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Resume • L’etude S.AGES avait pour objectif principal de decrire les caracteristiques cliniques et les modalites de prise en charge des patients diabetiques de type 2 (DT2) âges, suivis en France en medecine generale. • Il s’agit d’une etude de suivi de cohorte, non interventionnelle, nationale et multicentrique, qui a inclus 959 patients DT2 âges de plus de 65 ans, suivis par 227 medecins generalistes. Les resultats a l’inclusion montrent qu’une proportion importante de ces malades presentait une HbA 1c

ILC-France promotes health and activity in the aging population and its recent studies have shown that delaying by one year the retirement in self-employed persons is associated with a decrease in the incidence of Alzheimer Disease. In this country-comparative study, we first inspected the labor force participation of the 50+ in France in 2014: it has been very low. France is the only country with no gender difference in LFP. Most men are in high-skilled white-collar jobs, most women in high-skilled white and blue-collar jobs.

The main objective of the S.AGES (Elderly Subjects) cohort study is to describe the current therapeutic strategy for chronic pain in non-institutionalised elderly patients in France.In this prospective cohort study, non-institutionalised patients aged 65 years and over with chronic pain were recruited by general practitioners (GP) across France. All medicinal and non- medicinal prescriptions were recorded at inclusion and will be followed up over 3 years via an eCRF. Data recorded at baseline are presented in this paper.Two hundred and sixty GPs enrolled 1379 evaluable patients between June 3rd, 2009 and June 3rd, 2011. Pain was mainly of a mechanical nature, due to osteoarthritis or common back pain. 80% of the patients had moderate or severe pain. More than a third of patients were treated with a step 1 analgesic (mainly paracetamol), and approximately 30% received a step 2 analgesic (23% dextropropoxyphene and 40.3% tramadol/paracetamol combination). Only 3% received step 3 analgesics; this rate remained low even in patients with severe pain. The proportion of patients treated with an antiepileptic was higher in case of neuropathic pain. More than 25% of patients did not receive any analgesic medication.The baseline S.AGES study results exhibit a well-balanced therapeutic management of chronic pain by GPs for ambulatory elderly patients. Clinicaltrials.org NCT01065909.

In the present study, the socioeconomic impact of the use of the acetylcholinesterase inhibitor donepezil in patients with mild to moderate Alzheimer’s disease (AD) living in France was examined. A model was created to extrapolate over a 3-year period the results from placebo-controlled trials together with epidemiological and prevalence data. Costs considered in the model were net societal costs associated with paid and unpaid assistance, general medical consumption and institutional care. The model suggested that delays in cognitive decline and functional dependence due to treatment reduced the time spent in institutional care and the burden on caregivers. Over a 3-year period, total net costs of caring for untreated patients with an initial Mini-Mental State Examination score ranging from 10 to 26 were EUR 53,206 compared with EUR 42,720 for a patient treated with donepezil – an annual cost saving of approximately EUR 3,500 per patient. Cost savings were mainly due to savings in unpaid caregiver time, which, apart from patient institutionalization, represented the most costly component of total care in this study but had no direct budgetary impact. Overall, these data suggest that donepezil is a cost-effective treatment for mild to moderately impaired AD patients living in France.

RESUME Le nombre eleve de deces (environ 14000) observes en France durant la « canicule » de l’ete 2003 conduit a s’interroger sur la qualite de la prise en charge dans notre pays de l’etat sanitaire des personnes âgees voire tres âgees. Dans ce rapport preliminaire, l’Academie nationale de medecine s’attache a rechercher les raisons principales des difficultes rencontrees. Elles different evidemment lorsque l’hyperthermie a touche une personne âgee vivant seule a son domicile, ou en institution. L’Academie souligne l’efficacite des services d’urgences des hopitaux, mais aussi les difficultes qu’ils ont rencontrees pour la prise en charge immediate des personnes âgees tres fragiles dans des structures d’aval notoirement insuffisantes ou inadaptees. Ces evenements ont fait bien apparaitre la necessite de la mise en place d’une veritable chaine de vigilance, permanente et de proximite. Il convient que chacun des maillons de cette chaine accepte de recevoir une formation specifique a la geriatrie reguliere et repetee dont depend reellement son efficacite.

Resume Les relations entre pression arterielle et troubles cognitifs sont complexes et ont fait l'objet de nombreuses controverses. Objectif. L'objectif de ce travail a ete d'evaluer de facon transversale, les relations entre le fonctionnement cognitif et la pressionarterielle dans une population de sujets atteints de maladie d'Alzheimer. Methodes. Chez 520 sujets de la cohorte du reseau francais sur la maladie d'Alzheimer, des relations entre l'importance du declincognitif et les antecedents d'hypertension arterielle ou le niveau de pression arterielle ont ete recherchees. Tous les patients ont beneficie d'une evaluation des fonctions cognitives et de leur degre d'autonomie dans les activites de la vie quotidienne par plusieurs tests et echelles valides (Mini Mental State Examination [MMSE], Alzheimer's Disease Assessment Scale—Cognitive part [ADAS-Cog], Instrumental Activities of Daily Living [IADL], Activities of Daily Living [ADL], Clinical Dementia Rating [CDR], Global Deterioration Scale [GDS] de Reisberg) et 456 d'entre eux ont beneficie d'une mesure de la pression arterielle lors de la consultation. Resultats. Apres ajustement selon l'âge, le sexe, le niveau d'etude et les autres facteurs de risque cardiovasculaire, les resultats indiquent que les sujets avec un antecedent d'hypertension arterielle presentent une alteration cognitive et une atteinte de l'autonomie dans les activites de la vie quotidienne significativement plus marquees que ceux sans antecedent d'hypertension arterielle (ADAS-Cog 19,02 ± 8,48 vs 17,49 ± 8,53, p = 0,06 ; MMSE 19,55 ± 4,41 vs 20,30 ± 4,42, p = 0,08 ; ADL 5,31 ± 0,86 vs 5,51 ± 0,87, p = 0,01 ; somme CDR 6,94 ± 3,29 vs 6,19 ± 3,26 p = 0,03 ; score total CDR 1, 18 ± 0,62 vs 1,05 ± 0,60, p = 0,03 ; GDS de Reisberg 4,41 ± 0,74 vs 4,27 ± 0,75, p = 0,05). En revanche, il n'existe pas de relation entre le niveau de pression arterielle mesuree en consultation et les fonctions cognitives et au contraire une correlation inverse avec le retentissement des troubles cognitifs sur les activites de la vie quotidienne est retrouvee. Conclusions. Ce travail indique que les relations entre la pression arterielle et les fonctions cognitives sont plus complexes qu'unesimple relation lineaire. Ainsi, chez des patients avec une maladie d'Alzheimer, une histoire ancienne d'hypertension arterielle est associee a un declin cognitif plus important. En revanche, une fois la maladie degenerative declaree il n'existe plus de relation entre le niveau de pression arterielle et l'alteration cognitive, et au contraire une correlation inverse avec le retentissement des troubles cognitifs sur les activites de la vie quotidienne est retrouvee.

Resume Propos. – Cet article a pour objectif une mise au point sur les complications cerebrales de l’hypertension arterielle (accidents vasculaires cerebraux, troubles cognitifs, demence ainsi que depression et anxiete), qui representent les principales causes de morbidite et de mortalite chez le sujet âge. Actualites et points forts. – Lˈhypertension arterielle represente un risque de complications cerebrales. Chez le sujet âge, la pression arterielle systolique est un meilleur predicteur du risque des complications cerebrales que la pression arterielle diastolique. Differents essais randomises, controles versus placebo ont montre que la baisse de la pression arterielle reduisait efficacement et sans danger la morbidite et la mortalite chez le sujet âge de plus de 60 ans. Les nouvelles classes therapeutiques, en particulier les inhibiteurs calciques et les inhibiteurs de l’enzyme de conversion, apparaissent aussi efficaces que les diuretiques et les betabloquants initialement prescrits. Perspectives et projets. – Differents essais therapeutiques sont actuellement en cours et permettront d’obtenir des donnees sur le benefice du traitement antihypertenseur chez les personnes tres âgees (Hypertension in the Very Elderly Trial, HYVET) et dans la prevention secondaire des accidents vasculaires cerebraux (PROGRESS). La demonstration de l’interet des nouvelles classes d’antihypertenseurs et la reevaluation des classes existantes en utilisant de nouveaux dosages sont en attente. De plus, les resultats de l’etude Syst-Eur ouvrent la voie d’une prevention possible des demences par les traitements antihypertenseurs. En particulier, le benefice des inhibiteurs calciques dans la prevention des demences pourrait etre confirme par l’essai DEPHY (Dementia Prevention in Hypertension).

Summary The intention was to identify the instruments that can better assess cognitive, behavioral and functional characteristics of patients with severe dementia. Multiple scales were administered in a series of patients with mini mental state examination (MMSE) scores ≦ 10: the activity of daily living (ADL), the clinical dementia rating scale (CDR), the global deterioration scale (GDS), the severe impairment battery (SIB), the hierarchic dementia scale (HDS), the behavioral rating scale for dementia (BRSD), the behavioral pathology in Alzheimer's disease rating scale (BEHAVE-AD). All these scales were applied in their standardized French versions. Two geriatric long-term facilities in the Paris area participated: 12 elderly patients (mean age: 83.8 ± 5.3 years) with a clinical diagnosis of probable or possible Alzheimer's disease (AD) (DSM III-R, NINCDSADRDA) and an MMSE mean score: 4.8 ± 3.3. Functional and behavioral scales were administered by the nurses of long-term facilities, who knew the patients better. As main outcome measures, evaluation of feasibility of cognitive (SIB and HDS) and behavioral (BRSD and BEHAVE-AD) scales and their correlation with MMSE were considered. All the patients were partially or totally dependent on ADL (mean: 1.9 ± 1.1). Scores of GDS and CDR varied from 5 to 7 (mean: 5.8 ±0.8) and from 2 to 4 (mean: 3.1 ± 0.7), respectively. A significant correlation was found between MMSE and scores of SIB (mean: 56.3 ± 29.6, range: 3–86) and HDS (mean: 90.6 ± 43.5, range: 18–148) (r = 0.87 and r = 0.91, respectively; p

Frailty tends to be considered as a major risk for adverse outcomes in older persons, but some important aspects remain matter of debate.The purpose of this paper is to present expert's positions on the main aspects of the frailty syndrome in the older persons.Workshop organized by International Association of Gerontology and Geriatrics (IAGG), World Health Organization (WHO) and Société Française de Gériatrie et de Gérontologie (SFGG).Frailty is widely recognized as an important risk factor for adverse health outcomes in older persons. This can be of particular value in evaluating non-disabled older persons with chronic diseases but today no operational definition has been established. Nutritional status, mobility, activity, strength, endurance, cognition, and mood have been proposed as markers of frailty. Another approach calculates a multidimensional score ranging from "very fit" to "severely frail", but it is difficult to apply into the medical practice. Frailty appears to be secondary to multiple conditions using multiple pathways leading to a vulnerability to a stressor. Biological (inflammation, loss of hormones), clinical (sarcopenia, osteoporosis etc.), as well as social factors (isolation, financial situation) are involved in the vulnerability process. In clinical practice, detection of frailty is of major interest in oncology because of the high prevalence of cancer in older persons and the bad tolerance of the drug therapies. Presence of frailty should also be taken into account in the definition of the cardiovascular risks in the older population. The experts of the workshop have listed the points reached an agreement and those must to be a priority for improving understanding and use of frailty syndrome in practice.Frailty in older adults is a syndrome corresponding to a vulnerability to a stressor. Diagnostic tools have been developed but none can integrate at the same time the large spectrum of factors and the simplicity asked by the clinical practice. An agreement with an international common definition is necessary to develop screening and to reduce the morbidity in older persons.

Background and objective. This interim report from the Syst-Eur trial investigated the level of blood pressure control achieved during the double-blind period in patients followed in general practices. Methods. In the Syst-Eur trial elderly patients (60 years or older) with isolated systolic hypertension were randomized to either active or placebo treatment. Active treatment consisted of nitrendipine combined with enalapril and/or hydrochlorothiazide to reduce systolic pressure to Results. This analysis was restricted to patients of general practitioners who had been followed for at least 12 months. The placebo (N = 204) and active treatment (N = 217) groups had similar characteristics at randomization. At one year, the difference in sitting pressure between the two treatment groups was 10 mmHg systolic and 4 mmHg diastolic. Fewer patients remained on monotherapy in the placebo than in the active treatment group and on placebo the second and third line medications were started earlier. Nitrendipine tablets were discontinued in 10 patients on placebo and in 21 patients assigned to active treatment (P Conclusions. A significant blood pressure reduction can be achieved and maintained in older patients with isolated systolic hypertension followed by general practitioners. Whether this blood pressure reduction results in a clinically meaningful decrease of cardiovascular complications is under investigation. Keywords. Antihypertensive treatment, general practice, isolated systolic hypertension, randomized clinical trial.

The efficacy of tacrine in the treatment of patients with probable Alzheimer's disease (AD) was evaluated in a double-blind, placebo-controlled, enriched population multicenter study in France. A total of 280 patients entered the dose titration phase of the study. The assessment of potential benefit of tacrine ("best dose") was based on demonstrating improvement on the Alzheimer's Disease Assessment Scale (ADAS) total score versus a blinded placebo. One hundred and thirty of 242 (54%) patients achieved a "best dose" and were eligible for the double-blind, parallel group (pivotal) phase. Primary efficacy measures were ADAS-Cognitive and Clinical Global Impression of Change; secondary efficacy measures of cognition and activities of daily living were also included. Results indicated that tacrine-treated patients showed improved functioning based on the ADAS-Cognitive in comparison to placebo-treated patients. Transaminase elevations above the upper limit of normal occurred in 32% of patients, were more frequent in women than in men, demonstrated a delayed onset, and returned to normal limits for all patients following discontinuation of treatment The results from this study are supportive of the efficacy of tacrine in the treatment of AD as demonstrated in a study of similar design conducted in the US and studies using different designs.

Aging is associated with functional decline and loss of autonomy, and age is a major risk factor for a wide spectrum of clinical conditions, including cardiovascular disease, cognitive impairment, and physical disability. As life expectancy continues to rise, the maintain of physical functioning advanced age has emerged as a major clinical and public health priority. It is estimated that by 2025, 1.2 billion people worldwide will be over 60 years old, with similar prevalence in Europe. In France, men and women aged 50 years old can expect to live free of disability respectively for another 18.0 years and 19.7 years. These data are similar among all 25 EU countries where healthy aging in men and women is expected until age 67 and 68 years, respectively. However, in adults age 50 years and older, approximately 40% of men and 46% of women, will experience some functional limitation. Frailty has been operationally defined by Fried and colleagues based on a phenotypic definition in older adults. From a clinical perspective, frailty is marked by three or more of the following criteria: unintentional weight loss in the past year (>4 kg), self-reported exhaustion, weakness (measured by loss of grip strength), slow walking speed, low physical activity. The term "frailty" is commonly used to indicate a state of high vulnerability to negative health-related outcomes, such as falls, physical and cognitive decline, hospitalization, physical disability, and mortality. Clinically, frailty is a loss of functional homeostasis resulting in a pathophysiological state characterized by the accumulation of molecular, cellular, and tissue damage in different organ systems. When function has already been lost due to injury or illness, frailty can confound the loss and lead to disability. Frailty and functional decline are frequent consequences of aging, but their etiologies remain unclear. Older adults may experience progressive decline in function and develop disabilities without any clinical explanation. The frailty syndrome is possibly a result of the early stages and non-specific symptoms of both age-related diseases and complex pathophysiological processes not yet identified. Thus, early interventions aimed at preventing the progression of frailty and disability are critical in older adults. An intermediate status, "pre-frail", is characterized by the presence of one or two of the criteria defined above. Pre-frail older adults are at an increased risk of adverse outcomes, as well as increased risk of meeting criteria for frailty in three to four years. Together, pre-frail and frail adults represent almost half of the population aged 60 and older. In France and other countries of the EU, previous epidemiological studies have reported rates of frailty and pre-frailty in approximately 15% and 50% in community-dwelling adults aged 65 years and older, respectively. Although these groups are at an increased risk for disease and disability, they are also the most to benefit from interventions. More specifically, interventions designed for older adults with pre-frailty might reduce the risk of progression to a more serious condition. Given the global trend of an aging population, increased efforts are necessary to identify ways to better predict risk of frailty and interventions to prevent the occurrence of frailty in the elderly. Frailty is a medical syndrome characterized by multiple changes and deficits in different biological systems, including sarcopenia (i.e., the loss of both muscle mass and strength), osteoporosis (i.e., low bone mineral density), neuroendocrine and metabolic dysregulation, elevation in inflammatory factors, malnutrition, and cardiovascular abnormalities. Some of these manifestations have been largely studied in older adult populations. For instance, a slow gait speed is a criterion for the diagnosis of sarcopenia. People with slow gait speed have also been found to be more likely to exhibit several other age-related diseases (e.g., Mild Cognitive Impairment and osteoporosis). Thus, gait speed can be used as a reliable measure for frailty. Despite the empirical evidence for certain biological etiologies for frailty, there are many factors that warrant further investigation to better understand their role in aging and frailty in older adults. For example, Kaya and Saurat demonstrated that dermatoporosis, a condition of frail aging skin, frequently occurs in older adults, and more specifically in those who are frail. It is possible to restore the function of the skin after dermatoporosis begins; however, if it is left untreated it can produce ulceration and hypercatabolism. It can also contribute to pain, functional impairment, slow gait speed, and further disability. Frailty and concurrent age-related diseases are key targets for the prevention of disability in older age. Nearly half of adults over 50 are at risk of developing some functional limitations, however, healthy aging is possible well beyond this age and into later life. Although some functional decline is expected during the aging process, older adults are at higher risk of developing diseases and disabilities associated with changes that occur with aging. Established criteria have improved our ability to identify frailty and pre-frailty, yet there are no empirically supported interventions to delay or prevent this syndrome. Continuous efforts and well-designed intervention studies are needed to reduce frailty and consequent disability in our rapidly increasing aging population. Language: en

We present the first results of a cognitive stimulation programme for patients with dementia. Fifty-six subjects entered a study involving two parallel, randomized groups. Assessment was blind for the main criteria (neuropsychological tests). Twenty-nine patients were stimulated and were compared to 27 non-stimulated patients. The stimulated group attended 10 stimulation sessions over 5 weeks. Each group was assessed on the first and seventh week. Following stimulation, there was significant improvement of Mini-Mental State (MMS) scores (p < 0.01) and increased performance for the Word List Memory Test (one-tailed p = 0.09) in the Consortium to establish a Registry for Alzheimer's Disease (CERAD) battery. Verbal fluency remained unchanged. Stimulation tended to improve items of an additional battery (one-tailed p < 0.01). The composite sum of test scores showed a significant difference in favour of the stimulated group. These results were positively correlated with the initial MMS scores and negatively with education. The Activities of Daily Living (ADL) scale did not show a significant change. We concluded that global stimulation of cognitive functions improves certain parameters among demented outpatients.

OBJECTIVE To assess if very elderly people with hypertension obtain early benefit from antihypertensive treatment. DESIGN One year open label active treatment extension of randomised controlled trial (Hypertension in the Very Elderly Trial (HYVET)). SETTING Hospital and general practice based centres mainly in eastern and western Europe, China, and Tunisia. PARTICIPANTS People on double blind treatment at the end of HYVET were eligible to enter the extension. INTERVENTIONS Participants on active blood pressure lowering treatment continued taking active drug; those on placebo were given active blood pressure lowering treatment. The treatment regimen was as used in the main trial-indapamide SR 1.5 mg (plus perindopril 2-4 mg if required)-with the same target blood pressure of less than 150/80 mm Hg. MAIN OUTCOME MEASURES The primary outcome was all stroke; other outcomes included total mortality, cardiovascular mortality, and cardiovascular events. RESULTS Of 1882 people eligible for entry to the extension, 1712 (91%) agreed to participate. During the extension period, 1682 patient years were accrued. By six months, the difference in blood pressure between the two groups was 1.2/0.7 mm Hg. Comparing people previously treated with active drug and those previously on placebo, no significant differences were seen for stroke (n = 13; hazard ratio 1.92, 95% confidence interval 0.59 to 6.22) or cardiovascular events (n = 25; 0.78, 0.36 to 1.72). Differences were seen for total mortality (47 deaths; hazard ratio 0.48, 0.26 to 0.87; P = 0.02) and cardiovascular mortality (11 deaths; 0.19, 0.04 to 0.87; P = 0.03). CONCLUSION Very elderly patients with hypertension may gain immediate benefit from treatment. Sustained differences in reductions of total mortality and cardiovascular mortality reinforce the benefits and support the need for early and long term treatment. Trial registration Clinical trials NCT00122811.

Syst-Eur is a multicenter placebo-controlled outcome trial designed by the European Working Party on High Blood Pressure in the Elderly to investigate the effect of antihypertensive treatment on the incidence of stroke in elderly patients with isolated systolic hypertension (ISH). Eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160-219 mm Hg with a diastolic blood pressure less than 95 mm Hg. The present paper is an interim report on the first 316 patients randomized into this trial. The placebo (n = 170) and active treatment (n = 146) groups were similar at randomization with respect to age (73 +/- 8 years; mean +/- SD), sitting blood pressure (178 +/- 12 mm Hg systolic; 85 +/- 7 mm Hg diastolic), percentage of men (34%), and percentage of patients with cardiovascular complications (29%). After randomization blood pressure fell more (p less than 0.001) in patients on active treatment than in those in the placebo group (19 +/- 20 mm Hg systolic; 6 +/- 10 mm Hg diastolic vs. 7 +/- 19 and 1 +/- 10 mm Hg for sitting blood pressure). This first interim report on the Syst-Eur trial demonstrates that a multinational trial in elderly patients with ISH is feasible and that a significant blood pressure difference between the two treatment groups can be achieved and maintained. New centers are being recruited in order to randomize a total of 3,000 patients.

The purpose of our study was to determine influence of age on renal prostaglandin (PG) synthesis in man. Urinary prostaglandins 6-Keto-PGF 1α , TxB 2 , PGE 2 and PGF 2α were measured in 45 normotensive subjects aged from 20–95 years. Urinary 6-Keto-PGF 1α excretion, reflecting mainly renal cortical prostacyclin synthesis, decreased significantly with age, while urinary TxB 2 showed the opposite development. The ratio of urinary 6-Keto-PGF 1α /TxB 2 decreased with age. PGE 2 excretion was preserved in old subjects probably because the age-dependent decrease in renal function concerns mainly the cortex and spares the medulla. PGF 2α synthesis was least influenced by age. This age-dependent decrease in renal prostacyclin synthesis may play a role in the renal alterations of the elderly.

The rigorous diagnosis of dementia, especially in the early stages, requires clinical observation and neuropsychological tests. This article shows how a short strategy-oriented neuropsychological battery, the Cognitive Efficiency Profile (CEP), can contribute to the early diagnosis of Alheimer's disease. The CEP was given to 56 subjects who had been independently diagnosed as being cognitively unimpaired (N = 16), as having probable AD with mild dementia (N = 32) or as having “borderline” deterioration (N = 8). One-year follow-up showed that all the latter patients developed unequivocal dementia. There was a clear-cut separation in the test results between the controls and the probable AD cases when the scores were corrected for age and education. There was some overlap between the borderline cases and the probable AD patients but, in all cases, the corrected scores fell below those of normal controls. The usefulness of the CEP rests on the fact that it assesses the efficiency or the failure of strategies applied to a number of abilities related to cognitive efficiency. Coupled with clinical data, a good or a poor performance on the CEP strongly corroborates the diagnosis of normal cognitive functioning or of dementia in the elderly.

Under the auspices of the French Society of Gerontology and Geriatrics, a multidisciplinary group of experts, including geriatricians, neurologists, epidemiologists, psychiatrists, pharmacologists, and public health specialists developed consensus recommendations about care for patients with severe dementia. They defined 21 recommendations for general practitioners, long-term care physicians, and specialists, based on the knowledge currently available (2005). The aim of care at all stages is to mitigate the quality-of-life of patient, caregiver, and family insofar as possible, combining care and future planning until the end of life. Management, to take into account problems including nutritional status, behavior disorders, and ability (or inability) to perform activities of daily living, must be global, multidisciplinary, and coordinated and must optimize use of local medical and social resources. The group also stressed the importance of clinical research to improve knowledge of disease course and assess management strategies and recommended specific area for research.

To determine the evolution of blood pressure in patients with moderate Alzheimer's disease among a one year longitudinal survey and to evaluate the relationship between blood pressure and cognitive functions.In 327 subjects selected from the French research program on Alzheimer's disease (REAL.FR), systolic and diastolic blood pressure (SBP, DBP) were measured at the time of inclusion (M0), after 6 months (M6) and after 12 months (M12). All subjects were assessed to determine both cognitive functions and capabilities in the activities of daily living using validated cognitive scales [Mini Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale--Cognitive part (ADAS-Cog), Instrumental Activities of Daily Living (IADL), Activities of Daily Living (ADL), Clinical Dementia Rating (CDR)], at M0, M6, M12.In this population of patients with moderate Alzheimer's disease, mean age was 78 +/- 7 years and 242 subjects were females (74%). After adjustment for age, gender, body mass index (BMI) and antihypertensive therapy, a significant decrease of blood pressure was observed between M0 and M12, for SBP (139.1 +/- 18 to 136.5 +/- 17 mmHg, p0.05) and DBP, (77.6 +/- 12 to 75.8 +/- 10 mmHg , p0.05). Demented subjects with the worst cognitive impairment at baseline (tertile1 MMSE, tertile 3 ADAS-Cog, ADL scores between 0 and 4, CDR scores between 10 to 18) showed a larger decrease in SBP and DBP after 12 months. The worst impairment in dementia at baseline was associated with the highest SBP decrease between M0 and M12 (delta SBP tertile 1 MMSE vs tertile 3 MMSE = -5.9 vs + 1.0 mmHg , p0.05; Delta SBP tertile 3 ADAS-Cog vs tertile 1 ADAS-Cog = - 5.98 vs + 2.98 mmHg, p0.05, Delta SBP ADL 0-4 vs ADL -6 = - 8.7 vs -1.5 mmHg, p0.05, delta SBP CDR 10-18 vs CDR 0.5-9.5 = - 6.9 vs -1.7 mmHg, p0.05). All these results persisted after adjustment for age, gender and the antihypertensive therapy. Baseline SBP [OR 95% CI = 1.05 (1.02-1.08), BMI [OR 95% CI = 0.88 (0.81-0.95)], ADL score [OR 95% CI = 0.42 (0.22-0.81)] and ADAS-Cog score [OR 95% CI = 1.07 (1.01-1.14)] were significantly associated with the decrease of blood pressure after one year of follow up, independently of age, gender and antihypertensive therapy. In contrast, patients with larger blood pressure decrease (over 10 mmHg reduction of SBP and/or 5 mmHg of DBP) did not demonstrate a more significant worsening of dementia at 12 months in the different scales used.This study indicates a significant decrease in blood pressure in patients with Alzheimer's disease after one year of follow up, independently of age, gender, BMI and antihypertensive therapy. The largest decrease in blood pressure was observed in patients with the most severe impairment in dementia at baseline, suggesting that blood pressure decrease seems to be mainly a secondary phenomenon in Alzheimer's disorders.

The relationships between arterial hypertension and cognitive decline are complex and studies indicate controversial results.To evaluate, in a cross sectional study, the relationships between cognitive functions and blood pressure in a population of subjects with Alzheimer's disease.In 520 subjects of a survey in a French population with Alzheimer's disease, relationships between the severity of cognitive decline and a history of hypertension or blood pressure level have been searched. Cognitive functioning was assessed with validated neuropsychological tests evaluating cognitive functions and the capacities in the activities of daily living (Mini Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale--Cognitive part (ADAS-Cog), Instrumental Activities of Daily Living (IADL), Activities of Daily Living (ADL), Clinical Dementia Rating (CDR), Global Deterioration Scale (GDS) of Reisberg). In 456 subjects blood pressure was measured during the consultation.The results indicate that after adjustment on age, sex, education level, and the other cardiovascular risk factors, subjects with a history of hypertension have a more marked cognitive decline than subjects without history of hypertension. Indeed, in subjects with a history of hypertension, the cognitive impairment and its consequences on activities of daily living are more important than in subjects without history of hypertension (ADAS-cog 19.02 +/- 8.48 vs 17.49 +/- 8.53 p = 0.06, MMSE 19.55 +/- 4.41 vs 20.30 +/- 4.42, p = 0.08, score ADL 5.31 +/- 0.86 vs 5.51 +/- 0.87, p = 0.01, CDR 6.94 +/- 3.29 vs 6.19 +/- 3.26 p = 0.03; global CDR 1.18 +/- 0.62 vs 1.05 +/- 0.60, p = 0.03, GDS of Reisberg 4.41 +/- 0.74 vs 4.27 +/- 0.75, p = 0.05). In contrast, no relation between blood pressure measurements and cognitive function is observed, and moreover an inverse correlation between blood pressure and consequences on activities of daily living is found.This work indicates that relationships between blood pressure and cognitive functions are more complex than a simple linear relation. The present results show that a history of arterial hypertension is associated with a more marked cognitive decline in subjects with Alzheimer's disease. In contrast, when the Alzheimer's disease is already developed no relation between blood pressure and cognitive functions appears and moreover an inverse correlation with the consequences on activities of daily living is found.

This review focuses on cerebral complications of hypertension, which include stroke, impairment of cognitive function, dementia, and possibly depression and anxiety. These conditions are major causes of morbidity and mortality in the elderly.Not only elevated diastolic blood pressure, but also isolated systolic hypertension and elevated pulse pressure play an important role in the development of brain complications. Randomised placebo-controlled trials have provided evidence that reduction of hypertension decreases safely and effectively morbidity and mortality rates in the elderly. The new classes of drugs, in particular calcium-channels blockers and angiotensin-converting enzyme inhibitors, have been shown to be as effective as the originally used diuretics and beta-blockers.Several trials are currently in progress and should provide more information on the benefit of antihypertensive treatment in very elderly persons (Hypertension in the Very Elderly Trial, HYVET) and secondary prevention of stroke (PROGRESS). The importance of assessing new dosages of the presently used antihypertensive drugs as well as the benefit of new classes of drugs is emphasised. Further trials specifically focusing on the prevention of dementia by antihypertensive drugs are needed to confirm the results of the Syst-Eur Vascular Dementia Project. The benefit of calcium antagonists in the prevention of dementia in elderly hypertensive patients should be assessed in the Dementia Prevention in Hypertension trial (DEPHY).

Subclinical vitamin D insufficiency is characterized by mild secondary hyperparathyroidism and enhanced risk of osteoporotic fracture. However, although low levels of 25-hydroxyvitamin D (25OHD) are common in otherwise normal elderly people, vitamin D status has not generally been taken into account in the previously published reference values for serum PTH. We measured fasting morning serum (obtained from April through June) PTH, total calcium, albumin, phosphate, creatinine, bone markers, and 25OHD in 280 healthy subjects (140 men and 140 women), aged 60-79 yr. Serum PTH was measured by means of 2 immunoradiometric assays, the Allegro intact PTH assay (Nichols Institute Diagnostics) and the new CAP assay (Scantibodies Laboratory, Inc.). We found a high prevalence (167 of 280; 59.6%) of low 25OHD (or =30 nmol/L) in these otherwise healthy individuals. The PTH concentrations (95% confidence interval) obtained in the whole group of 280 subjects ranged from 13-64 ng/L for the Allegro assay and from 10-44 ng/L for the CAP assay. In the subjects with a serum 25OHD concentration greater than 30 nmol/L, values for both PTH assays were lower, 10-46 and 9-34 ng/L for the Allegro and the CAP assays, respectively. By using these values as a reference range, approximately 25% of the subjects with a serum 25OHD level of 30 nmol/L or less had a high serum PTH level (whatever the assay), reflecting secondary hyperparathyroidism. This might be missed if the reference PTH values are those obtained in the entire group, as is usually done. These results strongly suggest that vitamin D status should be taken into account when establishing reference values for serum PTH in elderly subjects.

The risk of hypertension and the benefits of antihypertensive treatment are well established in older patients aged up to 80 years. For people aged 85 and over, data are scarce and conflicting. A positive association between blood pressure and survival has been found in several cohort studies; this relationship held true after adjustment for many factors in some studies, but disappeared after adjustment for indicators of poor health in others. In randomized trials, the benefit of antihypertensive treatment was demonstrated in the Systolic Hypertension in the Elderly Program (SHEP) study, but it declined with age and was not observable after 80 years in the European Working Party on High Blood Pressure in the Elderly (EWPHE) study. The SYSTolic hypertension in elderly in EURope Trial (SYST-EUR) study evidenced a benefit on cardiovascular morbidity but not on mortality. People who reach a very old age share some characteristics that make them different from those '60 (or 65) and over' and justify special studies which are currently in progress. In the meantime, any treatment decision can only rely on extrapolations moderated by common sense, but the already demonstrated favorable results on morbidity argue against a threshold beyond which hypertension should not be treated.

The prevalence and incidence of both degenerative (Alzheimer) and vascular dementias rise exponentially with aging. In both forms of dementia hypertension is a predisposing factor. The interval between the onset of hypertension and the manifestation of dementia amounts to 12-15 years. A complicating factor is the observation that initial dementia may be accompanied by secondary decrease in blood pressure. A preventive effect of current antihypertensive treatment is likely, according to preliminary evidence (particularly with regard to the use of the calcium antagonist nitrendipine), but the hopeful perspective of protection against dementias through antihypertensive treatment remains to be confirmed by further prospective comparative trials.

The objective of our study was to evaluate the effects of the apolipoprotein E (ApoE) phenotype and gender on the response to tacrine treatment in Alzheimer's disease (AD). ApoE phenotyping was performed on 76 patients treated with tacrine for AD. This group comprised 33 ApoE epsilon4 allele carriers (epsilon4+) and 43 non-epsilon4 carriers (epsilon4-). Patients were treated blindly in relation to the ApoE phenotype, with incremental tacrine dosages ranging from 40 mg/day up to the highest dosage (160 mg) tolerated without side-effects. At least 6 weeks elapsed between each increase. Changes in the scores for the Alzheimer Disease Assessment Scale-Cognitive Component (ADAS-Cog) between baseline and each increment in dosage were assessed in the epsilon4- and epsilon4+ groups. The cut-off point for being considered as responsive to tacrine treatment was a 4-point decrease in the ADAS-Cog score. There was no tendency for the epsilon4- carriers to respond better than the epsilon4+ carriers. When patients were stratified by gender, no differences were found between the effects of the treatment on men and women. Consequently, these results do not support the hypothesis that the ApoE phenotype and gender are predictors of the response to tacrine in AD patients.

M.M., a right-handed, 74 year old professional musician and composer, presented with a progressive aphasia with a severe anomia. His musical competence was apparently totally preserved, and he continued his activity as a composer. There was a striking discrepancy between his impaired naming of nonmusical stimuli and his normal naming of musical instruments' sounds. We suggest that the preservation of skills in the musical domain results from an expanded cortical representation of this function in the left hemisphere, secondary to his lifelong formal training, and to the high level of his professional competence. As for his preserved naming of musical instruments, we argue that the early age-of-acquisition and higher than "normal" frequency/familiarity for names of musical instruments facilitate the access to their lexical representation and/or their retrieval within the lexicon.

The aim of the vascular dementia project, set up in the framework of the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial, was to investigate the influence of antihypertensive drug treatment on the incidence of vascular dementia. The study was run on non-demented patients, at least 60 years old, with isolated systolic hypertension (sitting blood pressure of 160-219 mmHg for systolic and below 95 mmHg for diastolic). Treatment was initiated with nitrendipine (10-40 mg/day) possibly associated with enalapril (5-20 mg/day) and/or hydrochlorothiazide (12.5-25 mg/day). Cognitive function was assessed at baseline and annually by the Mini Mental State Examination (MMSE). The diagnosis of dementia was based on the DSM-III-R criteria. The etiology of dementia was established using the Modified Ischemic Score or the Hachinski score when brain imaging was not available. Median follow-up by intention-to-treat was 2.0 years. The incidence of dementia was reduced by 50% from 7.7 per 1000 patient-years in the placebo group (number of patients 1,180) to 3.7 cases per 1000 p-a in the active treatment group (n = 1,238) (21 vs 11 patients, p = 0.05). At the last available evaluation, systolic and diastolic blood pressure were 8.3 mmHg and 3.8 mm Hg lower (por = 0.001) in the active-treatment group, but on average the MMSE scores remained stable in both groups.In older people with isolated systolic hypertension, antihypertensive treatment started with nitrendipine may reduce the incidence of dementia. At the rate observed in the placebo group, treating 1,000 patients for 5 years would prevent 19 cases of dementia.

The aim of the study was to assess the management of elderly hypertensives in general practice. A sample of 2,727 general practitioners filled a specially designed questionnaire between February and March 1998 in France. Areas covered by the questionnaire included risk of hypertension, blood pressure measurement and treatment. Most respondents (97%) considered that hypertension remains a cardiovascular risk factor in elderly but 4% thought that hypertension is usefull by improving target organ perfusion. Fifty-five percent recorded both standing and supine measurement, 34% reported measuring blood pressure with patient supine only. All respondents reported that they would start antihypertensive treatment on the basis of blood pressure level. A minimum systolic level of 160 and 180 mmHg was given by 65% and 27% practitioners respectively while 2% required a minimum level ranging from 139 to 149 mmHg. Among the respondents who considered that isolated systolic hypertension is pathological (74%), 73% and 19% used 160 and 180 mmHg as cut-off, respectively. Among those who considered that isolated systolic hypertension is physiological (23%), 43% and 46% initiated treatment above 160 and 180 mmHg, respectively. A minimum diastolic level of 90 mmHg was reported by many respondents (61%) while 34% required a cut-off level of 100 mmHg. Comparison of systolic and diastolic levels showed that 49% practitioners started antihypertensive therapy above 160/90 mmHg and 16% above 180/100 mmHg. Less than 1% reported a threshold level of 140/90 mmHg. Most practitioners 5%) treated hypertensive patients regardless of their age. The others treated patients younger than 65 years old (3%), 70 (2%), 80 (5%) and 90 (4%). All respondents reported that they would treat their patients to prevent vascular complications, mainly cerebrovascular (96%), cardiac (89%) and kidney (75%) disease. In conclusion, for all general practitioners, hypertension remains a cardiovascular risk factor in elderly and hypertensive therapy is beneficial to prevent cardiovascular complications. This study reveals some inter-physician variability in blood pressure measurement and treatment. The risk of standing blood pressure fall is not taken into account by 66% of respondents. Variability in age threshold is in accordance with the lack of published data on benefice of hypertensive treatment in the very old. The risk of isolated systolic hypertension is under-estimated by 27% of physicians who reported a minimum systolic blood pressure level of 180 mmHg to initiate therapy.

Recent reports suggest that calcium-channel blockers may be harmful in patients with diabetes and hypertension. We previously reported that antihypertensive treatment with the calcium-channel blocker nitrendipine reduced the risk of cardiovascular events. In this post hoc analysis, we compared the outcome of treatment with nitrendipine in diabetic and nondiabetic patients.After stratification according to center, sex, and presence or absence of previous cardiovascular complications, 4695 patients (age,or =60 years) with systolic blood pressure of 160 to 219 mm Hg and diastolic pressure below 95 mm Hg were randomly assigned to receive active treatment or placebo. Active treatment consisted of nitrendipine (10 to 40 mg per day) with the possible addition or substitution of enalapril (5 to 20 mg per day) or hydrochlorothiazide (12.5 to 25 mg per day) or both, titrated to reduce the systolic blood pressure by at least 20 mm Hg and to less than 150 mm Hg. In the control group, matching placebo tablets were administered similarly.At randomization, 492 patients (10.5 percent) had diabetes. After a median follow-up of two years, the systolic and diastolic blood pressures in the placebo and active-treatment groups differed by 8.6 and 3.9 mm Hg, respectively, among the diabetic patients. Among the 4203 patients without diabetes, systolic and diastolic pressures differed by 10.3 and 4.5 mm Hg, respectively, in the two groups. After adjustment for possible confounders, active treatment was found to have reduced overall mortality by 55 percent (from 45.1 deaths per 1000 patients to 26.4 deaths per 1000 patients), mortality from cardiovascular disease by 76 percent, all cardiovascular events combined by 69 percent, fatal and nonfatal strokes by 73 percent, and all cardiac events combined by 63 percent in the group of patients with diabetes. Among the nondiabetic patients, active treatment decreased all cardiovascular events combined by 26 percent and fatal and nonfatal strokes by 38 percent. In the group of patients receiving active treatment, reductions in overall mortality, mortality from cardiovascular disease, and all cardiovascular events were significantly larger among the diabetic patients than among the nondiabetic patients (P=0.04, P=0.02, and P=0.01, respectively).Nitrendipine-based antihypertensive therapy is particularly beneficial in older patients with diabetes and isolated systolic hypertension. Thus, our findings do not support the hypothesis that the use of long-acting calcium-channel blockers may be harmful in diabetic patients.

In 1989, the European Working Party on High Blood Pressure in the Elderly started the double-blind, placebo-controlled, Systolic Hypertension in Europe Trial to test the hypothesis that antihypertensive drug treatment would reduce the incidence of fatal and nonfatal stroke in older patients with isolated systolic hypertension. This report addresses whether the benefit of antihypertensive treatment varied according to sex, previous cardiovascular complications, age, initial blood pressure (BP), and smoking or drinking habits in an intention-to-treat analysis and explores whether the morbidity and mortality results were consistent in a per-protocol analysis.After stratification for center, sex, and cardiovascular complications, 4695 patients 60 years of age or older with a systolic BP of 160 to 219 mm Hg and diastolic BP less than 95 mm Hg were randomized. Active treatment consisted of nitrendipine (10-40 mg/d), with the possible addition of enalapril maleate (5-20 mg/d) and/or hydrochlorothiazide (12.5-25 mg/d), titrated or combined to reduce the sitting systolic BP by at least 20 mm Hg, to below 150 mm Hg. In the control group, matching placebo tablets were employed similarly.In the intention-to-treat analysis, male sex, previous cardiovascular complications, older age, higher systolic BP, and smoking at randomization were positively and independently correlated with cardiovascular risk. Furthermore, for total (P = .009) and cardiovascular (P = .09) mortality, the benefit of antihypertensive drug treatment weakened with advancing age; for total mortality (P = .05), the benefit increased with higher systolic BP at entry, while for fatal and nonfatal stroke (P = .01), it was most evident in nonsmokers (92.5% of all patients). In the perprotocol analysis, active treatment reduced total mortality by 24% (P = .05), reduced all fatal and nonfatal cardiovascular end points by 32% (P.001), reduced all strokes by 44% (P = .004), reduced nonfatal strokes by 48% (P = .005), and reduced all cardiac end points, including sudden death, by 26% (P = .05).In elderly patients with isolated systolic hypertension, stepwise antihypertensive drug treatment, starting with the dihydropyridine calcium channel blocker nitrendipine, improves prognosis. The per-protocol analysis suggested that treating 1000 patients for 5 years would prevent 24 deaths, 54 major cardiovascular end points, 29 strokes, or 25 cardiac end points. The effects of antihypertensive drug treatment on total and cardiovascular mortality may be attenuated in very old patients.

The main points of a workshop on the place of clinical trials in the memory clinics in France are reproduced schematically. The efficiency of these centres has been tested at the time of the numerous clinical trials performed in France on Alzheimer's disease. In parallel, several difficulties have been pointed out: inhomogeneity of the technical approaches, official role of psychologists in the hospital teams, integration of clinical research to individual care. A particular effort should be oriented towards specific research on the different types of dementia, on early stages, on information for both media and authorities as well as on specific technical and methodological problems.

The overlap between symptoms of depression and dementia in elderly patients has been well established. Depressed elderly patients often complain of poor memory. They may develop cognitive dysfunction which in some cases may be severe enough to meet the criteria for dementia. Some authors have suggested that depression in the elderly increases the risk of dementia. Alternatively, depression may be an early manifestation of dementia (Davanand et al., 1996).

Isolated systolic hypertension occurs in about 15% of people aged 60 years or older. In 1989, the European Working Party on High Blood Pressure in the Elderly investigated whether active treatment could reduce cardiovascular complications of isolated systolic hypertension. Fatal and non-fatal stroke combined was the primary endpoint.All patients (60 years) were initially started on masked placebo. At three run-in visits 1 month apart, their average sitting systolic blood pressure was 160-219 mm Hg with a diastolic blood pressure lower than 95 mm Hg. After stratification for centre, sex, and previous cardiovascular complications, 4695 patients were randomly assigned to nitrendipine 10-40 mg daily, with the possible addition of enalapril 5-20 mg daily and hydrochlorothiazide 12.5-25.0 mg daily, or matching placebos. Patients withdrawing from double-blind treatment were still followed up. We compared occurrence of major endpoints by intention to treat.At a median of 2 years' follow-up, sitting systolic and diastolic blood pressures had fallen by 13 mm Hg and 2 mm Hg in the placebo group (n = 2297) and by 23 mm Hg and 7 mm Hg in the active treatment group (n = 2398). The between-group differences were systolic 10.1 mm Hg (95% CI 8.8-11.4) and diastolic, 4.5 mm Hg (3.9-5.1). Active treatment reduced the total rate of stroke from 13.7 to 7.9 endpoints per 1000 patient-years (42% reduction; p = 0.003). Non-fatal stroke decreased by 44% (p = 0.007). In the active treatment group, all fatal and non-fatal cardiac endpoints, including sudden death, declined by 26% (p = 0.03). Non-fatal cardiac endpoints decreased by 33% (p = 0.03) and all fatal and non-fatal cardiovascular endpoints by 31% (p0.001). Cardiovascular mortality was slightly lower on active treatment (-27%, p = 0.07), but all-cause mortality was not influenced (-14%; p = 0.22).Among elderly patients with isolated systolic hypertension, antihypertensive drug treatment starting with nitrendipine reduces the rate of cardiovascular complications. Treatment of 1000 patients for 5 years with this type of regimen may prevent 29 strokes or 53 major cardiovascular endpoints.

To determinate cognitive status and its correlates in older patients with isolated systolic hypertension.Syst-Eur is a double-blind placebo-controlled outcome trial conducted in European patients over 60 years of age with isolated systolic hypertension. Moreover, a side-project--the Vascular Dementia Project--is designed to assess cognitive functions and to follow-up their evolution to determine the influence of antihypertensive therapy on vascular dementia incidence. Cognitive functions were evaluated at entry with the MiniMental State Examination (MMSE) in 2250 patients included in Syst-Eur. Cognitive impairment was defined with a MMSE scoreor = 23 and led to further evaluation. Baseline blood pressure (BP) was based on the average of six sitting blood pressure readings at three run-in visits 1 month apart. Statistical analysis used Spearman correlation.The MMSE was analysed in 1374 women and 751 men whose mean age was 70 years (range: 60-100). The median level of education expressed as the age at which they stopped their education at school, was 15 years. Baseline blood pressure averaged 173 +/- 10/86 +/- 6 mmHg. Before randomisation in the trial, 899 (40%) patients had received antihypertensive therapy and 602 (27%) had experienced cardiovascular complications. The MMSE-scores ranged from 15 to 30 (median = 29). The maximal score of 30 was reached by 609 (30%) subjects. Among the 59 (3%) patients with a MMSE-score of 23 or less, 5 were considered to be demented according to the DSM IIIR criteria. The MMSE-scores decreased with advancing age in men (r = -0.16; p0.001) and women alike (r = -0.24; p0.001). In both men and women, they were positively correlated with the level of education (r = 0.30 and 0.32, respectively; p0.001). They were negatively correlated with systolic blood pressure (r = 0.10; p0.001) and slightly positively correlated with diastolic blood pressure (r = 0.05; p = 0.03). Previously treated patients or patients reporting cardiovascular complications at baseline had lower MMSE-scores than their non-treated counterparts or subjects without cardiovascular complications (median = 28 and 29, respectively, p0.003).In a European cohort of 2225 patients over 60 years of age with isolated systolic hypertension, the level of cognitive functions evaluated with the MMSE decreases with advancing age or lesser educational level. It also decreases with higher systolic blood pressure or lower diastolic blood pressure. The influence of antihypertensive therapy on cognitive status will be prospectively evaluated in Syst-Eur Vascular Dementia Project.

Two suggested clinical trial designs for assessing progression of Alzheimer disease are the randomized withdrawal design and the randomized start design. The most promising of these, the randomized start design, has the potential to demonstrate a delay in progression, but there remain problematic design, ethical, and statistical issues to be solved before the protocol can be used in a clinical trial. The development of biological markers of the disease process using neuroimaging or other measures also may provide a robust method of measuring disease progression and demonstrating the biological effect of a drug on the disease process.

Up to now, Alzheimer's disease was a devastating, untreatable and irreversible condition leading to a complete physical and intellectual deterioration in a "no-care" zone. The past ten years have seen important progress. Substitutive drug treatments, mainly, cholinergic approaches are able to allow a significant symptomatic improvement in around 30 to 40% of responders. THA is the first antidementia drug released by the registration agencies in a number of countries. It does not alter the course of the disease but the symptomatic improvement may last for some years. Other cholinergic and non cholinergic treatments are under study. Future treatments are based on aetiological and physiopathological mechanisms. A number of pathological pathways lead to a final consequence, the production and deposit of the neurotoxic beta amyloid protein. Interventions on different infectious, inflammatory, degenerative processes are being tried. Abnormal cleavage of the precursor APP, production and deposition of non soluble beta amyloid appears as the central event in the aetiology of the disease. The most logical approach is to intervene on the production, deposition or neurotoxicity of the amyloid at early stages of the disease. Several mechanisms may be addressed: inhibition of proteolytic enzymes which abnormally cleave the precursor, inhibition of the amyloid neurotoxicity, reduction of APP synthesis, reduction of inflammatory reaction around the plaques, slowing of the polymerization of soluble proteins into amyloid fibrils etc.... The, now, well established genetic predisposition will help in detecting subjects at high risk to develop the disease. Alzheimer's disease is a striking medical and social challenge. The medical team may, today, treat many symptoms of the disease and care for the patient and family. Tomorrow, it will be possible to prevent or, at least slow down the course of the disease.

This interim report from the Syst-Eur trial investigated the level of blood pressure control achieved during the double-blind period in patients followed in general practices.In the Syst-Eur trial elderly patients (60 years or older) with isolated systolic hypertension were randomized to either active or placebo treatment. Active treatment consisted of nitrendipine combined with enalapril and/or hydrochlorothiazide to reduce systolic pressure to150 mmHg and byor = 20 mmHg. Matching placebos were used in the control group.This analysis was restricted to patients of general practitioners who had been followed for at least 12 months. The placebo (N = 204) and active treatment (N = 217) groups had similar characteristics at randomization. At one year, the difference in sitting pressure between the two treatment groups was 10 mmHg systolic and 4 mmHg diastolic. Fewer patients remained on monotherapy in the placebo than in the active treatment group and on placebo the second and third line medications were started earlier. Nitrendipine tablets were discontinued in 10 patients on placebo and in 21 patients assigned to active treatment (P0.001 for all comparisons).A significant blood pressure reduction can be achieved and maintained in older patients with isolated systolic hypertension followed by general practitioners. Whether this blood pressure reduction results in a clinically meaningful decrease of cardiovascular complications is under investigation.

Vascular dementia is the most common cause of dementia in the elderly after Alzheimer's disease. Many forms of vascular dementia have been described: multi-infarct dementia, lacunar dementia, Binswanger's subcortical encephalopathy, cerebral amyloid angiopathy, white matter lesions associated with dementias, single infarct dementia, dementia linked to hypoperfusion and haemorrhagic dementia. The difficulty of diagnosing vascular dementia must not be underestimated and an international consensus is needed for epidemiological studies. The NINCDS-AIREN group has recently published diagnostic criteria. The State of California Alzheimer's Disease Diagnostic and Treatment Centers also proposed some which differ from the NINCDS-AIREN criteria in considering only ischaemic vascular dementia and not other mechanisms such as haemorrhagic or hypoxic lesions. Most studies stress hypertension as the most powerful risk factor for all forms of vascular dementia. The incidence rate ranges from 7 per 1000 person-years in normal volunteers to 16 per 1000 person-years in hypertensive patients. No therapeutic attempt has influenced the course of the disease once the dementing condition is established. The only effective approach is preventive treatment. The objective of the SYST-EUR Vascular Dementia project is to confirm that the treatment of isolated systolic hypertension is able to reduce its incidence.

The prevalence of high blood pressure increases with age and, in elderly subjects, it is a major risk factor not only for cardiovascular diseases but also for other diseases including vascular dementia. Data concerning mortality are more controversial, but it is known that up to the age of 90, mortality is increased in hypertensive subjects. Two pathological conditions can be distinguished, systolo-diastolic hypertension with a systolic pressure above 160 mmHg and diastolic pressure above 95 mmHg and systolic hypertension alone when the systolic pressure is above 160 mmHg and diastolic below 95 (or 90) mmHg. The European working party on high blood pressure in the elderly (EWPHE) and the Medical Research Council trial of treatment of hypertension in older adults have demonstrated the beneficial effect of treating systolo-diastolic hypertension. Active therapy significantly reduces the risk of mortality due to cardiovascular disease, notably myocardial infarction, and in morbidity due to left ventricular failure and non-mortal cerebral vascular events. The current debate centers on the pressure level which should be attained, especially in patients with a history of ischaemic cardiopathy. Treatment of elderly patients with systolic hypertension alone is also probably beneficial, although only the systolic hypertension in the elderly program (SHEP) was able to demonstrate a significant reduction in cerebral vascular events and in the incidence of myocardial infarction, even in subjects over 80. A multicentric European study (Syst-Eur), which includes patients treated with calcium inhibiteurs and conversion enzyme inhibiteurs, is being conducted in order to confirm the beneficial effect of treating systolic hypertension in subjects over 60. In addition, this study also includes a complementary project specifically designed to evaluate the effect of treatment on vascular dementia.