[Lancet Commission on Hypertension Group position statement on the global improvement of accuracy standards for devices that measure blood pressurePosicionamento do Grupo da Lancet Commission on Hypertension sobre a melhoria global dos padrões de acurácia para aparelhos que medem a pressão arterial]. / Declaración de posición del Grupo de la Comisión Lancet de Hipertensión con respecto a la mejora mundial de las normas de exactitud para los dispositivos de medición de la presión arterial.

The Lancet Commission on Hypertension identified that a key action to address the worldwide burden of high blood pressure (BP) was to improve the quality of BP measurements by using BP devices that have been validated for accuracy. Currently, there are over 3 000 commercially available BP devices, but many do not have published data on accuracy testing according to established scientific standards. This problem is enabled through weak or absent regulations that allow clearance of devices for commercial use without formal validation. In addition, new BP technologies have emerged (e.g. cuffless sensors) for which there is no scientific consensus regarding BP measurement accuracy standards. Altogether, these issues contribute to the widespread availability of clinic and home BP devices with limited or uncertain accuracy, leading to inappropriate hypertension diagnosis, management and drug treatment on a global scale. The most significant problems relating to the accuracy of BP devices can be resolved by the regulatory requirement for mandatory independent validation of BP devices according to the universally-accepted International Organization for Standardization Standard. This is a primary recommendation for which there is an urgent international need. Other key recommendations are development of validation standards specifically for new BP technologies and online lists of accurate devices that are accessible to consumers and health professionals. Recommendations are aligned with WHO policies on medical devices and universal healthcare. Adherence to recommendations would increase the global availability of accurate BP devices and result in better diagnosis and treatment of hypertension, thus decreasing the worldwide burden from high BP.

A Comissão Lancet sobre Hipertensão Arterial identificou que uma iniciativa central para enfrentar a carga mundial da hipertensão arterial seria a melhoria na qualidade da mensuração da pressão arterial pelo uso aparelhos de pressão arterial validados quanto à acurácia. Atualmente, existem mais de 3 000 aparelhos de pressão arterial disponíveis comercialmente; entretanto, muitos não têm dados publicados sobre testes de acurácia realizados de acordo com padrões científicos estabelecidos. Este problema resulta de regulamentação fraca ou inexistente, o que permite a aprovação para uso comercial de dispositivos sem validação formal. Além disso, surgiram novas tecnologias de mensuração da pressão arterial (por exemplo, sensores sem algemas) sem consenso científico quanto aos padrões de acurácia. No conjunto, essas questões contribuem para a oferta generalizada de dispositivos de pressão arterial clínica e domiciliar com acurácia limitada ou incerta, levando a diagnóstico, gerenciamento e tratamento inadequados da hipertensão em escala global. Os problemas mais significativos relacionados com a acurácia dos dispositivos de pressão arterial podem ser resolvidos por regulamentação que imponha a obrigatoriedade de validação independente dos aparelhos de pressão arterial, de acordo com a norma universalmente aceita pela Organização Internacional de Normalização. Esta é uma recomendação fundamental para a qual existe uma necessidade internacional urgente. Outras recomendações essenciais incluem o desenvolvimento de padrões de validação especificamente para novas tecnologias de mensuração da pressão arterial e listas on-line de aparelhos com acurácia adequada que sejam acessíveis aos consumidores e profissionais de saúde. As recomendações estão alinhadas com as políticas da Organização Mundial da Saúde (OMS) sobre dispositivos médicos e atenção universal à saúde. A adesão às recomendações aumentaria a oferta global de dispositivos de pressão arterial com acurácia adequada e resultaria em melhor diagnóstico e tratamento da hipertensão arterial, diminuindo assim a carga mundial dessa doença.

Influence of Baseline Diastolic Blood Pressure on Effects of Intensive Compared With Standard Blood Pressure Control.

BACKGROUND: In individuals with a low diastolic blood pressure (DBP), the potential benefits or risks of intensive systolic blood pressure (SBP) lowering are unclear. METHODS: SPRINT (Systolic Blood Pressure Intervention Trial) was a randomized controlled trial that compared the effects of intensive (target <120 mm Hg) and standard (target <140 mm Hg) SBP control in 9361 older adults with high blood pressure at increased risk of cardiovascular disease. The primary outcome was a composite of cardiovascular disease events. All-cause death and incident chronic kidney disease were secondary outcomes. This post hoc analysis examined whether the effects of the SBP intervention differed by baseline DBP. RESULTS: Mean baseline SBP and DBP were 139.7±15.6 and 78.1±11.9 mm Hg, respectively. Regardless of the randomized treatment, baseline DBP had a U-shaped association with the hazard of the primary cardiovascular disease outcome. However, the effects of the intensive SBP intervention on the primary outcome were not influenced by baseline DBP level (P for interaction=0.83). The primary outcome hazard ratio for intensive versus standard treatment was 0.78 (95% confidence interval, 0.57-1.07) in the lowest DBP quintile (mean baseline DBP, 61±5 mm Hg) and 0.74 (95% confidence interval, 0.61-0.90) in the upper 4 DBP quintiles (mean baseline DBP, 82±9 mm Hg), with an interaction P value of 0.78. Results were similar for all-cause death and kidney events. CONCLUSIONS: Low baseline DBP was associated with increased risk of cardiovascular disease events, but there was no evidence that the benefit of the intensive SBP lowering differed by baseline DBP. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01206062.

Distinct age-related associations for body mass index and cognition in cognitively healthy very old veterans.

ABSTRACTAssociations between high body mass index (BMI) and subsequent cognitive decline, reported in elderly averaging below age 75, become less consistent at older ages. We compared the associations of BMI with cognition in moderately old (ages 75-84, N = 154) and oldest-old (85+, N = 93) samples. BMI and cognition were assessed cross-sectionally in cognitively intact elderly (mean age = 84.5, SD = 4.4) male veterans. Regression analyses of three cognitive domains - executive functions/language, attention, and memory-compared relationship with BMI between the moderately old and oldest-old. Higher BMI was associated with relatively poorer executive functions/language performance in the moderately old, while the opposite relationship, higher BMI associated with relatively better performance, was found in the oldest-old. Associations for the other two cognitive domains did not differ significantly between age groups. The reversal of association direction for executive functions/language performance with higher BMI is consistent with the protected survivor model. This model posits a minority subpopulation with a protective factor-genetic or otherwise-against both mortality and cognitive decline associated with risk factor status. The very old who remain cognitively intact despite the presence of risk factors are more likely to possess protection.

Antihypertensive Therapies and Cognitive Function: a Review.

Increasing life expectancy has made old age-related health problems like dementia and cognitive decline more prevalent, and these are rapidly becoming important causes of disability and poor quality of life, causing significant add-ons to health-care costs worldwide. Hypertension is the most important modifiable vascular risk factor for the development and progression of both cognitive decline and dementia. In many observational and randomized studies, antihypertensive therapies have been shown to be beneficial in slowing cognitive decline. However, due to observed discrepancies by these studies, there is a lack of consensus on the best antihypertensive strategy for the prevention or slowing of cognitive decline. It is also not clear whether the beneficial effect of antihypertensive therapy is due to the use of a specific class of agents or combination therapy. Thus, we present a comprehensive review of overall antihypertensive therapies and cognition and of the individual antihypertensive therapy classes with their specific protective mechanisms and available clinical evidence behind their effect on cognitive function.

Pravastatin and cardiovascular outcomes stratified by baseline eGFR in the lipid- lowering component of ALLHAT.

BACKGROUND/AIMS: The role of statins in preventing cardiovascular outcomes in patients with chronic kidney disease (CKD) is unclear. This paper compares cardiovascular outcomes with pravastatin vs. usual care, stratified by baseline estimated glomerular filtration rate (eGFR). METHODS: Post-hoc analyses of a prospective randomized open-label clinical trial; 10,151 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (lipid-lowering component) were randomized to pravastatin 40 mg/day or usual care. Mean follow-up was 4.8 years. RESULTS: Through Year 6, total cholesterol declined in pravastatin (-20.7%) and usualcare groups (-11.2%). Use of statin therapy in the pravastatin group was 89.8% (Year 2) and 87.0% (Year 6). Usual-care group statin use increased from 8.2% (Year 2) to 23.5% (Year 6). By primary intention-to-treat analyses, no significant differences were seen between groups for coronary heart disease (CHD), total mortality or combined cardiovascular disease; findings were consistent across eGFR strata. In exploratory "as-treated" analyses (patients actually using pravastatin vs. not using), pravastatin therapy was associated with lower mortality (HR = 0.76 (0.68 - 0.85), p<0.001) and lover CHD (HR=0.84 (0.73-0.97), p=0.01), but not combined cardiovascular disease (HR=0.95 (0.88-1.04), p=0.30). Total cholesterol reduction of 10 mg/dl from baseline to Year 2 was associated with 5% lower CHD risk. CONCLUSIONS: In hypertensive patients with moderate dyslipidemia, pravastatin was not superior to usual care in preventing total mortality or CHD independent of baseline eGFR level. However, exploratory "as-treated" analyses suggest improved mortality and CHD risk in participants using pravastatin, and decreased CHD events associated with achieved reduction in total cholesterol. Potential benefit from statin therapy may depend on degree of reduction achieved in total and LDL-cholesterol and adherence to therapy.

Homocysteine and cognitive function in very elderly nondemented subjects.

OBJECTIVES: To examine the association of homocysteine with cognitive functioning in very elderly community-dwelling individuals (80 years or older). METHODS: Two hundred twenty-eight nondemented community-dwelling individuals were assessed with a broad neuropsychological battery. Bloods were drawn to measure homocysteine, serum vitamin B12, and folate levels and APOE genotype. RESULTS: Higher homocysteine levels were associated with poorer executive-language functioning scores (r = -0.311). The association persisted when serum B12 and folate levels were controlled for (r = -0.308). Homocysteine levels were not associated with memory score (r = 0.120). CONCLUSIONS: In very elderly, nondemented community dwellers, high homocysteine levels are associated with poorer executive-language functioning but not with memory. This possible differential effect of homocysteine on cognitive functions suggests that it may affect only specific brain regions or mechanisms underlying healthy executive functioning.

The Impact of Environmental Factors on the Mortality of Patients With Chronic Heart Failure.

Outcomes of acute heart failure hospitalizations are worse during the winter than the rest of the year. Seasonality data are more limited for outcomes in chronic heart failure and the effect of environmental variables is unknown. In this population-level study, we merged 20-year data for 555,324 patients with heart failure from the national Veterans Administration database with data on climate from the National Oceanic and Atmospheric Administration and air pollutants by the Environmental Protection Agency. The outcome was the all-cause mortality rate, stratified by geographical location and each month. The impact of environmental factors was assessed through Pearson's correlation and multiple regression with a family-wise α = 0.05. The monthly all-cause mortality was 13.9% higher in the winter than the summer, regardless of gender, age group, and heart failure etiology. Winter season, lower temperatures, and higher concentrations of nitrogen dioxide were associated with a higher mortality rate in multivariate analysis of the overall population. Different environmental factors were associated in regions with similar patterns of temperature and precipitation. The only environmental factor associated with the mortality rate of patients dwelling in large urban centers was the air quality index. In conclusion, the mortality in chronic heart failure exhibits a seasonal pattern, regardless of latitude or climate. In this group of patients, particularly those of male gender, a higher mortality was associated with environmental factors and incorporating these factors in treatment plans and recommendations could have a favorable cost-benefit ratio.

The Effect of Calcium Channel Blockers on Moderate or Severe Albuminuria in Diabetic, Hypertensive Patients.

OBJECTIVES: Inhibitors of the renin-angiotensin system are recommended for the management of albuminuria in patients with hypertension and diabetes mellitus, but there is little consensus about alternative therapies. Calcium channel blockers are recommended for the management of hypertension, but the data are controversial regarding their role in patients with albuminuria. This review was designed to assess the efficacy of calcium channel blockers compared with inhibitors of the renin-angiotensin system in decreasing albuminuria in diabetic, hypertensive patients with nephropathy. METHODS: We searched MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov for records that compared calcium channel blockers to inhibitors of the renin-angiotensin system and reported pre- and postintervention albuminuria measurements. Two reviewers independently screened abstracts for randomized, controlled trials in adults. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to select 29 trials from 855 records. We synthesized the data through a random-effects model. RESULTS: We analyzed data from 2113 trial participants with hypertension and diabetes mellitus who had the equivalent of ≥30 mg/day of urinary albumin excretion. Inhibitors of the renin-angiotensin system were more effective than calcium channel blockers in decreasing albuminuria (standardized difference in means -0.442; confidence interval, -0.660 to -0.225; P < .001). This finding was independent of the blood pressure response to treatment. There was no difference between the 2 drug classes regarding markers of renal function. CONCLUSIONS: Inhibitors of the renin-angiotensin system are superior to calcium channel blockers for the reduction of albuminuria in nephropathy due to hypertension and diabetes mellitus. The net clinical benefit, however, is small.

Valsartan lowers brain beta-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease.

Recent epidemiological evidence suggests that some antihypertensive medications may reduce the risk for Alzheimer disease (AD). We screened 55 clinically prescribed antihypertensive medications for AD-modifying activity using primary cortico-hippocampal neuron cultures generated from the Tg2576 AD mouse model. These agents represent all drug classes used for hypertension pharmacotherapy. We identified 7 candidate antihypertensive agents that significantly reduced AD-type beta-amyloid protein (Abeta) accumulation. Through in vitro studies, we found that only 1 of the candidate drugs, valsartan, was capable of attenuating oligomerization of Abeta peptides into high-molecular-weight (HMW) oligomeric peptides, known to be involved in cognitive deterioration. We found that preventive treatment of Tg2576 mice with valsartan significantly reduced AD-type neuropathology and the content of soluble HMW extracellular oligomeric Abeta peptides in the brain. Most importantly, valsartan administration also attenuated the development of Abeta-mediated cognitive deterioration, even when delivered at a dose about 2-fold lower than that used for hypertension treatment in humans. These preclinical studies suggest that certain antihypertensive drugs may have AD-modifying activity and may protect against progressive Abeta-related memory deficits in subjects with AD or in those at high risk of developing AD.

Evidence for aggressive blood pressure-lowering goals in patients with coronary artery disease.

Lowering blood pressure (BP) reduces the risk of major cardiovascular mortality and morbidity. Current consensus targets for BP reduction are less than 140/90 mm Hg in uncomplicated hypertension and less than 130/80 mm Hg in those patients with diabetes, chronic kidney disease, and coronary artery disease or in those who are at high risk for developing coronary artery disease (defined as a Framingham risk score of > or = 10%). There is solid epidemiologic evidence for lower BP targets, supported by some clinical studies with surrogate end points. On the other hand, there are meager data from clinical trials using hard end points, and there is a concern that overly aggressive BP lowering, especially of diastolic BP, may impair coronary perfusion, particularly in patients with left ventricular hypertrophy and/or coronary artery disease. This review evaluates the evidence for the benefit of lower BP targets in hypertension management.

Lancet Commission on Hypertension group position statement on the global improvement of accuracy standards for devices that measure blood pressure.

: The Lancet Commission on Hypertension identified that a key action to address the worldwide burden of high blood pressure (BP) was to improve the quality of BP measurements by using BP devices that have been validated for accuracy. Currently, there are over 3000 commercially available BP devices, but many do not have published data on accuracy testing according to established scientific standards. This problem is enabled through weak or absent regulations that allow clearance of devices for commercial use without formal validation. In addition, new BP technologies have emerged (e.g. cuffless sensors) for which there is no scientific consensus regarding BP measurement accuracy standards. Altogether, these issues contribute to the widespread availability of clinic and home BP devices with limited or uncertain accuracy, leading to inappropriate hypertension diagnosis, management and drug treatment on a global scale. The most significant problems relating to the accuracy of BP devices can be resolved by the regulatory requirement for mandatory independent validation of BP devices according to the universally-accepted International Organisation for Standardization Standard. This is a primary recommendation for which there is an urgent international need. Other key recommendations are development of validation standards specifically for new BP technologies and online lists of accurate devices that are accessible to consumers and health professionals. Recommendations are aligned with WHO policies on medical devices and universal healthcare. Adherence to recommendations would increase the global availability of accurate BP devices and result in better diagnosis and treatment of hypertension, thus decreasing the worldwide burden from high BP.

Evidence for a lower target blood pressure for people with heart disease.

PURPOSE OF REVIEW: The review assesses the evidence for the benefit of lower blood pressure (BP) targets in hypertension management. RECENT FINDINGS: The current consensus target for the treatment of hypertension is a BP of below 140/90 mmHg for all patients, and a BP of below 130/80 mmHg for those with diabetes or chronic kidney disease. Recently added to the list of conditions warranting the lower BP target are coronary artery disease and coronary artery disease equivalents (stroke, carotid disease, aortic aneurysm, and peripheral vascular disease), as well as those individuals with a Framingham Risk Score of at least 10%. One theoretical issue with lower BP targets may be the existence of a J-shaped curve of BP versus cardiovascular event rate, implying a greater risk, especially of myocardial ischemia, of lowering diastolic BP, which is also the filling pressure of the coronary arteries, below the lower limit of coronary autoregulation. The evidence that this is not a compelling concern is provided by animal studies, clinical trials with both surrogate and hard endpoints, and epidemiologic data. SUMMARY: There is at present no proof that more aggressive treatment is harmful and much indirect evidence that it may be beneficial, although the clinical trials that specifically address this question are still in progress.

Hypertension and atrial fibrillation.

Atrial fibrillation (AF) is an emerging public health problem. The most important risk factor for developing chronic AF is uncontrolled hypertension. Uncontrolled hypertension promotes the initiation and perpetuation of AF through atrial remodeling. Experimental evidence has demonstrated the important role of the renin-angiotensin system in atrial remodeling. Retrospective analysis of several large clinical trials and small prospective trials suggests the beneficial role of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in preventing the onset and recurrence of AF in different populations. Several large prospective trials with longer follow-up periods are in progress. These trials may provide definitive evidence for the use of these agents in the prevention of AF.

The Effect of Vegan Diets on Blood Pressure in Adults: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Vegan diets are increasing in popularity and have beneficial effects on glycemia and blood lipids, but the evidence is inconclusive regarding their effect on blood pressure. The purpose of this study was to review the effect of vegan diets on blood pressure in adults. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and ClinicalTrials.gov for records that compared a vegan diet with any less restrictive diet and reported pre- and postintervention systolic and diastolic blood pressures. Two reviewers independently screened abstracts for randomized, controlled clinical trials in individuals ≥18 years of age and older. We used the PRISMA guidelines to select 11 clinical trials from 1673 records. Data synthesis was performed through a random-effects model. RESULTS: The pooled data included 983 participants. Compared with less restrictive diets, a vegan diet did not result in a significant change in systolic (-1.33 mm Hg; 95% confidence interval [CI], -3.50-0.84; P = .230) or diastolic (-1.21 mm Hg; 95% CI, -3.06-0.65; P = .203) blood pressure. A prespecified subgroup analysis of studies with baseline systolic blood pressure ≥130 mm Hg revealed that a vegan diet resulted in a mean decrease in the systolic (-4.10 mm Hg; 95% CI, -8.14 to -0.06; P = .047) and diastolic (-4.01 mm Hg; 95% CI, -5.97 to -2.05; P = 0.000) blood pressures. CONCLUSION: The changes in blood pressure induced by a vegan diet without caloric restrictions are comparable with those induced by dietary approaches recommended by medical societies and portion-controlled diets.

Heart Failure Prevention in Older Patients Using Intensive Blood Pressure Reduction: Potential Role of Diuretics.

OBJECTIVES: This study assessed the potential role of differential diuretic drugs in preventing incident acute decompensated heart failure (ADHF) in the SPRINT (Systolic Blood Pressure Intervention Trial) study. BACKGROUND: SPRINT showed that intensive blood pressure reduction in older patients (50 to 97 years of age) resulted in 36% fewer incident cases of ADHF. However, some investigators have questioned whether this was due merely to intergroup differences in diuretic medications. METHODS: Detailed use of medication data prospectively collected throughout the trial were examined. RESULTS: ADHF events occurred in 173 of 9,361 participants. Diuretic medication increased in both arms from screening to baseline visit (from 45% to 50% in the standard arm; and from 43% to 63% in the intensive arm) and then remained steady. The lowest use of diuretic agents was among participants in the standard arm who never had an ADHF event. Withdrawal of diuretic agents at the baseline visit occurred in 6.1% (n = 284) of participants in the standard arm and 2.3% (n = 107) of participants in the intensive arm. Of these, only 11 developed ADHF during the trial (10 in the standard arm, 1 in the intensive arm), and only 1 occurred ≤1 month after diuretic withdrawal. The benefit of ADHF reduction remained significant even after excluding those 11 participants (hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.5 to 0.94; p = 0.02). Most ADHF events occurred in participants who were taking prescribed diuretic therapy at the last visit, prior to the ADHF event. There was limited use of loop (<6%) and potassium-sparing diuretic agents (2%). Diuretic use was not a predictor of ADHF (HR: 0.96; 95% CI: 0.66 to 1.40; p = 0.83). CONCLUSIONS: No evidence was found to suggest that the reduction in new ADHF events in SPRINT was due to differential diuretic use. (Systolic Blood Pressure Intervention Trial [SPRINT]; NCT01206062).

Progression of kidney disease in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin versus usual care: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

BACKGROUND: Dyslipidemia is common in patients with chronic kidney disease. The role of statin therapy in the progression of kidney disease is unclear. STUDY DESIGN: Prospective randomized clinical trial, post hoc analyses. SETTING & PARTICIPANTS: 10,060 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (lipid-lowering component) stratified by baseline estimated glomerular filtration rate (eGFR): less than 60, 60 to 89, and 90 or greater mL/min/1.73 m(2). Mean follow-up was 4.8 years. INTERVENTION: Randomized; pravastatin, 40 mg/d, or usual care. OUTCOMES & MEASUREMENTS: Total, high-density lipoprotein, and low-density lipoprotein cholesterol; end-stage renal disease (ESRD), eGFR. RESULTS: Through year 6, total cholesterol levels decreased in the pravastatin (-20.7%) and usual-care groups (-11.2%). No significant differences were seen between groups for rates of ESRD (1.36 v 1.45/100 patient-years; P = 0.9), composite end points of ESRD and 50% or 25% decrease in eGFR, or rate of change in eGFR. Findings were consistent across eGFR strata. In patients with eGFR of 90 mL/min/1.73 m(2) or greater, the pravastatin arm tended to have a higher eGFR. LIMITATIONS: Proteinuria data unavailable, post hoc analyses, unconfirmed validity of the Modification of Diet in Renal Disease Study equation in normal eGFR range, statin drop-in rate in usual-care group with small cholesterol differential between groups. CONCLUSIONS: In hypertensive patients with moderate dyslipidemia and decreased eGFR, pravastatin was not superior to usual care in preventing clinical renal outcomes. This was consistent across the strata of baseline eGFR. However, benefit from statin therapy may depend on the degree of the cholesterol level decrease achieved.

Better memory functioning associated with higher total and low-density lipoprotein cholesterol levels in very elderly subjects without the apolipoprotein e4 allele.

OBJECTIVE: To examine the association of cholesterol with cognitive functioning in oldest old community dwelling individuals with and without the apolipoprotein e4 (APOE4) allele. METHOD: One hundred eighty-five nondemented, community dwelling individuals (>or=85) were assessed with a broad neuropsychological battery. Bloods were drawn to assess total, low-density lipoprotein (LDL), and high-density lipoprotein cholesterol, as well as for APOE genotyping. RESULTS: In contrast to our expectations, high total cholesterol and high LDL cholesterol were associated with higher memory scores for noncarriers of the APOE4 allele. No significant associations between cognitive performance and lipid profile were found for carriers of the APOE4 allele. CONCLUSIONS: In oldest old nondemented noncarriers of the APOE4 allele, high cholesterol is associated with better memory function. Further examination of the role of APOE genotype on the association between cholesterol and cognitive performance, especially in the oldest old is warranted.