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Background: Age is a major risk factor for venous thromboembolism (VTE), yet patients aged ≥90 years are under‐represented in clinical trials of anticoagulant therapy. The objectives were to describe and compare patient clinical characteristics, treatments, and outcomes (VTE recurrence, bleeding, and mortality) during the first 3 months of anticoagulation between VTE patients aged ≥90 years and those aged <90 years. Methods: We analyzed data from the Registro Informatizado Enfermedad TromboEmbὀlica (RIETE), an ongoing global observational registry of patients with objectively confirmed acute VTE. Results: From January 2001 to October 2022, 96,701 patients were registered in RIETE, of whom 3262 (3.4%) were aged ≥90 years. Patients aged ≥90 years were less likely to be men, and to have experienced cancer or recent surgery, but more likely to manifest immobility, chronic heart failure, anemia, renal insufficiency, or dementia than those aged <90 years. Most (99.6%) patients aged ≥90 years were receiving anticoagulant therapy. During the first 3 months, 26 patients aged ≥90 years developed VTE recurrences, 116 experienced major bleeding, and 564 died. Among patients initially presenting with pulmonary embolism (PE), deaths due to PE exceeded those due to fatal bleeding (76 vs. 19). Among those initially presenting with isolated deep‐vein thrombosis (DVT), it was the reverse (2 vs. 11 deaths). Conclusions: In patients aged ≥90 years, the difference in the outcome of anticoagulant treatment depending on the initial presentation of VTE could suggest a need for different management approaches. Clinical trials evaluating the optimal duration of anticoagulation according to initial VTE presentation are warranted to limit excess deaths in this particular population. [ABSTRACT FROM AUTHOR]

Introduction: From a patient-centered perspective, the assessment of risk factors of hypoglycemia is of critical importance for the management of type 2 diabetes (T2D). However, the association between the occurrence of hypoglycemia and high burden of comorbidities has been poorly studied in vulnerable older patients. Here, we aimed to determine whether a high burden of comorbidities is associated with hypoglycemia in very old patients with T2D. Methods: A total of 1552 elderly (age ≥ 80 years old) patients with T2D were recruited in a nationwide cross-sectional study performed in French geriatric care units. Hypoglycemia was defined as a confirmed blood glucose value level ≤ 70 mg/dL. Comorbidities were assessed using the Charlson Comorbidity Index (CCI). Results: Amongst the 1552 recruited patients (mean age 86.4 years), 415 (26.7%) had documented hypoglycemia. Compared to patients in whom hypoglycemia was not reported, they have a lower body weight ( p = 0.004), a reduced eGFR ( p < 0.001), a greater level of dependency ( p < 0.001) as well as history of dementia ( p = 0.006) and cardiovascular disease ( p < 0.001), and a higher CCI (4.7 vs 3.8, p < 0.001). Patients with hypoglycemia had a higher frequency of daily self-monitoring blood glucose (SMBG) ( p < 0.001) and insulin use ( p < 0.001), with reduced sulfonylurea use ( p < 0.001). In multivariate logistic regression analysis, insulin therapy (OR 3.32, p < 0.001), daily SMBG (OR 1.79, p = 0.02), CCI (OR 1.24, p = 0.01), and age (OR 0.96, p = 0.03) were independently associated with the risk of hypoglycemia. Conclusion: In addition to insulin therapy, a high burden of comorbidities was independently associated with hypoglycemia in older vulnerable patients with T2D. [ABSTRACT FROM AUTHOR]

In the case of venous thromboembolic disease (VTE), physicians are more and more facing the difficulties of managing VTE and their treatment in frail patients. These patients could present several at risk situation such as: chronic kidney disease (CKD), underweight or malnourished, falls, cognitive impairment, multi-medicated patients, cancer and pregnancy. Guidelines typically recommend anticoagulation. There are multiple challenges in the safe use of anticoagulation in frail patients, including bleeding risk, monitoring and adherence, and polypharmacy. The objective of this review is to explore these at-risk situations and to suggest adequate anticoagulation therapy, when possible, in each of these complex situations. [ABSTRACT FROM AUTHOR]

To examine the antihypertensive efficacy and safety of indapamide sustained-release (SR)/amlodipine compared with enalapril/amlodipine in patients 65 years and older with uncontrolled blood pressure (BP) on monotherapy, a post hoc analysis of the NESTOR trial (Natrilix SR vs Enalapril in Hypertensive Type 2 Diabetics With Microalbuminuria) was conducted. NESTOR randomized 570 patients (n=197, aged ≥65 years) with hypertension (systolic BP 140-180/diastolic BP <110 mm Hg) to indapamide SR 1.5 mg or enalapril 10 mg. If target BP (<140/85 mm Hg) was not achieved at 6 weeks, amlodipine 5 mg was added with uptitration to 10 mg if required. A total of 107 patients aged 65 years and older received dual therapy (53 indapamide SR/amlodipine and 54 enalapril/amlodipine). Amlodipine uptitration occurred in 22 and 24 patients, respectively. At 52 weeks, mean systolic BP (±SE) reduction was significantly greater with indapamide SR/amlodipine vs enalapril/amlodipine 6.2±2.7 mm Hg (P=.02). Indapamide SR/amlodipine was also associated with a greater BP response rate (88% vs 75%, respectively). Both regimens were well tolerated. Indapamide SR/amlodipine may be more effective than enalapril/amlodipine for lowering systolic BP in patients with hypertension aged 65 years and older. [ABSTRACT FROM AUTHOR]

Background Few studies describe oral anticoagulant (OAC) prescription practices in very elderly patients with atrial fibrillation (AF). Methods In this sub-analysis of the PREFER in AF study, performed in 2012, patients were stratified according to age (< 80 [n = 5565] and ≥ 80 years [n = 1660]) and OAC treatment. Factors associated with OAC prescription were analyzed in a multivariate logistic regression model with backward elimination of variables least associated with OAC use. Results Patients ≥ 80 years presented with permanent AF more often (p < 0.0001) and reported fatigue and dyspnea more frequently (p < 0.0001) and palpitations less frequently (p < 0.0001) than patients < 80 years. Hypertension, stroke, heart failure, coronary heart disease, peripheral arterial disease, cancer, chronic kidney disease, and prior major bleeding were significantly more frequent in ≥ 80 years. Most patients were treated with OACs in both age groups. The overall use of vitamin K antagonists was similar in both groups (78.2% vs.78.2% p = 0.98), while the use of non-vitamin K antagonist OACs was lower in the ≥ 80 years old group than in the < 80 years group (4.5% vs. 6.6% p = 0.001). Among patients ≥ 80 years, prior stroke and heart failure were significantly associated with OAC use, whereas higher age, prior bleeding, paroxysmal AF, chronic hepatic disease, and difficulties with self-care were associated with no OAC use. Conclusions The current use of OAC in European AF patients was satisfactorily high in octogenarians, suggesting reasonable implementation of current guidelines. Interestingly, patients with poor quality of life were less often anticoagulated. This may warrant further studies. [ABSTRACT FROM AUTHOR]

Background: For antithrombotic treatments, Patient Reported Outcomes (PRO) and patient satisfaction with treatment are essential data for physicians because of the strong relationship between patient satisfaction and adherence to treatment. The impact of rivaroxaban on patient satisfaction and quality of life was not sufficiently documented in phase III studies. There is a need for further data in this field especially in real life conditions. Methods: The SAFARI study is composed of patients with non-valvular atrial fibrillation (AF), previously treated with vitamin K antagonist (VKA) and switched to rivaroxaban. Patient satisfaction with anticoagulant therapy was measured by the Anti-Clot Treatment Scale (ACTS), a validated 15-item patient-reported scale including a 12-item ACTS Burdens scale and a 3-item ACTS Benefits scale. Satisfaction of medication was compared between baseline and 1, 3 and 6 months. Results: Study population was composed of 405 patients. Mean age was 74.8 (standard deviation = 9.0) years and 63.0% were male. Mean CHA2DS2-VASc score was 3.4 (1.5) and mean HAS-BLED score was 2.9 (1.0). After 3 months of treatment with rivaroxaban, patient satisfaction improved compared with VKA: mean ACTS burdens scores significantly increased by 8.3 (8.9) points (p<0.0001) and ACTS benefits scale by 0.4 (2.9) (p<0.001). Compared with baseline, the improvement in ACTS burdens and benefits became apparent at 1 month (46.5 vs. 53.6 p<0.001 and 10.4 vs. 10.7, p<0.05 respectively) and persisted at 6 months (46.5 vs. 54.76 p<0.001 and 10.4 vs. 10.8 p = 0.02 respectively). Rivaroxaban persistence was 88.7% at 6 months. Conclusions: SAFARI data support a good risk-benefit balance for rivaroxaban, with a good safety profile and encourage PRO design studies. The switch from VKA to rivaroxaban improved patient satisfaction at 1, 3 and 6 months after rivaroxaban initiation among patients with AF, particularly in reducing patient-reported anticoagulation burden. [ABSTRACT FROM AUTHOR]

Background: The relationship between the insulin-like growth factor-I (IGF-I) system and Alzheimer's disease (AD) is mostly based on transversal studies. It remains, however, to demonstrate whether IGF-I is associated with cognitive decline over time in AD.Objective: The objective of the study was to analyze the course of cognitive decline of AD subjects over a 24-month period in relation to serum IGF-I and insulin-like growth factor binding protein-3 (IGFBP-3) measured at baseline.Methods: Data are from the SIGAL follow-up study. IGF-I and IGFBP-3 were measured in AD subjects who performed a Mini-Mental State Examination (MMSE) every 6 months for 2 years. MMSE course was analyzed using a mixed model with random intercept and slope function.Results: Among the 200 AD participants, 146 (mean age = 81.1 (standard deviation (SD) = 5.9) years, 62.6% of women) had at least one follow-up visit. Mean IGF-I at baseline was 147.8 (74.2) ng/mL. Hundred forty-six participants (62.6%) had at least one follow-up visit. Mean MMSE was 21.7 (4.7)/30 and dropped on average by 2.28 points per year. MMSE decline was steeper among participants with lower IGF-I. For each decrease of 1 SD of IGF-I, subjects lost an additional 0.63 points per year in MMSE, e.g., participants with IGF-I level of 74 ng/mL lost 2.91 MMSE points per year whereas participants with IGF-I of 222 ng/mL lost 1.65 MMSE points per year. There was no association between IGFBP-3 and cognitive decline.Conclusion: Lower baseline serum IGF-I was associated with faster cognitive decline in AD over a 2-year period. [ABSTRACT FROM AUTHOR]

Background: Given the prevalence of non-valvular atrial fibrillation in the geriatric population, thromboembolic prevention by means of vitamin K antagonists (VKA) is one of the most frequent daily concerns of practitioners. The effectiveness and safety of treatment with VKA correlates directly with maximizing the time in therapeutic range, with an International Normalized Ratio (INR) of 2.0-3.0. The older population concentrates many of factors known to influence INR rate, particularly concomitant medications and concurrent medical conditions, also defined as comorbidities. Objective: Determine whether a high burden on comorbidities, defined by a Charlson Comorbidity Index (CCI) of 3 or greater, is associated a lower quality of INR control. Study-Design: Cross-sectional study. Settings: French geriatric care units nationwide. Participants: 2164 patients aged 80 and over and treated with vitamin K antagonists. Measurements: Comorbidities were assessed using the Charlson Comorbidity Index (CCI). The recorded data included age, sex, falls, kidney failure, hemorrhagic event, VKA treatment duration, and the number and type of concomitant medications. Quality of INR control, defined as time in therapeutic range (TTR), was assessed using the Rosendaal method. Results: 487 patients were identified the low-quality control of INR group. On multivariate logistic regression analysis, low-quality control of INR was independently associated with a CCI ≥3 (OR = 1.487; 95% CI [1.15; 1.91]). The other variables associated with low-quality control of INR were: hemorrhagic event (OR = 3.151; 95% CI [1.64; 6.07]), hospitalization (OR = 1.614, 95% CI [1.21; 2.14]). Conclusion: An elevated CCI score (≥3) was associated with low-quality control of INR in elderly patients treated with VKA. Further research is needed to corroborate this finding. [ABSTRACT FROM AUTHOR]

The Test Your Memory (TYM) test has been proposed for screening dementia. We present a French version and its validation in memory clinics. F-TYM was administered to 201 patients with memory complaints visiting five secondary referral hospital centers. Final diagnosis was dementia in 34%, amnestic mild cognitive impairment (MCI) in 32%, non-amnestic MCI in 11%, absence of cognitive disorder in 23% and F-TYM scores were respectively (M±SD) 30.9 ± 7.6, 40.5 ± 6.3, 44.3 ± 4.5 and 43.5 ± 6.6 (p< .0001). F-TYM showed high correlation with MMSE (r= .78), excellent internal consistency, no effect of educational level, sex, or mood but a significant effect of age (p= .004). A F-TYM score ? 39 had 0.90 sensitivity and 0.70 specificity for diagnosis of dementia. F-TYM was unable to discriminate MCI and patients without cognitive disorders. F-TYM could be proposed for screening of dementia in patients with memory complaints. [ABSTRACT FROM AUTHOR]

The aim of this multicenter observational study conducted in France was to determine the prevalence of memory impairment in ambulatory patients aged ≤70 years with chronic heart failure (HF). Two hundred ninety-one cardiologists recruited 912 ambulatory patients with HF (mean age 79.2 ± 5.8 years) from January to November 2009. Memory was evaluated by the delayed-recall Memory Impairment Screen (MIS-D). Memory impairment was defined as MIS-D score £6 and severe memory impairment as MIS-D score £4. HF was diagnosed 4.4 ± 4.8 years earlier and mean left ventricular ejection fraction was 43.6 ± 12.0%. Memory impairment was found in 416 subjects (45.6%, 95% confidence interval 42.4 to 48.8) and severe memory impairment in 213 subjects (23.4%, 95% confidence interval 20.6 to 26.1), whereas cardiologists only suspected memory impairment in 109 patients (12%; before evaluation by MIS). Determinants of memory disorders included older age, lower education level, depression, history of stroke, renal failure, and less regular physical activity. The severity of memory impairment increased with increasing severity of HF (New York Heart Association classification; p <0.00001). In conclusion, memory impairment in older patients with HF is common. The use of a simple-to-use tool such as the MIS-D may identify patients at risk and enable implementation of management strategies to improve therapeutic compliance. [ABSTRACT FROM AUTHOR]

Chronic hypertension is associated with an increased risk of both vascular dementia and Alzheimer's disease (AD). In this context, the role of anti-hypertensive therapy for the prevention and delay of cognitive decline and dementia is of central importance. Most longitudinal studies have shown a significant inverse association between anti-hypertensive therapies and dementia incidence and for some of these, particularly in AD. Seven randomized, double blind placebo-controlled trials have evaluated the benefit of antihypertensive treatments on cognition. Three of them found positive results in term of prevention of dementia (SYST-EUR) or cognitive decline (PROGRESS, HOPE). Others disclosed non-significant results (MRC, SHEP, SCOPE, HYVET-COG). This discrepancy emphasizes the difficulty to perform such trials: the follow-up has to be long enough to disclose a benefit, a large number of patients is needed for these studies, and because of ethical reasons some anti-hypertensive treatments are often prescribed in the placebo group. Results of the two more recent meta-analyses are inconsistent, possibly due to methodological issues. Antihypertensive treatments could be beneficial to cognitive function by lowering blood pressure and/or by specific neuroprotective effect. Three main antihypertensive subclasses have been associated with a beneficial effect on cognitive function beyond blood pressure reduction (calcium channel blockers, angiotensin converting enzyme inhibitor, angiotensin-AT1-receptor-blockers). Further long-term randomized trials, designed especially to assess a link between antihypertensive therapy and cognitive decline or dementia are therefore needed with cognition as the primary outcome. A low blood pressure threshold that could be deleterious for cognitive function should also be determined. [ABSTRACT FROM AUTHOR]

Data from several recent clinical trials have suggested a beneficial effect of antihypertensive medications on preservation of cognitive function. Eprosartan, an angiotensin type-1 receptor antagonist (ARA) with dual action on both pre- and postsynaptic angiotensin type 1 receptors, may be effective in the control of SBP and the prevention of cognitive decline. The OSCAR (Observational Study on Cognitive function And SBP Reduction) study is an international longitudinal observational study with a duration of 6 months intended to examine the impact of the ARA eprosartan on cognitive function (assessed using the Mini-Mental State Examination [MMSE]) and control of systolic blood pressure (SBP) in a large international population of hypertensive patients managed in a standard primary care setting. A total of 100 000 hypertensive patients, aged ≥50 years and with SBP of >140 mmHg will be recruited by more than 20 000 primary care physicians in 27 countries. These patients will receive eprosartan 600 mg once a day for 6 months. The MMSE, a globally validated cognitive screening test, will be performed at baseline, and after 6 months of treatment. After the first month of monotherapy, eprosartan treatment may, at the absolute discretion of individual investigators, be supplemented with other antihypertensive medications for the remainder of the study. The primary outcome indices are the mean relative change in MMSE score and the absolute change from baseline in SBP in the study population as a whole and in subsets of patients according to various factors among them: ethnicity, comorbidities (i.e. target organ damage, diabetes), baseline cognitive level and baseline blood pressure level. The secondary objectives are to identify factors influencing SBP and MMSE changes. The OSCAR trial is the first international observational study focusing on MMSE in a wide international cohort of hypertensive patients. The results are expected in 2007. [ABSTRACT FROM AUTHOR]

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

The GNB3 C825T gene polymorphism has recently been identified and associated with hypertension, obesity and left ventricular hypertrophy. The aim of the study was to determine the relationship between the C825T polymorphism of the gene encoding for the G protein β3 subunit (GNB3 C825T) and vascular hypertrophy. We studied a cohort of 306 subjects (age 49 ± 12 years) without evidence of cardiovascular disease and never treated with cardiovascular drugs. Vascular phenotypes were evaluated for the common carotid and radial arteries using high-resolution echo-tracking devices. Genotype frequencies were in agreement with the Hardy-Weinberg equilibrium. For the radial artery, mean wall thickness was significantly higher in subjects carrying the 825T allele than in CC genotype subjects (240 ± 54 μm for CT genotype and 241 ± 53 μm for TT genotype vs. 222 ± 52 μm for CC genotype, p = 0.01). The frequency of the 825T allele was significantly different in subjects with (52%) and without (35%) radial artery hypertrophy (χ[sup 2] = 10.88, p < 0.001). The relative risk of radial artery hypertrophy in subjects carrying the 825T allele compared with those with the CC genotype was 3.02 (95% CI 1.53– 5.95). A logistic regression analysis indicated that the positive and significant association between the 825T allele and radial artery hypertrophy was independent of age, blood pressure, gender and BMI. In contrast, no association between genotypes and carotid artery wall thickening was observed. These results suggest that some genetic characteristics determine in part the patterns of radial artery geometrical changes. As the 825T allele is associated with vascular hypertrophy of a muscular artery but not with structural changes of an elastic artery, we hypothesize that the 825T allele may be a genetic marker of arteriolosclerosis.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In subjects with essential hypertension, increased cardiac and radial artery mass are positively associated. The mechanical factor that contributes in the larger extent to their enhancement is pulse pressure, not mean arterial pressure. [ABSTRACT FROM AUTHOR]

Objectives: To examine the association of (1) high and low blood pressure (BP) and (2) antihypertensive (AH) drug use with incident frailty.Study Design: We conducted a secondary analysis of data from the Multidomain Alzheimer Preventive Trial (MAPT), in which 1394 non-frail community-dwelling participants aged ≥70 years were followed up for 5 years. BP was measured once at baseline in a lying position using a validated electronic device. High BP was defined as systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg, and low BP as systolic BP ≤ 110 mm Hg and/or diastolic BP ≤ 70 mm Hg. AH drugs were assessed at baseline and classified according to the Anatomical Therapeutic Chemical (ATC) code.Main Outcome Measures: Incident frailty over the 5 years was assessed using the Fried phenotype. Cox proportional hazards models were used for the analyses.Results: Low BP was associated with a greater risk of frailty (HR = 1.43, 95% CI [1.07-1.92], p = 0.02) after adjustment for age, sex, education, AH drug use, BMI, diabetes, ischemic heart disease, congestive heart failure, AF, stroke, MAPT randomization group, sit-to-stand chair test and pre-frailty. Participants with low BP and those on two or more AH drugs were at the greatest risk of frailty. Neither high BP (HR = 0.84, 95% CI [0.63-1.22], p = 0.24) nor AH drug use (HR = 1.21, 95% CI [0.89-1.64], p = 0.22) was independently associated with incident frailty.Conclusions: Low BP could be used as a new marker for identifying older adults at higher risk of frailty.Clinicaltrials: gov registration number: NCT00672685. [ABSTRACT FROM AUTHOR]

This study aimed to determine whether visit-to-visit blood pressure (BP) variability (BPV) is associated with incident frailty. We included 1 394 nonfrail community-dwelling participants aged ≥70 years from the Multidomain Alzheimer Preventive Trial (MAPT) who underwent repeated clinical examinations, including BP and frailty, over a 5-year follow-up period. Systolic BPV (SBPV), diastolic BPV (DBPV), mean arterial pressure variability (MAPV), and pulse pressure variability (PPV) were evaluated using standard deviation (SD), coefficient of variation (CV), average real variability, successive variation, variation independent of mean, and residual SD. Incident frailty was assessed using the Fried phenotype. Cox proportional hazards models were used for the analyses. Higher SBPV was significantly associated with greater risk of frailty (1-SD increase of CV: hazard ratio [HR] = 1.18, 95% confidence interval [CI]: 1.02-1.36) after adjustment for demographics, systolic BP, antihypertensive drugs, body mass index, diabetes, ischemic heart disease, congestive heart failure, stroke, atrial fibrillation, MAPT randomization group, and frailty status. Similar results were observed with all indicators of variability. Higher PPV was associated with a greater risk of developing frailty over time (1-SD increase of CV: HR = 1.17, 95% CI: 1.01-1.35). DBPV and MAPV were not significantly associated with incident frailty. Higher SBPV and PPV were associated with greater risk of incident frailty. Our findings support the concept of BP physiological dysregulation underlying the frail state and suggest that BP instability could be an early marker of frailty. [ABSTRACT FROM AUTHOR]

Neurofilament light chain (NfL) is a potential diagnostic and prognostic plasma biomarker for numerous neurological diseases including Alzheimer's disease (AD). In this study, we investigated the relationship between baseline plasma concentration of Nfl and Mild Cognitive Impairment in participants who did and did not have a clinically determined diagnosis of dementia by the end of the three-year study. Additionally, we explored the connection between baseline plasma concentration of NfL and AD dementia patients, considering their demographics, clinical features, and cognitive profiles. A total of 350 participants from the Biomarker of AmyLoid pepTide and AlZheimer's diseAse Risk (BALTAZAR) multicenter prospective study were investigated: 161 AD dementia participants and 189 MCI participants (of which 141 had amnestic MCI and 48 non-amnestic MCI). Plasma biomarkers were measured at baseline and the progression of clinical and cognitive profiles was followed over the three years of follow-up. Baseline plasma NfL concentration increased across the Alzheimer's disease continuum with a mean NfL value of 17.1 ng/mL [SD = 6.1] in non-amnestic MCI, 20.7 ng/mL [SD = 12.0] in amnestic MCI, and 23.1 ng/mL [SD = 22.7] in AD dementia patients. Plasma NfL concentration correlated with age, body mass index (BMI), and global cognitive performance and decline, as measured by the Mini-Mental State Examination (MMSE). MMSE scores decreased in parallel with increasing plasma NfL concentration, independently of age and BMI. However, NfL concentration did not predict MCI participants' conversion to dementia within three years. Discussion: Baseline plasma NfL concentration is associated with cognitive status along the AD continuum, suggesting its usefulness as a potential informative biomarker for cognitive decline follow-up in patients. [ABSTRACT FROM AUTHOR]

Background: In older patients with cancer, comorbidities compete with cancer for cause of death. The objectives were to evaluate cancer mortality and factors associated, according to metastatic status. Methods: Between 2007 and 2014, patients with cancer aged ≥70 referred for pre‐therapeutic geriatric assessment (GA) were included through the ELCAPA prospective cohort study. The underlying cause of death was defined according to the International Classification of Diseases, 10th Revision. The World Health Organisation definition was used to categorise the cause of death as cancer versus another disease (e.g. cardiovascular disease, infectious disease, etc.) Competing risk models were used. Results: Mean (SD) age of the 1445 included patients was 80.2 (5.8) and 48% were women. Most common tumour sites were colorectal (19%), breast (17%) and urinary (15%); 773 patients (49%) had metastases. After a 34‐month median follow‐up, 706 cancer deaths were observed among 843 deaths. The 6‐month and 3‐year cancer mortality rates (95% CI) were 12% (9–15) and 34% (29–38) for non‐metastatic patients and 43% (39–47) and 79% (75–82) for metastatic patients, respectively. Dependency in activities of daily living and comorbidities were associated with 6‐month and 3‐year cancer mortality in non‐metastatic (adjusted subhazard ratio [aSHR] = 1.68 [0.99–2.85] and 1.69 [1.16–2.45]; and 1.98 [1.08–3.63] and 3.38 [1.47–7.76], respectively) and metastatic patients (aSHR = 2.81 [2.01–3.93] and 2.95 [2.14–4.07]; and 1.63 [1.18–2.25] and 2.06 [1.39–3.05], respectively). Impaired Timed‐Get‐Up‐and‐Go test was associated with 6‐month and 3‐year cancer mortality in metastatic patients (aSHR = 1.5 [1.06–2.12] and 1.38 [1.06–1.81], respectively). Obesity was negatively associated with 3‐year cancer death in non‐metastatic (aSHR = 0.53 [0.29–0.97]) and metastatic patients (aSHR = 0.71 [0.51–1.00]). Conclusions: The majority of older adults with cancer referred for pre‐therapeutic GA die from cancer. Geriatric parameters are independently associated with cancer mortality and should be considered for prognosis assessment, decision‐making and care. [ABSTRACT FROM AUTHOR]

• Cancer-associated thrombosis (CAT) jeopardizes a patient's prognosis. • The available scores of CAT risk are poorly reproductible over cancer types. • The decision of thromboprophylaxis should be made on a case-by-case basis. • Low molecular weight heparin is recommended in most eligible patients. • Alternate choices should consider the risks of bleeding, frailty and/or DDI. Cancer-associated venous thrombosis (CAT) is a common, multifactor event known to complicate the course of cancer and jeopardize a patient's prognosis. The current guidelines regarding the prevention of CAT are sometimes considered insufficiently precise about specific situations, or are poorly applied. The expected benefits of thromboprophylaxis are balanced by the risk of major bleeding induced by anticoagulation, which implies a need to accurately identify ambulatory patients at high risk of thrombosis or hemorrhage. The Khorana score is commonly used for this, but is limited by the non-reproducibility of predicted performance across cancer types, and by the fact that antitumor treatment and cardiovascular risks are not included. The COMPASS-CAT score, which includes those two aspects, was found to be a more accurate predictor of venous thromboembolism in patients with lung cancer, and to better distinguish between patients at low or high risk of thrombosis. The frailty of patients with cancer is also a major issue, and should be taken into account when thromboprophylaxis is considered. According to current guidelines, CAT prophylaxis should be considered for hospitalized patients, those for whom surgery is scheduled, or those with pancreatic cancers. In ambulatory patients, decisions should be made according to patient, cancer and antitumoral treatment characteristics. Low molecular weight heparin is the gold standard of CAT prophylaxis. Despite increased risks of bleeding or drug-drug interactions in cancer patients, direct oral anticoagulants could be alternate options for high-risk ambulatory patients that should be accompanied by a careful global analysis of benefits, harms, and patient preferences. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Apathy and depression are two early behavioral symptoms in Alzheimer's disease (AD) and related disorders that often occur prior to the onset of cognitive decline and memory disturbances. Both have been associated with an increased risk of conversion to dementia, with a distinct neuropathology. Objective: The assessment of the trajectories of apathy and depression and their independent impact on dementia conversion. Methods: Apathy and Depression were measured using the Neuropsychiatric Inventory for caregiver (NPI) and clinician (NPI-C), among the nondemented individuals reporting subjective cognitive decline (SCD) at baseline. They were followed up over a 60-month period. Some converted to dementia, according to the methodology carried out by the French Memento Cohort. Results: Among individuals with SCD (n = 2,323), the levels of apathy and depression were low and did not evolve significantly over the 60-month period, despite a trend in apathy increasing as of month 24. Regarding SCD individuals who converted to dementia within the 60-month period (n = 27), the prevalence of depression remained globally steady, while the levels of apathy increased over time. Conclusion: Apathy and depression have different trajectories among individuals with SCD and apathy alone is more likely—compared to depression—to be associated with conversion to dementia. [ABSTRACT FROM AUTHOR]

Coronary artery disease (CAD) is highly prevalent in older adults, yet its management remains challenging. Treatment choices are made complex by the frailty burden of older patients, a high prevalence of comorbidities and body composition abnormalities (e.g., sarcopenia), the complexity of coronary anatomy, and the frequent presence of multivessel disease, as well as the coexistence of major ischemic and bleeding risk factors. Recent randomized clinical trials and epidemiological studies have provided new data on optimal management of complex patients with CAD. However, frail older adults are still underrepresented in the literature. This narrative review aims to highlight the importance of assessing frailty as an aid to guide therapeutic decision-making and tailor CAD management to the specific needs of older adults, taking into account age-related pharmacokinetic and pharmacodynamic changes, polypharmacy, and potential drug interactions. We also discuss gaps in the evidence and offer perspectives on how best in the future to optimize the global strategy of CAD management in older adults. [ABSTRACT FROM AUTHOR]

Objectives: Currently, two classes of oral anticoagulants are available in nursing home residents: vitamin K antagonists (VKA) and direct oral anticoagulants (DOAC). DOACs have a higher net clinical benefit than VKAs but DOACs are about 10 times more expensive than VKAs. The objective of our study was to assess and compare the overall costs of anti-coagulant strategy (VKA or DOAC), i.e., including drugs, laboratory costs and time spent in human capital (nurses and medical time) in nursing homes in France. Methods: This was an observational, multicenter, prospective study including nine nursing homes in France. Among these nursing homes, 241 patients aged 75 years and older and treated with VKA (n = 140) or DOAC (n = 101) therapy accepted to participate in the study. Results: During the 3-month follow-up period, the adjusted mean costs per patient were higher for VKA than DOACs for nurse care (€327 (57) vs. €154 (56), p<.0001) for general practitioner care (€297 (91) vs. €204 (91), p = 0.02), for coordinating physicians care (€13 (7) vs. €5 (7), p < 0.07), for laboratory tests (€23 (5) vs. €5 (5), p<.0001), but were lower for drug costs (€8 (3) vs. €165 (3), p<.0001). The average overall cost for 3 months per patient was €668 (140) with VKA vs. €533 (139) with DOAC (p = 0.02). Conclusion: Our study showed that in nursing homes despite a higher drug cost, DOAC therapy is associated with a lower total cost and less time used by nurses and physicians for drug monitoring when compared to VKA. [ABSTRACT FROM AUTHOR]

Background In older adults, physical activity (PA) is important in maintaining physical performance. Data on the effectiveness of public open-access community-based programs on physical performance and fall prevention are scarce. Methods Prospective observational controlled study in community centers providing an open-access public prevention program. Retirees aged ≥60 years who chose to participate in weekly PA workshops for 3 months were compared to those who chose the cognitive stimulation (CS) workshops. Collected data: handgrip strength, five times sit-to-stand, single-leg stance, Timed Up and Go tests, gait speed, short physical performance battery (SPPB) and frailty status at baseline (M0) and at 3 months (M3). The proportion of participants reporting a history of falls was assessed at baseline and using follow-up telephone interviews (F-Up). Results Two hundred eighty-eight participants (age 73.8 years, 87% women) were included. The sit-to-stand test, single-leg stance and SPPB scores improved significantly between M0 and M3 in both groups. A greater SPPB increase was observed in the PA than in the CS group (+0.39 vs. +0.32 points, P  = 0.02) after adjustment for age, sex, number of sessions attended, fall history and SPPB at baseline. During F-Up (median 22 months), the proportion of participants reporting at least one fall decreased from 55% to 31% (P  = 0.01) in the PA group and from 27% to 19% (P  = 0.12) in the CS group. Conclusion In a public open-access community-based program participants improved physical performance and reduced fall incidence when participating in the PA or the CS workshops. Older adults may benefit most from multifaceted prevention programs. [ABSTRACT FROM AUTHOR]

Background: It is not known if widespread vaccination can prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in subpopulations at high risk, like older adults in nursing homes (NH). Objective: The objective of the study was to know if coronavirus disease 2019 (COVID-19) outbreaks can occur in NH with high vaccination coverage among its residents. Methods: We identified, using national professional networks, NH that suffered COVID-19 outbreaks despite having completed a vaccination campaign, and asked them to send data, using predefined collecting forms, on the number of residents exposed, their vaccination status and the number, characteristics, and evolution of patients infected. The main outcome was to identify outbreaks occurring in NH with high vaccine coverage. Secondary outcomes were residents' risk of being infected, developing severe disease, or dying from COVID-19 during the outbreak. SARS-CoV-2 infection was defined by a positive reverse transcriptase-polymerase chain reaction. All residents were serially tested whenever cases appeared in a facility. Unadjusted secondary attack rates, relative risks, and vaccine effectiveness during the outbreak were estimated. Results: We identified 31 NH suffering an outbreak during March–April 2021, of which 27 sent data, cumulating 1,768 residents (mean age 88.4, 73.4% women, 78.2% fully vaccinated). BNT162b2 was the vaccine employed in all NH. There were 365 cases of SARS-CoV-2 infection. Median secondary attack rates were 20.0% (IQR 4.4%–50.0%) among unvaccinated residents and 16.7% (IQR 9.5%–29.2%) among fully vaccinated ones. Severe cases developed in 42 of 80 (52.5%) unvaccinated patients, compared with 56 of 248 (22.6%) fully vaccinated ones (relative risks [RR] 4.17, 95% CI: 2.43–7.17). Twenty of the unvaccinated patients (25.0%) and 16 of fully vaccinated ones (6.5%) died from COVID-19 (RR 5.11, 95% CI: 2.49–10.5). Estimated vaccine effectiveness during the outbreak was 34.5% (95% CI: 18.5–47.3) for preventing SARS-CoV-2 infection, 71.8% (58.8–80.7) for preventing severe disease, and 83.1% (67.8–91.1) for preventing death. Conclusions: Outbreaks of COVID-19, including severe cases and deaths, can still occur in NH despite full vaccination of a majority of residents. Vaccine remains highly effective, however, for preventing severe disease and death. Prevention and control measures for SARS-CoV-2 should be maintained in NH at periods of high incidence in the community. [ABSTRACT FROM AUTHOR]

Background: This work aimed to investigate the potential pathways involved in the association between social and lifestyle factors, biomarkers of Alzheimer's disease and related dementia (ADRD), and cognition. Methods: The authors studied 2323 participants from the Memento study, a French nationwide clinical cohort. Social and lifestyle factors were education level, current household incomes, physical activity, leisure activities, and social network from which two continuous latent variables were computed: an early to midlife (EML) and a latelife (LL) indicator. Brain magnetic resonance imaging (MRI), lumbar puncture, and amyloid-positron emission tomography (PET) were used to define three latent variables: neurodegeneration, small vessel disease (SVD), and AD pathology. Cognitive function was defined as the underlying factor of a latent variable with four cognitive tests. Structural equation models were used to evaluate cross-sectional pathways between social and lifestyle factors and cognition. Results: Participants' mean age was 70.9 years old, 62% were women, 28% were apolipoprotein-ε4 carriers, and 59% had a Clinical Dementia Rating (CDR) score of 0.5. Higher early to midlife social indicator was only directly associated with better cognitive function (direct β = 0.364 (0.322; 0.405), with no indirect pathway through ADRD biomarkers (total β = 0.392 (0.351; 0.429)). In addition to a direct effect on cognition (direct β = 0.076 (0.033; 0.118)), the association between latelife lifestyle indicator and cognition was also mostly mediated by an indirect effect through lower neurodegeneration (indirect β = 0.066 (0.042; 0.090) and direct β = − 0.116 (− 0.153; − 0.079)), but not through AD pathology nor SVD. Conclusions: Early to midlife social factors are directly associated with higher cognitive functions. Latelife lifestyle factors may help preserve cognitive functions through lower neurodegeneration. [ABSTRACT FROM AUTHOR]

Background: Chronic hypertension, particularly midlife high blood pressure, has been associated with an increased risk for cognitive decline and dementia. In this context, antihypertensive drugs might have a preventive effect, but the association remains poorly understood. Objectives: The aim of this systematic review was to examine all published findings that investigated this relationship and discuss the mechanisms underlying the potential benefits of antihypertensive medication use. Methods: A literature search was conducted using MEDLINE, Embase, and the Cochrane Library for publications from 1990 onwards mentioning hypertension, antihypertensive drugs, cognitive decline, and dementia. Results: A total of 38 relevant publications, corresponding to 18 longitudinal studies, 11 randomized controlled trials, and nine meta-analyses were identified from the 10,251 articles retrieved in the literature search. In total, 1,346,176 subjects were included in these studies; the average age was 74 years. In the seven longitudinal studies assessing the effect of antihypertensive medication on cognitive impairment or cognitive decline, antihypertensive drugs appeared to be beneficial. Of the 11 longitudinal studies that assessed the effect of antihypertensive medication on incidence of dementia, only three did not find a significant protective effect. Antihypertensive medication could decrease the risk of not only vascular dementia but also Alzheimer's disease. Four randomized controlled trials showed a potentially preventive effect of antihypertensive drugs on the incidence of dementia or cognitive decline: SYST-EUR (Systolic Hypertension in Europe Study) I and II, with a 55 % reduction in dementia risk (3.3 vs. 7.4 cases per 1,000 patient years; p < 0.001); HOPE (Heart Outcomes Prevention Evaluation), with a 41 % reduction in cognitive decline associated with stroke (95 % confidence interval [CI] 6-63); and PROGRESS (Perindopril Protection against Recurrent Stroke Study), with a 19 % reduction in cognitive decline (95 % CI 4-32; p = 0.01). Meta-analyses have sometimes produced conflicting results, but this may be due to methodological considerations. The lack of homogeneity across study designs, patient populations, exposition, outcomes, and duration of follow-up are the most important methodological limitations that might explain the discrepancies between some of these studies. Conclusion: Antihypertensive drugs, particularly calcium channel blockers and renin-angiotensin system blockers, may be beneficial in preventing cognitive decline and dementia. However, further randomized controlled trials with longer periods of follow-up and cognition as the primary outcome are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

To improve the management of hypertension in the French population, the French Society of Hypertension has decided to issue a new set of guidelines that include the following practical characteristics: usefulness for clinical practice, short, easy-to-read format, comprehensive writing for non-physicians, wide dissemination among healthcare professionals and the hypertensive population, assessment of their impact among healthcare professionals and with regard to public health goals. These guidelines, so-called the appointments of the hypertensive patient, include 15 recommendations, divided into three chapters, according to the timing of the medical management: prior to treatment initiation, the initial treatment plan (first 6 months) and the long-term care plan (beyond 6 months). We hope that a vast dissemination of these simple guidelines will help to improve hypertension control in the French population from 50% to 70%, an objective expected to be achieved in 2015 in France. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Studies have shown the importance of vascular risk factors in the pathogenesis and evolution of cognitive disorders and dementia especially among the very elderly. The aim of the present longitudinal 1-year cohort analysis was to evaluate the influence of arterial stiffness on cognitive decline in institutionalized subjects older than 80 years. Design: Longitudinal study. Setting: Nursing homes in France and Italy. Participants: A total of 873 subjects (79% women), aged 87 ± 5 years were included in this longitudinal analysis from the PARTAGE cohort. Measurements: All completed the Mini-Mental Status Examination (MMSE) on the 2 visits over 1 year and underwent a measurement of carotid-femoral pulse wave velocity (PWV), an indicator of aortic stiffness. Clinical and 3-day self-measurements of blood pressure (BP) and activities of daily living (ADL) were evaluated at baseline visit. Results: According to PWV tertiles and after adjustment for baseline MMSE, mean BP (MBP), age, education level, and ADL, Δ MMSE was –1.42 ± 3.60 in the first tertile, –1.78 ± 4.08 in the second tertile, and –2.20 ± 3.98 in the third tertile (P < .03). Similar analyses with self-measured MBP failed to show any association between BP on MMSE decline. Conclusion: This 1-year longitudinal study in institutionalized patients older than 80 years shows that the higher the aortic stiffness, the more pronounced the decline in cognitive function. These results point out the interest of measuring PWV, a simple noninvasive and validated method for arterial stiffness assessment, to detect high-risk patients for cognitive decline. [Copyright &y& Elsevier]

The article provides information on a study on the relationship between blood pressure and outdoor temperature in a large cohort of elderly individuals. Blood pressure of 8801 participants 65 years or older was measured at a baseline and a 2-year follow-up examination was employed on the subjects. Results showed that outdoor temperature and blood pressure were strongly associated in the elderly, particularly in those 80 years older. During periods of extreme temperatures, a strict observation of blood pressure and antihypertensive treatment can help in the reduction of the consequences of blood pressure variations in the elderly.

The authors report on the effect of treatment of acute heart failure in different hospital departments. They compare the care and prognosis for patients admitted to the geriatrics or cardiology department, the variation in treatment in the two departments, and whether the comprehensive approach in the geriatrics department has a better impact.

The role of treatment with renin-angiotensin-aldosterone system blockers at the onset of COVID-19 infection is not known in the geriatric population. The aim of this study was to assess the relationship between angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitor (ACEI) use and in-hospital mortality in geriatric patients hospitalized for COVID-19. This observational retrospective study was conducted in a French geriatric department. Patients were included between March 17 and April 18, 2020. All consecutive 201 patients hospitalized for COVID-19 (confirmed by reverse-transcriptase polymerase chain reaction methods) were included. All nondeceased patients had 30 days of follow-up and no patient was lost to follow-up. Demographic, clinical, and biological data and medications were collected. In-hospital mortality of patients treated or not by ACEI/ARB was analyzed using multivariate Cox models. Mean age of the population was 86.3 (8.0) years, 62.7% of patients were institutionalized, 88.6% had dementia, and 53.5% had severe disability (activities of daily living [ADL] score <2). Sixty-three patients were treated with ACEI/ARB and 138 were not. Mean follow-up was 23.4 (10.0) days, 66 (33.8%) patients died after an average of 10.0 days (6.0). Lower mortality rate was observed in patients treated with ACEI/ARB compared with patients not treated with ARB or ACEI (22.2% [14] vs 37.7% [52], hazard ratio [HR] 0.54; 95% confidence interval 0.30–0.97; P =.03). In a multivariate Cox regression model including age, sex, ADL score, Charlson index, renal function, dyspnea, C-reactive protein, and white blood cell count, use of ACEI/ARB was significantly associated with lower in-hospital mortality (HR 0.52 (0.27−0.99), P =.048). In very old subjects hospitalized in geriatric settings for COVID-19, mortality was significantly lower in subjects treated with ARB or ACEI before the onset of infection. The continuation of ACEI/ARB therapy should be encouraged during periods of coronavirus outbreak in older subjects. [ABSTRACT FROM AUTHOR]

Introduction: Evidence regarding safety and efficacy of oral anticoagulants for the treatment of atrial fibrillation (AFib) in older adults has been assessed regarding the age appropriateness of oral anticoagulants (OAC) according to the FORTA (Fit fOR The Aged) classification (OAC-FORTA). Three years after its first version (OAC-FORTA 2016), an update was initiated to create OAC-FORTA 2019. Methods: A structured review of randomized controlled clinical trials and summaries of individual product characteristics was performed to detect newly emerged evidence on oral anticoagulants in older patients with AFib. This review was used by an interdisciplinary panel of European experts (N = 10) in a Delphi process to label OACs according to FORTA. Results: A total of 202 records were identified and 11 studies finally included. We found four new trials providing relevant data on efficacy and safety of warfarin, apixaban, dabigatran or rivaroxaban in older patients with AFib. In the majority of studies comparing the non-vitamin-K oral anticoagulants (NOACs) with warfarin, NOACs were superior to warfarin regarding at least one relevant clinical endpoint. The mean consensus coefficient significantly increased from 0.867 (OAC-FORTA 2016) to 0.931 (p < 0.05) and the proposed FORTA classes were confirmed in all cases during the first round (consensus coefficient > 0.8). Warfarin, dabigatran, edoxaban and rivaroxaban were assigned to the FORTA B label, acenocoumarol, fluindione and phenprocoumon were labeled FORTA C and only apixaban was rated as FORTA A. Conclusion: OAC-FORTA 2019 confirms that AFib can be successfully treated with positively labeled antithrombotics at advanced age. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Peripheral inflammatory processes are involved in Alzheimer's disease (AD). We aimed to determine whether plasma inflammatory mediator levels at diagnosis are associated with cognitive decline through a 2-year follow-up in AD patients. Patients (n = 109, mean age 79.44 (6.82) years) were included at diagnosis with MMSE scores between 16 and 25, with C-reactive protein <10 mg/L, and without any acute or chronic inflammation status. Plasma IL-1β, IL-6, TNF-α, and CCL5 were measured using Luminex X-MAP technology at baseline, and after one year and two years of follow-up. The mean values of IL-1β, IL-6, TNF-α, and CCL5 at diagnosis were 0.3, 1.94, 6.57, and 69,615.81 pg/mL, respectively. Mean cognitive decline in MMSE was 3.35 points. No correlation between plasmatic value of IL-1β, IL-6, TNF-α, or CCL5 at diagnosis and cognitive decline during the two years of follow-up was found. Cognitive decline in AD does not appear to be predictable by the tested inflammatory mediators. [ABSTRACT FROM AUTHOR]

Background: Olfactory impairment is reported in mild cognitive impairment (MCI) and Alzheimer's disease (AD) and is associated with hippocampal atrophy. In elderly people, dementia with AD neuropathology and white matter lesions (WML) is common. In this context, olfactory impairment could also depend on the presence of WML.Objective: To assess the cross-sectional relationship between olfaction and WML in elderly subjects with MCI.Methods: Consecutive subjects, >65 years old, diagnosed as MCI after a comprehensive neuropsychological assessment in an expert memory center, with a brain MRI performed within a year and without major depressive state, were included. Olfaction was assessed by the Brief Smell Identification Test (BSIT). Two trained neuroradiologists, blind to cognitive and olfaction status, visually assessed hippocampal atrophy according to Scheltens' scale and WML according to Fazekas criteria.Results: Seventy-five MCI subjects (mean age (SD) = 77.1 (6.2) years, 74.7% of women) were included. After adjustment for age and sex, factors associated with low BSIT scores were older age (p = 0.007), lower BMI (p = 0.08), lower MMSE score (p = 0.05), lower FCRST (p = 0.008), hippocampal atrophy (p = 0.04), periventricular WML (p = 0.007), and deep WML burden (p = 0.005). In multivariate analysis, severe deep WML (OR (95% CI) = 6.29 (1.4-35.13), p = 0.02) remained associated with low BSIT score independently from hippocampal atrophy.Conclusion: In elderly MCI subjects, low olfactory performances are associated with WML, whose progression may be slowed by vascular treatments. A longitudinal study to evaluate whether the progression of WML, hippocampal atrophy and low olfactory function, can predict accurately conversion from MCI to dementia is ongoing. [ABSTRACT FROM AUTHOR]

Background: The natural history and disease mechanisms of Alzheimer's disease and related disorders (ADRD) are still poorly understood. Very few resources are available to scrutinise patients as early as needed and to use integrative approaches combining standardised, repeated clinical investigations and cutting-edge biomarker measurements. Methods: In the nationwide French MEMENTO cohort study, participants were recruited in memory clinics and screened for either isolated subjective cognitive complaints (SCCs) or mild cognitive impairment (MCI; defined as test performance 1.5 SD below age, sex and education-level norms) while not demented (Clinical Dementia Rating [CDR] <1). Baseline data collection included neurological and physical examinations as well as extensive neuropsychological testing. To be included in the MEMENTO cohort, participants had to agree to undergo both brain magnetic resonance imaging (MRI) and blood sampling. Cerebral 18F-fluorodeoxyglucose positon emission tomography and lumbar puncture were optional. Automated analyses of cerebral MRI included assessments of volumes of whole-brain, hippocampal and white matter lesions. Results: The 2323 participants, recruited from April 2011 to June 2014, were aged 71 years, on average (SD 8.7), and 62% were women. CDR was 0 in 40% of participants, and 30% carried at least one apolipoprotein E ε4 allele. We observed that more than half (52%) of participants had amnestic mild cognitive impairment (17% single-domain aMCI), 32% had non-amnestic mild cognitive impairment (16.9% single-domain naMCI) and 16% had isolated SCCs. Multivariable analyses of neuroimaging markers associations with cognitive categories showed that participants with aMCI had worse levels of imaging biomarkers than the others, whereas participants with naMCI had markers at intermediate levels between SCC and aMCI. The burden of white matter lesions tended to be larger in participants with aMCI. Independently of CDR, all neuroimaging and neuropsychological markers worsened with age, whereas differences were not consistent according to sex. Conclusions: MEMENTO is a large cohort with extensive clinical, neuropsychological and neuroimaging data and represents a platform for studying the natural history of ADRD in a large group of participants with different subtypes of MCI (amnestic or not amnestic) or isolated SCCs. [ABSTRACT FROM AUTHOR]

Background: Age appropriateness of anticoagulants for stroke prevention in atrial fibrillation is uncertain. Objective: To review oral anticoagulants for the treatment of atrial fibrillation in older (age >65 years) people and to classify appropriate and inappropriate drugs based on efficacy, safety and tolerability using the Fit-fOR-The-Aged (FORTA) classification. Methods: We performed a structured comprehensive review of controlled clinical trials and summaries of individual product characteristics to assess study and total patient numbers, quality of major outcome data and data of geriatric relevance. The resulting evidence was discussed in a round table with an interdisciplinary panel of ten European experts. Decisions on age appropriateness were made using a Delphi process. Results: For the eight drugs included, 380 citations were identified. The primary outcome results were reported in 32 clinical trials with explicit and relevant data on older people. Though over 24,000 patients aged >75/80 years were studied for warfarin, data on geriatric syndromes were rare (two studies reporting on frailty/falls/mental status) and missing for all other compounds. Apixaban was rated FORTA-A (highly beneficial). Other non-vitamin K antagonist oral anticoagulants (including low/high-intensity dabigatran and high-intensity edoxaban) and warfarin were assigned to FORTA-B (beneficial). Phenprocoumon, acenocoumarol and fluindione were rated FORTA-C (questionable), mainly reflecting the absence of data. Conclusions: All non-vitamin K antagonist oral anticoagulants and warfarin were classified as beneficial or very beneficial in older persons (FORTA-A or -B), underlining the overall positive assessment of the risk/benefit ratio for these drugs. For other vitamin-K antagonists regionally used in Europe, the lack of evidence should challenge current practice. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the interest of brain natriuretic peptide (BNP) for heart failure (HF) diagnosis in very old patients.Methods and Results: A total of 383 patients aged 80 years or older, hospitalized in geriatrics care for dyspnoea, had a BNP measurement at the acute phase. Independent cardiologists blinded to BNP values classified the patients into cardiac vs. respiratory aetiology according to the European Society of Cardiology guidelines. Mean (SD) age was 88.5 (5.4) years, 66% (n = 254) of patients were women, 62% (n = 238) had cardiac dyspnoea and 38% (n = 145) had respiratory dyspnoea. The BNP levels were significantly higher in the cardiac group (median = 385.5 ng/L, interquartile range = 174.0-842.0) than in the respiratory group (median = 172.0 ng/L, interquartile range = 70.8-428.0; P < 0.001). On its own, BNP showed poor discriminative ability [area under the curve (AUC) = 0.68; 95% confidence interval (CI) 0.62-0.73] for the diagnostic. In multivariate analysis, BNP remained independently associated with the cardiac aetiology after full-adjustment (odds ratio 1 log increase = 1.87; 95% CI 1.28-2.74), but did not improve the discrimination between the cardiac and the respiratory aetiologies (ΔAUC = 0.013, P = 0.16). In addition, although adding BNP to the other predictive covariates yielded a significant continuous NRI of 57.8% (95% CI 31.2-83.5%), the mean changes in individual predicted probabilities were too low (<3%) to be clinically relevant.Conclusion: In this population of very old patients with acute dyspnoea, despite being independently associated with the cardiac aetiology, BNP was not useful for better discriminating cardiac vs. respiratory origin. [ABSTRACT FROM AUTHOR]

Aims To evaluate the interest of brain natriuretic peptide (BNP) for heart failure (HF) diagnosis in very old patients. Methods and results A total of 383 patients aged 80 years or older, hospitalized in geriatrics care for dyspnoea, had a BNP measurement at the acute phase. Independent cardiologists blinded to BNP values classified the patients into cardiac vs. respiratory aetiology according to the European Society of Cardiology guidelines. Mean (SD) age was 88.5 (5.4) years, 66% (n=254) of patients were women, 62% (n=238) had cardiac dyspnoea and 38% (n=145) had respiratory dyspnoea. The BNP levels were significantly higher in the cardiac group (median=385.5 ng/L, interquartile range=174.0-842.0) than in the respiratory group (median=172.0 ng/L, interquartile range=70.8-428.0; P <0.001). On its own, BNP showed poor discriminative ability [area under the curve (AUC)=0.68; 95% confidence interval (CI) 0.62-0.73] for the diagnostic. In multivariate analysis, BNP remained independently associated with the cardiac aetiology after full-adjustment (odds ratio 1 log increase=1.87; 95% CI 1.28-2.74), but did not improve the discrimination between the cardiac and the respiratory aetiologies (ΔAUC=0.013, P =0.16). In addition, although adding BNP to the other predictive covariates yielded a significant continuous NRI of 57.8% (95% CI 31.2-83.5%), the mean changes in individual predicted probabilities were too low (<3%) to be clinically relevant. Conclusion In this population of very old patients with acute dyspnoea, despite being independently associated with the cardiac aetiology, BNP was not useful for better discriminating cardiac vs. respiratory origin. [ABSTRACT FROM AUTHOR]

Aging is characterized by alterations in neuro-cardiovascular regulatory mechanisms, leading to impaired physiological variability patterns. Repeated evidence has shown that increased Blood Pressure Variability (BPV) is associated with organ damage and exerts independent predictive value on several health outcomes: cardiovascular events, neurocognitive impairment, metabolic disorders and typical geriatric syndromes such as sarcopenia and frailty. Accordingly, it may constitute the epiphenomenon of the alterations in homeostatic mechanisms, typical of late life. Aging and altered BPV share the same molecular mechanisms, in particular the clinical state of subclinical inflammation has been widely ascertained in advanced age and it is also related to BP dysregulation through altered endothelial function and increased production of ROS. Arterial stiffness and autonomic dysfunction have been associated to impairment in BPV and also represent key features in elderly patients. Furthermore, accumulating evidence in the field of Geroscience has reported that several molecular changes described in cardiovascular aging and altered BPV also relate with the majority of the 9 identified hallmarks of aging. Indeed, BPV may be linked to genomic instability, epigenetic modification and mitochondrial oxidative damage, which represent milestones of aging process. The aim of the present paper is to analyse the interplay between BPV and the pathophysiology of the ageing process, in order to stimulate discussion about the potential role of BPV as a new marker of aging. • Alterations in neurocardiovascular regulatory mechanisms occur with aging, resulting in impaired physiological variability patterns. • Repeated evidence has shown BPV to independently predict organ damage and several health outcomes in late life. • Increased BPV shares pathophysiological modifications with cardiovascular aging and relates to several hallmarks of aging. • Further studies are needed to assess whether BPV could be a potential new marker of aging. [ABSTRACT FROM AUTHOR]

The article presents a response to a letter to the editor from the authors of the article "Renal Function in Older Hospital Patients Is More Accurately Estimated Using the Cockcroft-Gault Formula Than the Modification Diet in Renal Disease Formula" published in a previous issue.

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. [ABSTRACT FROM AUTHOR]

Rationale Intravenous administration of stable isotope labeled amino acid (13C6-leucine) to humans recently made it possible to study the metabolism of specific biomarkers in cerebrospinal fluid (CSF) using targeted mass spectrometry (MS). This labeling approach could be of great interest for monitoring many leucine-containing peptides in parallel, using high-resolution MS. This will make it possible to quantify the rates of synthesis and clearance of a large range of proteins in humans with a view to obtaining new insights into protein metabolism processes and the pathophysiology of diseases such as Alzheimer's disease. Methods Proteins from human lumbar and ventricular CSF samples collected at different times after intravenous 13C6-leucine infusion were digested enzymatically with LysC/trypsin after being denatured, reduced and alkylated. Desalted tryptic peptides were fractionated using Strong Cation eXchange chromatography (SCX) and analyzed using nanoflow liquid chromatography (nano-LC) coupled to a QTOF Impact II (Bruker Daltonics) mass spectrometer. Data-dependent acquisition (DDA) mode was used to identify and quantify light and heavy 13C6-leucine peptides. The ratios of 13C6-leucine incorporation were calculated using the Skyline software program in order to determine the rates of appearance and clearance of proteins in the CSF. Results After SCX fractionation and quadrupole time-of-flight (QTOF) analysis, 4528 peptides containing leucine were identified in five fractions prepared from 40 μL of CSF. Upon analyzing one of these fractions, 66 peptides (2.7%) corresponding to 61 individual proteins had significant and reproducible rate of 13C6-leucine incorporation at various time points. The plots of the light-to-heavy peptide ratios showed the existence of proteins with different patterns of appearance and clearance in the CSF. Conclusions The Stable Isotope Labeling Amino acid in Vivo (SILAV) method presented here, which yields unprecedented information about protein metabolism in humans, constitutes a promising new approach which certainly holds great potential in the field of clinical proteomics. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Concern about the renal safety of commonly used cardiovascular drugs with demonstrated clinical benefit appears to be an obstacle to their use in the elderly. The objective was to describe the relationship between cardiovascular drugs and chronic kidney disease ( CKD) in elderly individuals in the real-life setting. This is an ancillary study of the prospective non-interventional S. AGE (aged individuals) cohort. General physicians were free to prescribe any drug their patients needed. The participants were non-institutionalized patients aged 65 years and older treated by their primary physician for either chronic pain or atrial fibrillation or type 2 diabetes mellitus. The estimated glomerular filtration rate ( eGFR) derived from the CKD- EPI formula was determined at inclusion and every year during 2 years of follow-up. This study comprised 2505 patients aged 77.8 ± 6.2 years. At inclusion, the factors associated with CKD ( eGFR < 60 ml/min/1.73 m2) in multivariate analysis were age, female gender, hypertension, heart failure, history of atherothrombotic disease and renin angiotensin system blockers, loop diuretics and calcium channel inhibitors. Introduction of each of these three drug classes during the follow-up period led to only a small decrease in the eGFR: −3.8 ± 12.7 ( p < 0.0006), −2.2 ± 12.0 ( p < 0.003) and −1.0 ± 13.4 ml/min./1.73 m2 ( NS), respectively. Only the introduction of loop diuretics was associated with CKD ( OR 1.91, 95% CI: 1.25-2.90; p = 0.002). Renal safety of cardiovascular drugs in the elderly appears acceptable and should not be a barrier to their use. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives Several studies have highlighted a link between vascular alterations and cognitive decline. The PARTAGE study showed that arterial stiffness as evaluated by carotid-femoral pulse wave velocity (cfPWV) was associated with a more pronounced cognitive decline over a 1-year period in very old frail institutionalized individuals. The aim of the present analysis was to assess the role of hemodynamic parameters, such as blood pressure (BP), heart rate (HR), cfPWV, and central/peripheral pulse pressure amplification (PPA) on cognitive decline over 2 years in very old frail individuals. Methods A total of 682 individuals from the PARTAGE study cohort, aged older than 80 years (mean age at inclusion: 87.5 ± 5.0 years) and living in French and Italian nursing homes, were analyzed. Mini-Mental State Examination (MMSE) score was assessed at baseline (BL) and at the end of the first and second year of follow-up (2y-FU). Those with a decrease in MMSE of 3 or more points between BL and 2y-FU were considered as “decliners.” The cfPWV and PPA at baseline were assessed with an arterial tonometer. Results After adjustment for baseline MMSE, HR, body mass index, age, education level, and activities of daily living (ADLs), cfPWV was higher and PPA lower in “decliners” compared with “nondecliners,” whereas BP did not differ between the 2 groups. Logistic multivariate analysis also revealed that high cfPWV, low PPA, high HR, and low ADLs were all determinants of MMSE decline. Conclusion This 2-year longitudinal study in very old institutionalized individuals shows that arterial stiffness and high HR enabled us to identify subjects at higher risk of cognitive decline, whereas BP alone did not appear to have a significant predictive value. These findings highlight the contribution of vascular determinants in cognitive decline even in this very old population. [ABSTRACT FROM AUTHOR]

Background: Insulin-like growth factor-I (IGF-I) serum level decreases with age, and this decrease may underlie hemoglobin (Hb) decrease. The objective of the study was to assess the relationship between IGF-I and insulin-like growth factor binding protein-3 (IGFBP-3) serum levels and Hb, after adjustment especially for major nutritional factors in an elderly population because IGF-I system depends on nutritional state, often impaired in the elderly. Methods: Hemoglobin concentration was tested for 672 participants evaluated during an outpatient geriatric assessment. IGF-I and IGFBP-3 serum levels were assessed by Enzyme Linked Immunosorbent Assay. The molar ratio of IGF-I/IGFBP-3 that reflects the bioavailable IGF-I was calculated. Levels of IGF-I and IGFBP-3 were plotted against quartiles of Hb. Final linear models for IGF-I, IGFBP-3 and ratio molar included factors that could modify the Hb level. Results: Mean age (SD) of the sample was 78.0 (8.5) years old and 32% were men. After adjustment for age and sex, IGF-I serum level, IGFBP-3 serum level and molar ratio significantly increased with increasing quartiles of Hb. After adjustment for age, gender, diabetes, albumin, pre-albumin, renal function, total cholesterol, angiotensin converting enzyme inhibitors and angiotensin II receptor blockers consumption, C-Reactive Protein, Hb was significantly associated and with IGF-I level (p = .002) and molar ratio (p = .02). Conclusions: IGF-I serum level and IGF-I/IGFBP-3 molar ratio were associated with Hb in an elderly population, independently of nutritional biological parameters. Thus, the association between the IGF-I system and Hb merits further investigation to determine whether interventions that modulate circulating IGF-I or IGF-I/BP3 ratio might preserve Hb in the elderly. [ABSTRACT FROM AUTHOR]

A correction to this paper has been published: https://doi.org/10.1007/s40266-021-00873-3 [ABSTRACT FROM AUTHOR]