in SCD is challenging, mainly due to the lack of sensitivity in assessment tools. The present study investigated the potential contribution of two verbal fluency tasks with high executive processing loads to the identification of cognitive impairment in SCD. Methods: A total of 60 adults with SCD and 60 healthy controls (HCs) performed one free action (verb) fluency task and two fluency tasks with more executive processing load—an alternating fluency task and an orthographic constraint fluency task—and the results were compared. Result: In the free action fluency task, the performance of the participants with SCD and the HCs was similar. However, HCs performed significantly better than SCD in the alternating fluency task, which required mental flexibility, and the orthographic constraint fluency task, which required inhibition. Discussion: The study findings suggest that verbal fluency tasks with high executive processing load could be useful in detecting cognitive deficits at the preclinical stage of AD. The inclusion of such tests in assessment batteries should be considered in order to improve the detection of subtle cognitive impairment in preclinical major neurocognitive disorder populations

Alternative avenues in the assessment of driving capacities in older drivers and implications for training

The population aging, combined with the overrepresentation of older drivers in car crashes, engendered a whole body of research destined at finding simple and efficient assessment methods of driving capacities. However, this quest is little more than a utopian dream, given that car crashes and unsafe driving behaviours can result from a plethora of interacting factors. This review highlights the main problems of the current assessment methods and training programs, and presents theoretical and empirical arguments justifying the need of reorienting the research focus. Our discussion is elaborated in light of the fundamental principle of specificity in learning and practice. We also identify overlooked variables that are deterministic when assessing, and training, a complex ability like driving. We especially focus on the role of the sensorimotor transformation process. Finally, we propose alternative methods that are in-line with the recent trends in educational programs that use virtual reality and simulation technologies

Normative data for phonemic and semantic verbal fluency test in the adult french-Quebec population and validation study in Alzheimer's disease and depression

Objective: Verbal fluency tasks are principally used to assess lexical access and have shown usefulness for differential diagnosis. The purpose of Study 1 was to provide normative data in the adult French–Quebec population (Canada) for semantic verbal fluency (animals), for two sets of phonemic verbal fluency (TNP and PFL), and for letter P alone (60 seconds per category/letter). The objectives of Study 2 were to establish the diagnostic and predictive validity of the present tasks and normative data in Alzheimer’s disease (AD) and major depressive episode (MDE). Method: The normative sample consisted of 932 participants aged 19–91 years. Based on multiple linear regressions, equations to calculate Z-scores were provided. To assess validity, performance of 62 healthy participants was compared to 62 participants with AD and 41 with MDE aged over 50. Results: Age and education, but not gender, predicted performance on each verbal fluency task. Healthy adults aged 50 and younger had a better performance on semantic than phonemic verbal fluency. In comparison to MDE, AD participants had lower performance on animals and TNP, but not on letter P. Ninety percent of people with a Z-score ≤ −1.50 on semantic verbal fluency had AD and the global accuracy was 76.6%. Test–retest reliability over one year was high for both animals (r = .711) and TNP (r = .790) in healthy older participants, but dropped for animals in people with AD (r = .493). Conclusions: These data will strengthen accurate detection of verbal fluency deficits in French–Quebec adults

DNA methylation and single nucleotide variants in the brain-derived neurotrophic factor (BDNF) and oxytocin receptor (OXTR) genes are associated with anxiety/depression in older women

Background: Environmental effects and personal experiences could be expressed in individuals through epigenetic non-structural changes such as DNA methylation. This methylation could up- regulate or down-regulate corresponding gene expressions and modify related phenotypes. DNA methylation increases with aging and could be related to the late expression of some forms of mental disease. The objective of this study was to evaluate the association between anxiety disorders and/or depression in older women and DNA methylation for four genes related to anxiety or depression. Methods: Women aged 65 and older with (n = 19) or without (n = 24) anxiety disorders and/or major depressive episode (DSM-IV), were recruited. DNA methylation and single nucleotide variant (SNV) were evaluated from saliva, respectively by pyrosequencing and by PCR, for the following genes: brain-derived neurotrophic factor (BDNF; rs6265), oxytocin receptor (OXTR; rs53576), serotonin transporter (SLC6A4; rs25531), and apolipoprotein E (APOE; rs429358 and rs7412). Results: A greater BDNF DNA methylation was observed in subjects with anxiety/depression compared to control group subjects (Mean: 2.92 SD ± 0.74 vs. 2.34 ± 0.42; p= 0.0026). This difference was more pronounced in subjects carrying the BDNF rs6265 CT genotype (2.99 ± 0.41 vs. 2.27 ± 0.26; p= 0.0006) than those carrying the CC genotype (p= 0.0332); no subjects with the TT genotype were observed. For OXTR, a greater DNA methylation was observed in subjects with anxiety/depression, but only for those carrying the AA genotype of the OXTR rs53576 SNV, more particularly at one out of the seven CpGs studied (7.01 ± 0.94 vs. 4.44 ± 1.11; p= 0.0063). No significant differences were observed for APOE and SLC6A4. Conclusion: These results suggest that DNA methylation in interaction with SNV variations in BDNF and OXTR, are associated with the occurrence of anxiety/depression in older women

Anxiety and cognitive impairment

Background : Anxiety symptoms are highly prevalent in elders with mild cognitive disorders, but little is known about the associations of specific anxiety disorders to mild cognitive disorders. Objective : To identify the clinical and subclinical anxiety disorders associated with cognitive impairment no dementia (CIND) and to determine whether these associations differ depending on sex and concomitant depressive episodes. Method : Participants constituted a random sample (n  = 2414) of community‐dwelling adults aged 65–96 years. The following clinical and subclinical DSM‐IV anxiety disorders were identified with a semi‐structured interview: specific phobia, social phobia, agoraphobia, panic disorder, obsessive–compulsive, and generalized anxiety disorder (GAD). Major depressive episodes or minor depression (MDE/MD) were also determined based on the DSM‐IV criteria. CIND cases were defined based on Mini‐Mental State Examination (MMSE) cut‐offs (15th percentile) stratified for age, education, and sex. Potentially confounding variables (age, education, MDE/MD, chronic diseases, and psychotropic drug use) were statistically controlled. Results : In men, after adjusting for confounding variables, CIND was associated with subclinical GAD (odds ratio (OR): 4.93, 95% confidence interval: 1.84–13.23). Further analyses showed that in men, CIND was related to clinical/subclinical GAD whether MDE/MD was present (7.05, 1.88–26.43) or absent (9.33, 3.24–26.83). In women, CIND was not linked to any clinical or subclinical anxiety disorder. Conclusions : These results suggest that in community‐dwelling elders, GAD is the main anxiety disorder associated with poor global cognitive functioning. Moreover, this association is modified by sex, but not by the presence of depressive episodes. Copyright © 2010 John Wiley & Sons, Ltd

Are Verbal Fluency and Nonliteral Language Comprehension Deficits Related to Depressive Symptoms in Parkinson's Disease?

Depression in Parkinson's disease (PD) is frequently associated with executive deficits, which can influence nonliteral comprehension and lexical access. This study explores whether depressive symptoms in PD modulate verbal fluency and nonliteral language comprehension. Twelve individuals with PD without depressive symptoms, 13 with PD and depressive symptoms (PDDSs), and 13 healthy controls completed a semantic and phonemic verbal fluency task and an indirect speech acts comprehension task. All groups had the same performance in the phonemic fluency task while the PDDS group was impaired in the semantic task. For the indirect speech act comprehension task, no difference was observed between the groups. However, the PDDS group had difficulty answering direct speech act questions. As some language impairments in PD become apparent when depressive symptoms are associated with the disease, it would appear to be important to take the presence of depressive symptoms into account when evaluating language abilities in PD

Older adults with mild cognitive impairments show less driving errors after a multiple sessions simulator training program but do not exhibit long term retention

The driving performance of individuals with mild cognitive impairment (MCI) is suboptimal when compared to healthy older adults. It is expected that the driving will worsen with the progression of the cognitive decline and thus, whether or not these individuals should continue to drive is a matter of debate. The aim of the study was to provide support to the claim that individuals with MCI can benefit from a training program and improve their overall driving performance in a driving simulator. Fifteen older drivers with MCI participated in five training sessions in a simulator (over a 21-day period) and in a 6-month recall session. During training, they received automated auditory feedback on their performance when an error was noted about various maneuvers known to be suboptimal in MCI individuals (for instance, weaving, omitting to indicate a lane change, to verify a blind spot, or to engage in a visual search before crossing an intersection). The number of errors was compiled for eight different maneuvers for all sessions. For the initial five sessions, a gradual and significant decrease in the number of errors was observed, indicating learning and safer driving. The level of performance, however, was not maintained at the 6-month recall session. Nevertheless, the initial learning observed opens up possibilities to undertake more regular interventions to maintain driving skills and safe driving in MCI individuals

Anxiety, depression and incident cognitive impairment in community-dwelling older adults

Objectives: To examine in men and women the independent associations between anxiety and depression and 1-year incident cognitive impairment and to examine the association of cognitive impairment, no dementia (CIND) and incident cognitive impairment with 1-year incident anxiety or depression. Design: Prospective cohort study. Setting: General community. Participants: Population-based sample of 1,942 individuals aged 65 to 96. Measurements: Two structured interviews 12 months apart evaluated anxiety and mood symptoms and disorders according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. Incident cognitive impairment was defined as no CIND at baseline and a follow-up Mini-Mental State Examination score at least 2 points below baseline and below the 15th percentile according to normative data. The associations between cognitive impairment and anxiety or depression were assessed using logistic regression adjusted for potential confounders. Results: Incident cognitive impairment was, independently of depression, associated with baseline anxiety disorders in men (odds ratio (OR)=6.27, 95% confidence interval (CI)=1.39-28.29) and anxiety symptoms in women (OR=2.14, 95%=1.06-4.34). Moreover, the results indicated that depression disorders in men (OR=8.87, 95%=2.13-36.96) and anxiety symptoms in women (OR=4.31, 95%=1.74-10.67) were particularly linked to incident amnestic cognitive impairment, whereas anxiety disorders in men (OR=12.01, 95%=1.73-83.26) were especially associated with incident nonamnestic cognitive impairment. CIND at baseline and incident cognitive impairment were not associated with incident anxiety or depression. Conclusion: Anxiety and depression appear to have different relationships with incident cognitive impairment according to sex and the nature of cognitive impairment. Clinicians should pay particular attention to anxiety in older adults because it may shortly be followed by incident cognitive treatment