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The Alzheimer's disease (AD) is a disease that's quite common nowadays, and it's getting more and more frequent as the population ages. There' s no cure for it at this moment but we do have some treatments to diminish the symptoms which are most effective if used in the early stages of the disease. The diagnosis is essentially clinical according to the criteria determined by the DSM IV. An imaging scan and a blood sample can contribute to its establishment and especially exclude a reversible cause of dementia. A large number of findings have been observed on this topic regarding the utility of the PET scan, lumbar puncture... The symptomatology of dementia starts gradually and worsens as it progresses. There's also a phase of pre-dementia called MCI (Mild Cognitive Impairment) which causes mild cognitive impairment but it doesn't interfere with the autonomy patients.Patients with MCI can either stay steady, improve or unfortunately lead to dementia in particular AD. Neuropsychological tests are useful to determine which cognitive functions are altered and to what degree. It would be interesting to predict which person is more at risk.Objectives : Inthis thesis, we shall study the neuropsychological monitoring of patients with MCI. The objective of this study is to discover if one or more tests in particular can predict the conversion towards dementia and if the monitoring of a few months interval is useful.Methods :We base our studies on a sample of 118 patients aged 50 to 79 who consulted at "Clinique de la mémoire des Cliniques Saint Luc" between 1994 and 2004. Every patient is have MCI and had 2 or 3 times a series of 15 neuropsychological tests at an average of 33 months (ET=34) interval between the first and second test and 42 months (ET=25) between the second and third test. We have two groups of patients: those who became demented (D) and those who didn't become demented (ND). We then compared, using the Wilcoxon test, the range of the results to each test in Tl with the ones to each test in T2 and T3, to see if there was a significant evolution between the first, second and third test for the future demented patients and future non demented patients. We also calculated the percentage of patients properly classified in the first, second and third test, to see if the percentage increased in time. Results : the results obtained revealed that the future ND's performances do not usually waver. lndeed, there's no significant difference between Tl , T2 and T3 by contrast the upcoming ND's meager results especially regarding the exams of the mnesic functions, the verbal fluency and the denomination. We can also observe that the number of patients who are correctly classified in T2 isn't greatly superior to that obtained in Tl, this gain isn't significant. However, if we repeat those tests on the patients with low performances who acquired results between -2 and 0 in Tl, the gain becomes more important and non-negligible .Conclusion :ln the various studies already published (cf. IVANOIU, 2005), it is said that the first cognitive functions tbat are affected are the visual and verbal memory which is also what cornes out of our study. According to T. Mura and his partners (cf. MURA, 2013), the memory and the verbal fluencies are the most sensitive tests and they are also those to be repeated in the follow up of the low performers . The semantic verbal fluency has a higher sensitivity to cognitive changes for subjects with high level of cognition.In conclusion, we can say that the neuropsychological tests have an important place in the setting of memory impairment. Nonetheless they do not suffice to establish alone a proper diagnostic of dementia . Certain tests are more useful than others, particularly the tests evaluating the mnesic functions, the denomination and eventually the fluencies. The benefit of a repetition of the tests is however a more controversial subject. lndeed, this repetition isn't necessary for all patients. It can however reveal itself useful for the subjects with low performances who have a Jow score but not pathologie. But all these tests aren't meant to be repeated : only the visual and verbal memories and the denomination are to be repeated with, eventually, the semantic verbal fluency for the high levels of performance . La maladie d'Alzheimer est une maladie fréquente et elle est d'autant plus un sujet d'actualité tant notre population compte de plus en plus de personnes âgées. Nous ne possédons pas à l'heure actuelle de traitement curatif mais uniquement des traitements symptomatiques qui sont plus efficaces lorsqu'ils sont administrés en début de maladie. Le diagnostic est essentiellement clinique suivant des critères bien déterminés par le DSM IV. Une imagerie et une prise de sang peuvent contribuer à son établissement et permettent d'exclure une cause réversible de démence. De nombreuses découvertes sont observées récemment sur ce sujet concernant l'utilité du PET scan, la ponction lombaire,... La symptomatologie de démence débute progressivement. On reconnaît d'ailleurs l'existence d'un stade de pré-démence appelé MCI (Mild Cognitive Impairment), dans lequel on observe des troubles cognitifs légers qui n'interfèrent pas avec l'autonomie du patient. Les patients MCI peuvent soit rester stables, soit s'améliorer, soit progresser vers une démence, notamment vers la maladie d'Alzheimer. Les tests neuropsychologiques sont alors utiles pour déterminer quelles fonctions cognitives sont atteintes et à quel degré. Il serait intéressant de prédire quels patients sont plus à risque d'évoluer vers une démence. Objectif : Dans ce mémoire de recherche clinique, nous étudierons le suivi neuropsychologique de patients MCI. Le but de cette étude est donc de découvrir si un (ou plusieurs) test(s) en particulier peut (peuvent) prédire une conversion vers la démence et si le suivi à quelques mois d'intervalle est utile.Méthode :Nous avons basé notre étude sur un échantillon de 118 patients âgés de 50 à 79 ans ayant consulté à la Clinique de la mémoire des Cliniques Saint Luc entre 1994 et 2004.Chaque patient est MCI et a passé deux ou trois fois une série de 15 tests neuropsychologiques à, en moyenne, 33 mois d'intervalle (ET=31) entre le premier et le deuxième test et 42 mois (ET=25) entre le deuxième et le troisième. Nous avons deux groupes de patients : ceux qui sont devenus déments (D) et ceux qui ne sont pas devenus déments (ND). Nous avons alors comparé grâce au test de Wilcoxon les rangs des résultats à chaque test en Tl avec ceux des résultats à chaque test en T2 et en T3, afin de voir s'il y avait une évolution significative entre le premier, le deuxième et le troisième test pour les futurs déments et les futurs non déments. Nous avons également calculé le pourcentage de patients correctement classés au premier, deuxième et troisième test, pour savoir si ce pourcentage augmentait avec le temps. Résultats : Les résultats obtenus nous montrent que les futurs non déments ont tendance à rester stables dans leurs performances. En effet, nous ne retrouvons pas de différence significative entre Tl, T2 et T3 contrairement aux futurs non déments qui péjorent leurs résultats surtout en ce qui concerne les examens de la fonction mnésique, les fluences et la dénomination. Nous observons également que le nombre de patients correctement classés en T2 n'est pas grandement supérieur à celui obtenu en Tl, ce gain n'est pas significatif.Par contre, si nous répétons ces tests chez les patients limites, ayant eu un score entre - 2 et 0 en Tl, le gain devient plus important et non négligeable. Conclusion :Dans les différentes études déjà parues (cf. IvANOIU, 2005), on décrit la mémoire verbale et visuelle comme les premières fonctions cognitives touchées, ce qui ressort également dans notre étude. Selon T. Mura et ses associés (cf. MURA, 2013), la mémoire et les fluences sont les tests les plus sensibles et ce sont ceux-là qu'il faut répéter dans le suivi longitudinal des patients à faible performance. La fluence sémantique est quant à elle plus sensible pour les patients à haute performance.En conclusion, nous pouvons dire que les tests neuropsychologiques ont une place importante dans la mise au point des troubles de la mémoire. Ils ne peuvent par contre pas suffire au diagnostic d'une démence. Certains tests sont plus utiles que d'autres, en particulier les tests évaluant les fonctions mnésiques et la dénomination, éventuellement les fluences. L'intérêt d'une répétition de ces tests est par contre davantage sujet à discussion. En effet, cette répétition n'est pas nécessaire pour tous les patients. Elle peut néanmoins se révéler utile pour les patients « limites » qui ont un score faible mais non pathologique. Mais tous les tests ne sont pas à répéter : seules les mémoires visuelle et verbale et la dénomination sont à refaire avec éventuellement la fluence sémantique pour les hauts niveaux de performance.

Mild Cognitive Impairment --- Mild Cognitive Impairment --- Mild Cognitive Impairment --- Alzheimer Disease --- Alzheimer Disease

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Cognition Disorders --- Mild Cognitive Impairment --- Therapeutics --- Diagnosis

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Improving psychological well-being and cognitive health is now listed as the priority on the healthy aging agenda. Depression and cognitive impairment are great challenges for the elderly population. There have been numerous studies on depression and cognitive impairment and dementia. However, the neural correlates of depression and cognitive impairment have not yet been elucidated. With the development of neuroscience and relevant technologies, studies on anatomical and functional neural networks, neurobiological mechanisms of mood and cognition in old age will provide more insight into the potential diagnosis, prevention and intervention in depression and cognitive impairment. For example, longitudinal neuroimaging studies depicting the trajectories of patterns of structural and functional brain networks of mild cognitive impairment may provide potential imaging markers for the onset of dementia. Population-based studies have addressed the potential interaction between mood and cognitive impairment in old age. However, there are few studies to explore the potential neural mechanism of the relationship between depression and cognitive impairment in old age. In all of this process the contribution of multiple biological events cannot be neglected, particularly the underlying influence of chronic diseases and concomitant polymedication as well as the geriatric conditions, like frailty, frequently present in this elderly population, which also compromise the cognitive function and mood determining depression and conducing to worse outcomes with more morbidity and mortality.

mood disorder --- mild cognitive impairment --- Alzheimer

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This e-book focuses primarily on the role of the fornix as a functional, prognostic, and diagnostic marker of Alzheimer’s disease (AD), and the application of such a marker in clinical practice. Researchers have long been focused on the cortical pathology of AD, since the most important pathologic features are the senile plaques found in the cortex, and the neurofibrillary tangles and neuronal loss that start from the entorhinal cortex and the hippocampus. In addition to gray matter structures, histopathological studies indicate that the white matter is also altered in AD. The fornix is a white matter bundle that constitutes a core element of the limbic circuits, and is one of the most important anatomical structures related to memory. The fornices originate from the bilateral hippocampi, merge at the midline of the brain, again divide into the left and right side, and then into the precommissural and the postcommissural fibers, and terminate at the septal nuclei, nucleus accumbens (precommissural fornix), and hypothalamus (postcommissural fornix). These functional and anatomical features of the fornix have naturally captured researchers’ attention as possible diagnostic and prognostic markers of AD. Growing evidence indicates that the alterations seen in the fornix are potentially a good marker with which to predict future conversion from mild cognitive impairment to AD, and even from a cognitively normal state to AD. The degree of alteration is correlated with the degree of memory impairment, indicating the potential for the use of the fornix as a functional marker. Moreover, there have been attempts to stimulate the fornix to recover the cognitive function lost with AD. Our goal is to provide information about the status of current research and to facilitate further scientific and clinical advancement in this topic.

Fornix --- Limbic --- Memory --- normal aging --- Cognition --- Mild Cognitive Impairment --- Alzheimer's disease --- Diffusion Tensor Imaging

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The number of older subjects is rapidly increasingly worldwide. As a consequence, the nature of clinical conditions is also changing. Traditional medicine and models of care have been based on the evaluation and treatment of single and usually acute conditions occurring in relatively young individuals. Today, the usual clinical manifestation of diseases is characterized by multiple and often chronic conditions affecting older people. In this scenario, frailty and dementia have been triggering special interest both in research and clinical settings due to their high prevalence, impact on the individual’s quality of life, and consequences for public health worldwide. These conditions aptly reflect the complexity of age-related pathological conditions, finding as causal factor a myriad of heterogeneous, interacting, and often still unclear pathophysiological processes. Indeed, their study is strongly affected by the difficulty to differentiate the effects of a normal aging process from eventual pathological deviations of the underlying systems. Their occurrence and trajectories over time are strongly affected by a wide array of factors and determinants that can be hardly attributed to the deficit/involvement of single biological systems and/or health domains. Moreover, environment and social factors also play a key role in the determination of phenotypes. The present Research Topic is aimed at widening our understanding of the frailty and dementia phenomena occurring with aging, in order to improve the clinical and public health approaches to these burdening conditions.

Dementia. --- Aging --- Psychological aspects. --- cognition --- caregiver --- Frailty --- dementia --- mild cognitive impairment --- aging --- cognitive frailty --- Alzheimer