Evidence of parietal hyperactivation in individuals with mild cognitive impairment who progressed to dementia: A longitudinal fMRI study.

Hyperactivation, which is defined as a higher level of activation in patients compared to cognitively unimpaired older adults (controls; CTL), might represent an early signature of Alzheimer's Disease (AD). The goal of this study was to assess the presence and location of hyperactivation in individuals with mild cognitive impairment (MCI) who were later diagnosed with dementia, examine how hyperactivation changes longitudinally, and whether it is related to time before dementia. Forty participants, 26 with MCI and 14 CTL were enrolled in the study. Magnetic resonance imaging was used to measure functional activation while participants encoded word-pairs as well as cortical thickness and regional brain volume at study entry (Y0) and two years later (Y2). Clinical follow-up was completed every two years following study entry to identify progressors (pMCI), that is, individuals who later received a diagnosis of dementia. Task-related activation was assessed in pMCI in both hippocampi and in regions showing greater cortical thinning from Y0 to Y2 compared to CTLs. Hyperactivation was found in pMCI individuals in the right supramarginal gyrus. Persons with pMCI also showed hypoactivation in the left hippocampus and left pars opercularis. Both hyper- and hypoactivation were present at Y0 and Y2 and did not change longitudinally. Activation was not associated with time before dementia diagnosis. Smaller volume and thinner cortical thickness were associated with shorter time to diagnosis in the left hippocampus and left pars opercularis. In conclusion, hyperactivation was found in individuals who later progressed to dementia, confirming that it might represent an early biomarker to identify individuals in the prodromal phase of AD and that its understanding could contribute to elucidate the key brain mechanisms that precede dementia.

Executive functions in mild cognitive impairment: emergence and breakdown of neural plasticity.

INTRODUCTION: Our goal was to test the effect of disease severity on the brain activation associated with two executive processes: manipulation and divided attention. METHOD: This was achieved by administrating a manipulation task and a divided attention task using functional magnetic resonance imaging to 24 individuals with mild cognitive impairment (MCI) and 14 healthy controls matched for age, sex and education. The Mattis Dementia Rating Scale was used to divide persons with MCI into those with better and worse cognitive performances. RESULTS: Both tasks were associated with more brain activation in the MCI group with higher cognition than in healthy controls, particularly in the left frontal areas. Correlational analyses indicated that greater activation in a frontostriatal network hyperactivated by the higher-cognition group was related with better task performance, suggesting that these activations may support functional reorganization of a compensatory nature. By contrast, the lower-cognition group failed to show greater cerebral hyperactivation than controls during the divided attention task and, during the manipulation task, and showed less brain activation than controls in the left ventrolateral cortex, a region commonly hypoactivated in patients with Alzheimer's disease. CONCLUSION: These findings indicate that, during the early phase of MCI, executive functioning benefits from neural reorganization, but that a breakdown of this brain plasticity characterizes the late stages of MCI.

Effect of disease severity on neural compensation of item and associative recognition in mild cognitive impairment.

It is proposed that the prodromal phase of Alzheimer's disease is associated with additional brain activation in key regions involved in memory, reflecting compensatory brain plasticity. Very little is known, however, about the evolution of these compensatory mechanisms as the brain acquires more damages. We conducted an fMRI memory study measuring brain activation related to old/new (item recognition) and intact/rearranged (associative recognition) word-pair recognition paradigms in 26 persons with mild cognitive impairment (MCI) and 14 healthy older adults. The Mattis Dementia Rating Scale was used to divide persons with MCI into those with higher and lower cognitive performances. Results indicated more brain activation in MCIs than in controls but disease severity determined which cognitive process was associated with larger activation: Persons with less severe MCI showed hyperactivation during associative recognition only, whereas persons with more severe MCI showed hyperactivation during item recognition only. These hyperactivations were found mainly in brain areas that are typically associated with retrieval mode (e.g., bilateral prefrontal cortex). These findings indicate that neural plasticity occurs during the entire MCI phase but that it is associated with different cognitive components. As they progress in the disease, individuals with MCI will experience a breakdown in the compensatory mechanisms for associative recognition accompanied by emergence of compensatory mechanisms for item recognition.

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

Subjects with mild cognitive impairment are at risk of developing Alzheimer's 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.

Compensation and disease severity on the memory-related activations in mild cognitive impairment.

BACKGROUND: Alzheimer's disease is a neurodegenerative disease with progressive cognitive impairments that are likely to affect the compensatory mechanisms and the cerebral activation patterns of the patients. METHODS: Functional neuroimaging was used to test the effect of disease severity on the brain activation of persons at risk for Alzheimer's disease and to highlight the process of compensation in some of these individuals. This was done for the verbal learning of either semantically related or semantically unrelated word pairs. Twenty-six persons with mild cognitive impairment (MCI) were separated into two groups, MCI higher-cognition and MCI lower-cognition, with a split-median on their scores for the Mattis Dementia Rating Scale. A group of 14 healthy older adults were matched to the MCI participants. RESULTS: In both task conditions, MCI higher-cognition activated additional regions, relative to control subjects, in the right ventrolateral and dorsolateral prefrontal brain areas. Additional areas of hyperactivation were found in the right prefrontal area 45 when encoding semantically related word pairs and in the left hippocampus during encoding of unrelated word pairs. In contrast, MCI lower-cognition failed to show additional prefrontal activations when compared with healthy control subjects and showed decreased activation in posterior areas. CONCLUSIONS: These results are in line with compensation occurring at the beginning of the MCI continuum and with the breakdown of compensation in patients experiencing more severe symptoms.

Functional neuroanatomy of the encoding and retrieval processes of verbal episodic memory in MCI.

INTRODUCTION: The goal of this study was to explore the association between disease severity and performance on brain activation associated with episodic memory encoding and retrieval in persons with mild cognitive impairment (MCI). METHOD: This was achieved by scanning 12 MCI persons and 10 age- and education-matched healthy controls while encoding words and while retrieving them in a recognition test. RESULTS: Behaviorally, there was no significant group difference on recognition performance. However, MCI and healthy controls showed different patterns of cerebral activation during encoding. While most of these differences demonstrated reduced activation in the MCI group, there were areas of increased activation in the left ventrolateral prefrontal cortex. Reduced activation was found in brain areas known to be either structurally compromised or hypometabolic in Alzheimer's disease (AD). In contrast, very few group differences were associated with retrieval. Correlation analyses indicated that increased disease severity, as measured with the Mattis Dementia Rating Scale, was associated with smaller activation of the right middle and superior temporal gyri. In contrast, recognition success in MCI persons was associated with larger activation of the left ventrolateral prefrontal cortex during the encoding phase. CONCLUSION: Overall, our results indicate that most of the memory-related cerebral network changes in MCI persons occur during the encoding phase. They also suggest that a prefrontal compensatory mechanism could occur in parallel with the disease-associated reduction of cerebral activation in temporal areas.

Personality and psychological health in persons with mild cognitive impairment.

An increasing number of studies have documented the cognitive profile of individuals with mild cognitive impairment (MCI), but few studies have investigated the individuals' psychological health and personality traits or how these factors interact with cognition. In the present study, 27 healthy older adults and 30 persons with MCI completed questionnaires covering psychological health, morale, personality, self-efficacy, and self-actualization. The results indicated that individuals with MCI are more depressed, anxious, hostile, and have lower morale than matched healthy older adults. Furthermore, our results show a positive association between the level of depression of MCI persons and the severity of their cognitive dysfunctions. In contrast, there were no group differences on measures of personality traits. Thus, while psychological distress is present in persons with MCI, those individuals are not characterized by differences in personality traits relative to older adults who experience no cognitive impairment.

Test-retest reliability of fMRI verbal episodic memory paradigms in healthy older adults and in persons with mild cognitive impairment.

This study investigated test-retest functional magnetic resonance imaging (fMRI) reproducibility in 10 healthy older adults and in 10 mild cognitive impairment (MCI) persons using a two-condition (encoding and retrieval) verbal episodic memory task as well as a two-condition (with and without a motor response) phonological processing task. Reproducibility measures included an overlap ratio with four different thresholds, statistical comparisons of the condition contrasts across sessions (test-retest contrasts), ANCOVAs, and intraclass correlation (ICC) on selected regions of interests (ROIs). In all four conditions and for all reproducibility measures, MCI individuals showed fMRI test-retest reproducibility indices that were comparable to those of healthy older adults. At the group level, the comparison of the test-retest condition contrasts yielded very few differences in the areas and level of activation and those differences tended to show a slight reduction of activation in the second session. In addition, the results from the ANCOVAs showed that the fMRI signal measured at the group level does not vary significantly from one session to another. Overlap ratios, however, showed that the fMRI signal failed to produce a reliable pattern of significantly activated voxels across sessions. ICC analyses on selected ROIs indicated that there is high within-subject variability, suggesting reduced reliability at the individual level. Overall, these findings indicate that MCI individuals show fMRI test-retest reproducibility comparable to those of healthy controls and hence that MCI do not alter fMRI reproducibility. Furthermore, they indicate that monitoring treatment effects is reliable when comparing groups but reduced when comparing single individuals. These results have precise implications for the design of longitudinal studies relying on fMRI measures in older adults.

Cognitive complaint in mild cognitive impairment and Alzheimer's disease.

Whereas the presence of a subjective memory complaint is a central criteria for mild cognitive impairment (MCI), little work has been done to empirically measure its nature and severity. The Self-Evaluation Questionnaire (QAM) assessed memory complaints relative to 10 domains of concrete activities of daily life in 68 persons with MCI, 26 persons with Alzheimer's disease (AD), and 81 healthy older adults. In addition, a neuropsychological battery was administered to assess whether subjective complaints were linked to actual cognitive performance. The findings indicate that individuals with MCI report more memory complaints than controls for a range of specific materials/circumstances. MCI and AD individuals did not differ in their level of memory complaints. Correlational analyses indicated that a higher level of memory complaints relative to conversations and to movies and books were associated with a higher level of objective cognitive deficits in persons with MCI but not in AD. Furthermore, complaints increased in parallel with global cognitive deficits in MCI. These results suggest that persons with MCI report more memory complaints than healthy older controls, but only in specific domains and circumstances, and that anosognosia is more characteristic of the demented than of the MCI phase of Alzheimer's disease.

A rose by any other name: would it smell as sweet?

We examined whether presenting an odor with a positive, neutral, or negative name would influence how people perceive it. In experiment 1, 40 participants rated 15 odors for their pleasantness, intensity, and arousal. In experiment 2, 30 participants passively smelled 10 odors while their skin conductance (SC), heart rate (HR), and sniffing were recorded. We found significant overall effects of odor names on perceived pleasantness, intensity, and arousal. Pleasantness showed the most robust effect of odor names: the same odors were perceived as more pleasant when presented with positive than with neutral and negative names and when presented with neutral than with negative names. In addition, odorants were rated as more intense when presented with negative than with neutral and positive names and as more arousing when presented with positive than with neutral names. Furthermore, SC and sniff volumes, but not HR, were modified by odor names, and the SC changes could not be accounted for by sniffing changes. Importantly, odor names presented with odorless water did not produce any effect on skin conductance and sniff volumes, ruling out the possibility that the naming-related findings were triggered by an emotional reaction to odor names. Taken together, these experiments show that there is a lot to a name, at least when it comes to olfactory perception.