Sleep oscillations related to memory consolidation during aromatases inhibitors for breast cancer.

Aromatase inhibitors (AIs) are associated with sleep difficulties in breast cancer (BC) patients. Sleep is known to favor memory consolidation through the occurrence of specific oscillations, i.e., slow waves (SW) and sleep spindles, allowing a dialogue between prefrontal cortex and the hippocampus. Interestingly, neuroimaging studies in BC patients have consistently shown structural and functional modifications in these two brain regions. With the aim to evaluate sleep oscillations related to memory consolidation during AIs, we collected polysomnography data in BC patients treated (AI+, n = 17) or not (AI-, n = 17) with AIs compared to healthy controls (HC, n = 21). None of the patients had received chemotherapy and radiotherapy was finished since at least 6 months, that limit the confounding effects of other treatments than AIs. Fast and slow spindles were detected during sleep stage 2 at centro-parietal and frontal electrodes respectively. SW were detected at frontal electrodes during stage 3. Here, we show lower frontal SW densities in AI + patients compared to HC. These results concord with previous reports about frontal cortical alterations in cancer following AIs administration. Moreover, AI + patients tended to have lower spindle density at C4 electrode. Regression analyses showed that, in both patient groups, spindle density at C4 electrode explained a large variance of memory performances. Slow spindle characteristics did not differ between groups and sleep oscillations characteristics of AI- patients did not differ significantly from those of both AI + patients and HC. Overall, our results add to the compelling evidence of the systemic effects of AIs previously reported in animals, with deleterious effects on cortical activity during sleep and associated memory consolidation in the current study. There is thus a need to further investigate sleep modifications during AIs administration. Longitudinal studies are needed to confirm these findings and investigation in other cancers on this topic should be conducted.

Sleep macro- and microstructure in breast cancer survivors.

Complaints of sleep disturbance are prevalent among breast cancer (BC) patients and are predictors of quality of life. Still, electrophysiological measures of sleep are missing in patients, which prevents from understanding the pathophysiological consequences of cancer and its past treatments. Using polysomnography, sleep can be investigated in terms of macro- (e.g. awakenings, sleep stages) and micro- (i.e. cortical activity) structure. We aimed to characterize sleep complaints, and macro- and microstructure in 33 BC survivors untreated by chemotherapy and that had finished radiotherapy since at least 6 months (i.e. out of the acute effects of radiotherapy) compared to 21 healthy controls (HC). Compared to HC, BC patients had a larger number of awakenings (p = 0.008); and lower Delta power (p < 0.001), related to sleep deepening and homeostasis; greater both Alpha (p = 0.002) and Beta power (p < 0.001), related to arousal during deep sleep; and lower Theta power (p = 0.004), related to emotion regulation during dream sleep. Here we show that patients have increased cortical activity related to arousal and lower activity related to sleep homeostasis compared to controls. These results give additional insights in sleep pathophysiology of BC survivors and suggest sleep homeostasis disruption in non-advanced stages of BC.

Energy allocation during the maturation of adults in a long-lived insect: implications for dispersal and reproduction.

Energy allocation strategies have been widely documented in insects and were formalized in the context of the reproduction process by the terms 'capital breeder' and 'income breeder'. We propose here the extension of this framework to dispersal ability, with the concepts of 'capital disperser' and 'income disperser', and explore the trade-off in resource allocation between dispersal and reproduction. We hypothesized that flight capacity was sex-dependent, due to a trade-off in energy allocation between dispersal and egg production in females. We used Monochamus galloprovincialis as model organism, a long-lived beetle which is the European vector of the pine wood nematode. We estimated the flight capacity with a flight mill and used the number of mature eggs as a proxy for the investment in reproduction. We used the ratio between dry weights of the thorax and the abdomen to investigate the trade-off. The probability of flying increased with the adult weight at emergence, but was not dependent on insect age or sex. Flight distance increased with age in individuals but did not differ between sexes. It was also positively associated with energy allocation to thorax reserves, which increased with age. In females, the abdomen weight and the number of eggs also increase with age with no negative effect on flight capacity, indicating a lack of trade-off. This long-lived beetle has a complex strategy of energy allocation, being a 'capital disperser' in terms of flight ability, an 'income disperser' in terms of flight performance and an 'income breeder' in terms of egg production.

French version of the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) version 3.

PURPOSE: Impairment of cognitive function, a common complaint in patients receiving chemotherapy, is usually measured through neuropsychological tests. Patient self-evaluation of cognitive difficulties is an important complement to those tests. The Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) is a self-report questionnaire with potential to be used in standard clinical practice as a tool for evaluating patient's cognitive function before, during, and after chemotherapy. The purpose of our study was to conduct linguistic validation of the French version of the FACT-Cog. METHODS: Both qualitative and quantitative methods were used in this study. After undergoing a rigorous translation methodology, the French FACT-Cog version was pretested in France with 35 cancer patients undergoing chemotherapy treatment. Interviews were conducted with all patients to ascertain their understanding of each item. The validation of the final version was conducted among 63 cancer patients, and sociodemographic information was collected as well as brief measure of cognitive function and depression score. RESULTS: Patient comments obtained through the cognitive debriefing interviews indicated that patients understand the French FACT-Cog items as they are intended and that the measure is culturally appropriate. Internal consistency reliability of the subscales, evaluated using Cronbach's coefficient alpha, was high for all four subscales: Perceived Cognitive Impairments = 0.93, Impact On QOL = 0.85, Comments From Others = 0.70, and Perceived Cognitive Abilities = 0.89. All item-total correlations for each subscale were greater than 0.20, and most were greater than 0.50. CONCLUSIONS: Results from this study effectively demonstrate that the French FACT-Cog is a reliable instrument for the self-reporting of cognitive abilities in patients undergoing chemotherapy.

[Alzheimer's disease and human memory]. / La maladie d'Alzheimer et la mémoire humaine.

Memory disorders observed in Alzheimer's disease gave rise, from the eighties, to a detailed analysis into the framework of cognitive neuropsychology which aimed at describing the deficits of very specific processes. Beyond their clinical interest, these studies contributed to the modelisation of human memory thanks to the characterization of different memory systems and their relationships. The first part of this paper gives an overview of the memory deficits in Alzheimer's disease and insists on particular cognitive phenomena. Hence, several examples are developed in the domains of semantic memory (such as hyperpriming and hypopriming effects) and autobiographical memory. Recent results highlight the existence of severe autobiographical amnesia observed in all neurodegenerative diseases, though with contrasting profiles: Ribot's gradient in Alzheimer's disease (showing that remote memories are better preserved than recent ones), reverse gradient in semantic dementia and no clear gradient in the frontal variant of frontotemporal dementia. The second part of this article presents advances in cognitive neuroscience searching to disclose the cerebral substrates of these cognitive deficits in Alzheimer's disease. The studies using functional imaging techniques are the most informative regarding this problematic. While showing the dysfunctions of an extended network, they emphasize the selectivity of cerebral damages that are at the root of very specific cognitive dysfunctions, coming close in that way to the conceptions of cognitive neuropsychology. These neuroimaging studies unravel the existence of compensatory mechanisms, which until recently were clearly missing in the literature on neurodegenerative diseases. These different researches lead to a wide conception of human memory, not just limited to simple instrumental processes (encoding, storage, retrieval), but necessarily covering models of identity and continuity of the subject, which interact in a dynamic way with eminently changing memory representations.

[Schizophrenia and semantic priming effects]. / Schizophrénie et effets d'amorçage sémantique.

INTRODUCTION: This article is a review of studies using the semantic priming paradigm to assess the functioning of semantic memory in schizophrenic patients. CONTEXT: Semantic priming describes the phenomenon of increasing the speed with which a string of letters (the target) is recognized as a word (lexical decision task) by presenting to the subject a semantically related word (the prime) prior to the appearance of the target word. This semantic priming is linked to both automatic and controlled processes depending on experimental conditions (stimulus onset asynchrony (SOA), percentage of related words and explicit memory instructions). Automatic process observed with short SOA, low related word percentage and instructions asking only to process the target, could be linked to the "automatic spreading activation" through the semantic network. Controlled processes involve "semantic matching" (the number of related and unrelated pairs influences the subjects decision) and "expectancy" (the prime leads the subject to generate an expectancy set of potential target to the prime). These processes can be observed whatever the SOA for the former and with long SOA for the later, but both with only high related word percentage and explicit memory instructions. LITERATURE FINDINGS: Studies evaluating semantic priming effects in schizophrenia show conflicting results: schizophrenic patients can present hyperpriming (semantic priming effect is larger in patients than in controls), hypopriming (semantic priming effect is lower in patients than in controls) or equal semantic priming effects compared to control subjects. DISCUSSION: These results could be associated to a global impairment of controlled processes in schizophrenia, essentially to a dysfunction of semantic matching process. On the other hand, efficiency of semantic automatic spreading activation process is controversial. These discrepancies could be linked to the different experimental conditions used (duration of SOA, proportion of related pairs and instructions), which influence on the degree of involvement of controlled processes and therefore prevent to really assess its functioning. In addition, manipulations of the relation between prime and target (semantic distance, type of semantic relation and strength of semantic relation) seem to influence reaction times. However, the relation between prime and target (mediated priming) frequently used could not be the most relevant relation to understand the way of spreading of activation in semantic network in patients with schizophrenia. Finally, patients with formal thought disorders present particularly high priming effects relative to controls. CONCLUSION: These abnormal semantic priming effects could reflect a dysfunction of automatic spreading activation process and consequently an exaggerated diffusion of activation in the semantic network. In the future, the inclusion of different groups schizophrenic subjects could allow us to determine whether semantic memory disorders are pathognomonic or specific of a particular group of patients with schizophrenia.

The nature of semantic memory deficits in Alzheimer's disease: new insights from hyperpriming effects.

While semantic memory deficits are a common landmark of Alzheimer's disease, the nature of these impairments remains to be clarified. Implicit tasks which assess semantic priming effects are often used to understand semantic deficits in Alzheimer's disease, but they have led to unclear conclusions because of methodological problems such as intervention of attentional mechanisms. To explore the effects of semantic priming in Alzheimer's disease and their relationship with semantic memory deficits, we used two tasks, one implicit and the other explicit. The implicit task was a lexical decision task to assess semantic priming, and in which pairs of words had coordinate (tiger-lion) or attribute relationships (zebra-stripe). The explicit task was a semantic knowledge task composed of namings and questions involving superordinate categories and attribute knowledge of concepts. The two tasks systematically assessed the integrity of the same concepts. This protocol was given to 53 Alzheimer's disease patients with mild to moderate dementia and to 20 controls. The Alzheimer's disease group as a whole obtained significantly greater priming effects (hyperpriming) than controls in the coordinate condition, and equivalent priming in the attribute condition. In the coordinate condition, a subgroup of 26 patients, with attribute knowledge deficits, had larger priming effects than both a subgroup without semantic deficits and the control group. These results show that in Alzheimer's disease the semantic priming effects vary according to the degree of attribute loss, and the presence of hyperpriming would reflect semantic memory deficits. This study unravels the fine-grained structure of semantic memory disturbances in Alzheimer's disease with mild to moderate dementia, affecting initially the attributes of concepts within a hierarchical network in which superordinate concepts remain preserved.

[Contribution of positron emission tomography to functional neuroimaging in Alzheimer's disease]. / Contribution de la tomographie par émission de positons à la neuro-anatomie fonctionnelle de la maladie d'Alzheimer.

When combined with cognitive investigations, functional neuroimaging methods such as positron emission tomography allow to depict the neural substrates that underlie the neuropsychological alterations in Alzheimer's disease. Capitalising on the variance in both cognitive performances and resting cerebral metabolic rate of glucose (CMRGlc) in Alzheimer's disease, it is possible to correlate these two quantitative variables on a pixel-by-pixel basis and to generate maps showing the significant correlations in stereotaxic space. Some examples using this approach in the domain of memory disorders are presented in this brief review. We notably show that the localisation of the significant correlations differs from one memory system to another, as evaluated by clinical memory tasks. This approach also unravels the compensatory mechanisms that take place with evolution of the disease. Over and above its interest in clinical neuropsychology, this method constitutes a new source of inferences complementary to the classic activation paradigm in normal subjects, as the latter identifies the cerebral structures that are involved with, but not necessarily indispensable for, the normal execution of the task. This approach highlights the interest of combining functional neuroimaging and neuropsychology to better understand the neural substrates of cognitive deficits in both patients with memory disorders and elderly normal subjects.

Entorhinal cortex disruption causes memory deficit in early Alzheimer's disease as shown by PET.

Voxel-based mapping of the correlations between cognitive scores and resting-state brain glucose utilization measured by PET has recently emerged as a novel way to reveal in living patients with Alzheimer's disease (AD) the neural systems whose disruption underlies particular neuropsychological, especially mnemonic, deficits. We have now applied this approach using a novel cognitive paradigm designed to selectively assess verbal episodic memory, and show that in early AD disruption of the left entorhinal cortex underlies this memory deficit, consistent with post mortem data showing that this brain area is affected earliest and most severely by tau pathology in AD.