Sylvie Belleville

Mild Cognitive Impairment

Mild cognitive impairment is a syndrome defined as cognitive decline greater than expected for an individuals age and education level but that does not interfere notably with activities of daily life. Prevalence in population-based epidemiological studies ranges from 3% to 19% in adults older than 65 years. Some people with mild cognitive impairment seem to remain stable or return to normal over time, but more than half progress to dementia within 5 years. Mild cognitive impairment can thus be regarded as a risk state for dementia, and its identification could lead to secondary prevention by controlling risk factors such as systolic hypertension. The amnestic subtype of mild cognitive impairment has a high risk of progression to Alzheimers disease, and it could constitute a prodromal stage of this disorder. Other definitions and subtypes of mild cognitive impairment need to be studied as potential prodromes of Alzheimers disease and other types of dementia.

Improvement of Episodic Memory in Persons with Mild Cognitive Impairment and Healthy Older Adults: Evidence from a Cognitive Intervention Program

The efficacy of cognitive training was assessed in persons with mild cognitive impairment (MCI) and persons with normal cognitive aging. Forty-seven participants were included in this study: 28 with MCI and 17 controls. Twenty-one participants received intervention (20 MCI and 9 controls) and 16 participants (8 MCI and 8 controls) received no intervention (waiting-list group). The intervention focused on teaching episodic memory strategies. Three tasks of episodic memory (list recall, face-name association, text memory) were used as primary outcome measures. Results were analyzed using analyses of variance. The intervention effect (pre- and post-intervention difference) was significant on two of the primary outcome measures (delayed list recall and face-name association). A significant pre-post-effect was also found on measures of subjective memory and well-being. There was no improvement in the performance of groups of individuals with MCI and normal elderly persons who did not receive the intervention. These results suggest that persons with MCI can improve their performance on episodic memory when provided with cognitive training.

Working memory and control of attention in persons with Alzheimer's disease and mild cognitive impairment.

The goal of the present study was to assess 3 attentional control processes--divided attention, manipulation capacities, and inhibition--in persons with mild cognitive impairment (MCI) and with mild Alzheimers disease (AD). Manipulation capacities were tested by comparing immediate serial recall with alphabetical-order recall of words. Divided attention was tested with the Brown-Peterson procedure, in which participants divide their attention between simple addition tasks and consonant trigrams over delays. Inhibition was tested with the Hayling procedure, in which participants complete sentences with words irrelevant to their context. Persons with AD showed severe impairment on the 3 attentional control components. Persons with MCI exhibited impaired performance on the Brown-Peterson procedure but normal performance on the other 2 tasks. With AD and MCI participants, there was a negative correlation between general cognitive deficits and impairment on attentional control tasks, indicating that attentional control deficits increase in the MCI/AD continuum. When separating MCI with and without significant subsequent decline, those with subsequent decline showed impaired performance on both the Brown-Peterson procedure and manipulation task. These data suggest that control of attention tasks can track AD at a preclinical stage and that impairment increases gradually during the preclinical phase of AD.

Training-related brain plasticity in subjects at risk of developing Alzheimer’s disease

Subjects with mild cognitive impairment are at risk of developing Alzheimers disease. Cognitive stimulation is an emerging intervention in the field of neurology and allied sciences, having already been shown to improve cognition in subjects with mild cognitive impairment. Yet no studies have attempted to unravel the brain mechanisms that support such improvement. This study uses functional magnetic resonance imaging to measure the effect of memory training on brain activation in older adults with mild cognitive impairment and to assess whether it can reverse the brain changes associated with mild cognitive impairment. Brain activation associated with verbal encoding and retrieval was recorded twice prior to training and once after training. In subjects with mild cognitive impairment, increased activation was found after training within a large network that included the frontal, temporal and parietal areas. Healthy controls showed mostly areas of decreased activation following training. Comparison with pre-training indicated that subjects with mild cognitive impairment used a combination of specialized areas; that is, areas activated prior to training and new alternative areas activated following training. However, only activation of the right inferior parietal lobule, a new area of activation, correlated with performance. Furthermore, the differences between the brain activation patterns of subjects with mild cognitive impairment and those of healthy controls were attenuated by training in a number of brain regions. These results indicate that memory training can result in significant neural changes that are measurable with brain imaging. They also show that the brains of people with mild cognitive impairment remain highly plastic.

Cognitive training for persons with mild cognitive impairment

Recent randomized control trials and meta-analyses of experimental studies indicate positive effects of non-pharmacological cognitive training on the cognitive function of healthy older adults. Furthermore, a large-scale randomized control trial with older adults, independent at entry, indicated that training delayed their cognitive and functional decline over a five-year follow-up. This supports cognitive training as a potentially efficient method to postpone cognitive decline in persons with mild cognitive impairment (MCI). Most of the research on the effect of cognitive training in MCI has reported increased performance following training on objective measures of memory whereas a minority reported no effect of training on objective cognitive measures. Interestingly, some of the studies that reported a positive effect of cognitive training in persons with MCI have observed large to moderate effect size. However, all of these studies have limited power and few have used long-term follow-ups or functional impact measures. Overall, this review highlights a need for a well-controlled randomized trial to assess the efficacy of cognitive training in MCI. It also raises a number of unresolved issues including proper outcome measures, issues of generalization and choice of intervention format.

Local Bias in Autistic Subjects as Evidenced by Graphic Tasks: Perceptual Hierarchization or Working Memory Deficit?

In the present study, copying tasks were used to assess hierarchical aspects of visual perception in a group of 10 nonsavant autistic individuals with normal intelligence. In Experiment 1, the hierarchical order of graphic construction and the constancy of this order were measured for the copying of objects and nonobjects. In comparison to control participants, autistic individuals produced more local features at the start of the copying. However, they did not differ from controls with respect to graphic constancy. Experiment 2 measured the effect of geometrical impossibility on the copying of figures. Results revealed that autistic individuals were less affected by figure impossibility than were controls. Therefore, these experiments seem to support the notion of a local bias for visual information processing in individuals with autism. Two interpretations are proposed to account for this effect. According to the hierarchical deficit hypothesis, individuals with autism do not manifest the normal global bias in perceiving scenes and objects. Alternatively, the executive function hypothesis suggests that autism brings about limitations in the complexity of information that can be manipulated in short-term visual memory during graphic planning.

Examination of the working memory components in normal aging and in dementia of the Alzheimer type

The verbal and attentional components of working memory were examined in patients with Alzheimers disease, normal elderlies, and young controls. Patients with Alzheimers disease, showed a reduced span but were sensitive to word length. This is indicative of a functional rehearsal procedure. However, the effect of phonological similarity on immediate recall was smaller in patients with Alzheimers disease and these patients showed a depressed performance in tasks of phonological analysis. There was also a significant decrement in a task that assessed the attentional component of working memory. Examination of individual patterns of performance showed that the phonological deficiency was severe in a subgroup of patients while the attentional deficit was more general.

Regional brain activity during tasks devoted to the central executive of working memory.

Most previous PET studies investigating the central executive (CE) component of working memory found activation in the prefrontal cortex. However, the tasks used did not always permit to distinguish precisely the functions of the CE from the storage function of the slave systems. The aim of the present study was to isolate brain areas that subserve manipulation of information by the CE when the influence of storage function was removed. A PET activation study was performed with four cognitive tasks, crossing conditions of temporary storage and manipulation of information. The manipulation of information induced an activation in the right (BA 10/46) and left (BA 9/6) middle frontal gyrus and in the left parietal area (BA7). The interaction between the storage and manipulation conditions did not reveal any significant changes in activation. These results are in agreement with the hypothesis that CE functions are distributed between anterior and posterior brain areas, but could also reflect a simultaneous involvement of controlled (frontal) and automatic (parietal) attentional systems. In the other hand, the absence of interaction between the storage and manipulation conditions demonstrates that the CE is not necessarily related to the presence of a memory load.

Effect of normal aging on the manipulation of information in working memory

The goal of this study is to examine the central executive of working memory in normal aging, specifically focusing on its capacities to manipulate or modify the format of the to-be-recalled material. The central executive was measured with the alphabetical span procedure, during which subjects were asked to recall a random series of words in their alphabetical order. The storage demand was equalized across subjects by adjusting the list lengths according to individual span. Experiments 1, 2, and 3 showed that elderly subjects were not impaired in manipulating information, relative to young controls, even when the difficulty of the task was increased. In Experiment 4, validity was tested by asking young subjects to perform the task under the conditions of full or divided attention. Alphabetical recall was more impaired than direct recall during the divided attention condition, which suggests a larger involvement of the central executive component in the former. These results are discussed in relation to the hypothesis of a central executive impairment being associated with normal aging.

Diagnosis and treatment of dementia: 3. Mild cognitive impairment and cognitive impairment without dementia.

Background: Mild cognitive impairment and cognitive impairment, no dementia, are emerging terms that encompass the clinical state between normal cognition and dementia in elderly people. Controversy surrounds their characterization, definition and application in clinical practice. In this article, we provide physicians with practical guidance on the definition, diagnosis and treatment of mild cognitive impairment and cognitive impairment, no dementia, based on recommendations from the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia, held in March 2006. Methods: We developed evidence-based guidelines using systematic literature searches, with specific criteria for study selection and quality assessment, and a clear and transparent decision-making process. We selected studies published from January 1996 to December 2005 that had mild cognitive impairment or cognitive impairment, no dementia, as the outcome. Subsequent to the conference, we searched for additional articles published between January 2006 and January 2008. We graded the strength of evidence using the criteria of the Canadian Task Force on Preventive Health Care. Results: We identified 2483 articles, of which 314 were considered to be relevant and of good or fair quality. From a synthesis of the evidence in these studies, we made 16 recommendations. In brief, family physicians should be aware that most types of dementia are preceded by a recognizable phase of mild cognitive decline. They should be familiar with the concepts of mild cognitive impairment and of cognitive impairment, no dementia. Patients with these conditions should be closely monitored because of their increased risk for dementia. Leisure activities, cognitive stimulation and physical activity could be promoted as part of a healthy lifestyle in elderly people and those with mild cognitive impairment. Vascular risk factors should be treated optimally. No other specific therapies can yet be recommended. Interpretation: Physicians will increasingly see elderly patients with mild memory loss, and learning an approach to diagnosing states such as mild cognitive impairment is now warranted. Close monitoring for progression to dementia, promotion of a healthy lifestyle and treatment of vascular risk factors are recommended for the management of patients with mild cognitive impairment.