Longitudinal assessment of neural activity in Parkinson’s disease with mild cognitive impairment using task based fMRI

La maladie de Parkinson (PD) a été uniquement considérée pour ses endommagements sur les circuits moteurs dans le cerveau. Il est maintenant considéré comme un trouble multisystèmique, avec aspects multiples non moteurs y compris les dommages intérêts pour les circuits cognitifs. La présence d’un trouble léger de la cognition (TCL) de PD a été liée avec des changements structurels de la matière grise, matière blanche ainsi que des changements fonctionnels du cerveau. En particulier, une activité significativement réduite a été observée dans la boucle corticostriatale ‘cognitive’ chez des patients atteints de PD-TCL vs. PD non-TCL en utilisant IRMf. On sait peu de cours de ces modèles fonctionnels au fil du temps. Dans cette étude, nous présentons un suivi longitudinal de 24 patients de PD non démente qui a subi une enquête neuropsychologique, et ont été séparés en deux groupes - avec et sans TCL (TCL n = 11, non-TCL n = 13) en fonction du niveau 2 des recommandations de la Movement Disrders Society pour le diagnostic de PD-TCL. Ensuite, chaque participant a subi une IRMf en effectuant la tâche de Wisconsin pendant deux sessions, 19 mois d'intervalle. Nos résultats longitudinaux montrent qu'au cours de la planification de période de la tâche, les patients PD non-TCL engageant les ressources normales du cortex mais ils ont activé en plus les zones corticales qui sont liés à la prise de décision tel que cortex médial préfrontal (PFC), lobe pariétal et le PFC supérieure, tandis que les PD-TCL ont échoué pour engager ces zones en temps 2. Le striatum n'était pas engagé pour les deux groupes en temps 1 et pour le groupe TCL en temps 2. En outre, les structures médiales du lobe temporal étaient au fil du temps sous recrutés pour TCL et Non-TCL et étaient positivement corrélés avec les scores de MoCA. Le cortex pariétal, PFC antérieur, PFC supérieure et putamen postérieur étaient négativement corrélés avec les scores de MoCA en fil du temps. Ces résultats révèlent une altération fonctionnelle pour l’axe ganglial-thalamo-corticale au début de PD, ainsi que des niveaux différents de participation corticale pendant une déficience cognitive. Cette différence de recrutement corticale des ressources pourrait refléter longitudinalement des circuits déficients distincts de trouble cognitive légère dans PD.

16/6-idiotype expressing antibodies induce brain inflammation and cognitive impairment in mice: the mosaic of central nervous system involvement in lupus

Background: The 16/6-idiotype (16/6-Id) of the human anti-DNA antibody was found to induce experimental lupus in naive mice, manifested by production of autoantibodies, leukopenia and elevated inflammatory markers, as well as kidney and brain involvement. We assessed behavior and brain pathology of naive mice injected intracerebra-ventricularly (ICV) with the 16/6-Id antibody. Methods: C3H female mice were injected ICV to the right hemisphere with the human 16/6-Id antibody or commercial human IgG antibodies (control). The mice were tested for depression by the forced swimming test (FST), locomotor and explorative activity by the staircase test, and cognitive functions were examined by the novel object recognition and Y-maze tests. Brain slices were stained for inflammatory processes. Results: 16/6-Id injected mice were cognitively impaired as shown by significant differences in the preference for a new object in the novel object recognition test compared to controls (P = 0.012). Similarly, the preference for spatial novelty in the Y-maze test was significantly higher in the control group compared to the 16/6-Id-injected mice (42% vs. 9%, respectively, P = 0.065). Depression-like behavior and locomotor activity were not significantly different between the16/6-Id-injected and the control mice. Immunohistochemistry analysis revealed an increase in astrocytes and microglial activation in the hippocampus and amygdala, in the 16/6-Id injected group compared to the control. Conclusions: Passive transfer of 16/6-Id antibodies directly into mice brain resulted in cognitive impairments and histological evidence for brain inflammation. These findings shed additional light on the diverse mosaic pathophysiology of neuropsychiatric lupus.

Cognitive function in normal aging and in older adults with mild cognitive impairment

Resumen tomado de la publicación

Strategies to prevent falls and fractures in hospitals and care homes and effect of cognitive impairment: systematic review and meta-analyses

OBJECTIVES: To evaluate the evidence for strategies to prevent falls or fractures in residents in care homes and hospital inpatients and to investigate the effect of dementia and cognitive impairment. DESIGN: Systematic review and meta-analyses of studies grouped by intervention and setting (hospital or care home). Meta-regression to investigate the effects of dementia and of study quality and design. DATA SOURCES: Medline, CINAHL, Embase, PsychInfo, Cochrane Database, Clinical Trials Register, and hand searching of references from reviews and guidelines to January 2005. RESULTS: 1207 references were identified, including 115 systematic reviews, expert reviews, or guidelines. Of the 92 full papers inspected, 43 were included. Meta-analysis for multifaceted interventions in hospital (13 studies) showed a rate ratio of 0.82 (95% confidence interval 0.68 to 0.997) for falls but no significant effect on the number of fallers or fractures. For hip protectors in care homes (11 studies) the rate ratio for hip fractures was 0.67 (0.46 to 0.98), but there was no significant effect on falls and not enough studies on fallers. For all other interventions (multifaceted interventions in care homes; removal of physical restraints in either setting; fall alarm devices in either setting; exercise in care homes; calcium/vitamin D in care homes; changes in the physical environment in either setting; medication review in hospital) meta-analysis was either unsuitable because of insufficient studies or showed no significant effect on falls, fallers, or fractures, despite strongly positive results in some individual studies. Meta-regression showed no significant association between effect size and prevalence of dementia or cognitive impairment. CONCLUSION: There is some evidence that multifaceted interventions in hospital reduce the number of falls and that use of hip protectors in care homes prevents hip fractures. There is insufficient evidence, however, for the effectiveness of other single interventions in hospitals or care homes or multifaceted interventions in care homes.

Deficient acquisition and consolidation: intertrial free recall performance in Alzheimer's disease and mild cognitive impairment

Previous research demonstrates that dementia of the Alzheimer type (DAT) is characterised by deficits of episodic memory, especially in the acquisition of new material. As well as this deficit in acquisition, some researchers have also argued for a deficit in consolidation in DAT. We examined acquisition and consolidation by measuring the intertrial gained and lost access in DAT, Mild Cognitive Impairment (MCI) and controls. We report findings from a study of clinical data based on assessment of patients using three free recall trials of a word list. We found that both DAT and MCI groups showed a deficit in acquisition and consolidation of items between trials relative to controls. Moreover, the DAT group was significantly impaired relative to the MCI group for both acquisition and consolidation. Correlations within each group showed that there were strong relationships between intertrial measures and standard measures of memory function. Importantly in no group was there a significant correlation between our measures of acquisition and consolidation: we argue that these measures reflect different underlying processes, and the failure to consolidate in DAT and MCI is not related to the deficit in acquisition. Finally, we showed strong correlations between our measure and dementia severity, suggesting that acquisition and consolidation both get worse as the dementia progresses.

Neural correlates of true and false memory in mild cognitive impairment

The goal of this research was to investigate the changes in neural processing in mild cognitive impairment. We measured phase synchrony, amplitudes, and event-related potentials in veridical and false memory to determine whether these differed in participants with mild cognitive impairment compared with typical, age-matched controls. Empirical mode decomposition phase locking analysis was used to assess synchrony, which is the first time this analysis technique has been applied in a complex cognitive task such as memory processing. The technique allowed assessment of changes in frontal and parietal cortex connectivity over time during a memory task, without a priori selection of frequency ranges, which has been shown previously to influence synchrony detection. Phase synchrony differed significantly in its timing and degree between participant groups in the theta and alpha frequency ranges. Timing differences suggested greater dependence on gist memory in the presence of mild cognitive impairment. The group with mild cognitive impairment had significantly more frontal theta phase locking than the controls in the absence of a significant behavioural difference in the task, providing new evidence for compensatory processing in the former group. Both groups showed greater frontal phase locking during false than true memory, suggesting increased searching when no actual memory trace was found. Significant inter-group differences in frontal alpha phase locking provided support for a role for lower and upper alpha oscillations in memory processing. Finally, fronto-parietal interaction was significantly reduced in the group with mild cognitive impairment, supporting the notion that mild cognitive impairment could represent an early stage in Alzheimer’s disease, which has been described as a ‘disconnection syndrome’.

Impact of serving method on the consumption of nutritional supplement drinks: randomised trial in older adults with cognitive impairment

Aim: To analyse the influence of serving method on compliance and consumption of nutritional supplement drinks in older adults with cognitive impairment. Background: Oral nutritional supplement drinks have positive benefits on increasing nutritional status within undernourished elderly people leading to weight gain. However, consumption of these drinks is low and therefore limits their effectiveness. Design: This study was a non blind randomised control trial where participants either consumed nutritional supplement drinks in a glass/beaker or consumed them through a straw inserted directly into the container. Method: Participants with longstanding cognitive impairment were recruited from nursing homes (n=31) and hospitals (n=14). Participants were randomised to serving method. Nursing and care staff were instructed to give the supplement drinks three times per day on alternate days over a week by the allocated serving method. The researcher weighed the amount of supplement drink remaining after consumption. Data were collected over 12 months in 2011-2012. Results: 45 people participated in this study mean age 86.7 (SD 7.5 ) years. After randomisation there was no significant difference between the baseline characteristics of the two groups. Participants randomised to consume nutritional drinks from a glass / beaker drank significantly more than those who consumed them via a straw inserted directly into the container. However, supplements allocated to be given in a glass/beaker were more frequently omitted. Conclusion: Nutritional supplement drinks should be given to people with dementia who are able to feed themselves in a glass or a beaker if staffing resources allow (NIHR CSP ref 31101).

Enhancing prospective memory in mild cognitive impairment: the role of enactment

Prospective memory (PM) is a fundamental requirement for independent living which might be prematurely compromised in the neurodegenerative process, namely in mild cognitive impairment (MCI), a typical prodromal Alzheimer's disease (AD) phase. Most encoding manipulations that typically enhance learning in healthy adults are of minimal benefit to AD patients. However, there is some indication that these can display a recall advantage when encoding is accompanied by the physical enactment of the material. The aim of this study was to explore the potential benefits of enactment at encoding and cue-action relatedness on memory for intentions in MCI patients and healthy controls using a behavioral PM experimental paradigm. Method: We report findings examining the influence of enactment at encoding for PM performance in MCI patients and education-matched controls using a laboratory-based PM task with a factorial independent design. Results: PM performance was consistently superior when physical enactment was used at encoding and when target-action pairs were strongly associated. Importantly, these beneficial effects were cumulative and observable across both a healthy and a cognitively impaired lifespan as well as evident in the perceived subjective difficulty in performing the task. Conclusions: The identified beneficial effects of enacted encoding and semantic relatedness have unveiled the potential contribution of this encoding technique to optimize attentional demands through an adaptive allocation of resources strategies. We discuss our findings with respect to their potential impact on developing strategies to improve PM in AD sufferers.

A Genetic Algorithm for the selection of structural MRI features for classification of Mild Cognitive Impairment and Alzheimer's Disease

This work investigates the problem of feature selection in neuroimaging features from structural MRI brain images for the classification of subjects as healthy controls, suffering from Mild Cognitive Impairment or Alzheimer’s Disease. A Genetic Algorithm wrapper method for feature selection is adopted in conjunction with a Support Vector Machine classifier. In very large feature sets, feature selection is found to be redundant as the accuracy is often worsened when compared to an Support Vector Machine with no feature selection. However, when just the hippocampal subfields are used, feature selection shows a significant improvement of the classification accuracy. Three-class Support Vector Machines and two-class Support Vector Machines combined with weighted voting are also compared with the former and found more useful. The highest accuracy achieved at classifying the test data was 65.5% using a genetic algorithm for feature selection with a three-class Support Vector Machine classifier.

Peripheral Oxidative Stress Biomarkers in Mild Cognitive Impairment and Alzheimer`s Disease

Oxidative stress has been associated with normal aging and Alzheimer`s disease (AD). However, little is known about oxidative stress in mild cognitive impairment (MCI) patients who present a high risk for developing AD. The aim of this study was to investigate plasma production of the lipid peroxidation marker, malonaldehyde (MDA) and to determine, in erythrocytes, the enzymatic antioxidant activity of catalase, glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST) in 33 individuals with MCI, 29 with mild probable AD and 26 healthy aged subjects. GR/GPx activity ratio was calculated to better assess antioxidant defenses. The relationship between oxidative stress and cognitive performance was also evaluated by the Mini Mental State Examination (MMSE). AD patients showed higher MDA levels than both MCI and healthy elderly subjects. MCI subjects also exhibited higher MDA levels compared to controls. Catalase and GPx activity were similar in MCI and healthy individuals but higher in AD. GR activity was lower in MCI and AD patients than in healthy aged subjects. Additionally, GR/GPx ratio was higher in healthy aged subjects, intermediate in MCI and lower in AD patients. No differences in GST activity were detected among the groups. MMSE was negatively associated with MDA levels (r = -0.31, p = 0.028) and positively correlated with GR/GPx ratio in AD patients (r = 0.68, p < 0.001). MDA levels were also negatively correlated to GR/GPx ratio (r = -0.31, p = 0.029) in the AD group. These results suggest that high lipid peroxidation and decreased antioxidant defenses may be present early in cognitive disorders.

Graph analysis of verbal fluency test discriminate between patients with Alzheimer’s disease, Mild Cognitive Impairment and normal elderly controls

Verbal fluency is the ability to produce a satisfying sequence of spoken words during a given time interval. The core of verbal fluency lies in the capacity to manage the executive aspects of language. The standard scores of the semantic verbal fluency test are broadly used in the neuropsychological assessment of the elderly, and different analytical methods are likely to extract even more information from the data generated in this test. Graph theory, a mathematical approach to analyze relations between items, represents a promising tool to understand a variety of neuropsychological states. This study reports a graph analysis of data generated by the semantic verbal fluency test by cognitively healthy elderly (NC), patients with Mild Cognitive Impairment – subtypes amnestic(aMCI) and amnestic multiple domain (a+mdMCI) - and patients with Alzheimer’s disease (AD). Sequences of words were represented as a speech graph in which every word corresponded to a node and temporal links between words were represented by directed edges. To characterize the structure of the data we calculated 13 speech graph attributes (SGAs). The individuals were compared when divided in three (NC – MCI – AD) and four (NC – aMCI – a+mdMCI – AD) groups. When the three groups were compared, significant differences were found in the standard measure of correct words produced, and three SGA: diameter, average shortest path, and network density. SGA sorted the elderly groups with good specificity and sensitivity. When the four groups were compared, the groups differed significantly in network density, except between the two MCI subtypes and NC and aMCI. The diameter of the network and the average shortest path were significantly different between the NC and AD, and between aMCI and AD. SGA sorted the elderly in their groups with good specificity and sensitivity, performing better than the standard score of the task. These findings provide support for a new methodological frame to assess the strength of semantic memory through the verbal fluency task, with potential to amplify the predictive power of this test. Graph analysis is likely to become clinically relevant in neurology and psychiatry, and may be particularly useful for the differential diagnosis of the elderly.

Prevalence and Correlates of Cognitive Impairment among the Elderly in a General Hospital

Aims: To estimate the prevalence and correlates of cognitive impairment (CI) among the elderly in a general hospital. Methods: A cross-sectional study, including 200 Brazilian inpatients aged 60 years or over, using the Mini Mental State Examination to evaluate CI (dependent variable), and the Geriatric Depression Scale and the Katz and Lawton Index to evaluate basic (BADL) and instrumental activities of daily living (IADL). Results: 56% were women, 29% were dependent for BADL and 77.5% for IADL. The prevalence of CI was 29% and, in the logistic regression, it remained associated with higher age (1 74 years old), number of previous hospitalizations (1 3) and dependency for BADL (being dependent raised the odds of being cognitively impaired). Conclusions: It is essential to train the hospital staff to properly assist these patients, and to orient and support their caregivers. Copyright (C) 2009 S. Karger AG, Basel