Brain profile of hypometabolism in early Alzheimer's disease: relationships with cognitive deficits and atrophy

While accurate and early prediction of patients that will develop Alzheimer's disease (AD) in the near future is urgently needed, the amnestic Mild Cognitive Impairment (MCI) state is of particular interest since it most conveniently represents the pre-dementia stage of AD. Consistently, the profile of brain functional alteration constantly evidenced in resting-state SPECT and PET studies is similar to that observed in mild AD, mainly involving the posterior cingulate and temporo-parietal regions. While the former is a characteristic feature of MCI, since it is present in each patient at this stage, the latter seems specifically associated with the future conversion to AD. Moreover, right temporo-parietal hypometabolism has been found to be the best predictor of subsequent global cognitive decline, over and above neuropsychological and MRI volumetric measurements. This review also presents a discussion on the relationships between the brain profile of hypometabolism on the one hand, and cognitive impairment as well as cerebral structural alterations on the other. Thus, firstly, while functional impairment in the posterior cingulate region seems to be associated with deficits in retrieval of episodic memories in MCI, the relationship between right temporo-parietal hypometabolism and cognitive impairment is still obscure. However, several arguments point to its relation with visuo-spatial deficits, which are often associated with future conversion to AD. Secondly, the discordance between brain areas of major functional changes, and those of highest structural alterations, leads to some relevant questions about the relations between both pathological manifestations and their underlying mechanisms. More specifically, additional hypometabolism-inducing factors could occur in areas of highest hypometabolism compared to atrophy, i.e. mainly in posterior associative cortical regions, leading to genuine functional perturbation in early AD before the development of real atrophy and perhaps of disease as well. By contrast, the hippocampus is the main site of atrophy while its functional alteration is still debated, suggesting that compensation/protective mechanisms probably specifically occur in this structure to maintain a high level of metabolism relative to its structural alteration.     

Alzheimer's disease and human memory

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.     

Temporal characteristics of the augmentation of paradoxal sleep following learning in the rat

In a previous work, we have shown that an avoidance conditioning is followed by an increased number of Paradoxical Sleep (PS) phases during the first hour after learning. In Experiment 1, sleep is experimentally delayed after each conditioning session. When sleep is delayed for 180 min, learning is severely impaired and PS doesn't increase; but the 90-min sleep delay after the conditioning session is followed by the same PS increase as that when sleep is free immediately after learning. In Experiment 2, we show that a 90-min free sleep period, between learning and a 180-min sleep deprivation allowed a learning as good as that without any sleep deprivation. In our experimental conditions, PS increase after avoidance conditioning is brief and immediate when sleep is possible and if it begins less than 180 min after learning.     

Rôle du conditionnement dans l’effet placebo

Résumé  En psychopharmacologie, on constate régulièrement que les effets affectifs (plaisants/déplaisants) d’une substance pharmacologique s’associent, au niveau de l’organisme, avec les stimuli environnementaux présents au moment de la prise de la substance. Ce processus de conditionnement (apprentissage associatif) permet de comprendre les aspects particuliers de nombreux phénomènes comme la tolérance aux opiacés ou le syndrome de sevrage. II semble, de plus, jouer un r?le prépondérant dans l’effet placebo que l’on observe au cours du traitement de la douleur. Au cours de cette analyse, nous nous attacherons à expliciter les connaissances modernes en matière de conditionnement, à comprendre le r?le de celui-ci dans les effets des opiacés, et enfin à appréhender son impact dans l’effet placebo tel qu’observé au cours de l’analgésie. Summary  Conditioning is a useful tool to analyse associative learning processes in many different species. This is especially obvious in psychopharmacology, where it is regularly observed that the affective effect (aversive/appetitive) of a drug can enter into association with the surrounding environmental stimuli. Such a conditioning processes (associative learning) allows us to better understand various phenomena like opites-induced tolerance or withdrawal syndromes. Moreover, conditioning seems to play a crucial role in the placebo effect, at least, as it is observed during analgesia. The purpose of the present analysis is to have a closer insight into modern theories of associative learning and their impact on the effects of opiates. Ultimately, we will discuss the placebo effect during analgesia in the framework of conditioning processes.

     

云纹干涉法应用于金瓷界面抗断裂能力研究的初步探讨

目的探讨云纹干涉法在金瓷界面抗断裂能力研究中的应用。方法在5组金瓷厚度不同的试件表面制作光栅,加载后采集u场及。场云纹干涉条纹,推算各组金瓷界面断裂韧性Jc值并观测裂纹扩展方向。结果加载条件下,裂纹周围显示应力集中区,条纹随载荷增加逐渐变密。由云纹干涉图位移场算得各组试件金瓷界面断裂韧性各不相同,其裂纹扩展方向也有差异。结论云纹干涉法适用于金瓷界面断裂韧性的研究,也可用于观测并预测裂纹的扩展方向及趋势。     

Building and validation of a test evaluating verbal recognition memory: The Forty test (f40)

Introduction

Neuropsychologic evaluation is a primordial diagnostic tool. Numerous tests explore episodic memory but few tests exist to assess incidental verbal episodic memory or verbal recognition memory. This memory is however impaired early in certain neurodegenerative diseases such as Alzheimer's disease. Our objective was to create a test sensitive and specific to this cognitive dysfunction.

Method

Our test was performed by 33 healthy volunteers and 51 patients (19 with idiopathic Parkinson's disease, 16 with Alzheimer's disease at the prodromal stage and 16 with Alzheimer's disease).

Results and discussion

Independently of age, education level and global cognitive impairment, the young and old healthy volunteers and the patients with idiopathic Parkinson's disease displayed results significantly better than the group of Alzheimer's disease at the prodromal stage and Alzheimer's disease patients. Our test appears to be sensitive to dysfunction of verbal recognition memory. A score of 30/40 or less on the Forty test discriminates 91% of subjects with a cortical pattern of memory. This test could be recommended for clinical neuropsychological practice.     

Les mouvements oculaires comme moyen de contourner l’insight lors de l’évaluation des comportements de vérification dans le trouble obsessionnel compulsif (TOC)

Rotge et al. [2] demonstrated that asking patients with obsessive compulsive disorder to compare separately presented images was a good way to assess the intensity of their checking behavior. However, the patients with good insight could consciously refrain from checking (Jaafari et al. [1]). To get rid of this problem, the images were presented simultaneously while the patients’ eye movements were recorded. Whatever their insight patients made more gaze moves to compare the images than controls. The patients’ checking behavior was actually related to a reduced working memory span.     

Délires de reduplication mnésique : connaissance de soi et perplexité identitaire

Objective

An inconsistency in the sense of self does not necessarily follow from a deficit of autobiographical memory.

Patients and methods

We report two cases of memory reduplication with delusion, one concerning an event reduplication memory, the other one a spatial reduplication memory.

Results

The first patient, J.M., presents with a confusion of identity, which forces him to search for some evidence in his imaginary memory. The second patient, R.B., remembered having juxtaposed two separate geographical sites, became aware of his false conviction, and finally attempted to find explanations for this perceptual illusion.

Conclusion

Impairment of self-knowledge can be caused not only by a memory deficit, but also by a difficulty of subject to incorporate an imaginary history in his memory (narrative identity), particularly when reality is not coherent with the imaginary history.