Clinical value of plasma ALZpath pTau217 immunoassay for assessing mild cognitive impairment.

BACKGROUND: Among plasma biomarkers for Alzheimer's disease (AD), pTau181 and pTau217 are the most promising. However, transition from research to routine clinical use will require confirmation of clinical performance in prospective cohorts and evaluation of cofounding factors. METHOD: pTau181 and pTau217 were quantified using, Quanterix and ALZpath, SIMOA assays in the well-characterised prospective multicentre BALTAZAR (Biomarker of AmyLoid pepTide and AlZheimer's diseAse Risk) cohort of participants with mild cognitive impairment (MCI). RESULTS: Among participants with MCI, 55% were Aß+ and 29% developed dementia due to AD. pTau181 and pTau217 were higher in the Aß+ population with fold change of 1.5 and 2.7, respectively. MCI that converted to AD also had higher levels than non-converters, with HRs of 1.38 (1.26 to 1.51) for pTau181 compared with 8.22 (5.45 to 12.39) for pTau217. The area under the curve for predicting Aß+ was 0.783 (95% CI 0.721 to 0.836; cut-point 2.75 pg/mL) for pTau181 and 0.914 (95% CI 0.868 to 0.948; cut-point 0.44 pg/mL) for pTau217. The high predictive power of pTau217 was not improved by adding age, sex and apolipoprotein E ε4 (APOEε4) status, in a logistic model. Age, APOEε4 and renal dysfunction were associated with pTau levels, but the clinical performance of pTau217 was only marginally altered by these factors. Using a two cut-point approach, a 95% positive predictive value for Aß+ corresponded to pTau217 >0.8 pg/mL and a 95% negative predictive value at <0.23 pg/mL. At these two cut-points, the percentages of MCI conversion were 56.8% and 9.7%, respectively, while the annual rates of decline in Mini-Mental State Examination were -2.32 versus -0.65. CONCLUSIONS: Plasma pTau217 and pTau181 both correlate with AD, but the fold change in pTau217 makes it better to diagnose cerebral amyloidosis, and predict cognitive decline and conversion to AD dementia.

The role of nutrition in the prevention of cognitive decline.

PURPOSE OF REVIEW: Dementia is a growing concern and underscores the urgent need for effective preventive measures targeting modifiable risk factors. Nutrition is a key player in the onset and progression of inflammation and cognitive decline. This review provides a comprehensive overview of the effects of different dietary patterns, vitamins and nutrients for preventing cognitive decline, mainly among healthy individuals and those with mild cognitive impairment. RECENT FINDINGS: The Mediterranean diet, omega-3 long-chain polyunsaturated fatty acids and B vitamins are the most investigated, with evidence supporting protection against cognitive decline among older adults varying across studies. More recent interventions examined in this review, such as MIND Diet, are promising with positive results, but further research is needed to conclusively establish their efficacy. It is also crucial to consider complete lifestyle as physical activity for preventing cognitive decline. SUMMARY: Definitive conclusions are difficult to draw. Future studies should adopt a comprehensive approach and focus on multinutrient strategies and whole diets.

Association between low eosinophil count and acute bacterial infection, a prospective study in hospitalized older adults.

BACKGROUND: The incidence of sepsis increases significantly with age, including a high incidence of bacterial infection in the old adults. Eosinopenia and the CIBLE score have been proposed in critically ill adults and in internal medicine wards. This study aimed to assess whether a low eosinophil count was associated with acute bacterial infection among hospitalized older adults, and to find the most efficient eosinophil count cut-off to differentiate acute bacterial infection from other inflammatory states. METHODS: This was a prospective study from July 2020 to July 2022 in geriatric wards of the University Paul Brousse Hospital (Villejuif, France) including patients aged of 75 y/o or over suffering from fever or biological inflammation. Acute bacterial infection was assessed using biological identification and/or clinical and radiological data. RESULTS: A total of 156 patients were included. Eighty-two (53%) patients suffered from acute bacterial infection (mean age (SD) 88.7 (5.9)). Low eosinophil count was independently associated with acute bacterial infection: OR [CI95%] 3.03 [1.04-9.37] and 6.08 [2.42-16.5] for eosinophil count 0-0.07 G/L and 0.07-0.172 G/L respectively (vs. eosinophil count > 0.172 G/L). Specificity and sensitivity for eosinophil count < 0.01 G/L and CIBLE score were 84%-49% and 72%-62%, respectively with equivalent AUCs (0.66 and 0.67). CONCLUSION: Eosinophil count < 0.01 G/L is a simple, routinely used and inexpensive tool which can easily participate in antibiotic decisions for older adults. Further studies are needed to assess clinical benefits. TRIAL REGISTRATION: The study was registered at Clinical trial.gov (NCT04363138-23/04/2020).

Blood Neurofilament Levels Predict Cognitive Decline across the Alzheimer's Disease Continuum.

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.

Head-to-Head Comparison of Two Plasma Phospho-tau Assays in Predicting Conversion of Mild Cognitive Impairment to Dementia.

BACKGROUND: Among blood biomarkers, phospho-tau181 (pTau181) is one of the most efficient in detecting Alzheimer disease across its continuum. However, transition from research to routine clinical use will require confirmation of clinical performance in prospective cohorts and evaluation of cofounding factors. METHODS: Here we tested the Lumipulse assay for plasma pTau181 in mild cognitive impairment (MCI) participants from the Baltazar prospective cohort. We compared the performance of this assay to the corresponding Simoa assay for the prediction of conversion to dementia. We also evaluated the association with various routine blood parameters indicative of comorbidities. RESULTS: Lumipulse and Simoa gave similar results overall, with hazard ratios for conversion to dementia of 3.48 (95% CI, 2.23-5.45) and 3.70 (95%CI, 2.39-5.87), respectively. However, the 2 tests differ somewhat in terms of the patients identified, suggesting that their use may be complementary. When combined with age, sex, and apolipoprotein E (APOE)ε4 status, areas under the curves for conversion detection were 0.736 (95% CI, 0.682-0.791) for Lumipulse and 0.733 (95% CI, 0.679-0.788) for Simoa. Plasma pTau181 was independently associated with renal dysfunction (assessed by creatinine and glomerular filtration) for both assays. Cardiovascular factors (adiponectin and cholesterol), nutritional, and inflammatory markers (total protein content, C-reactive protein) also impacted plasma pTau181 concentration, although more so with the Simoa than with the Lumipulse assay. CONCLUSIONS: Plasma pTau181 measured using the fully automated Lumipulse assay performs as well as the Simoa assay for detecting conversion to dementia of MCI patients within 3 years and Lumipulse is less affected by comorbidities. This study suggests a pathway to routine noninvasive in vitro diagnosis-approved testing to contribute to the management of Alzheimer disease. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT01315639.

Association between car driving and successful ageing. A cross sectional study on the "S.AGES" cohort.

BACKGROUND: Assessing successful ageing (SA) is essential to identify modifiable factors in order to enforce health promotion and prevention actions. SA comprises 3 dimensions: an active engagement with life, a low probability of disease and disease-related disability, and a high cognitive and physical functional capacity. Driving seems to be linked to SA as it is a mean to preserve social interactions and requires preserved functional and cognitive status. This study aims to investigate whether driving status can be considered a proxy of SA, by describing determinants associated with driving status in the 65+. METHODS: This cross-sectional study is ancillary to the S.AGES (Sujets AGÉS-Aged Subjects) study, an observational prospective cohort study which included patients suffering from chronic pain, type-2 diabetes mellitus or atrial fibrillation from 2009 to 2014. SA was defined by the success of three dimensions: physiological comprised of comorbidity and autonomy scores, psychological comprised of cognitive status and emotional state, and a social dimension. RESULTS: 2,098 patients were included of whom 1,226 (58.4%) reported being drivers. 351/2,092 (16.7%) were classified as successful agers: 292/1,266 (23.8%) in the driver group vs. 59/872 (6.8%) in the non-driver group; p < .001. In the final logistic model, after adjustment for relevant variables, SA was associated with driver status OR 1.94 [1.36-2.77]. CONCLUSION: Driving may be considered as a proxy to SA: it reflects elders' independence, cognitive ability and a means to maintain social interactions. To preserve their mobility and enable them to achieve SA, regular screening of driving skills, specific rehabilitation programs are needed. Moreover development and communication on special transports services, communal rides or even driverless car to avoid apprehension around older adults driving could be solutions.

Plasma phosphorylated tau 181 predicts amyloid status and conversion to dementia stage dependent on renal function.

OBJECTIVES: Plasma P-tau181 is an increasingly established diagnostic marker for Alzheimer's disease (AD). Further validation in prospective cohorts is still needed, as well as the study of confounding factors that could influence its blood level. METHODS: This study is ancillary to the prospective multicentre Biomarker of AmyLoid pepTide and AlZheimer's diseAse Risk cohort that enrolled participants with mild cognitive impairment (MCI) who were examined for conversion to dementia for up to 3 years. Plasma Ptau-181 was measured using the ultrasensitive Quanterix HD-X assay. RESULTS: Among 476 MCI participants, 67% were amyloid positive (Aß+) at baseline and 30% developed dementia. Plasma P-tau181 was higher in the Aß+ population (3.9 (SD 1.4) vs 2.6 (SD 1.4) pg/mL) and in MCI that converted to dementia (3.8 (SD 1.5) vs 2.9 (SD 1.4) pg/mL). The addition of plasma P-tau181 to a logistic regression model combining age, sex, APOEε4 status and Mini Mental State Examination improved predictive performance (areas under the curve 0.691-0.744 for conversion and 0.786-0.849 for Aß+). The Kaplan-Meier curve of conversion to dementia, according to the tertiles of plasma P-tau181, revealed a significant predictive value (Log rank p<0.0001) with an HR of 3.8 (95% CI 2.5 to 5.8). In addition, patients with plasma P-Tau(181) ≤2.32 pg/mL had a conversion rate of less than 20% over a 3-year period. Using a linear regression approach, chronic kidney disease, creatinine and estimated glomerular filtration rate were independently associated with plasma P-tau181 concentrations. CONCLUSIONS: Plasma P-tau181 effectively detects Aß+ status and conversion to dementia, confirming the value of this blood biomarker for the management of AD. However, renal function significantly modifies its levels and may thus induce diagnostic errors if not taken into account.

Medico-economic comparison of two anticoagulant treatment strategies: Vitamin K antagonists vs. direct oral anticoagulants in older adults in nursing homes in France. The "MIKADO" study.

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.

Impact of a public open-access community-based physical activity and fall prevention program on physical performance in older adults.

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.

Blood pressure variability: A potential marker of aging.

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.

Blood pressure, antihypertensive drugs, and incident frailty: The Multidomain Alzheimer Preventive Trial (MAPT).

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.

Plasma amyloid beta predicts conversion to dementia in subjects with mild cognitive impairment: The BALTAZAR study.

INTRODUCTION: Blood-based biomarkers are the next challenge for Alzheimer's disease (AD) diagnosis and prognosis. METHODS: Mild cognitive impairment (MCI) participants (N = 485) of the BALTAZAR study, a large-scale longitudinal multicenter cohort, were followed-up for 3 years. A total of 165 of them converted to dementia (95% AD). Associations of conversion and plasma amyloid beta (Aß)1-42 , Aß1-40 , Aß1-42 /Aß1-40 ratio were analyzed with logistic and Cox models. RESULTS: Converters to dementia had lower level of plasma Aß1-42 (37.1 pg/mL [12.5] vs. 39.2 [11.1] , P value = .03) and lower Aß1-42 /Aß1-40 ratio than non-converters (0.148 [0.125] vs. 0.154 [0.076], P value = .02). MCI participants in the highest quartile of Aß1-42 /Aß1-40 ratio (>0.169) had a significant lower risk of conversion (hazard ratio adjusted for age, sex, education, apolipoprotein E ε4, hippocampus atrophy = 0.52 (95% confidence interval [0.31-0.86], P value = .01). DISCUSSION: In this large cohort of MCI subjects we identified a threshold for plasma Aß1-42 /Aß1-40 ratio that may detect patients with a low risk of conversion to dementia within 3 years.

Use of potentially driver-impairing drugs among older drivers.

BACKGROUND: Road safety is a major issue among seniors. Potentially Driver-Impairing (PDI) drugs are known to increase the risk of car accident. The aim of this cross-sectional study was to describe PDI-drug consumption among older drivers and determine associated factors. METHODS: The S.AGES cohort is a French non-interventional real-life prospective study of 3700 community-dwelling participants aged ≥65 years old, suffering from type 2 diabetes (T2DM), chronic pain or atrial fibrillation (AF). Baseline data of drivers with known treatment (n = 1783) were used for the analyses. PDI drugs were defined according to the French classification. RESULTS: One thousand seven hundred eighty-three drivers were included (66% males; mean age 76 (Standard deviation = 5.78) years old). 21% (n = 373) took PDI drugs, 64% of which took only one (n = 239). The most frequent PDI drugs were: Zolpidem (11%; n = 60); Zopiclone (8%; n = 45); Bromazepam (8%; n = 44); Tramadol (7%; n = 39); Pregabalin (6%; n = 31). Drivers taking PDI drugs had more often chronic pain (OR [95% CI] = 2.30 [1.54-3.46]), history of depressive disorder (4.28 [3.00-6.14]) and polypharmacy (taking at least 5 different medications; 4.32 [2.97-6.41]), and less often T2DM (0.54 [0.37-0.79]), and AF (0.48 [0.32-0.71]). Conversely, they had a lower Activities of Daily Living score (0.34 [0.17-0.68]). CONCLUSIONS: The rate of aged drivers in the S.AGES cohort taking PDI drugs is concerning and highlights the need to carefully assess and reassess PDI-drug prescriptions in this population, particularly hypnotics, anxiolytics and opioids. TRIAL REGISTRATION: ClinicalTrials.gov NCT01065909 (First posted: February 9th, 2010).

Multiple sclerosis: Is there a risk of worsening after yellow fever vaccination?

BACKGROUND: Yellow fever vaccine (YFV) is not advised for multiple sclerosis (MS) patients because of the potential risk of post-vaccine relapses. OBJECTIVE: To assess the risk of relapsing-remitting multiple sclerosis (RR-MS) worsening after YFV. METHODS: Non-interventional observational retrospective, exposed/non-exposed cohort study nested in the French national cohort including MS. RESULTS: 128 RR-MS were included. The 1-year annualized relapse rate (ARR) following YFV did not differ between exposed: 0.219 (0.420) and non-exposed subjects: 0.208 (0.521) (p = 0.92). Time to first relapse was not different between groups (adjusted hazard ratio (HR) = 1.33; 95% confidence interval (CI) = 0.53-3.30, p = 0.54). CONCLUSION: These results suggest that YFV does not worsen the course of RR-MS.

Visit-to-Visit Blood Pressure Variability and Incident Frailty in Older Adults.

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.

Asymptomatic SARS COV-2 carriers among nursing home staff: A source of contamination for residents?

OBJECTIVES: To show that circulation of SARS-COV-2 in nursing homes in France can come from staff as well as residents' families, whether they are known or not to have had COVID-19. METHODS: This study reports a screening campaign of asymptomatic staff working in elderly nursing homes in Paris where the virus had been circulating actively in March and April 2020. RESULTS: Before the screening campaign, the rate of symptomatic COVID-19 was 23.3% among the residents and 12.1% among their home employees. Within a 72 h screening period, all employees not known to have the virus were screened by RT-PCR in nasopharyngeal swabs. Among the 241 screened employees, 32 (13.3%) tested positive for SARS-CoV-2 on RT-PCR. SARS-CoV-2 carriers and non-carriers did not differ in term of gender, age or type of staff. Staff carrying SARS-CoV-2 were strictly asymptomatic in 75% of cases while during the days following or before the test, 25% presented mild symptoms of COVID-19. Considering both symptomatic and asymptomatic cases, 66 out of 281 (23.5%) of the home employees had been carriers for COVID-19. CONCLUSION: Screening for viral carriage of asymptomatic staff in nursing homes can avoid contact and transmission to frequently severely vulnerable residents.

Bleeding risk with rivaroxaban compared with vitamin K antagonists in patients aged 80 years or older with atrial fibrillation.

OBJECTIVE: Direct oral anticoagulants have been evaluated in the general population, but proper evidence for their safe use in the geriatric population is still missing. We compared the bleeding risk of a direct oral anticoagulant (rivaroxaban) and vitamin K antagonists (VKAs) among French geriatric patients with non-valvular atrial fibrillation (AF) aged ≥80 years. METHODS: We performed a sequential observational prospective cohort study, using data from 33 geriatric centres. The sample comprised 908 patients newly initiated on VKAs between September 2011 and September 2014 and 995 patients newly initiated on rivaroxaban between September 2014 and September 2017. Patients were followed up for up to 12 months. One-year risks of major, intracerebral, gastrointestinal bleedings, ischaemic stroke and all-cause mortality were compared between rivaroxaban-treated and VKA-treated patients with propensity score matching and Cox models. RESULTS: Major bleeding risk was significantly lower in rivaroxaban-treated patients (7.4/100 patient-years) compared with VKA-treated patients (14.6/100 patient-years) after multivariate adjustment (HR 0.66; 95% CI 0.43 to 0.99) and in the propensity score-matched sample (HR 0.53; 95% CI 0.33 to 0.85). Intracerebral bleeding occurred less frequently in rivaroxaban-treated patients (1.3/100 patient-years) than in VKA-treated patients (4.0/100 patient-years), adjusted HR 0.59 (95% CI 0.24 to 1.44) and in the propensity score-matched sample HR 0.26 (95% CI 0.09 to 0.80). Major lower bleeding risk was largely driven by lower risk of intracerebral bleeding. CONCLUSIONS: Our study findings indicate that bleeding risk, largely driven by lower risk of intracerebral bleeding, is lower with rivaroxaban than with VKA in stroke prevention in patients ≥80 years old with non-valvular AF.

COVID-19 In-Hospital Mortality and Use of Renin-Angiotensin System Blockers in Geriatrics Patients.

OBJECTIVE: 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. DESIGN: This observational retrospective study was conducted in a French geriatric department. Patients were included between March 17 and April 18, 2020. SETTING AND PARTICIPANTS: 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. METHODS: 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. RESULTS: 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). CONCLUSION AND IMPLICATIONS: 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.