[Treating mental disorders in the elderly: avant-garde control or... lost cause? Address].
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
F Forette
Publications and source records attributed to F Forette.
[Consensus statement on severe dementia].
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.
Aged↗
Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial.
BACKGROUND: AN1792 (beta-amyloid [Abeta]1-42) immunization reduces Abeta plaque burden and preserves cognitive function in APP transgenic mice. The authors report the results of a phase IIa immunotherapy trial of AN1792(QS-21) in patients with mild to moderate Alzheimer disease (AD) that was interrupted because of meningoencephalitis in 6% of immunized patients. METHODS: This randomized, multicenter, placebo-controlled, double-blind trial of IM AN1792 225 microg plus the adjuvant QS-21 50 microg (300 patients) and saline (72 patients) included patients aged 50 to 85 years with probable AD, Mini-Mental State Examination (MMSE) 15 to 26. Injections were planned for months 0, 1, 3, 6, 9, and 12. Safety and tolerability were evaluated, and pilot efficacy (AD Assessment Scale-Cognitive Subscale [ADAS-Cog], MRI, neuropsychological test battery [NTB], CSF tau, and Abeta42) was assessed in anti-AN1792 antibody responder patients (immunoglobulin G titer > or = 1:2,200). RESULTS: Following reports of meningoencephalitis (overall 18/300 [6%]), immunization was stopped after one (2 patients), two (274 patients), or three (24 patients) injections. Of the 300 AN1792(QS-21)-treated patients, 59 (19.7%) developed the predetermined antibody response. Double-blind assessments were maintained for 12 months. No significant differences were found between antibody responder and placebo groups for ADAS-Cog, Disability Assessment for Dementia, Clinical Dementia Rating, MMSE, or Clinical Global Impression of Change, but analyses of the z-score composite across the NTB revealed differences favoring antibody responders (0.03 +/- 0.37 vs -0.20 +/- 0.45; p = 0.020). In the small subset of subjects who had CSF examinations, CSF tau was decreased in antibody responders (n = 11) vs placebo subjects (n = 10; p < 0.001). CONCLUSION: Although interrupted, this trial provides an indication that Abeta immunotherapy may be useful in Alzheimer disease.
Aged↗
[Consensus statement on severe dementia].
Under the auspices of the French Society of Gerontology and Geriatrics, a multidisciplinary team including geriatritians, neurologists, epidemiologists, psychiatrists, pharmacologists and public health specialists developed a consensus on care for patients with severe dementia. They defined 21 recommendations for general practitioners, long-term care physicians and specialists based on knowledge available in 2005. At all stages of the disease, the objective of care is to improve as much as possible quality-of-life for the patient and his/her family, including a life project until the end of life. It is always possible to do something for these patients and their family: nutritional status, behavior disorders, and incapacities to deal with basic activities of daily life have to be taken in consideration. Resource allocation and proximity care have to be targeted. Research areas necessary to improve the care of patients with severe dementia has been selected.
Aged↗
[Cognitive functions and hypertension].
The prevention of cognitive disorders and dementia represents a major challenge in the coming years. Hypertension is one of the principal risk factors for cerebrovascular diseases and is also closely correlated with cognitive decline and dementia. Most longitudinal studies have shown that cognitive functioning is often inversely proportional to blood pressure values measured 15 or 20 years previously. The higher blood pressure was, the poorer cognitive function is. Data from recent therapeutic trials (SYST-EUR, PROGRESS) open the way toward the prevention of dementia (vascular or Alzheimer's type) by antihypertensive treatments. In this context, the effect of antihypertensive treatment on cognitive functions should represent one of the primary criteria of assessment in future morbidity and mortality studies in hypertensive patients.
Antihypertensive Agents↗
Evolution of blood pressure in patients with Alzheimer's disease: a one year survey of a French Cohort (REAL.FR).
OBJECTIVES: 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. METHODS: 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. RESULTS: 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, p < 0.05) and DBP, (77.6 +/- 12 to 75.8 +/- 10 mmHg , p < 0.05). 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 , p < 0.05; Delta SBP tertile 3 ADAS-Cog vs tertile 1 ADAS-Cog = - 5.98 vs + 2.98 mmHg, p < 0.05, Delta SBP ADL 0-4 vs ADL -6 = - 8.7 vs -1.5 mmHg, p < 0.05, delta SBP CDR 10-18 vs CDR 0.5-9.5 = - 6.9 vs -1.7 mmHg, p < 0.05). 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. CONCLUSIONS: 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.
Activities of Daily Living↗
[Is there evidence that treatment of hypertension in the aged decreases the risk of cerebral ischaemic disease?].
Explore the source record for details and available documents.
Aged↗
Diuretics for cardiovascular prevention in the elderly.
High blood pressure (BP) is a major risk factor for cardiovascular and cerebrovascular diseases in elderly subjects. Antihypertensive drugs have shown clinical benefit both in primary and secondary prevention of cardiovascular events. If BP lowering represents the major determinant of the effects conferred by the antihypertensive treatment for prevention, recent studies have suggested some differences between classes of antihypertensive drugs according to age. Based on the available clinical data, the recent medical guidelines have recommended thiazide-type diuretics as the preferred drug for the treatment of elderly hypertensive patients, followed by long-acting calcium antagonists. Indeed, diuretics constitute one of the most valuable classes of antihypertensive drugs, and in the elderly, diuretic-based treatment studies have been clearly shown to prevent major cardiovascular events, including stroke, heart failure and coronary heart disease.
Aged↗
Donepezil for the treatment of mild to moderate Alzheimer's disease in France: the economic implications.
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.
Aged↗
[Relationship between arterial pressure and cognitive functions. Data for the French Network on Alzheimer's disease (REAL.FR)].
UNLABELLED: The relationships between arterial hypertension and cognitive decline are complex and studies indicate controversial results. OBJECTIVES: To evaluate, in a cross sectional study, the relationships between cognitive functions and blood pressure in a population of subjects with Alzheimer's disease. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Aged↗
[Cognitive decline and hypertension].
The prevalence and incidence of degenerative and vascular dementia increase exponentially with age. Several studies in recent years have implicated hypertension as a risk factor not only for vascular dementia but also for degenerative dementia such as Alzheimer's disease. This is an important finding because it suggests that the treatment of hypertension could reduce the incidence of dementia. In particular, the results of the Syst-Eur study, showing that a calcium inhibitor, nitrendipine, could reduce not only the incidence of stroke but also that of dementia, should be confirmed.
Adult↗
[Reflexion of French experts on the key points of the symposium].
The French experts present at the Eutherapy Symposium held in Prague confirmed the importance of left ventricular hypertrophy (LVH) and microalbuminuria as major independent risk factors for cardiovascular disease. Factors that must be considered for the treatment of hypertension in patients, particularly with type 2 diabetes. Professor J.M. Mallion stressed the contribution of thiazide and thiazide-like diruetics as indapamid, especially the 1.5 mg SR formulation. Professor F. Forette and Doctor O. Hanon recalled that the HYVET study is expected to confirm the beneficial effect of this same treatment on morbidity and mortality in very elderly patients. Professor O. Dubourg recalled the beneficial effect of indapamid SR on LVH demonstrated in the LIVE study. Likewise, Professor M. Marre emphasized its important impact on microalbuminuria as shown in the NESTOR study.
Adult↗
Blood pressure, cognitive functions, and prevention of dementias in older patients with hypertension.
The prevalence and incidence of degenerative and vascular dementias increase exponentially with age, from 70 years onward. In view of the increasing longevity of humans, both varieties are bound to evolve into a major problem worldwide. According to several longitudinal studies, hypertension appears to predispose individuals to the development of cognitive impairment and ensuing dementia, after a period varying from a few years to several decades. Antihypertensive drug treatment, according to preliminary evidence, may serve to reduce the rates of such events. Such findings await to be confirmed by formal therapeutic trials against a backdrop of "historical" observational sources.
Aged↗
Hypertension and dementia.
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. The fact that antihypertensive treatment has been demonstrated to decrease that risk offers a new opportunity to reduce the prevalence of such related disorders and promote healthy aging.
Antihypertensive Agents↗
[Cerebral complications of hypertension in the elderly].
PURPOSE: 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. CURRENT KNOWLEDGE AND KEY POINTS: 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. FUTURE PROSPECTS AND PROJECTS: 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).
Aged↗
Association of the apolipoprotein E epsilon4 allele with late-onset depression.
Apolipoprotein E (ApoE) phenotyping was determined in 42 subjects with Alzheimer's disease (AD), 49 with depression, including 26 with early-onset depression (EOD) and 23 with late-onset depression (LOD), and 49 controls. In the EOD group, the frequency of the ApoE epsilon4 allele was not different from the control frequency (p = 0.532) but was significantly lower than in AD (p < 0.001). In the LOD group, the ApoE epsilon4 frequency was significantly higher than in the controls (p = 0.034) but was not different from that in the AD group (p = 0.229). Individuals with ApoE epsilon4 were at greater risk of getting AD (odds ratio, OR = 5.5, 95% confidence interval, CI, 2.0-14.0) or LOD (OR = 6.1, 95% CI, 1.9-19.0) than of EOD (OR = 0.7, 95% CI, 0.2-2.5). These results suggest an association between the ApoE epsilon4 allele frequency and LOD. Patients with LOD could be at risk of developing AD by an epsilon4-dependent pathway.
Age of Onset↗
Vitamin D status and redefining serum parathyroid hormone reference range in the elderly.
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.
Aged↗
Hypertension in the Very Elderly Trial (HYVET): protocol for the main trial.
A number of trials and meta-analyses have demonstrated clear benefits of blood pressure (BP) reduction in patients aged <80 years with regard to the reduction in stroke and cardiovascular events. However, a variety of studies have suggested that the positive relationship between BP and cardiovascular mortality is weakened or indeed reversed in the very elderly. Most intervention trials to date have either excluded or not recruited sufficient patients aged > or =80 years to determine whether there is a significant benefit from treatment in this age group. A meta-analysis of intervention trials that recruited patients aged > or =80 years has suggested a benefit in terms of stroke reduction but has also raised the possibility of an increase in total mortality. The benefit to risk ratio therefore needs to be clearly established before recommendations can be made for treating very elderly patients with hypertension. The Hypertension in the Very Elderly Trial (HYVET) pilot recruited 1283 patients aged > or =80 years and showed the feasibility of performing such a trial in this age group. It was a Prospective Randomised Open Blinded End-Points (PROBE) design but the main trial has additional pharmaceutical sponsorship to run a double-blind trial. Therefore, the main trial is a randomised, double-blind, placebo-controlled trial designed to assess the benefits of treating very elderly patients with hypertension. It compares placebo with a low dose diuretic (indapamide sustained release 1.5mg daily) and additional ACE inhibitor (perindopril) therapy if required. As in the pilot trial, the primary end-point is stroke events (fatal and non-fatal) and the trial is designed to determine whether or not a 35% difference occurs between placebo and active treatment. The main objective will be achieved with 90% power at the 1% level of significance. Secondary outcome measures will include total mortality, cardiovascular mortality, cardiac mortality, stroke mortality and skeletal fracture. 2100 patients aged > or =80 years are to be recruited and followed up for an average of 5 years. Entry BP criteria after 2 months of a single-blind placebo run-in period are a sustained sitting systolic BP (SBP) of 160 to 199mm Hg and a diastolic BP of 90 to 109mm Hg. The standing SBP must be >140mm Hg. The trial will be carried out in accordance with the principles of Good Clinical Practice. We describe in detail the protocol for the main trial and discuss the reasons for the changes from the pilot, the use of the drug regimen, and the BP criteria to be used in the trial.
Age Factors↗