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Biomedical subjects

Françoise Forette

Publications and source records attributed to Françoise Forette.

At least 19 recordsLinked to original sources

Relationship between antihypertensive drug therapy and cognitive function in elderly hypertensive patients with memory complaints.

OBJECTIVE: To evaluate the relationship between antihypertensive treatments and cognitive function in elderly hypertensive patients with memory complaints. METHODS: The association between cognitive function and antihypertensive drug therapy was studied in 1241 hypertensive elderly patients with memory complaints attending a geriatric outpatient clinic. Cognitive function was assessed using the Mini Mental State Examination (MMSE) and validated neuropsychological tests (Cognitive Efficiency Profile; CEP). Patients were classified into four categories according to their cognitive status: normal cognitive function, mild cognitive impairment (MCI), Alzheimer's disease (AD) or vascular dementia (VaD). RESULTS: In this population aged 78 +/- 8 years, with a mean blood pressure of 152 +/- 19/86 +/- 12 mmHg, antihypertensive treatment was prescribed for 57% of patients. After adjustment for age, sex and education, treated hypertensive patients had better cognitive function than untreated patients (MMSE score 23.9 +/- 5.6/30 versus 22.7 +/- 6.4/30, P < 0.001, CEP score 49.1 +/- 24.9/100 versus 45.4 +/- 23.7/100, P < 0.001). This association was observed independently of the cognitive status, both in normal, MCI, AD and VaD hypertensive patients. The odds ratio (OR) for AD was 0.58 [95% confidence interval (CI) 0.42-0.81] in treated compared with untreated hypertensive patients. In patients on antihypertensive therapy, higher cognitive function was observed in patients using calcium antagonists compared with those without calcium antagonists (CEP 52.9 +/- 24.6/100 versus 46.4 +/- 23.4/100, P < 0.001; OR for AD 0.67; 95% CI 0.45-0.99), independently of blood pressure level. CONCLUSIONS: Antihypertensive therapy was associated with a lower risk of cognitive impairment and AD. In particular, the use of calcium antagonists was associated with a decreased risk of cognitive impairment and AD independently of the blood pressure level, suggesting a specific neuroprotective effect of these antihypertensive agents.

Aged↗

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 <24 prompts further investigation for possible incident dementia. This includes use of the Diagnostic and Statistical Manual-IV criteria, the modified Hachinski scale and CT scanning. In cases where a CT scan cannot be obtained the full Hachinski scale is used. Additional information is provided when available from the clock drawing test and Geriatric Depression Scale. Data are also gathered from all trial participants with regard to education, blood pressure, alcohol use, co-morbidities and concomitant treatments. At the end of the trial, changes in cognitive function and incident dementia cases will be compared in those receiving active treatment (indapamide slow-release +/- perindopril) and those receiving matching placebo. RESULTS: The protocol has been applied successfully and the data collection phase is underway. DISCUSSION: Previous population studies have been unable to study antihypertensive use in a controlled manner and randomised, controlled trials suggest a positive or mixed picture regarding an association between use of antihypertensive therapy and reduction in incident cognitive decline and/or dementia. No such trial has yet been performed exclusively in subjects > 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.

Aged, 80 and over↗

Relationship between arterial stiffness and cognitive function in elderly subjects with complaints of memory loss.

BACKGROUND AND PURPOSE: To evaluate the relationship between arterial stiffness and cognitive function in a population of elderly subjects reporting memory loss. METHODS: We studied the association between cognitive function and arterial stiffness in 308 consecutive elderly subjects attending a geriatric outpatient clinic reporting memory impairment. Subjects were classified into 4 categories according to neuropsychological evaluation: normal cognitive function, mild cognitive impairment (MCI), Alzheimer disease (AD), or vascular dementia (VaD). Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (PWV) measurement using Complior. RESULTS: In this population, 78+/-8 years of age (women 64%), AD was present in 41%, VaD in 6%, MCI in 27%, and 26% of subjects had normal cognitive function. After adjustment for age, gender, systolic blood pressure, education level, cardiovascular diseases, and antihypertensive therapy, a significant association was observed between PWV and cognitive status (P<0.0001). PWV appears significantly higher in subjects with VaD (15.2+/-3.9 m/s) or AD (13.3+/-2.9 m/s) than in those without cognitive impairment (11.5+/-2.0 m/s; P<0.001). Moreover, PWV was higher in subjects with MCI (12.6+/-2.6 m/s) than in those without cognitive impairment (11.5+/-2.0 m/s; P=0.01). For each 2 m/s increment in PWV, the adjusted odds ratio (95% CI) was 1.73 (1.27 to 2.47) for AD and 3.52 (1.87 to 8.05) for VaD. CONCLUSIONS: Our results showed a relationship between arterial stiffness and cognitive impairment, suggesting that functional changes of the arterial system could be involved in the onset of dementia (VaD or AD types).

Age Factors↗

Prevention of dementia: lessons from SYST-EUR and PROGRESS.

Hypertension is one of the principal risk factors for cerebrovascular diseases, closely correlated also with cognitive decline and dementia. Data from recent therapeutic trials (SYST-EUR, PROGRESS) open the way toward the prevention of dementia (vascular or Alzheimer's type) by antihypertensive treatments. The results of these two studies suggest different mechanisms of action of antihypertensive drugs in the prevention of cognitive decline. The use of angiotensin converting enzyme (ACE) inhibitors, with or without diuretics, resulted in decrease incidence of stroke-related dementia, but dementia without stroke was not reduced. With the dihydropyridine calcium antagonists, a reduction in both Alzheimer's type and vascular dementia was demonstrated.

Angiotensin-Converting Enzyme Inhibitors↗

Prevention of dementia and cerebroprotection with antihypertensive drugs.

High blood pressure is a major risk factor for stroke and is also closely correlated with cognitive decline and dementia. Indeed, most longitudinal studies showed that cognitive functioning is often inversely proportional to blood pressure values measured 15 or 20 years previously. Because of the aging of the population, the frequency of stroke and dementia will dramatically increase in the coming years. Therefore, the prevention of cerebrovascular and cognitive disorders represents a major challenge. Antihypertensive drugs have shown clinical benefits in both primary and secondary prevention of strokes. Consensus is generally that blood-pressure lowering represents the major determinant of the benefit conferred by the antihypertensive treatment for stroke prevention; however, recent studies have suggested some differences between classes of antihypertensive drugs. The results of therapeutic trials (Systolic Hypertension in Europe, Perindopril Protection Against Recurrent Stroke Study [PROGRESS]) open the way to the prevention of dementia (vascular or Alzheimer's type) by antihypertensive treatments. These two studies suggest different mechanisms for the prevention of cognitive decline using antihypertensive drugs. In this context, reduced incidence of dementia should be the primary outcome of future trials comparing different classes of antihypertensive drugs.

Antihypertensive Agents↗

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.

Antihypertensive Agents↗

Maintaining cognitive health in an ageing society.

A significant concern associated with growing old is the loss of cognitive function, resulting in dementia. Fortunately, the current research on ageing indicates that cognitive decline is not an inevitable function of the ageing process. Moreover, individuals can take steps to maintain cognitive health throughout life. This paper reviews the research findings and recommendations for maintaining cognitive health that were presented at a meeting sponsored by the Alliance for Health and the Future in November 2003. The meeting, 'Placing Cognitive Health on Europe's Social and Economic Agenda', reviewed the current state of knowledge about cognitive health and discussed its implications for an ageing Europe. Although the brain, for reasons that remain unclear, changes with age, a growing body of research suggests that social engagement, intellectual stimulation, and physical activity play a key role in maintaining cognitive health and preventing cognitive decline. As the number of older people increases and people live longer, developing and implementing strategies for maintaining cognitive health should be a priority for both individuals and societies.

Aged↗

Effect of 1-year oral administration of dehydroepiandrosterone to 60- to 80-year-old individuals on muscle function and cross-sectional area: a double-blind placebo-controlled trial.

BACKGROUND: The age-related decline of dehydroepiandrosterone and its sulfate ester levels is thought to be related to the development of age-associated usual modifications, such as neuromuscular function impairments. It is often claimed that individuals can enhance their muscular capacity by boosting dehydroepiandrosterone levels through oral supplementation. However, to our knowledge, there have been no controlled studies on a significant number of individuals demonstrating positive effects on the neuromuscular system. This study determines if 1-year administration of a replacement dose of dehydroepiandrosterone, 50 mg/d, orally administered, could have a beneficial influence on several determinants of the muscular function altered during aging. METHODS: This work was completed within the frame of the DHEAge Study, which was conducted in France from March 1, 1998, to October 31, 1999. It was performed on 280 healthy ambulatory and independent men and women aged 60 to 80 years. The study design was a double-blind placebo-controlled trial. Dehydroepiandrosterone sulfate serum concentration, handgrip strength, isometric and isokinetic knee muscle strength, and thigh (fat and muscle) cross-sectional area were analyzed before and just after 12 months of placebo or dehydroepiandrosterone treatment. RESULTS: The results give evidence that dehydroepiandrosterone administration restores dehydroepiandrosterone sulfate serum concentrations to the normal range for young adults (aged 20-50 years). However, no positive effect inherent to dehydroepiandrosterone treatment was observed either on muscle strength or in muscle and fat cross-sectional areas. CONCLUSIONS: The compensation of the deficit of dehydroepiandrosterone during aging using a 50-mg/d dose does not induce beneficial effects on muscle state in healthy subjects. The conditions in which dehydroepiandrosterone could contribute to preserve or improve muscle strength and morphological features still need to be determined.

Aged↗

Hypertension and dementia.

Hypertension is one of the principal risk factors for cerebrovascular diseases. Several epidemiologic studies have also indicated a positive correlation between cognitive decline or dementia and blood pressure level. Indeed, the results of most longitudinal studies show that cognitive functioning is often inversely proportional to blood pressure values measured 15 or 20 years previously. Cerebral infarcts, lacunae, and white matter changes are implicated in the pathogenesis of vascular dementia, but may also favor the development of Alzheimer's disease. Microcirculation disorders and endothelial dysfunctions are also advanced to explain the deterioration in cognitive functions in hypertensive subjects. Data from recent therapeutic trials open the way to the prevention of dementia (vascular or Alzheimer's type) by antihypertensive treatments and must be confirmed by other studies.

Antihypertensive Agents↗

Patients with Alzheimer's disease living at home in France: costs and consequences of the disease.

Alzheimer's disease (AD) creates a substantial burden on human and financial resources. However, there are few data relating to the cost of AD in France. This retrospective study assesses the total costs of caring for home-based patients with mild to moderate AD. Pattern of care, sociodemographic data, caregiver burden, and estimated net costs of caring for AD patients were assessed in a stratified sample of 50 untreated AD patients. The net costs of caring for all AD patients who completed all study parameters increased with decreasing cognitive ability. Unpaid assistance was the most costly component of the total cost of care. Mini-Mental State Examination scores correlated strongly with functional status, and instrumental activities of daily living scores were a robust indicator of the magnitude of behavioral, cognitive, and dependence problems. This study suggested a significant link between costs of caring for an AD patient at home and disease severity.

Activities of Daily Living↗

Are low dehydroepiandrosterone sulphate levels predictive for cardiovascular diseases? A review of prospective and retrospective studies.

STUDY OBJECTIVE: It has been suggested that low levels of dehydroepiandrosterone sulphate (DHEAS) are predictive for cardiovascular diseases in men. We aimed to review the available evidence from prospective cohort studies and retrospective case-control studies. METHODS: We extracted summary statistics from 4 case-control studies and 8 cohort studies, and calculated the pooled relative risk associated with a 2 micromol/l increase in DHEAS. MAIN RESULTS: The number of subjects included in each of the individual studies ranged from 94 to 2134, mean age from 48 to 83 years and mean DHEAS levels from 1.2 to 7.3 pmol/l. In men, coronary mortality was available as outcome in 3 cohort studies and 1 case-control study. Combining data from these 4 studies showed a 15% (95% CI: 4%-28%, p = 0.008) increase in fatal coronary heart disease associated with a 2 micromol/l decrease in DHEAS. However, statistical significance was lost when the retrospective study causing significant heterogeneity (p = 0.02) was excluded. Fatal and non-fatal coronary events were reported in 1 cohort study and 3 case-control studies. The average increase in fatal plus non-fatal coronary heart disease associated with a 2 micromol/l decrease in DHEAS amounted to 13% (2%-26%, p = 0.02). The available data did not allow drawing any conclusions on the prognostic value of DHEAS in women, nor on the relationship between DHEAS and total or cardiovascular mortality or stroke in men. CONCLUSIONS: The present findings suggest that, in men, low serum levels of DHEAS may be associated with coronary heart disease. However, whether DHEA supplementation has any cardiovascular benefit is not clear. Data from prospective randomised trials are needed.

Aged↗

Apolipoprotein E epsilon 4 allele frequency in demented and cognitively impaired patients with and without cerebrovascular disease.

Controversy exists regarding the apolipoprotein E (ApoE) epsilon 4 allele association with vascular dementia (VaD). The results range from increased epsilon 4 frequency, similar to that found for Alzheimer's disease (AD), to no association at all. Our objective was to clarify the relationship between ApoE epsilon 4 allele and cerebrovascular disease (CVD) in demented and cognitively impaired patients. We examined the ApoE phenotypes in a sample of 452 subjects: 219 with AD, 45 with VaD, 62 with mixed dementia (MD), 45 with mild cognitive impairment (MCI) without CVD, 27 in which vascular disease was the most probable cause of cognitive decline (vascular mild cognitive impairment, VMCI) and 54 normal controls (NC). The study of the epsilon 4 allele frequency showed significant differences between: AD group and the VaD, VMCI and NC groups; MCI group compared with VMCI and NC groups; and MD group versus the VaD and NC groups (p<0.05-0.0001). The frequency of the epsilon 4 allele in the VaD and VMCI groups did not differ significantly from NC. In contrast to other studies, we did not detect a relationship between ApoE epsilon 4 allele and clinically diagnosed VaD. Our results also show that the epsilon 4 allele is not associated with cognitive impairment of vascular origin. In addition, we have confirmed that the ApoE epsilon 4 allele occurs frequently in late-onset AD and we have found similar association in cognitively impaired individuals without clinical CVD. These findings should contribute to the assessment of dementia risk profile in the elderly.

Aged↗

The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study.

BACKGROUND: After the double-blind, placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial ended in February 1997, randomized patients were offered active study medication for a further period of observation. OBJECTIVE: To refine the estimates of the long-term effects of antihypertensive therapy on the incidence of dementia. METHODS: Eligible patients had no dementia and were at least 60 years old. Their systolic blood pressure at entry was 160 to 219 mm Hg, with diastolic blood pressure below 95 mm Hg. Antihypertensive therapy was started immediately after randomization in the active treatment group, but only after termination of the double-blind trial in the control patients. Treatment consisted of nitrendipine (10-40 mg/d), with the possible addition of enalapril maleate (5-20 mg/d), hydrochlorothiazide (12.5-25 mg/d), or both add-on drugs. RESULTS: Median follow-up increased from 2.0 years in the double-blind trial to 3.9 years overall. The incidence of dementia doubled from 32 to 64 cases, 41 of whom had Alzheimer disease. Throughout follow-up, systolic/diastolic blood pressure was 7.0/3.2 mm Hg higher in the 1417 control patients than in the 1485 subjects randomized to active treatment. At the last examination, the blood pressure difference was still 4.2/2.9 mm Hg; 48.1%, 26.4%, and 11.4% of the control patients were taking nitrendipine, enalapril, and/or hydrochlorothiazide, whereas in the active treatment group these proportions were 70.2%, 35.4%, and 18.4%, respectively. Compared with the controls, long-term antihypertensive therapy reduced the risk of dementia by 55%, from 7.4 to 3.3 cases per 1000 patient-years (43 vs 21 cases, P<.001). After adjustment for sex, age, education, and entry blood pressure, the relative hazard rate associated with the use of nitrendipine was 0.38 (95% confidence interval, 0.23-0.64; P<.001). Treatment of 1000 patients for 5 years can prevent 20 cases of dementia (95% confidence interval, 7-33). CONCLUSION: The extended follow-up of Syst-Eur patients reinforces the evidence that blood pressure-lowering therapy initiated with a long-acting dihydropyridine protects against dementia in older patients with systolic hypertension.

Aged↗

[Difficulty in assessing renal function in elderly hypertensive patients. Results of a survey in the geriatric environment].

OBJECTIVES: In elderly patients, modifications observed in renal function often make difficult the differentiation between the pathological cause and the physiological consequences of aging. The presence of arterial hypertension can enhance these hemodynamic modifications. The state of renal function is often assessed only on creatinemia, which is not a marker adapted to the elderly, since creatinine levels often remain normal even in cases of altered renal function. The aim of this study was to determine the prevalence of chronic renal failure (CRF) in elderly hypertensive patients, based on the calculation of creatinine clearance using Cockcroft and Gault's method, and comparing it with the prevalence of CRF when renal function is assessed by methods currently used by practitioners. METHODS: In 841 treated hypertensive patients aged over 65, hospitalized in geriatric wards (median or long term hospitalization), the state of renal function was assessed in two ways: on the one hand by the physicians themselves, according to their method of choice and, on the other, by calculating creatinine clearance according to Cockcroft and Gault's method. These assessments were then compared and the main conflicting factors were revealed by logistics regression. Furthermore, the importance given to the state of renal function in the therapeutic attitude of the physician was determined using a graduated scale from 0 to 5. Logistics regression analysis identified the principle determinants of this attitude. RESULTS: In this population with a mean age of 81 +/- 8 years, predominantly composed of women (65%), the prevalence of renal failure (clearance calculated according to Cockcroft and Gault's formula < 80 ml/min) was of 89%, and of 42% at the stage of severe or pre-terminal renal failure (clearance < 30 ml/min). Conversely, when assessed by the physicians according to their method of choice, it was only of 64% and 16% respectively. The agreement between calculated and assessed renal function was of 35%. Renal damage is often underestimated by the physicians compared with calculated values (for 61% of patients). Logistics regression revealed the following determinating discrepancies: gender (p = 0.0001), age (p = 0.0025) and body weight (p = 0.0031), which are the principle variables of Cockcroft and Gault's formula. The principle elements taken into account in the assessment of renal function in the therapeutic attitude of the physicians towards these elderly patients are: the existence of an alteration in renal function (p = 0.0001), the level of systolic arterial pressure (p = 0.001), the number of cardiovascular risk factors (p = 0.002), notably diabetes (p = 0.003) and the female gender (p = 0.024). CONCLUSIONS: This study emphasizes the great prevalence of renal failure in elderly hypertensive patients, with only 11% of hypertensive patients exhibiting normal renal function after the age of 80. Assessment of renal function by the physicians according to their method of choice suggests an underestimation of renal damage compared with the calculated values of creatinine clearance. Availability of simple calculation tools would facilitate the systematic application of Cockcroft and Gault's formula and provide enhanced appreciation of renal function in the elderly.

Aged↗

Antihypertensive drugs and cognitive function.

The increase in life expectancy is associated with a sharp rise in cognitive disorders, particularly after the age of 80 years. The identification and management of risk factors for these invalidating and distressing conditions must be considered a priority. Hypertension has been shown to carry an increased risk not only for cerebrovascular morbidity and mortality, but also for cognitive impairment and dementia. The fact that antihypertensive treatment has been demonstrated to decrease those risks offers a new opportunity to reduce the prevalence of such related disorders and to promote healthy aging.

Age Factors↗