Verbal learning in mild cognitive impairment and alzheimer's disease : behavioural and neural approaches

The main focus of the present thesis was at verbal episodic memory processes that are particularly vulnerable to preclinical and clinical Alzheimer’s disease (AD). Here these processes were studied by a word learning paradigm, cutting across the domains of memory and language learning studies. Moreover, the differentiation between normal aging, mild cognitive impairment (MCI) and AD was studied by the cognitive screening test CERAD. In study I, the aim was to examine how patients with amnestic MCI differ from healthy controls in the different CERAD subtests. Also, the sensitivity and specificity of the CERAD screening test to MCI and AD was examined, as previous studies on the sensitivity and specificity of the CERAD have not included MCI patients. The results indicated that MCI is characterized by an encoding deficit, as shown by the overall worse performance on the CERAD Wordlist learning test compared with controls. As a screening test, CERAD was not very sensitive to MCI. In study II, verbal learning and forgetting in amnestic MCI, AD and healthy elderly controls was investigated with an experimental word learning paradigm, where names of 40 unfamiliar objects (mainly archaic tools) were trained with or without semantic support. The object names were trained during a 4-day long period and a follow-up was conducted one week, 4 weeks and 8 weeks after the training period. Manipulation of semantic support was included in the paradigm because it was hypothesized that semantic support might have some beneficial effects in the present learning task especially for the MCI group, as semantic memory is quite well preserved in MCI in contrast to episodic memory. We found that word learning was significantly impaired in MCI and AD patients, whereas forgetting patterns were similar across groups. Semantic support showed a beneficial effect on object name retrieval in the MCI group 8 weeks after training, indicating that the MCI patients’ preserved semantic memory abilities compensated for their impaired episodic memory. The MCI group performed equally well as the controls in the tasks tapping incidental learning and recognition memory, whereas the AD group showed impairment. Both the MCI and the AD group benefited less from phonological cueing than the controls. Our findings indicate that acquisition is compromised in both MCI and AD, whereas long13 term retention is not affected to the same extent. Incidental learning and recognition memory seem to be well preserved in MCI. In studies III and IV, the neural correlates of naming newly learned objects were examined in healthy elderly subjects and in amnestic MCI patients by means of positron emission tomography (PET) right after the training period. The naming of newly learned objects by healthy elderly subjects recruited a left-lateralized network, including frontotemporal regions and the cerebellum, which was more extensive than the one related to the naming of familiar objects (study III). Semantic support showed no effects on the PET results for the healthy subjects. The observed activation increases may reflect lexicalsemantic and lexical-phonological retrieval, as well as more general associative memory mechanisms. In study IV, compared to the controls, the MCI patients showed increased anterior cingulate activation when naming newly learned objects that had been learned without semantic support. This suggests a recruitment of additional executive and attentional resources in the MCI group.

Cognitive, affective and behavioural characteristics of mothers with anxiety disorders in the context of child anxiety disorder

Parental emotional distress, particularly high maternal anxiety, is one of the most consistent predictors of child anxiety treatment outcome. In order to identify the cognitive, affective and behavioural parenting characteristics of mothers of children with anxiety disorders who themselves have an anxiety disorder, we assessed the expectations and appraisals of 88 mothers of anxious children (44 not anxious (NONANX) and 44 with a current anxiety disorder (ANX)) before and after interacting with their 7-12 year old children. There were no observed differences in anxiety and avoidance among children of ANX and NONANX mothers, but, compared to NONANX mothers, ANX mothers held more negative expectations and differed on observations of intrusiveness, expressed anxiety, warmth and the quality of the relationship. Associations were moderated by the degree to which children expressed anxiety during the tasks. Maternal reported negative emotions during the task significantly mediated the association between maternal anxiety status and the observed quality of the relationship. These findings suggest that maternal anxiety disorder is associated with reduced tolerance of children’s negative emotions. This may interfere with the maintenance of a positive, supportive mother-child interaction under conditions of stress, and as such impede optimum treatment outcomes. The findings identify potential cognitive, affective and behavioural targets to improve treatment outcomes for children with anxiety disorders in the context of a current maternal anxiety disorder.

Cognitive and behavioural assessment of parkinsonian syndromes at onset: a longitudinal study

Background: cognitive impairment is one of the non motor features widely descripted in parkinsonian syndrome, it has been related to the motor characteristics of the parkinsonian syndrome, associated with neuropsychiatric dysfunction and the characteristic sleep and autonomic features. It has been shown to be highly prevalent at all disease stages and to contribute significantly to disability. Objectives: aim of this study is to evaluate longitudinally the cognitive and behavioral characteristics of patients with a parkinsonian syndrome at onset; to describe the cognitive and behavioral characteristics of each parkinsonian syndrome; to define in PD patients at onset the presence of MCI or Parkinson disease dementia; to correlate the cognitive and behavioral characteristics with the features of the parkinsonian syndrome and with the associated sleep and autonomic features. Results: we recruited 55 patients, 22 did not present cognitive impairment both at T0 and at T1. 18 patients presented a progression of cognitive impairment. Progressive cognitively impaired patients were older and presented the worst motor phenotype. Progression of cognitive impairment was not associated to sleep and autonomic features. Conclusion: the evaluation of cognitive impairment could not be useful as a predictor of a correct diagnosis but each non motor domain will help to clarify and characterize the motor syndrome. The diagnosis of parkinsonian disorders lies in building a clinical profile in conjunction with other clinical characteristics such as mode of presentation, disease progression, response to medications, sleep and autonomic features.

The complexity of drinking: Interactions between the cognitive and behavioural determinants of alcohol consumption

This study expanded the earlier work conducted by this laboratory ( Hasking, P.A. and Oei, T.P.S. (2002a) . The differential role of alcohol expectancies, drinking refusal self-efficacy and coping resources in predicting alcohol consumption in community and clinical samples. Addiction Research and Theory , 10 , 465-494), by examining the independent and interactive effects of avoidant coping strategies, positive and negative expectancies and self-efficacy, in predicting volume and frequency of alcohol consumption in a sample of community drinkers. Differential relationships were found between the variables when predicting the two consumption measures. Specifically, while self-efficacy, seeking social support for emotional reasons and using drugs or alcohol to cope were independently related to both volume and frequency of drinking, complex interactions with positive and negative alcohol expectancies were also found. These interactions are discussed in terms of the cognitive and behavioural mechanisms thought to underlie drinking behaviour.

All in Good Time: Exploring Change in Neanderthal Behavioural Complexity

Since their discovery 150 years ago, Neanderthals have been considered incapable of behavioural change and innovation. Traditional synchronic approaches to the study of Neanderthal behaviour have perpetuated this view and shaped our understanding of their lifeways and eventual extinction. In this thesis I implement an innovative diachronic approach to the analysis of Neanderthal faunal extraction, technology and symbolic behaviour as contained in the archaeological record of the critical period between 80,000 and 30,000 years BP. The thesis demonstrates patterns of change in Neanderthal behaviour which are at odds with traditional perspectives and which are consistent with an interpretation of increasing behavioural complexity over time, an idea that has been suggested but never thoroughly explored in Neanderthal archaeology. Demonstrating an increase in behavioural complexity in Neanderthals provides much needed new data with which to fuel the debate over the behavioural capacities of Neanderthals and the first appearance of Modern Human Behaviour in Europe. It supports the notion that Neanderthal populations were active agents of behavioural innovation prior to the arrival of Anatomically Modern Humans in Europe and, ultimately, that they produced an early Upper Palaeolithic cultural assemblage (the Châtelperronian) independent of modern humans. Overall, this thesis provides an initial step towards the development of a quantitative approach to measuring behavioural complexity which provides fresh insights into the cognitive and behavioural capabilities of Neanderthals.

Governing coordination: Behavioural principles and neural correlates

The coordination of movement is governed by a coalition of constraints. The expression of these constraints ranges from the concrete—the restricted range of motion offered by the mechanical configuration of our muscles and joints; to the abstract—the difficulty that we experience in combining simple movements into complex rhythms. We seek to illustrate that the various constraints on coordination are complementary and inclusive, and the means by which their expression and interaction are mediated systematically by the integrative action of the central nervous system (CNS). Beyond identifying the general principles at the behavioural level that govern the mutual interplay of constraints, we attempt to demonstrate that these principles have as their foundation specific functional properties of the cortical motor systems. We propose that regions of the brain upstream of the motor cortex may play a significant role in mediating interactions between the functional representations of muscles engaged in sensorimotor coordination tasks. We also argue that activity in these ldquosupramotorrdquo regions may mediate the stabilising role of augmented sensory feedback.

A Randomized Clinical Trial to Examine Enhancing Cognitive-Behavioral Group Therapy for Obsessive-Compulsive Disorder with Motivational Interviewing and Thought Mapping

Background: Obsessive-compulsive disorder (OCD) is characterized by repeated and persistent attempts to control thoughts and actions with rituals. These rituals are used in order to prevent feared or personally distressing outcomes. Cognitive behavioral group therapy (CBGT) has been reported to be effective for treating OCD patients. However, about one-third (30%) of patients do not benefit from CBGT. Some of these patients do not show significant improvement and continue to use rituals following CBGT, partially because they fail to complete the exposure and ritual prevention (ERP) exercises. Consequently, it is important to motivate patients to fully engage in CBGT treatment and complete the ERP exercises. Aims: A randomized behavioral trial examined 12 weeks of manual directed CBGT, with the addition of individual sessions of Motivational Interviewing (MI) and Thought Mapping (TM), and compared treatment outcome to the effectiveness of CBGT group alone. Method: Subjects were randomized (n = 93) into a CBGT group or a CBGT group with MI+TM. Results: When the two groups were compared, both groups reduced OCD symptoms. However, symptom reduction and remission were significantly higher in the MI+TM CBGT group. Positive outcomes were also maintained, with additional symptom reduction at the 3-month follow-up for the MI TM CBGT group. Conclusions: Adding two individual sessions of MI and TM before CBGT successfully reduced OCD symptoms and was more effective than using CBGT group alone.