L'interaction complexe des différentes fonctions cognitives ne permet pas de trouver la source précise des manifestations démentielles dans l'organe du cerveau. Dans une perspective organiciste, ne répondant pas aux critères d'inclusion, ils sont la part énigmatique d'un tableau démentiel dans lequel ils ne trouvent pas à strictement s'insérer. On les dit donc «associés». Nous tentons dans ce travail de souligner la complexité d’avoir à penser la cause d’un comportement de manière univoque et nous avançons l’idée selon laquelle la démence sévère se motive d’un rapport nouveau à la «cause» comme telle. Nous posons la démence comme produisant l’être dément : effet d’un délitement du langage dont le sujet n’est ni comptable, ni l’observateur passif. Le sujet dément se trouverait donc pris dans une situation qui engage son être en tant qu’il est non-causé par la métamorphose qui le caractérise pourtant. Une fois posée la démence sévère comme la manifestation d’un manque réel au champ du manque dans l’Autre, il nous sera possible de saisir dans une même logique l’effondrement de la dimension réflexive de l’identité et celle du désir. Nous orientant de l’angoisse que suscite la destruction du code de l’Autre et de l’aliénation imaginaire, nous postulerons que les manifestations psycho-comportementales démentielles ont valeurs de tentatives d’injection du manque au champ de l’Autre. Ces tentatives, par définitions subjectives et singulières, devront donc être entendues avant que d’être comprises, puis accompagnées. De ce point de vue, la démence sévère ne se qualifierait pas de ses déficits, mais de ce qui du manque lui fait défaut. / The complex interaction of the various cognitive functions does not allow finding the precise source of insane events in the brain organ. In organismic perspective which does not cater for the inclusion criteria, they are enigmatic part from an insane board into which they fail to fit strictly. That’s why they are called "associates".We attempt in this work to emphasize the complexity of having to think about the cause of a behavior in an unambiguous way, and we advance the idea that severe dementia motivates a new report to the "cause" as such. We argue dementia as producing be denied: effect of a disintegration of the language whose the subject is neither accountant, nor passive observer. The insane subject would therefore be caught in a situation that involves his (her) being as it is not caused by the transformation which characterizes him (her) nevertheless.Once installed severe dementia as the manifestation of a real lack face to the Lack in the Other, we will be able to apprehend, in the same sense, the collapse of reflective dimension of identity and that of desire. By directing us the distress generated by the destruction of the code of the Other and of the imaginary alienation, we will postulate that insane psycho-behavioral symptoms would in fact be injection attempts of lack in the field of the Other. These attempts, by subjective and singular definitions, will have to be heard before being understood, then accompanied. From this point of view, severe insanity would not be qualified by its deficits, but by what of lack default.

Yes / Quality of residential care for people with severe dementia is in urgent need of improvement. One reason for this may be the assumption that people with severe dementia are unaware of what is happening to them. However, there is converging evidence to suggest that global assumptions of unawareness are inappropriate. This trial platform study aims to assist care staff in perceiving and responding to subtle signs of awareness and thus enhance their practice. Methods/Design: In Stage One, a measure of awareness in severe dementia will be developed. Two focus groups and an expert panel will contribute to item and scale development. In Stage Two observational data will be used to further develop the measure. Working in four care homes, we will recruit 40 individuals with severe dementia who have no, or very limited, verbal communication. Data on inter-rater reliability and frequency of all items and exploratory factor analysis will be used to identify items to be retained. Test-retest and inter-rater reliability for the new measure will be calculated. Correlations with scores for well-being and behaviour and with proxy ratings of quality of life will provide an indication of concurrent validity. In Stage Three the new measure will be used in a single blind cluster randomised trial. Eight care homes will participate, with 10 residents recruited in each giving a total sample of 80 people with severe dementia. Homes will be randomised to intervention or usual care conditions. In the intervention condition, staff will receive training in using the new measure and will undertake observations of designated residents. For residents with dementia, outcomes will be assessed in terms of change from baseline in scores for behaviour, well-being and quality of life. For care staff, outcomes will be assessed in terms of change from baseline in scores for attitudes, care practice, and well-being. Discussion: The results will inform the design of a larger-scale trial intended to provide definitive evidence about the benefits of increasing the sensitivity of care staff to signs of awareness in residents with severe dementia. Trial Registration: ISRCTN59507580 http://www.controlled-trials.com.

Decreased amyloid-ß42 (Aß42), increased total tau (t-tau) and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) reflect histopathological core changes in the most common dementia disorder, Alzheimer’s disease (AD). They discriminate AD from healthy controls and predict conversion to AD with a relatively high accuracy. Memantine, an uncompetitive NMDA-receptor antagonist, is indicated for symptomatic treatment of AD. The first aim of this thesis was to investigate effects of memantine on CSF concentrations of Aβ42, tau and p-tau. Secondly, the aim was to explore the relation between these CSF biomarkers and retention of the amyloid biomarker Pittsburgh compound B using positron emission tomography (PIB PET), regional glucose metabolism measured with 18Fluoro-2-deoxy-d-glucose (FDG) PET and neuropsychological test performance. The third aim was to investigate their possible utility as predictors of future rate of AD dementia deterioration. All patients in the studies were recruited from the Memory Clinic, Uppsala University Hospital. In study I CSF p-tau concentrations in 11 AD patients were reduced after twelve months treatment with memantine, indicating that this compound may affect a key pathological process in AD. Results from study II showed that the concentrations of CSF Aß42 are lower in PIB+ patients than in PIB- patients, and that the PIB retention was stable during 12 months. In study III 10 patients with the diagnoses AD (6 PIB+/4 PIB-) and 8 subjects (1 PIB+/7 PIB-) with frontotemporal dementia were included. PIB+ patients had lower psychomotor speed measured by performance on the Trail Making Test A and impaired visual episodic memory compared to the PIB- patients. The initial clinical diagnoses were changed in 33% of the patients (6/18) during follow-up. Study IV is the first-ever report of an association between high CSF tau and dying in severe dementia. These 196 AD patients were followed up to nine years after baseline lumbar puncture. Moreover, CSF t-tau concentrations above median was associated with an increased risk of rapid cognitive decline (OR 3.31 (95% CI 1.53-7.16), independently of baseline functional stage. Thus, a clear association between high levels of CSF t-tau and p-tau and a more aggressive course of the disease was shown.