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.

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.

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.

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).

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 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.

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).

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.

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.

National survey on the management of heart failure in individuals over 80 years of age in French geriatric care units.

BACKGROUND: To evaluate the prevalence and management of heart failure (HF) in very old patients in geriatric settings. METHODS: Members of the French Society of Geriatrics and Gerontology throughout France were invited to participate in a point prevalence survey and to include all patients ≥80 years old, hospitalized in geriatric settings, with HF (stable or decompensated) on June 18, 2012. General characteristics, presence of comorbidities, blood tests and medications were recorded. RESULTS: Among 7,197 patients in geriatric institution, prevalence of HF was 20.5% (n = 1,478): (27% in acute care, 24.2% in rehabilitation care and 18% in nursing home). Mean age was 88.2 (SD = 5.2) and Charlson co morbidity score was high (8.49 (SD = 2.21)). Left ventricular ejection fraction (LVEF) was available in 770 (52%) patients: 536 (69.6%) had a preserved LVEF (≥ 50%), 120 (15.6%) a reduced LVEF (< 40%), and 114 (14.8%) a midrange LVEF (40-49%). Prescription of recommended HF drugs was low: 42.6% (629) used Angiotensin Converting Enzyme Inhibitors (ACEI) or Angiotensin Receptor Blockers (ARBs), 48.0% (709) ß-blockers, and 21.9% (324) ACEI or ARB with ß-blockers, even in reduced LVEF. In multivariate analysis ACEI or ARBs were more often used in patients with myocardial infarction (1.36 (1.04-1.78)), stroke (1.42 (1.06-1.91)), and diabetes (1.54 (1.14-2.06)). ß blockers were more likely used in patients with myocardial infarction (2.06 (1.54-2.76)) and atrial fibrillation (1.70 (1.28-2.28)). CONCLUSION: In this large very old population, prevalence of HF was high. Recommended HF drugs were underused even in reduced LVEF. These results indicate that management of HF in geriatric settings can still be improved.

Plasma amyloid levels within the Alzheimer's process and correlations with central biomarkers.

INTRODUCTION: Diagnostic relevance of plasma amyloid ß (Aß) for Alzheimer's disease (AD) process yields conflicting results. The objective of the study was to assess plasma levels of Aß42 and Aß40 in amnestic mild cognitive impairment (MCI), nonamnestic MCI, and AD patients and to investigate relationships between peripheral and central biomarkers. METHODS: One thousand forty participants (417 amnestic MCI, 122 nonamnestic MCI, and 501 AD) from the Biomarker of AmyLoïd pepTide and AlZheimer's diseAse Risk multicenter prospective study with cognition, plasma, cerebrospinal fluid (CSF), and magnetic resonance imaging assessments were included. RESULTS: Plasma Aß1-42 and Aß1-40 were lower in AD (36.9 [11.7] and 263 [80] pg/mL) than in amnestic MCI (38.2 [11.9] and 269 [68] pg/mL) than in nonamnestic MCI (39.7 [10.5] and 272 [52] pg/mL), respectively (P = .01 for overall difference between groups for Aß1-42 and P = .04 for Aß1-40). Globally, plasma Aß1-42 correlated with age, Mini-Mental State Examination, and APOE Îµ4 allele. Plasma Aß1-42 correlated with all CSF biomarkers in MCI but only with CSF Aß42 in AD. DISCUSSION: Plasma Aß was associated with cognitive status and CSF biomarkers, suggesting the interest of plasma amyloid biomarkers for diagnosis purpose.

Allometric scaling of brain regions to intra-cranial volume: An epidemiological MRI study.

There is growing evidence that sub-structures of the brain scale allometrically to total brain size, that is, in a non-proportional and non-linear way. Here, scaling of different volumes of interest (VOI) to intra-cranial volume (ICV) was examined. It was assessed whether scaling was allometric or isometric and whether scaling coefficients significantly differed from each other. We also tested to what extent allometric scaling of VOI was introduced by the automated segmentation technique. Furthermore, reproducibility of allometric scaling was studied different age groups and study populations. Study samples included samples of cognitively healthy adults from the community-based Age Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik Study) (N = 3,883), the Coronary Artery Risk Development in Young Adults Study (CARDIA) (N =709), and the Alzheimer's Disease Neuroimaging Initiative (ADNI) (N = 180). Data encompassed participants with different age, ethnicity, risk factor profile, and ICV and VOI obtained with different automated MRI segmentation techniques. Our analysis showed that (1) allometric scaling is a trait of all parts of the brain, (2) scaling of neo-cortical white matter, neo-cortical gray matter, and deep gray matter structures including the cerebellum are significantly different from each other, and (3) allometric scaling of brain structures cannot solely be explained by age-associated atrophy, sex, ethnicity, or a systematic bias from study-specific segmentation algorithm, but appears to be a true feature of brain geometry. Hum Brain Mapp 38:151-164, 2017. © 2016 Wiley Periodicals, Inc.

A Tablet-PC-Based Cancellation Test Assessing Executive Functions in Older Adults.

OBJECTIVE: To examine older adults' performance on a newly developed tablet-PC-based cancellation test (e-CT) and to study its psychometric properties. METHODS: 94 older adults with normal cognitive functioning were recruited. The effects of age, education, sex, and experience with computer-based devices on the e-CT were examined. Construct validity was tested by correlating the e-CT with established measures of executive functions (EF) and episodic memory. Correlation coefficients were used to assess short-term test-retest reliablity. RESULTS: The mean age of participants was 74.6 (SD: 7.3) years and 78% were women. Sixty-nine percent had higher education level (> high school) and 76% used computer-based devices daily. The correct cancellations (CC) on the e-CT ranged from 18 to 56, with a mean (SD) of 40.3 (5.7). The CC was inversely correlated with advancing age (rs = -0.59, N = 94, p <0.001) and positively associated with higher education level (U(94) = 646.5, p = 0.02). No relationship was observed between the e-CT and sex or computer-based device experience. In multivariate analysis, only age remained significantly associated with CC (ß = -0.46, SE = 0.07, t = -6.47, df = 93, p <0.001). The e-CT correlated significantly with most of measures of EF. Highest correlations were found between the e-CT and the K-T test, a paper-and-pencil cancellation test (rs = 0.63, N = 90, p <0.001) and TMT-B (rs = -0.41, N = 85, p <0.001). The e-CT did not correlate with the RL-RI 16 episodic memory test. The correlation between the first and second e-CT indicated good reliability (rs = 0.89, N = 13, p <0.001). CONCLUSIONS: Results suggested that e-CT has good psychometric properties and may be useful for assessing EF in older adults.

Correction: 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.

[This corrects the article DOI: 10.1371/journal.pone.0283604.].

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.

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.

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.

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.