ABSTRACT
BACKGROUND: Frailty has emerged as one of the major risk factors of loss of autonomy and it can be reverted through early and appropriate interventions. A wide range of available frailty screening tools are administered, mainly in clinical settings. However, few frailty instruments are self-administered. OBJECTIVES: The aim of this study was to determine the diagnostic test accuracy of a modified self-administered questionnaire derived from the Study of Osteoporotic Fractures (SOF) index against the Fried frailty phenotype in identifying frailty. DESIGN: Observational, multicenter, diagnostic test accuracy study. PARTICIPANTS: Participants aged 70 and over, living at home or in community-dwelling (n=5134) in two centers in France were contacted. MEASUREMENTS: Participants were mailed self-administered questionnaires derived from the SOF index. Responders who accepted the home evaluation were assessed by trained nurses, blinded to results of the questionnaire, using the Fried frailty phenotype as the reference method. RESULTS: The questionnaire was sent to 5134 participants, of which 1878 (36.6%) met inclusion criteria and returned the questionnaire. Fried frailty assessments were obtained in 691 (35.4%) participants. A total of 639 subjects had a complete evaluation on both the self-administered questionnaire and the Fried phenotype. Mean age was 78.9 (standard deviation [SD]: 5.95) years and 359 (56.2%) participants were women. According to the questionnaire, 159 (24.9%) subjects were considered frail, 172 (26.9%) pre-frail, and 308 (48.2) robust. With the home evaluation, Fried frailty phenotype results were respectively, 114 (17.8%), 295 (46.2%) and 230 (36%). The self-administered questionnaire presented a sensitivity of 66.6% (95% CI: 57.2-75.2) and a specificity of 84.2% (95% CI: 80.8-87.2). CONCLUSIONS: A self-administered questionnaire can be used in elders and represents an opportunity for empowering them in the management of their health in the context of frailty.
Subject(s)
Frailty , Humans , Female , Aged , Male , Frailty/diagnosis , Frailty/prevention & control , Frail Elderly , Predictive Value of Tests , Postal Service , Geriatric Assessment/methods , Independent LivingABSTRACT
PURPOSE: Evaluation of neuropsychological benefits of cataract surgery for 46 Alzheimer patients on the basis of neuropsychiatric index (NPI), as the principal criterion of analysis of the VIVA study. METHODS: Prospective, monocentric neuropsychiatric study, performed from 2005 to 2011. All Alzheimer's patients with 10Subject(s)
Alzheimer Disease/complications
, Cataract Extraction/psychology
, Cataract/complications
, Mental Disorders/complications
, Vision Disorders/etiology
, Activities of Daily Living
, Aged
, Aged, 80 and over
, Alzheimer Disease/psychology
, Alzheimer Disease/surgery
, Caregivers/psychology
, Cataract/psychology
, Cataract/rehabilitation
, Cataract Extraction/rehabilitation
, Cataract Extraction/statistics & numerical data
, Cost of Illness
, Female
, Humans
, Male
, Mental Disorders/psychology
, Mental Disorders/surgery
, Neuropsychological Tests
, Vision Disorders/psychology
, Vision Disorders/surgery
, Visual Acuity
ABSTRACT
BACKGROUND: The aim of this volumetric study was to explore the neuroanatomical correlates of the Free and Cued Selective Reminding Test (FCSRT) and the Delayed Matching-to-Sample-48 items (DMS-48), two tests widely used in France to assess verbal and visual anterograde memory. We wanted to determine to what extent the two tests rely on the medial temporal lobe, and could therefore be predictive of Alzheimer's disease, in which pathological changes typically start in this region. METHODS: We analysed data from a cohort of 138 patients with mild cognitive impairment participating in a longitudinal multicentre clinical research study. Verbal memory was assessed using the FCSRT and visual recognition memory was evaluated using the DMS-48. Performances on these two tests were correlated to local grey matter atrophy via structural MRI using voxel-based morphometry. RESULTS: Our results confirm the existence of a positive correlation between the volume of the medial temporal lobe and the performance on the FCSRT, prominently on the left, and the performance on the DMS-48, on the right, for the whole group of patients (family-wise error, P < 0.05). Interestingly, this region remained implicated only in the subgroup of patients who had deficient scores on the cued recall of the FCSRT, whereas the free recall was associated with prefrontal aspects. For the DMS-48, it was only implicated for the group of patients whose performances declined between the immediate and delayed trial. Conversely, temporo-parietal cortices were implicated when no decline was observed. Within the medial temporal lobe, the parahippocampal gyrus was prominently involved for the FCSRT and the immediate trial of the DMS-48, whereas the hippocampus was solely involved for the delayed trial of the DMS-48. CONCLUSIONS: The two tests are able to detect an amnestic profile of the medial temporal type, under the condition that the scores remain deficient after the cued recall of the FCSRT or decline on the delayed recognition trial of the DMS-48. Strategic retrieval as well as perceptual/attentional processes, supported by prefrontal and temporo-parietal cortices, were also found to have an impact on the performances. Finally, the implication of the hippocampus appears time dependent, triggered by a longer delay than the parahippocampus, rather than determined by the sense of recollection or the encoding strength associated with the memory trace.
Subject(s)
Amnesia, Anterograde/etiology , Brain/diagnostic imaging , Cognitive Dysfunction/complications , Cognitive Dysfunction/diagnostic imaging , Magnetic Resonance Imaging , Aged , Aged, 80 and over , Brain Mapping , Cohort Studies , Female , Humans , Image Processing, Computer-Assisted , Male , Neuropsychological Tests , Photic Stimulation , Psychiatric Status Rating Scales , Recognition, Psychology/physiologyABSTRACT
Tumor protein 53 induced nuclear protein 1 (TP53INP1) is a p53 target gene that induces cell growth arrest and apoptosis by modulating p53 transcriptional activity. TP53INP1 interacts physically with p53 and is a major player in the p53-driven oxidative stress response. Previously, we demonstrated that TP53INP1 is downregulated in an early stage of pancreatic cancerogenesis and when restored is able to suppress pancreatic tumor development. TP53INP1 downregulation in pancreas is associated with an oncogenic microRNA miR-155. In the present work, we studied the effects of TP53INP1 on cell migration. We found that TP53INP1 inactivation correlates with increased cell migration both in vivo and in vitro. The impact of TP53INP1 expression on cell migration was studied in different cellular contexts: mouse embryonic fibroblast and different pancreatic cancer cell lines. Its expression decreases cell migration by the transcriptional downregulation of secreted protein acidic and rich in cysteine (SPARC). SPARC is a matrix cellular protein, which governs diverse cellular functions and has a pivotal role in regulating cell-matrix interactions, cellular proliferation and migration. SPARC was also showed to be upregulated in normal pancreas and in pancreatic intraepithelial neoplasia lesions in a pancreatic adenocarcinoma mouse model only in the TP53INP1-deficient animals. This novel TP53INP1 activity on the regulation of SPARC expression could explain in part its tumor suppressor function in pancreatic adenocarcinoma by modulating cellular spreading during the metastatic process.
Subject(s)
Carrier Proteins/physiology , Cell Movement/physiology , Heat-Shock Proteins/physiology , Osteonectin/metabolism , Pancreatic Neoplasms/pathology , Down-Regulation , HumansABSTRACT
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.
Subject(s)
Alzheimer Disease/physiopathology , Blood Pressure/physiology , Activities of Daily Living , Aged , Alzheimer Disease/psychology , Cognition Disorders/etiology , Cognition Disorders/physiopathology , Female , Follow-Up Studies , Humans , Longitudinal Studies , Male , Regression AnalysisABSTRACT
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.
Subject(s)
Antihypertensive Agents/therapeutic use , Cognition Disorders/etiology , Dementia/etiology , Hypertension/complications , Clinical Trials as Topic , Cognition Disorders/prevention & control , Dementia/prevention & control , Humans , Hypertension/drug therapy , Hypertension/physiopathologyABSTRACT
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.
Subject(s)
Antihypertensive Agents/therapeutic use , Benzothiadiazines , Blood Pressure/drug effects , Cardiovascular Diseases/prevention & control , Hypertension/drug therapy , Sodium Chloride Symporter Inhibitors/therapeutic use , Aged , Aged, 80 and over , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/pharmacology , Calcium Channel Blockers/administration & dosage , Calcium Channel Blockers/pharmacology , Calcium Channel Blockers/therapeutic use , Cardiovascular Diseases/etiology , Diuretics , Drug Therapy, Combination , Humans , Hypertension/complications , Middle Aged , Randomized Controlled Trials as Topic , Sodium Chloride Symporter Inhibitors/administration & dosage , Sodium Chloride Symporter Inhibitors/pharmacology , Treatment OutcomeABSTRACT
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.
Subject(s)
Alzheimer Disease/drug therapy , Alzheimer Disease/economics , Indans/economics , Indans/therapeutic use , Nootropic Agents/economics , Nootropic Agents/therapeutic use , Piperidines/economics , Piperidines/therapeutic use , Aged , Cost-Benefit Analysis , Donepezil , France , Health Expenditures , Humans , Models, Econometric , Practice Patterns, Physicians' , Severity of Illness IndexABSTRACT
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.
Subject(s)
Cognition Disorders/etiology , Dementia, Vascular/etiology , Hypertension/complications , Adult , Aged , Aging , Antihypertensive Agents/therapeutic use , Clinical Trials as Topic , Cognition Disorders/prevention & control , Dementia, Vascular/prevention & control , Humans , Hypertension/drug therapy , Middle Aged , Nitrendipine/therapeutic use , Risk FactorsABSTRACT
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.
Subject(s)
Alzheimer Disease/physiopathology , Alzheimer Disease/psychology , Blood Pressure , Cognition , Aged , Alzheimer Disease/complications , Cognition Disorders/complications , Cross-Sectional Studies , Female , France , Humans , Hypertension/complications , Male , Prospective StudiesABSTRACT
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.
Subject(s)
Antihypertensive Agents/therapeutic use , Dementia/etiology , Hypertension/complications , Antihypertensive Agents/pharmacology , Dementia/epidemiology , Dementia, Vascular/epidemiology , Dementia, Vascular/etiology , Humans , Hypotension , Longitudinal Studies , Risk FactorsABSTRACT
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.
Subject(s)
Alzheimer Disease/prevention & control , Blood Pressure , Cognition , Dementia, Vascular/prevention & control , Hypertension/complications , Hypertension/psychology , Aged , Aged, 80 and over , Alzheimer Disease/etiology , Alzheimer Disease/physiopathology , Antihypertensive Agents/therapeutic use , Cognition/drug effects , Cognition/physiology , Dementia, Vascular/etiology , Dementia, Vascular/physiopathology , Humans , Hypertension/drug therapyABSTRACT
Ischaemic and degenerative brain diseases are a major health problem leading to a devastating loss of autonomy. Hypertension has been shown to carry an increased risk not only for cerebrovascular morbidity and mortality but also for cognitive impairment and dementia. Although diastolic blood pressure is considered an important risk factor, it is now clear that isolated systolic hypertension and elevated pulse pressure also play an important role in the development of brain complications. Therefore the treatment of these conditions must urgently become a widespread tool of prevention. All the randomised placebo-controlled trials completed for the last 30 years have shown a reduction in fatal and/or non-fatal strokes. In the most recent trials in isolated systolic hypertension in older patients, the benefit was even greater because of the higher risk in these populations. 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. Active treatment in the Syst-Eur trial based on nitrendipine as first step, possibly associated with enalapril and/or hydrochlorthiazide reduced not only stroke and cardiovascular complications but also the incidence of dementia including Alzheimer's disease. This important finding must be confirmed by further trials specifically focusing on the prevention of dementia. In addition, the importance of pulse pressure as a risk factor, underlines the need for new drugs which could increase aortic distensibility and decrease systolic blood pressure without greatly reducing diastolic pressure. Improving the management of hypertension offers new opportunities to reduce age-related disease in older people and to promote healthy aging.
Subject(s)
Brain Ischemia/etiology , Dementia/etiology , Hypertension/complications , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Blood Pressure , Brain Ischemia/epidemiology , Brain Ischemia/prevention & control , Calcium Channel Blockers/therapeutic use , Dementia/epidemiology , Dementia/prevention & control , Diuretics/therapeutic use , Drug Therapy, Combination , Humans , Hypertension/drug therapy , Hypertension/epidemiology , Hypertension/physiopathology , Incidence , Prognosis , Randomized Controlled Trials as Topic , Survival RateABSTRACT
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.
Subject(s)
Antihypertensive Agents , Hypertension/drug therapy , Hypertension/physiopathology , Age Factors , Aged , Aged, 80 and over , Antihypertensive Agents/adverse effects , Antihypertensive Agents/therapeutic use , Blood Pressure , Humans , Treatment OutcomeABSTRACT
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.
Subject(s)
Antihypertensive Agents/therapeutic use , Dementia/prevention & control , Hypertension/complications , Hypertension/drug therapy , Antihypertensive Agents/pharmacology , Calcium Channel Blockers/therapeutic use , Cognition Disorders/prevention & control , Dementia/etiology , Dementia/physiopathology , Humans , Hypertension/physiopathology , Nitrendipine/therapeutic useABSTRACT
UNLABELLED: 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 (p < or = 0.001) in the active-treatment group, but on average the MMSE scores remained stable in both groups. CONCLUSION: 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.
Subject(s)
Antihypertensive Agents/therapeutic use , Dementia/prevention & control , Hypertension/drug therapy , Aged , Dementia/epidemiology , Double-Blind Method , Europe/epidemiology , Female , Humans , Incidence , MaleABSTRACT
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.
Subject(s)
Family Practice , Health Care Surveys , Hypertension/therapy , Adult , Aged , Aged, 80 and over , Blood Pressure/physiology , Female , France , Humans , Hypertension/diagnosis , Male , Middle Aged , Risk Factors , Surveys and QuestionnairesABSTRACT
The Systolic Hypertension in Europe (Syst-Eur) trial proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in older (> or = 60 years) patients with isolated systolic hypertension (systolic BP > or = 160 mm Hg and diastolic BP < 95 mm Hg). After the completion of the Syst-Eur trial on 14 February 1997, 3506 consenting patients (93.0% of those eligible) were enrolled in phase 2 of the Syst-Eur trial. This open follow-up study aims to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine. To lower the sitting systolic BP below 150 mm Hg (target BP), the first-line agent nitrendipine (10-40 mg/day) may be associated with enalapril (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), both add-on study drugs, or if required any other antihypertensive agent. On 1 November 1998, 3248 patients were still being followed, 86 patients had proceeded to non-supervised follow-up, and 43 had died. The median follow-up in Syst-Eur 2 was 14.3 months. At the last available visit, systolic/diastolic BP in the patients formerly randomised to placebo (n = 1682) or active treatment (n = 1824), had decreased by 13.2/5.2 mm Hg and by 4.6/1.6 mm Hg, respectively, so that the between-group BP difference was 1.7 mm Hg systolic (95% Ci: 0.8 to 2.6 mm Hg; P < 0.001) and 0.9 mm Hg diastolic (95% Cl: 0.4 to 1.5 mm mm Hg; P < 0.001). At the beginning of Syst-Eur 2, the goal BP was reached by 25.4% and 50.6% of the former placebo and active-treatment groups; at the last visit these proportions were 55.9% and 63.1%, respectively. At that moment, 45.9% of the patients were on monotherapy with nitrendipine, 29.3% took nitrendipine in combination with other study drugs. Until the end of 2001, BP control of the Syst-Eur 2 patients will be further improved. Cardiovascular complications and adverse events, such as cancer or gastro-intestinal bleeding, will be monitored and validated by blinded experts.
Subject(s)
Antihypertensive Agents/therapeutic use , Calcium Channel Blockers/therapeutic use , Hypertension/drug therapy , Aged , Aged, 80 and over , Blood Pressure Determination , Dihydropyridines/administration & dosage , Drug Administration Schedule , Drug Therapy, Combination , Enalapril/administration & dosage , Europe , Female , Follow-Up Studies , Humans , Hydrochlorothiazide/administration & dosage , Hypertension/diagnosis , Hypertension/mortality , Male , Nifedipine/administration & dosage , Prognosis , Survival Rate , Treatment OutcomeABSTRACT
Hypertension is a risk factor for dementia, particularly vascular dementia. The objective of the "Vascular Dementia" project of the European multicentre Syst-Eur trial was to study the influence of antihypertensive therapy on the incidence of dementia in elderly patients with isolated systolic hypertension included in this trial. Patients were over the age of 60, with systolic blood pressure between 160 and 219 mmHg and diastolic blood pressure less than 95 mmHg in the sitting position and were not demented. After randomization, they were treated under double-blind conditions with nitrendipine associated with or replaced by enalapril or hydrochlorothiazide or an equivalent placebo. Cognitive functions were evaluated by the Mini-Mental State test (MMS) on inclusion then annually. When the MMS score was < or = 23, a complementary assessment was performed to establish the diagnosis of dementia according to DSM III-R criteria. The Modified Ischaemia score specified the aetiology of dementia. A total of 1180 and 1238 subjects were randomized to the placebo and active treatment groups, respectively. They presented comparable characteristics on inclusion. The median intent to treat duration of follow-up was 2.0 years. The incidence of dementia was decreased by 50%, from 7.7 per thousand patient-years in the placebo group to 3.8 per thousand patient-years in the active group (p = 0.05). There were 15 and 8 cases of dementia of the Alzheimer type, 4 and 3 cases of mixed dementia, 2 and 0 cases of vascular dementia in the placebo and active treatment groups, respectively. In conclusion, in subjects over the age of 60 years with isolated systolic HT, antihypertensive treatment initiated with nitrendipine can reduce the incidence of dementia.