Blood pressure lowering and prevention of dementia: an individual patient data meta-analysis.

AIMS: Observational studies indicate U-shaped associations of blood pressure (BP) and incident dementia in older age, but randomized controlled trials of BP-lowering treatment show mixed results on this outcome in hypertensive patients. A pooled individual participant data analysis of five seminal randomized double-blind placebo-controlled trials was undertaken to better define the effects of BP-lowering treatment for the prevention of dementia. METHODS AND RESULTS: Multilevel logistic regression was used to evaluate the treatment effect on incident dementia. Effect modification was assessed for key population characteristics including age, baseline systolic BP, sex, and presence of prior stroke. Mediation analysis was used to quantify the contribution of trial medication and changes in systolic and diastolic BP on risk of dementia. The total sample included 28 008 individuals recruited from 20 countries. After a median follow-up of 4.3 years, there were 861 cases of incident dementia. Multilevel logistic regression reported an adjusted odds ratio 0.87 (95% confidence interval: 0.75, 0.99) in favour of antihypertensive treatment reducing risk of incident dementia with a mean BP lowering of 10/4 mmHg. Further multinomial regression taking account of death as a competing risk found similar results. There was no effect modification by age or sex. Mediation analysis confirmed the greater fall in BP in the actively treated group was associated with a greater reduction in dementia risk. CONCLUSION: The first single-stage individual patient data meta-analysis from randomized double-blind placebo-controlled clinical trials provides evidence to support benefits of antihypertensive treatment in late-mid and later life to lower the risk of dementia. Questions remain as to the potential for additional BP lowering in those with already well-controlled hypertension and of antihypertensive treatment commenced earlier in the life-course to reduce the long-term risk of dementia. CLASSIFICATION OF EVIDENCE: Class I evidence in favour of antihypertensive treatment reducing risk of incident dementia compared with placebo.

Healthcare costs associated with elderly chronic pain patients in primary care.

OBJECTIVE: This study aimed to estimate the total healthcare costs associated with elderly chronic pain (CP) patients, define cost-related factors in this population, and examine cost evolution over two years. METHOD: This is an ancillary study from the CP S.AGE subcohort, including non-institutionalized patients aged over 65 suffering from CP. 1190, 1108, 1042, and 950 patients were reviewed with available healthcare data at follow-up visits at 6, 12, 18, and 24 months, respectively. Healthcare components included medical and paramedical visits, medication prescription, and hospitalization. RESULT: The mean total cost in the first semester was estimated at 2548 ± 8885 per patient. Hospitalization represented the largest cost component (50%) followed by paramedical care (24%), medications (21%), and medical visits (5%). Significant cost-associated factors were comorbidity (OR 1.49, 95% CI 1.35-1.64), dependency in daily activities (OR 1.85, 95% CI 1.39-2.47), probable depression (OR 1.71, 95% CI 1.09-2.69), permanent pain (OR 1.48, 95% CI 1.18-1.86), neuropathic pain (OR 1.94, 95% CI 1.38-2.73), living alone (OR 1.45, 95% CI 1.16-1.82), chronic back pain (OR 1.35, 95% CI 1.07-1.71), and vertebral fracture/compression (OR 1.47, 95% CI 1.08-2.01). Healthcare costs increased significantly by 48% (p < 0.0001) during follow-up namely due to hospitalizations. Elevated costs were associated with a higher risk of future hospitalization (OR 1.95, CI 95% 1.33-2.87). CONCLUSION: Healthcare costs increased rapidly over time, largely due to hospitalization. Prevention strategies to limit hospitalizations in elderly appear to be the most useful in order to achieve cost savings in the future.

Do male and female general practitioners differently prescribe chronic pain drugs to older patients?

OBJECTIVE: The aim of this study was to identify the relationship between general practitioner (GP) gender and prescribing practice of chronic pain drugs in older adults. DESIGN: Cross-sectional observational study. SETTING: GPs in private practice throughout France. SUBJECTS: Two hundred and sixty GPs (80.8% male and 19.2% female) enrolled 1,379 (28.4% male and 71.6% female) noninstitutionalized patients over 65 years of age, suffering from chronic pain. METHODS: A comparison of prescribing habits between male and female GPs was performed on baseline data with univariate analyses followed by multivariate analyses after taking several confounding factors into account. RESULTS: No significant differences were found when comparing male and female GPs' prescriptions of World Health Organization step 1, step 2, and step 3 analgesics. Male GPs were more likely than female GPs to prescribe antineuropathic pain drugs (11.3% of patients with male GPs versus 4.8% of patients with female GPs, P = 0.004) and less likely to prescribe symptomatic slow-acting drugs for osteoarthritis (SySADOA) (10.2% of male GPs' patients versus 18.8% of female GPs' patients, P = 0.0003). After adjusting for several confounding factors, male GPs were still more likely to prescribe antineuropathic pain drugs (OR 2.43, 95% CI 1.15-5.14, P = 0.02) and less likely to prescribe symptomatic slow-acting drugs (OR 0.64, 95% CI 0.42-0.97, P = 0.03). CONCLUSION: Male and female GPs prescribe analgesics in a similar manner. However, male GPs prescribe more antineuropathic pain drugs, but fewer SySADOA.

Predicting falls in elderly patients with chronic pain and other chronic conditions.

BACKGROUND: The aim was to identify fall predictors in elderly suffering from chronic pain (CP) and to test their applicability among patients with other chronic conditions. METHODS: 1,379 non-institutionalized patients aged 65 years and older who were suffering from CP (S.AGE CP sub-cohort) were monitored every 6 months for 1 year. Socio-demographic, clinical and pain data and medication use were assessed at baseline for the association with falls in the following year. Falls were assessed retrospectively at each study visit. Logistic regression analyses were performed to identify fall predictors. The derived model was applied to two additional S.AGE sub-cohorts: atrial fibrillation (AF) (n = 1,072) and type-2 diabetes mellitus (T2DM) (n = 983). RESULTS: Four factors predicted falls in the CP sub-cohort: fall history (OR: 4.03, 95 % CI 2.79-5.82), dependency in daily activities (OR: 1.81, 95 % CI 1.27-2.59), age ≥75 (OR: 1.53, 95 % CI 1.04-2.25) and living alone (OR: 1.73, 95 % CI 1.24-2.41) (Area Under the Curve: AUC = 0.71, 95 % CI 0.67-0.75). These factors were relevant in AF (AUC = 0.71, 95 % CI 0.66-0.75) and T2DM (AUC = 0.67, 95 % CI 0.59-0.73) sub-cohorts. Fall predicted probability in CP, AF and T2DM sub-cohorts increased from 7, 7 and 6 % in patients with no risk factors to 59, 66 and 45 % respectively, in those with the four predictors. Fall history was the strongest predictor in the three sub-cohorts. CONCLUSION: Fall history, dependency in daily activities, age ≥75 and living alone are independent fall predictors in CP, AF and T2DM patients.

Older age at retirement is associated with decreased risk of dementia.

To test the hypothesis that age at retirement is associated with dementia risk among self-employed workers in France, we linked health and pension databases of self-employed workers and we extracted data of those who were still alive and retired as of December 31st 2010. Dementia cases were detected in the database either through the declaration of a long-term chronic disease coded as Alzheimer's disease and other dementia (International Classification of Disease codes G30, F00, F01, F03) or through the claim for reimbursement of one of the anti-dementia drugs. Data were analyzed using Cox proportional hazard model adjusting for potential confounders. Among the 429,803 retired self-employed workers alive on December 31st 2010, prevalence of dementia was 2.65 %. Multivariable analyses showed that the hazard ratio of dementia was 0.968 [95 % confidence interval = (0.962-0.973)] per each extra year of age at retirement. After excluding workers who had dementia diagnosed within the 5 years following retirement, the results remained unchanged and highly significant (p < 0.0001). We show strong evidence of a significant decrease in the risk of developing dementia associated with older age at retirement, in line with the "use it or lose it" hypothesis. Further evidence is necessary to evaluate whether this association is causal, but our results indicate the potential importance of maintaining high levels of cognitive and social stimulation throughout work and retiree life.

Consequences of dextropropoxyphene market withdrawal in elderly patients with chronic pain.

OBJECTIVE: Describe the consequences of dextropropoxyphene (DXP) market withdrawal on analgesic prescriptions and on the quality of therapeutic management of chronic pain. PATIENTS AND METHODS: From a cohort of non-institutionalised elderly patients with chronic pain recruited by general practitioners, we selected patients who were treated with DXP daily for at least 6 months just prior to DXP market withdrawal and who had an evaluation of pain and its impact on daily activities before and after DXP withdrawal. RESULTS: One hundred three patients took DXP daily for chronic pain. Immediately after DXP market withdrawal, 42 (40.8%), 55 (53.4%) and 3 (2.9%) patients were treated with step 1, 2 and 3 analgesics, respectively, and 3 patients (2.9%) were no longer receiving any analgesic medication. Among the 55 patients who continued on step 2 analgesics, 37 were treated with tramadol, 14 with codeine and 9 with opium. Pain intensity and the impact of pain on daily activities remained stable. CONCLUSION: DXP market withdrawal had no consequences on the intensity or impact of chronic pain in elderly patients.

[Evaluation of a workplace health promotion program]. / Évaluation d'un programme de promotion de la santé conduit en entreprise.

OBJECTIVE: Some studies suggest that a workplace prevention programme could reduce health inequalities related to education level and improve the health status of the employees. The objective of the study was to demonstrate the advantages for a company to implement a health prevention programme in the workplace in order to: 1-improve health literacy 2 - change health-related behaviours 3-improve the company image. METHODS: A "before - after" methodology was used in a population of 2153 employees of three companies. Three areas of prevention were considered: nutrition, physical activity and prevention of back pain. The successive steps of the EBS programme included general communication, group workshops and individual coaching. Data collection was carried out using anonymous questionnaires sent by e-mail. A global assessment was performed based on the companies' pooled data, with separate analysis according to the steps of the programme. RESULTS: The programme mobilized employees with participation rates ranging from 25% to 45.5%. After completion of the full programme, 77.5% of respondents reported an improvement of their health knowledge versus 50.3% of those who only received general communication. Behavioural modification was observed, especially in the fields of nutrition and back pain.. EBS can be considered to be a vector of the company image for almost 7 out of 10 employees. CONCLUSION: A health prevention education programme provided by the company in the workplace mobilizes employees and contributes to improvement of health knowledge and behaviour change. All approaches tested were important and applicable to various types of companies or workers.

National observatory on the therapeutic management in ambulatory care patients aged 65 and over, with type 2 diabetes, chronic pain or atrial fibrillation.

The primary objective of the S.AGES cohort is to describe the real-life therapeutic care of elderly patients. Patients and methods. This is a prospective observational cohort study of 3 700 non-institutionalized patients over the age of 65 years with either type 2 diabetes mellitus (T2DM), chronic pain or atrial fibrillation (AF) recruited by French general practitioners (GPs). Follow-up is planned for 3 years. Baseline characteristics. In the chronic pain sub-cohort, 33% of patients are treated with only grade 1 analgesics, 29% with grade 2 analgesics and 3% with grade 3 analgesics, and 22% have no pain treatment. In the T2DM sub-cohort, 61% of patients have well-controlled diabetes (Hb1c<7%) and 18% are treated with insulin. In the AF sub-cohort, 65% of patients have a CHADS2 score greater than 2, 77% are treated with oral anticoagulants, 17% with platelet inhibitors, 40% with antiarrhythmic drugs and 56% with rate slowing medications. Conclusion. The S.AGES cohort presents a unique opportunity to clarify the real-life therapeutic management of ambulatory elderly subjects and will help to identify the factors associated with the occurrence of major clinical events.

Treatment of hypertension in patients 80 years of age or older.

BACKGROUND: Whether the treatment of patients with hypertension who are 80 years of age or older is beneficial is unclear. It has been suggested that antihypertensive therapy may reduce the risk of stroke, despite possibly increasing the risk of death. METHODS: We randomly assigned 3845 patients from Europe, China, Australasia, and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the diuretic indapamide (sustained release, 1.5 mg) or matching placebo. The angiotensin-converting-enzyme inhibitor perindopril (2 or 4 mg), or matching placebo, was added if necessary to achieve the target blood pressure of 150/80 mm Hg. The primary end point was fatal or nonfatal stroke. RESULTS: The active-treatment group (1933 patients) and the placebo group (1912 patients) were well matched (mean age, 83.6 years; mean blood pressure while sitting, 173.0/90.8 mm Hg); 11.8% had a history of cardiovascular disease. Median follow-up was 1.8 years. At 2 years, the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group. In an intention-to-treat analysis, active treatment was associated with a 30% reduction in the rate of fatal or nonfatal stroke (95% confidence interval [CI], -1 to 51; P=0.06), a 39% reduction in the rate of death from stroke (95% CI, 1 to 62; P=0.05), a 21% reduction in the rate of death from any cause (95% CI, 4 to 35; P=0.02), a 23% reduction in the rate of death from cardiovascular causes (95% CI, -1 to 40; P=0.06), and a 64% reduction in the rate of heart failure (95% CI, 42 to 78; P<0.001). Fewer serious adverse events were reported in the active-treatment group (358, vs. 448 in the placebo group; P=0.001). CONCLUSIONS: The results provide evidence that antihypertensive treatment with indapamide (sustained release), with or without perindopril, in persons 80 years of age or older is beneficial. (ClinicalTrials.gov number, NCT00122811 [ClinicalTrials.gov].).

[Treatment of Alzheimer's disease and future approaches]. / Traitement symptomatique de la maladie d'Alzheimer et perspectives thérapeutiques.

The progressive neuronal loss in Alzheimer's disease leads to neurochemical abnormalities which provide the basis for symptomatic treatments. Four cholinesterase inhibitors were released in this indication. Meta-analyses have confirmed a beneficial effect on cognitive functioning and activities of daily living. The NMDA receptor antagonist, memantine, was also approved for the treatment of moderate to severe and may be associated. Progress in the patho-physiology of the disease offers some hope of new treatments acting on the cerebral lesions. The amyloid hypothesis allowed the emergence of active or passive immunotherapies, and of secretase inhibitors or modulators. Recent studies have targeted the P tau protein. The brain plasticity and the uses of stem cells offer more distant hope.

Visit-to-Visit Blood Pressure Variability Is Associated With Cognitive Decline and Incident Dementia: The S.AGES Cohort.

To investigate the impact of visit-to-visit systolic blood pressure variability (BPV), diastolic BPV, mean arterial pressure variability, and pulse pressure variability on cognitive decline and incident dementia in noninstitutionalized patients aged ≥65 years. A total of 3319 subjects from the S.AGES (Sujets AGÉS-Aged Subjects) cohort underwent clinical examinations every 6 months during 3 years. Variability was evaluated using standard deviation (SD), coefficient of variation, average real variability, successive variation, variation independent of mean, and residual SD. Cognition was assessed using the Mini-Mental State Examination and dementia with the Diagnostic Statistical Manual of Mental Disorders. Linear mixed models and Cox proportional hazards models were used. Higher systolic BPV was associated with poorer cognition independently of baseline SBP: adjusted 1-SD increase of coefficient of variation: ß (SE)=-0.12 (0.06), P=0.04. Similar results were observed for diastolic BPV and mean arterial pressure variability: ß (SE)=-0.20 (0.06), P<0.001 for both. Higher pulse pressure variability was no longer associated with cognitive function after adjustment for age, except with residual SD (P=0.02). Among the 3319 subjects, 93 (2.8%) developed dementia. Higher systolic BPV was associated with greater dementia risk (adjusted 1-SD increase of coefficient of variation: hazard ratios=1.23 [95% CI, 1.01-1.50], P=0.04). Similar results were found for diastolic BPV and mean arterial pressure variability (P<0.01). Pulse pressure variability was not associated with dementia risk. Beyond hypertension, higher BPV is a major clinical predictor of cognitive impairment and dementia. Further studies are needed to assess whether controlling BP instability could be a promising interventional target in preserving cognition among older adults.

Sex Differences in the Occurrence of Major Clinical Events in Elderly People with Type 2 Diabetes Mellitus Followed up in the General Practice.

AIMS: The main aim of the present work was to assess if sex influences the occurrence of major clinical events in elderly people with type 2 diabetes followed up in the primary care. METHODS: 983 subjects aged ≥65years with type 2 diabetes were included by 213 general practitioners and followed up prospectively for three years. Major clinical events were recorded every six month. The first endpoint was a composite of all-cause death and major vascular events (acute coronary syndrome, non-fatal stroke or transient ischemic attack, or revascularization for peripheral artery disease). The second endpoint was all-cause hospitalization. The occurrence of each endpoint was analyzed in order to estimate the role of sex and determine other predictors of major clinical events. RESULTS: At baseline, women were older than men but they had a lower prevalence of coexisting diseases (cardiovascular disease and cancer) and equivalent diabetes control (Glycated hemoglobin A1C: 6.9%±0.9 vs. 7.0%±1.1). Over the follow-up period, women were at lower risk to develop the composite endpoint (HR 0.60, 95% CI 0.40-0.91, p=0.016) and the hospitalization endpoint (OR 0.71, 95% CI 0.52-0.96, p=0.029). Coexisting diseases, functional ability and concomitant medications emerged as significant predictors of both endpoints. CONCLUSIONS: Elderly women with well-controlled type 2 diabetes were less likely to experience major clinical events than their male counterparts. More studies are needed to determine the reasons for the higher hospitalization rate in men.

Investigation of antihypertensive class, dementia, and cognitive decline: A meta-analysis.

OBJECTIVE: High blood pressure is one of the main modifiable risk factors for dementia. However, there is conflicting evidence regarding the best antihypertensive class for optimizing cognition. Our objective was to determine whether any particular antihypertensive class was associated with a reduced risk of cognitive decline or dementia using comprehensive meta-analysis including reanalysis of original participant data. METHODS: To identify suitable studies, MEDLINE, Embase, and PsycINFO and preexisting study consortia were searched from inception to December 2017. Authors of prospective longitudinal human studies or trials of antihypertensives were contacted for data sharing and collaboration. Outcome measures were incident dementia or incident cognitive decline (classified using the reliable change index method). Data were separated into mid and late-life (>65 years) and each antihypertensive class was compared to no treatment and to treatment with other antihypertensives. Meta-analysis was used to synthesize data. RESULTS: Over 50,000 participants from 27 studies were included. Among those aged >65 years, with the exception of diuretics, we found no relationship by class with incident cognitive decline or dementia. Diuretic use was suggestive of benefit in some analyses but results were not consistent across follow-up time, comparator group, and outcome. Limited data precluded meaningful analyses in those ≤65 years of age. CONCLUSION: Our findings, drawn from the current evidence base, support clinical freedom in the selection of antihypertensive regimens to achieve blood pressure goals. CLINICAL TRIALS REGISTRATION: The review was registered with the international prospective register of systematic reviews (PROSPERO), registration number CRD42016045454.

[Preventing dependency: the longevity challenge]. / Prévention de la dépendance: le défi de la longévité.

Longevity can only be considered a privilege if the majority of the elderly population is active and in good health. In contrast to certain statistical interpretations, the HID study gives cause for optimism. It showed that only 7% of subjects aged 60 years and over suffer from dependency and, therefore, that 93% of the population remains independent. Of course, the rate of dependency increases with age, particularly in women and after 90 years of age. Dependency is mostly due to age-related diseases. The second cause is "frailty" and the third is inactivity, or more generally, lifestyle. All age-related diseases have modifiable risk factors and are thus accessible to prevention. Prevention must be started as soon as possible. It has been demonstrated that a mother's educational level influences her children's health in adulthood. It is never too late. The Hyvet study recently showed that the treatment of hypertension after 80 years of age is still able to significantly reduce the risk of death, stroke, heart failure and other cardiovascular complications. Inadequate disease management may also lead to avoidable dependency. This is the case of congestive heart failure and osteoporosis, which are not always treated in very old patients according to evidence-based principles. Another means of prevention is the detection and management of the frailty syndrome, which carries a measurable risk of loss of independence. In addition to these medical approaches, occupational activity involving strong cognitive stimulation has been shown to postpone the onset of cognitive impairment.

Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-COG): a double-blind, placebo controlled trial.

BACKGROUND: Observational epidemiological studies have shown a positive association between hypertension and risk of incident dementia; however, the effects of antihypertensive therapy on cognitive function in controlled trials have been conflicting, and meta-analyses of the trials have not provided clear evidence of whether antihypertensive treatment reduces dementia incidence. The Hypertension in the Very Elderly trial (HYVET) was designed to assess the risks and benefits of treatment of hypertension in elderly patients and included an assessment of cognitive function. METHODS: Patients with hypertension (systolic pressure 160-200 mm Hg; diastolic pressure <110 mm Hg) who were aged 80 years or older were enrolled in this double-blind, placebo-controlled trial. Participants were randomly assigned to receive 1.5 mg slow release indapamide, with the option of 2-4 mg perindopril, or placebo. The target systolic blood pressure was 150 mm Hg; the target diastolic blood pressure was 80 mm Hg. Participants had no clinical diagnosis of dementia at baseline, and cognitive function was assessed at baseline and annually with the mini-mental state examination (MMSE). Possible cases of incident dementia (a fall in the MMSE score to <24 points or a drop of three points in 1 year) were assessed by standard diagnostic criteria and expert review. The trial was stopped in 2007 at the second interim analysis after treatment resulted in a reduction in stroke and total mortality. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00122811. FINDINGS: 3336 HYVET participants had at least one follow-up assessment (mean 2.2 years) and were included: 1687 participants were randomly assigned to the treatment group and 1649 to the placebo group. Only five reports of adverse effects were attributed to the medication: three in the placebo group and two in the treatment group. The mean decrease in systolic blood pressure between the treatment and placebo groups at 2 years was systolic -15 mm Hg, p<0.0001; and diastolic -5.9 mm Hg, p<0.0001. There were 263 incident cases of dementia. The rates of incident dementia were 38 per 1000 patient-years in the placebo group and 33 per 1000 patient-years in the treatment group. There was no significant difference between treatment and placebo groups (hazard ratio [HR] 0.86, 95% CI 0.67-1.09); however, when these data were combined in a meta-analysis with other placebo-controlled trials of antihypertensive treatment, the combined risk ratio favoured treatment (HR 0.87, 0.76-1.00, p=0.045). INTERPRETATION: Antihypertensive treatment in elderly patients does not statistically reduce incidence of dementia. This negative finding might have been due to the short follow-up, owing to the early termination of the trial, or the modest effect of treatment. Nevertheless, the HYVET findings, when included in a meta-analysis, might support antihypertensive treatment to reduce incident dementia.

[Alzheimer's disease: from brain lesions to new drugs]. / La maladie d'Alzheimer: des lesions cérébrales aux perspectives thérapeutiques.

We review the main therapeutic targets in Alzheimer's disease. Current treatments include cholinesterase inhibitors and the glutamate-modulating drug memantin. Other neurotransmitters such as serotonin, histamine and noradrenaline may also be targeted. Although useful, however, these symptomatic treatments do not prevent neuronal degeneration and death. Epidemiological studies suggest that treatments given for other reasons, such as antiinflammatory agents (including NSAIDs), cholesterol-lowering drugs, hormone replacement therapy and antioxidants, may prevent or improve Alzheimer-type dementia, but this is not always borne out in controlled clinical trials. Prevention of hypertension significantly reduces the incidence of vascular dementia and of Alzheimer-type dementia, albeit through an unknown mechanism. Alzheimer's disease is characterized by two main lesions: amyloid plaques and neurofibrillary tangles composed of aggregated A Beta peptides and hyperphosphorylated tau. Active and passive immunization against A beta has given promising results. Other exciting approaches include modulation of A beta processing by inhibiting BACE1 or gamma-secretase or upregulating alpha-secretase; A beta peptide catabolism; inhibition of beta fibrillization; and reducing tau phosphorylation or inhibiting tau aggregation. More remote possibilities include gene therapy and the use of growth factors to increase neurogenesis.

Gender-Related Differences in the Control of Cardiovascular Risk Factors in Primary Care for Elderly Patients With Type 2 Diabetes: A Cohort Study.

OBJECTIVE: The aim of this study was to estimate the association between gender and control of diabetes and other cardiovascular risk factors in elderly patients with type 2 diabetes mellitus. METHODS: The sujets âgés cohort is an observational study whose main objective was to describe the real-life management of elderly patients with type 2 diabetes mellitus in France. Nine hundred eighty-three patients with diabetes (517 men and 466 women) were recruited by 213 general practitioners and were followed up prospectively every 6 months for 3 years. Diabetes, hypertension and dyslipidemia were considered controlled if the glycated hemoglobin (A1C) was ≤7%, blood pressure was <140/90 mm Hg and low-density lipoprotein (LDL) cholesterol was ≤100 mg/dL. A1C levels and blood pressure measurements were recorded every 6 months for all patients. LDL cholesterol levels were optionally sampled every year. RESULTS: Women were older than men (77.3±5.72 vs. 76.1±6.01 years), more likely to be alone, less likely to be smokers/ex-smokers and less likely to have cardiovascular disease at baseline. Mean A1C levels of female patients (6.98%±1.03%) did not differ from those of male patients (6.91%±0.96%). Mean blood pressure measurements during follow up were not different between male and female patients. In contrast, female patients had significantly higher LDL cholesterol levels than male counterparts (105.2±32.6 vs. 94.9±29.1 mg/dL), regardless of statin therapy. CONCLUSION: Our results suggest no difference in the management of cardiovascular risk factors between elderly female patients with type 2 diabetes mellitus and their male counterparts, except for LDL cholesterol, which is significantly higher in women.

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.

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.

Cardiovascular Drugs and Metformin Drug Dosage According to Renal Function in Non-Institutionalized Elderly Patients.

Adaptation of drug dosage to kidney function is a common problem in general practice. The aim was to describe adaptation of cardiovascular drugs and metformin according to renal function and its association with mortality with regard to metformin in a cohort of elderly patients. This was an ancillary study to the S.AGES cohort made up of patients over 65 years of age managed by their general practitioner under real-life conditions and followed up prospectively for 3 years. The medications studied were digoxin, spironolactone and metformin. Adaptation of their daily dose according to renal function (eGFR according to CKD/EPI) was compared to that recommended in the summaries of product characteristics (SPCs) or international scientific societies (ISS). A total of 900 patients were included, including 588 on metformin. At baseline, dose adjustment according to renal function was 100% and 87.6% (95% CI: 82.6-92.6) for patients on digoxin and spironolactone respectively. For metformin, only 71.3% (95% CI: 67.6-74.9) or 78.1% (95% CI: 74.7-81.4) of patients had their dosage adapted at inclusion according to their renal function depending on whether the SPCs or ISS recommendations were considered. During the 3-year follow-up period, 42/588 patients died (none from lactic acidosis). At inclusion, a metformin dosage not adapted for renal function according to ISS was not associated with an increase in all-cause mortality (OR 1.7; 95% CI 0.6-5.0, p = 0.32). In conclusion, approximately one-quarter of elderly patients treated with metformin do not have their dosage adapted for renal function according to ISS although there is no increase in mortality after follow-up for 3 years.