Traitement symptomatique de la maladie d’Alzheimer et perspectives thérapeutiques

La dégénérescence progressive des neurones au cours de la maladie d’Alzheimer entraîne des anomalies des systèmes de neurotransmetteurs qui sont à la base des traitements substitutifs. Quatre inhibiteurs de l’acetyl-cholinesterase ont été mis sur le marché dans l’indication du traitement symptomatique de la maladie : les méta-analyses ont confirmé le bénéfice sur les fonctions cognitives, le comportement et les activités de la vie quotidienne. La mémantine, inhibiteur des récepteurs glutamatergiques, a démontré une activité sur les fonctions cognitives et le déclin fonctionnel aux stades sévères de la maladie. Les considérables progrès de la connaissance de la maladie permettent maintenant d’envisager des approches qui agiront sur la cascade des lésions du cerveau et permettront de retarder, voire d’enrayer le processus pathologique. L’hypothèse amyloïde permet d’envisager des approches immunologiques actives ou passives et des inhibiteurs de gamma ou bêta sécrétases. Des travaux plus récents ont pour cible la protéine tau hyperphosphorylée. La plasticité cérébrale, l’utilisation de cellules souches offre des espoirs plus lointains

Maladie d’Alzheimer : vision d’ensemble, aspects cliniques, facteurs de risque et prévention

Un numéro thématique de médecine/sciences sur la maladie d’Alzheimer ne pouvait se concevoir sans aborder les questions cliniques, diagnostiques et thérapeutiques de cette maladie. En effet, si depuis une vingtaine d’années, des avancées considérables ont été effectuées dans la compréhension des mécanismes physiopathologiques de la maladie, son diagnostic, en revanche, est resté avant tout clinique devant un faisceaux d’arguments, en l’absence de marqueur biologique spécifique. Et la certitude diagnostique n’est encore acquise que lors de l’examen anatomopathologique. De même, la seule thérapeutique utilisée en pratique, les anticholinestérasiques, repose sur les données neurochimiques qui ont été obtenues il y a déjà plus de vingt ans

Dementia and antihypertensive treatment

PURPOSE OF REVIEW: We present an updated overview on the long-term effects of hypertension on the occurrence of cognitive dysfunction and overt degenerative or vascular dementia later in life. The preventative effects of antihypertensive treatment in this regard are examined, with a focus on placebo-controlled, double-blind, randomized prospective trials. RECENT FINDINGS: The stereotypical straightforward linear relationship between mid-life hypertension and dementia later in life can no longer be considered strictly invariable. Successfully treated hypertensive patients who are still at risk for clinical dementia late in life may ultimately fare better in the presence of a slightly elevated rather than low systolic blood pressure. The mechanisms underlying this 'J-curve' phenomenon are currently being explored. Recently completed prospective randomized antihypertensive trials (Syst-Eur 2, PROGRESS and SCOPE) have yielded variable results, and merit cautious interpretation. SUMMARY: The incidence and prevalence of dementia are increasing exponentially worldwide, particularly in those older than 70 years. Because hypertension predisposes to dementia, therapeutic blood pressure titration should be maintained over the years, and intensified beyond 70 years in order to avoid over-treatment in the latter period.status: publishe

A substudy protocol of the hypertension in the Very Elderly Trial assessing cognitive decline and dementia incidence (HYVET-COG) : An ongoing randomised, double-blind, placebo-controlled trial.

BACKGROUND AND OBJECTIVE: Randomised, controlled trials and population studies have suggested a link between hypertension and the development of dementia (vascular dementia and Alzheimer's disease) although the results are not conclusive. The very elderly are at highest risk for both hypertension and dementia but have been underrepresented in studies to date. The Hypertension in the Very Elderly Trial (HYVET), an international, randomised, double-blind, placebo-controlled trial of antihypertensive medication for those > or =80 years of age, is currently underway. The protocol for the assessment of cognitive decline and detection of incident dementia cases is described in this article. The objective of this protocol is to determine whether treatment of hypertension in this very elderly group affects the incidence of dementia and decline in cognitive function during the period of the HYVET trial. METHODS: Cognitive function in all HYVET trial participants is assessed at baseline and annually thereafter using the Mini-Mental State Examination (MMSE). An MMSE score that decreases more than three points per year or decreases to or =80 years of age with hypertension. The HYVET trial is placebo controlled and while investigating the cardiovascular effect of treatment also assesses cognitive function and quality of life in both the placebo and actively treated arms of the trial. The HYVET cognitive substudy trial (HYVET-COG) design has been successfully applied and the instruments chosen appear to be appropriate, valid and pragmatic. CONCLUSION: HYVET-COG provides the first opportunity to examine the effect of antihypertensive treatment on incident dementia in a high-risk very elderly population

Healthy Working Life Expectancies at age 50 in Europe: a new indicator

International audienc

Blood pressure, cognitive functions, and prevention of dementias in older patients with hypertension

The prevalence and incidence of degenerative and vascular dementias increase exponentially with age, from 70 years onward. In view of the increasing longevity of humans, both varieties are bound to evolve into a major problem worldwide. According to several longitudinal studies, hypertension appears to predispose individuals to the development of cognitive impairment and ensuing dementia, after a period varying from a few years to several decades. Antihypertensive drug treatment, according to preliminary evidence, may serve to reduce the rates of such events. Such findings await to be confirmed by formal therapeutic trials against a backdrop of "historical" observational sources

Cardiovascular and biochemical risk factors for incident dementia in the Hypertension in the Very Elderly Trial.

OBJECTIVES: Several cardiovascular and biochemical factors including hypertension have been associated with cognitive decline and dementia, although both epidemiological and intervention evidence is mixed with the majority of studies examining those in midlife or younger elderly and the recent Hypertension in the Very Elderly Trial showing no significant association between blood pressure lowering and incident dementia. It has also been suggested that risk factors may differ in the very elderly. The aim of these analyses was to examine the impact of baseline cardiovascular and biochemical factors upon incident dementia and cognitive decline in a very elderly hypertensive group. METHODS: Participants of the Hypertension in the Very Elderly Trial were aged at least 80 years and hypertensive. Cognitive function was assessed at baseline and annually with diagnostic information collected for dementia and relationships between baseline total and high-density lipoprotein cholesterol, creatinine, glucose, haemoglobin, heart failure, atrial fibrillation, diabetes, previous stroke and later dementia/cognitive decline were examined. RESULTS: There were 3336 participants with longitudinal cognitive function data. In multivariate analyses higher creatinine was associated with a lower risk of incident dementia and cognitive decline. Higher total and lower high-density lipoprotein cholesterol were associated with lower risk of cognitive decline. Other variables were not significant. CONCLUSIONS: In very elderly hypertensive patients heart failure, diabetes, atrial fibrillation, prior stroke, glucose and haemoglobin levels did not demonstrate a relationship with cognitive decline or dementia. Higher creatinine (excluding moderate renal impairment) was associated with a lower risk of dementia and cognitive decline. The findings for total and high-density lipoprotein cholesterol add to the varied literature in this area and together these findings may add weight to the suggestion that risk factor profiles differ in the very elderly

Expert consensus of the French Society of Geriatrics and Gerontology and the French Society of Cardiology on the management of atrial fibrillation in elderly people

SummaryAtrial fibrillation (AF) is a common and serious condition in the elderly. AF affects between 600,000 and one million patients in France, two-thirds of whom are aged above 75 years. AF is a predictive factor for mortality in the elderly and a major risk factor for stroke. Co-morbidities are frequent and worsen the prognosis. The management of AF in the elderly should involve a comprehensive geriatric assessment (CGA), which analyses both medical and psychosocial elements, enabling evaluation of the patient's functional status and social situation and the identification of co-morbidities. The CGA enables the detection of “frailty” using screening tools assessing cognitive function, risk of falls, nutritional status, mood disorders, autonomy and social environment. The objectives of AF treatment in the elderly are to prevent AF complications, particularly stroke, and improve quality of life. Specific precautions for treatment must be taken because of the co-morbidities and age-related changes in pharmacokinetics or pharmacodynamics. Preventing AF complications relies mainly on anticoagulant therapy. Anticoagulants are recommended in patients with AF aged 75 years or above after assessing the bleeding risk using the HEMORR2HAGES or HAS-BLED scores. Novel oral anticoagulants (NOACs) are promising treatments, especially due to a lower risk of intracerebral haemorrhage. However, their prescriptions should take into account renal function (creatinine clearance assessed with Cockcroft formula) and cognitive function (for adherence to treatment). Studies including frail patients in “real life” are necessary to evaluate tolerance of NOACs. Management of AF also involves the treatment of underlying cardiomyopathy and heart rate control rather than a rhythm-control strategy as first-line therapy for elderly patients, especially if they are paucisymptomatic. Antiarrhythmic drugs should be used carefully in elderly patients because of the frequency of metabolic abnormalities and higher risk of drug interactions and bradycardia