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Biomedical subjects

F Forette

Publications and source records attributed to F Forette.

At least 19 recordsLinked to original sources

Phospholipid abnormalities in early Alzheimer's disease. In vivo phosphorus 31 magnetic resonance spectroscopy.

OBJECTIVE: To determine whether changes in phosphomonoester and phosphodiester levels could be detected in vivo with phosphorus magnetic resonance spectroscopy in the early stage of Alzheimer's disease (AD). DESIGN: Survey-type of case-control study using neuropsychological testing as criterion standard with blinded data analysis. SETTING: Patients were from a neurology clinic in Paris, France. The controls were from the community. Magnetic resonance measurements were performed in the prefrontal region of the brain with a clinical 1.5-T scanner. Blinded data analysis. PARTICIPANTS: Twenty-four patients with mild AD and 15 age-matched healthy volunteers. Subjects were separated into two groups, both composed of patients with AD and healthy volunteers. Two successive acquisition protocols were used in the two groups. RESULTS: A significant increase in the phosphomonoester-total phosphorus ratio was found in patients with AD compared with controls. In this series, use of a ratio above 11% as a threshold to test our sample yielded an 83.3% sensitivity and a 73.3% specificity test for AD. Other metabolite ratios (inorganic phosphate, phosphodiesters, phosphocreatine, and nucleotide phosphates to total phosphorus) were not significantly different between patients and controls. No metabolite ratio correlated with the neuropsychological status as assessed by the Mini-Mental State Examination. CONCLUSION: Changes in phospholipid metabolism can be detected in vivo in the early stage of AD. Discrepancies in the literature may be due to differences in technical setting or in subject population types.

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Survival in institutionalized patients. Influence of dementia and loss of functional capacities.

BACKGROUND: Several studies have shown a negative correlation between dementia and survival. To our knowledge, the simultaneous effect of other factors has not been systematically studied in institutionalized patients. OBJECTIVE: To determine survival in demented inpatients compared with that in a matched population of nondemented patients institutionalized for other chronic debilitating diseases. DESIGN: The sample consisted of 213 patients with dementia and 157 patients without dementia. We studied the effect on survival of gender, age, loss of functional capacities, and cognitive functions with the method of Kaplan and Meier and with the model of Cox. RESULTS: Demented patients had significantly shorter survival when other factors were kept constant in the multivariate analysis. There was a strong correlation between survival and the degree of autonomy as measured by ability to walk, continence, and preserved activities of daily living. Survival was significantly shorter for men. No correlation was found with neuropsychological measures of severity of dementia or with age on admission. CONCLUSIONS: Survival of demented patients is shorter than that of patients institutionalized for other invalidating conditions. The lack of correlation between neuropsychological test results and survival indicates that in the population we studied, the severity of dementia did not predict length of survival. The data show that the combination of dementia and loss of functional capacities is the most important factor in predicting survival.

Activities of Daily Living

[Treatment of arterial hypertension in elderly patients. Value and indications].

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.

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Are calcium antagonists the best option in elderly hypertensives?

SUITABILITY OF CALCIUM ANTAGONISTS FOR THE ELDERLY: The efficacy and safety of calcium antagonists have been clearly demonstrated in elderly hypertensive patients. In a double-blind placebo-controlled study in 31 elderly hypertensives treated with nicardipine, we found no consistent electrocardiogram changes, nor in the heart rate, plasma levels of potassium, sodium or creatinine, or uric acid; nor did we find any postural hypotension. The mechanism of action of this class of drugs appears to be particularly appropriate in the treatment of elderly patients, in whom hypertension is characterized by an increase in peripheral resistance and a decrease in arterial compliance. Since vascular tone is ultimately controlled by the intracellular calcium concentration in smooth muscles, agents such as calcium inhibitors, which inhibit calcium influx and induce dilation of small and large arteries, are of particular interest. EXPERIMENTAL EVIDENCE: There is some experimental evidence in hypertensive rats and hypercholesterolaemic rabbits that calcium antagonists can provide some protection against atherosclerotic degeneration. However, the validity of extrapolating these findings to humans is still disputed. POSSIBLE CEREBRAL EFFECT: Calcium antagonists might also have a beneficial cerebral effect. The acute administration of these drugs has been shown to increase cerebral blood flow. Moreover, several studies have shown a protective action against cerebral ischaemia and this may be of particular importance in the very elderly.

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[Neuropathology of 20 centenarians. I. Clinical data].

We report a clinical study of 20 patients aged more than 100 years, and deceased in Charles Foix Hospital, Ivry/Seine, France, where they had stayed for 10 days to 16 years (mean: 3.3 years, median: 4 years). Each of them was studied neuropathologically (the results of this study will be published later on). The case selection excluded only those patients whose neuropathological study could not be complete. The prevalence of sensorial deficits was high: 15/20 patients had deterioration of hearing, 8 of them were deaf; 14/20 patients had deterioration of sight, 4 of them were blind. Motor deficits were numerous: 15 patients were not ambulatory. The patients were classified as demented or not, according to the criteria of the DSMIII R (American Psychiatric Association 1987), on the basis of a retrospective evaluation of clinical records, and of an inquiry among the caring staff. Their mental status was also evaluated by the Global Deterioration Scale of Reisberg et al (1985). Five patients had been demented, four had been intellectually normal, and 11 had suffered from mild disturbances of memory or cognitive functions. This series was not representative of the general population of centenarians, but probably of those institutionalized in France. We observed a low proportion of demented patients despite the prevalence expected from epidemiological studies. This is difficult to interpret. The low proportion of dementia in this small sample is not due to the short duration of the course of diseases responsible for dementia.(ABSTRACT TRUNCATED AT 250 WORDS)

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[Prevention of pathological aging. The arterial hypertension example].

Studies conducted during the last decade have made it increasingly easier to distinguish between normal and pathological ageing. Previous studies on general populations had established a dogma: most of the major body functions, such as cardiac output, glomerular clearance, muscular strength, visual acuity and so forth, were supposed to decline with age. However, in recent studies on the effects of age on cardiac output all subjects with heart disease were excluded and as a result the negative correlation found between cardiac output and age disappeared, which shows that a phenomenon attributed to ageing was in fact caused by disease. This does not mean that there is no such thing as fundamental ageing, and indeed the mechanisms that maintain cardiac output are different in young and elderly subjects. These data are of more than theoretical interest, since it may be presumed that prevention, the instruments of which are already available in some fields, will modify the profile of ageing. The risk of arterial hypertension is not restricted to the classical cardiovascular diseases: it extends to other diseases, such as vascular dementia, which are potent factors of pathological ageing. Most of the controlled trials carried out in arterial hypertension have demonstrated that treating certain types of hypertension significantly reduces the morbidity and/or mortality of cardiovascular diseases. The specific properties of new antihypertensive drugs, such as angiotensin-converting enzyme inhibitors, open stimulating vistas on arterial ageing.

Adult

Clinical trials in cognitive impairment in the elderly.

The pharmacological treatment of dementia is particularly difficult because of the uncertainty of the diagnosis and of the underlying pathogenetic processes, and because of the variable severity of the syndrome. This paper suggests several lines for future therapeutic trials in dementia. These include the need to work with homogenous populations and to take into account the natural history of the disease, the pharmacologic characteristics of the drugs, and the particular ethical considerations pertaining to demented patients. We review the diagnostic criteria for dementia, Alzheimer's disease (AD) and vascular dementia. We discuss the different types of therapeutic trial design, the problem of the duration of the protocol, the tools to evaluate the cognitive effects and the activities of daily living, and the use of a Clinical Global Impression of Change (CGIC). The results of some therapeutic trials in AD and vascular dementia are given as examples.

Activities of Daily Living

Syst-Eur--a multicenter trial on the treatment of isolated systolic hypertension in the elderly: first interim report.

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.

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Dermatoglyphic patterns in dementia of the Alzheimer type: a case-control study.

STUDY OBJECTIVE: The aim was to compare digital and palmar dermatoglyphics in subjects with dementia of Alzheimer type and in mentally healthy elderly controls. DESIGN: This design was a case-control study. SETTING: The study was carried out in geriatric units and retirement communities in the Paris area. PARTICIPANTS: Cases were women with clinically diagnosed Alzheimer type dementia according to DSM III-R criteria (n = 82), mainly with late onset of the disease. Controls were women aged 85 years or older without cognitive deterioration (n = 76). MEASUREMENTS AND MAIN RESULTS: Finger and palm prints obtained from both hands by the classical ink method were examined. Fingerprints were classified into four types of figures. On palms, palmar flexion creases, palmar axial triradii, true patterns of the hypothenar area, and main line terminations were described. Examinations were performed by two examiners blind to the subjects's diagnostic category. For the different patterns studied, no major differences between dementia patients and elderly controls were found. Nor was there evidence of high frequencies of features commonly observed in Down's syndrome (trisomy 21), which have previously, though sporadically, been reported. CONCLUSIONS: On one of the largest samples of Alzheimer dementia patients studied, and with evaluation blind to diagnosis, no evidence has been found that particular dermatoglyphic patterns occur like those observed in Down's syndrome, a disease which is related to dementia of the Alzheimer type.

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[SYST-EUR: a multicenter trial of treatment of systolic hypertension in aged subjects. An initial report].

Syst-Eur is a multicentre placebo-controlled outcome trial, designed by the European Working Party on High Blood Pressure in the Elderly (EWPHE), 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 mmHg with a diastolic blood pressure less than 95 mmHg. The present paper in 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 +/- standard deviation), sitting blood pressure (178 +/- 12/85 +/- 7 mmHg), percentage men (34%) and percentage of patients with cardiovascular complications (29%). After randomization blood pressure fell more (p < 0.001) on active treatment than in the placebo group (19 +/- 20/6 +/- 10 mmHg versus 7 +/- 19/1 +/- 10 mmHg for the 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 2 treatment groups can be achieved and maintained. New centres are being recruited in order to randomize a total of 3,000 patients.

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Syst-Eur. A multicentre trial on the treatment of isolated systolic hypertension in the elderly: objectives, protocol, and organization.

The Syst-Eur Trial is a concerted action of the European Community's Medical and Health Research Programme. The trial is carried out in consultation with the World Health Organization, the International Society of Hypertension, the European Society of Hypertension and the World Hypertension League. This article describes the objectives and the protocol of Syst-Eur, a multicentre trial designed by the European Working Party on High Blood Pressure in the Elderly (EWPHE), to test the hypothesis that antihypertensive treatment of elderly patients with isolated systolic hypertension results in a significant change in stroke morbidity and mortality. Secondary endpoints include cardiovascular events, such as myocardial infarction and congestive heart failure. To be eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160-219 mmHg with a diastolic pressure less than 95 mmHg. Patients must give their informed consent and be free of major cardiovascular and non-cardiovascular diseases at entry. The patients are randomized to active treatment or placebo. Active treatment consists of nitrendipine (10-40 mg/day), combined with enalapril (5-20 mg/day) and hydrochlorothiazide (12.5-25 mg/day), as necessary. The patients of the control group receive matching placebos. The drugs (or matching placebos) are stepwise titrated and combined in order to reduce systolic blood pressure by 20 mmHg at least to a level below 150 mmHg. Morbidity and mortality are monitored to enable an intention-to-treat and per-protocol comparison of the outcome in the 2 treatment groups. A one-year pilot trial (1989) showed that the protocol is practicable. The Ethics Committee therefore decided to start the definite study (1990), in which randomized patients will be followed for 5 years. Recruitment of new centres and of the required 3,000 patients will last 3 years (until 1993).

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Is prevention of vascular dementia possible? The Syst-Eur Vascular Dementia Project.

Vascular dementia (VD) is the second most common cause of dementia in the elderly after Alzheimer's disease (AD). Prevalence estimates from community surveys indicate that, on average, 5% of persons over 65 and 15 to 20% of people over 80 suffer from "severe dementia". Clinico-pathological studies have shown that AD accounts for 50 to 60% of the cases and VD for about 10 to 20%; 20% of the patients have both disorders. The incidence rate of VD ranges from 7 per 1,000 person-years in normal volunteers to 16 per 1,000 person-years in subjects with risk factors for strokes, particularly high blood pressure. The only effective therapeutic approach to VD is the prevention of strokes, mainly through the treatment of hypertension; however, none of the therapeutic trials has included VD prevention as one of its treatment goals. Syst-Eur Study is a European placebo controlled trial which aims to determine whether morbidity and mortality are changed when elderly patients (60 years and over) with isolated systolic hypertension are treated. In this trial, the incidence of VD will be carefully recorded during the five year follow-up of the expected 3,000 patients. The present side project to the Syst-Eur trial will specifically address the following questions: does antihypertensive treatment reduce the incidence of VD?, and how do the cognitive functions of elderly patients change when treated with active or placebo treatment? The protocol is based on the administration of the MMS (Folstein) once a year to all patients. If the MMS score is 23 or less, a set of criteria will be used to establish the diagnosis of vascular dementia. A pilot study has demonstrated the feasibility of the trial. The main study is in progress.

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Hypertension and the risk of dementia in the elderly.

Vascular dementia is the second most common type of dementia in the elderly after the dementia of Alzheimer's disease. Six 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, and single-infarct dementia. Each is described. Severe dementia is found in 5% of persons over age 65 and in 15% to 20% of persons over age 80 years. Alzheimer's disease accounts for 50% to 60% of cases of severe dementia and vascular dementia for 10% to 20%; 20% of the patients have both disorders. The incidence of vascular dementia, which seems to be declining, is about 7/1,000 persons/year. Hypertension is the most powerful risk factor for all vascular dementias. Vascular dementias can be accurately diagnosed by using clinical and mental state examinations, Diagnostic and Statistical Manual of Mental Disorders criteria, ischemic scores, and computed tomography or magnetic resonance imaging. The most successful treatment of vascular dementia is the prevention of cerebral infarcts. Study of the incidence of vascular dementias and their treatment will be included in the European Trial on Systolic Hypertension in the Elderly (SYST-EUR) of 3,000 elderly hypertensive patients.

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The influence of age on renal prostaglandin synthesis in man.

The purpose of our study was to determine influence of age on renal prostaglandin (PG) synthesis in man. Urinary prostaglandins 6-Keto-PGF1 alpha, TxB2, PGE2 and PGF2 alpha were measured in 45 normotensive subjects aged from 20-95 years. Urinary 6-Keto-PGF1 alpha excretion, reflecting mainly renal cortical prostacyclin synthesis, decreased significantly with age, while urinary TxB2 showed the opposite development. The ratio of urinary 6-Keto-PGF1 alpha/TxB2 decreased with age. PGE2 excretion was preserved in old subjects probably because the age-dependent decrease in renal function concerns mainly the cortex and spares the medulla. PGF2 alpha 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.

Adult

Age-related effects of placebo and active treatment in patients beyond the age of 60 years: the need for a proper control group.

The age-related response to placebo and active antihypertensive treatment was evaluated in 742 elderly hypertensive patients who were followed in the double-blind placebo-controlled trial conducted by the European Working Party on High blood pressure in the Elderly (EWPHE). In the two treatment groups, the fall in systolic and diastolic blood pressures after 3 months was negatively correlated with age (P less than 0.02), indicating that the hypotensive effect of placebo and active treatment was more pronounced in older patients. Further comparison of the two treatment groups failed to demonstrate any statistical differences in the slopes of the hypotensive effect on age. These conclusions were not altered by cumulative adjustments for baseline blood pressure, pulse rate, serum creatinine and the presence of cardiovascular complications at entry. In conclusion, in the present study, a similar blood-pressure-lowering action which increased with age was observed on active and placebo treatment; thus, proof that an observed age-related hypotensive effect is caused by a particular drug requires comparison with a control group on placebo.

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[Value and limits of medical treatment of hypertension in the aged person].

Most of the therapeutic trials (VA Study, HDFP, Australian Therapeutic Trial, EWPHE Study, Coope's Study) are in favour of the benefit of antihypertensive treatment over the age of sixty. But, on the other hand, information is lacking on:--The effectiveness of treatment of isolated systolic hypertension;--The effectiveness of treatment in very old people, particularly over eighty;--The effectiveness of treatment in preventing conditions which were not included in the former trials such as vascular dementias. Two trials concerning elderly patients with systolic hypertension are in progress, the SHEP Study in the USA and the European study called Syst-Eur. It is expected that these trials will give answers allowing a more accurate management of this major risk factor for cardiovascular diseases in the Elderly.

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