Publications by authors named "Marc Paccalin"

80 Publications

Consensus of experts from the French Society of Geriatrics and Gerontology on the management of heart failure in very old subjects.

Arch Cardiovasc Dis 2021 Mar 14;114(3):246-259. Epub 2021 Jan 14.

Pôle de Gériatrie, CHU La Milétrie, 86021 Poitiers, France; CIC 1402, Inserm, centre hospitalier universitaire de Poitiers, université de Poitiers, 86000 Poitiers, France.

The prevalence of heart failure increases with age. In France, the 1-year mortality rate is 35% in subjects aged 80-89 years with heart failure, and 50% after the age of 90 years. In octogenarians, heart failure is associated with high rates of cardiovascular and non-cardiovascular events, and is one of the main causes of hospitalization and disability. The prevalence of frailty increases in elderly subjects with heart failure, and the co-occurrence of heart failure and frailty increases the risk of mortality in patients with heart failure. In the elderly, the presence of frailty must be evaluated using a comprehensive geriatric assessment to manage geriatric syndromes, such as cognitive disorders, malnutrition, falls, depression, polypharmacy, disability and social isolation. The objective of heart failure therapy in octogenarians is to reduce symptoms, mortality and hospitalizations, but also to improve quality of life. In the absence of specific studies involving very old subjects, most recommendations are extrapolated from evidence-based data from younger populations. Overall, the epidemiological studies in patients with heart failure aged>80 years highlight the underprescription of recommended drugs. This underprescription may be related to comorbidity, a fear of side-effects and the lack of specific recommendations for drug prescription in heart failure with preserved ejection fraction, which is common in this very old population. The benefit/risk ratio related to heart failure treatment and comorbidity should be carefully weighed and reassessed on a regular basis. Consideration of disease prognosis according to factors that predict mortality can help to better define the care plan and promote palliative and supportive care when needed.
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http://dx.doi.org/10.1016/j.acvd.2020.12.001DOI Listing
March 2021

Anticoagulant treatment in elderly patients with atrial fibrillation: a position paper.

Geriatr Psychol Neuropsychiatr Vieil 2019 Dec;17(4):341-354

CHU Nantes, Pôle hospitalo-universitaire de gérontologie clinique, France, Gérontopôle Autonomie Longévité Pays de la Loire, France.

Atrial fibrillation (AF) is common in the elderly. The treatment of this condition is based on anticoagulation to prevent stroke and systemic arterial embolism. Vitamin K antagonists (VKAs) have long been the only anticoagulants available for the management of AF. Administration is complex and is one of the main causes of iatrogenic disease in the elderly. In the past 10 years, direct-acting oral anticoagulants (DOACs) have emerged, and large randomised trials (RE-LY, ROCKET-AF, ARISTOTLE, ENGAGE-AF) have demonstrated their superiority over VKAs in the management of AF. These trials were conducted on large numbers of patients (n=71,683), including 27,500 patients aged ≥75 years and nearly 8,000 subjects aged >80 years. Results from 11 recent meta-analyses of randomised trials and observational real-world studies of 660,896 elderly patients indicate that DOACs are more effective than VKA-based prophylaxis in preventing stroke (with a reduction in risk ranging from 13% to 26%), and carry a lower risk of cerebral haemorrhaging (50% reduction in risk). The risk of major haemorrhaging appears to be similar to, or lower than that with DOACs relative to VKAs (depending on the dosage, renal function, haemorrhagic site or type of DOAC). Moreover, improved outcomes with DOACs over VKA therapy have been demonstrated based on subgroup analyses in subjects aged over 75, in patients with renal insufficiency (creatinine clearance: 30-50 mL/min) and in those with a history of falls. Analyses indicate that DOACs are a better choice than VKAs in the elderly because elderly patients are at greatest risk of stroke and cerebral haemorrhaging. In summary, DOACs have a better efficacy/tolerance profile than VKAs, which justifies their first-line use in subjects over 75 years of age.
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http://dx.doi.org/10.1684/pnv.2020.0883DOI Listing
December 2019

Comprehensive geriatric assessment in older patients with cancer: an external validation of the multidimensional prognostic index in a French prospective cohort study.

BMC Geriatr 2020 08 18;20(1):295. Epub 2020 Aug 18.

Department of Geriatrics, Poitiers University Hospital, Poitiers, France.

Background: Older patients with cancer require specific and individualized management. The 3-group Multidimensional Prognostic Index (MPI) based on the Comprehensive Geriatric Assessment (CGA) has shown a predictive interest in terms of mortality. The objective of our study was to assess the prognostic value of MPI for 1-year mortality in an external prospective French cohort of elderly patients with cancer.

Methods: From March 2015 to March 2017 a prospective single-center cohort study enrolled all patients with cancer, aged 75 years and older referred to the geriatric oncology clinic. We used a proportional hazard model for 1-year mortality adjusted for age, sex, tumor sites and metastatic status. C-statistics were used to assess the incremental predictive value of MPI index to these risk factors.

Results: overall, 433 patients underwent CGA with MPI (women 42%; mean age 82.8 ± 4.8 years). The most common tumor sites were prostate (23%), skin (17%), colorectum (15%) and breast (12%); 29% of patients had a metastatic disease; 231 patients (53%) belonged to the "MPI-1" group, 172 (40%) to the "MPI-2" group and 30 patients were classified in the "MPI-3" group. One-year mortality rate was 32% (23% in MPI-1, 41% in MPI-2 and 53% in MPI-3, p = 0.024). All domains of MPI except cognition and living status were significantly associated with mortality at one-year, as well as tumor sites and metastatic status. Higher MPI was associated with a higher mortality risk (adjusted HR 1.56 [95%CI 1.70-2.09] and 1.72 [1.33-2.22] for MPI groups 2 and 3 compared to 1; p < 0.0001).

Conclusions: In addition to established risk factors, MPI improves risk prediction of 1-year mortality. This practical prognostic tool may help to optimize management of these vulnerable patients.
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http://dx.doi.org/10.1186/s12877-020-01692-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433061PMC
August 2020

Subcutaneous Antibiotic Therapy: The Why, How, Which Drugs and When.

J Am Med Dir Assoc 2021 01 14;22(1):50-55.e6. Epub 2020 Jul 14.

CHU de Bordeaux, Pôle de Gérontologie Clinique, Bordeaux, France; Université Bordeaux, INSERM UMR 1053 BaRITOn, France. Electronic address:

Objectives: To describe the rationale for subcutaneous (SC) administration of antibiotics from available published data and to make propositions to help clinicians in daily practice.

Design: Narrative review.

Setting And Participants: Hospitalized patients, persons in long-term care facilities and ambulatory care.

Methods: We searched the MEDLINE/PubMed electronic database for evidence supporting SC administration of antibiotics up to September 2019; the results of this primary search were supplemented by searching the references of the identified articles, as well as by searching in Google Scholar.

Results: Regarding tolerability, efficacy, and pharmacokinetic/pharmacodynamic profiles, most studies suggest that the SC route could be an alternative to the intravenous route, particularly for time-dependent antibiotics and among certain patient populations, such as patients with poor venous access, swallowing disorders, or behavioral disturbance. However, clinical evidence of the benefits and risks of SC antibiotic administration is still scarce and of low level.

Conclusions And Implications: SC administration of antibiotics may be useful in various settings such as in hospitalized patients and among those in long-term care facilities or being cared for at home. However, further clinical studies are needed to assess the pharmacokinetic/pharmacodynamic properties, as well as the risks and benefits of SC administration of antibiotics. In this review, we highlight the potential benefits of SC administration of antibiotics and address practical recommendations for its use. This information will enable improvement of treatment strategies and present the SC route as a potential option in specific situations.
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http://dx.doi.org/10.1016/j.jamda.2020.04.035DOI Listing
January 2021

Prognostic value of Charlson Comorbidity Index in the elderly with a cardioverter defibrillator implantation.

Int J Cardiol 2020 09 26;314:64-69. Epub 2020 Mar 26.

CHU Poitiers, Service de Cardiologie, 2 rue de la Milétrie, F-86021 Poitiers, France; Univ Poitiers, Faculté de Médecine et Pharmacie, F-86021 Poitiers, France; INSERM CIC 1402, CHU Poitiers, 2 rue de la Milétrie, F-86021 Poitiers, France. Electronic address:

Background: Elderly patients are often underrepresented in implantable cardioverter defibrillator (ICD) trials, and ICD implantation in patients ≥75 years consequently remains controversial. We aimed to evaluate mortality, appropriate ICD therapy rates and survival gain in an elderly population after risk stratification according to the Charlson Comorbidity Index (CCI).

Methods: This monocentric retrospective study included elderly ICD patients ≥75 years. They were subdivided according to their CCI score into 3 categories (0-1, 2-3 or ≥4 points). Elderly patients were matched 1:2 with younger control ICD patients on gender, type of prevention (primary or secondary) and type of device (associated cardiac resynchronization therapy or not).

Results: Between January 2009 and July 2017, 121 elderly patients (mean age 78 ± 3; 83% male) matched with 242 controls (mean age 66 ± 5) were included. At 5 year follow-up after ICD implantation, overall survival was 78%, 57%, and 29% (P = 0.002) in the elderly with a CCI score of 0-1, 2-3 and ≥4 respectively, and 72% in controls. There was no significant difference regarding ICD appropriate therapy between the 3 subgroups despite a trend towards lower rates of therapy in CCI ≥ 4 points patients (34.2%, 39.7% and 22.8% respectively; P = 0.45). Median potential survival gain after an appropriate therapy was >5, 4.7 and 1.4 years, with a CCI score of 0-1, 2-3 and ≥4 respectively (P = 0.01).

Conclusion: Elderly patients with CCI score ≥ 4 had the lowest survival after ICD implantation and little survival gain in case of appropriate defibrillator therapy. More than age alone, the burden of comorbidities assessed by the CCI could be helpful to better select elderly patients for ICD implantation.
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http://dx.doi.org/10.1016/j.ijcard.2020.03.060DOI Listing
September 2020

Using the Multidimensional Prognostic Index (MPI) to improve cost-effectiveness of interventions in multimorbid frail older persons: results and final recommendations from the MPI_AGE European Project.

Aging Clin Exp Res 2020 May 16;32(5):861-868. Epub 2020 Mar 16.

Department of Geriatric Care, Orthogeriatrics and Rehabilitation, E.O. Galliera Hospital, Mura delle Cappuccine 14, 16128, Genoa, Italy.

MPI_AGE is a European Union co-funded research project aimed to use the Multidimensional Prognostic Index (MPI), a validated Comprehensive Geriatric Assessment (CGA)-based prognostic tool, to develop predictive rules that guide clinical and management decisions in older people in different European countries. A series of international studies performed in different settings have shown that the MPI is useful to predict mortality and risk of hospitalization in community-dwelling older subjects at population level. Furthermore, studies performed in older people who underwent a CGA before admission to a nursing home or receiving homecare services showed that the MPI successfully identified groups of persons who could benefit, in terms of reduced mortality, of specific therapies such as statins in diabetes mellitus and coronary artery disease, anticoagulants in atrial fibrillation and antidementia drugs in cognitive decline. A prospective trial carried out in nine hospitals in Europe and Australia demonstrated that the MPI was able to predict not only in-hospital and long-term mortality, but also institutionalization, re-hospitalization and receiving homecare services during the one-year follow-up after hospital discharge. The project also explored the association between MPI and mortality in hospitalized older patients in need of complex procedures such as transcatheter aortic valve implantation or enteral tube feeding. Evidence from these studies has prompted the MPI_AGE Investigators to formulate recommendations for healthcare providers, policy makers and the general population which may help to improve the cost-effectiveness of appropriate health care interventions for older patients.
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http://dx.doi.org/10.1007/s40520-020-01516-0DOI Listing
May 2020

Frailty and diabetes status in older patients with cancer: impact on mortality in the ANCRAGE cohort.

Aging Clin Exp Res 2020 Sep 2;32(9):1809-1819. Epub 2020 Jan 2.

Department of Geriatrics, CHU Poitiers, 2 rue de la Milétrie, 86021, Poitiers Cedex, France.

Background: Frailty, diabetes and cancer are associated with aging, but the relationship between these conditions is not well defined.

Aims: We studied older patients with cancer from the prospective single-center cohort ANCRAGE (ANalyses of CanceR in AGEd) aiming to determine the impact of type 2 diabetes (T2D) and its vascular complications (VC) on frailty and adverse outcomes (mortality, unplanned readmission) during follow-up.

Methods: Analysis of cohort patients ≥ 75 years, included between 2009 and 2017, who underwent a comprehensive geriatric assessment (CGA). Variables of interest were history of T2D and VC, tumor site and metastatic status, CGA including eight domains (social environment, functional status, mobility, nutrition, mood, cognition, polypharmacy and comorbidities) and frailty.

Results: Among 1092 patients (47% female, mean age 82 ± 5 years), 219 (20%) had a reported diagnosis of T2D at baseline including 152 (69%) with VC. The most common tumor sites were prostate (15%), breast (15%), skin (12%), and colorectum (11%); 29% of patients had a metastatic disease. Frailty was highly prevalent (84%). During follow-up (median of 15.3 months), 653 (60%) patients died (60% no T2D, 43% T2D without VC, 66% with VC). After adjustment for age, gender and metastatic status, diabetics with VC had a higher risk of all-cause death (aHR1.89, 1.24-2.86, p = 0.004). Death was more frequently due to a non-cancer cause (p < 0.001). No difference in unplanned readmissions was observed in the three groups. Frailty was an independent risk factor for mortality and unplanned readmissions (p < 0.001 both).

Conclusion: In older cancer patients from the prospective ANCRAGE cohort, all-cause mortality was significantly higher in frail patients and those with complicated T2D, a finding questioning the quality of care management in such vulnerable patients, and stimulating further research in this multidisciplinary field.
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http://dx.doi.org/10.1007/s40520-019-01362-9DOI Listing
September 2020

[Anticoagulant treatment in elderly patients with atrial fibrillation: position paper].

Geriatr Psychol Neuropsychiatr Vieil 2019 12;17(4):341-355

CHU Nantes, Pôle hospitalo-universitaire de gérontologie clinique, France, Gérontopôle Autonomie Longévité Pays de la Loire, France.

Atrial fibrillation (AF) is common in the elderly. The treatment of this condition is based on anticoagulation in preventing Stroke and systemic arterial embolism. Vitamin K antagonists (VKAs) have long been the only anticoagulants available for the management of AF. Difficulties handling VKAs have made them one of the main causes of iatrogenic disease in the elderly. In the last 10 years, direct-acting oral anticoagulants (DOACs) have emerged and large randomized trials (RE-LY, ROCKET-AF, ARISTOTLE, ENGAGE-AF) have demonstrated their superiority over VKAs in the management of AF. These trials were conducted with large numbers of patients (n=71,683), including 27,500 aged ≥75 years and nearly 8,000 subjects aged >80 years. Results from 11 recent meta-analyses of randomized trials and observational real-world studies of 660,896 elderly patient indicate that DOACs are more effective than VKA-based prophylaxis in preventing stroke (risk reduction ranging from 13% to 26%) and carry a lower risk of cerebral hemorrhage (risk reduction 50%). The risk of major hemorrhage appears to be similar to or lower with DOACs than with VKAs (depending on the dosage, renal function, hemorrhagic site or type of DOACs). Moreover, a greater benefit of DOACs over VKA therapy has been found in subgroup analyses in subjects aged over 75 years, in patients with renal insufficiency (creatinine clearance 30-50 mL/min) and in those with a history of falls. Analyses indicate that DOACs are a better choice than VKAs in the elderly because elderly patients are those with the highest risk of stroke and cerebral hemorrhages. In summary, DOACs have a better efficacy/tolerance profile than VKAs, which justifies their first-line use in subjects over 75 years of age.
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http://dx.doi.org/10.1684/pnv.2019.0834DOI Listing
December 2019

Ageing stereotypes and prodromal Alzheimer's disease (AGING): study protocol for an ongoing randomised clinical study.

BMJ Open 2019 10 7;9(10):e032265. Epub 2019 Oct 7.

Aix Marseille Univ, CNRS, LPC, Marseille, France

Introduction: The number of older people diagnosed with amnestic mild cognitive impairment (aMCI), the prodromal state of Alzheimer's disease (AD), is increasing worldwide. However, some patients with aMCI never convert to the AD type of dementia, with some remaining stable and others reverting to normal. This overdiagnosis bias has been largely overlooked and gone unexplained. There is ample evidence in the laboratory that negative ageing stereotypes (eg, the culturally shared belief that ageing inescapably causes severe cognitive decline) contribute to the deteriorating cognitive performances of healthy older adults, leading them to perform below their true abilities. The study described here is intended to test for the first time whether such stereotypes also impair patients' cognitive performances during neuropsychological examinations in memory clinics, resulting in overdiagnosis of aMCI.

Methods And Analysis: The ongoing study is a 4-year randomised clinical trial comparing patients' physiological stress and cognitive performances during neuropsychological testing in memory clinics. A total of 260 patients attending their first cognitive evaluation will be randomised to either a standard condition of test administration, assumed here to implicitly activate negative ageing stereotypes or a reduced-threat instruction condition designed to alleviate the anxiety arising from these stereotypes. Both groups will be tested with the same test battery and stress biomarkers. For 30 patients diagnosed with aMCI in each group (n=60), biomarkers of neurodegeneration and amyloidopathy will be used to distinguish between aMCI with normal versus abnormal AD biomarkers. A 9-month follow-up will be performed on all patients to identify those whose cognitive performances remain stable, deteriorate or improve.

Ethics And Dissemination: This protocol has been approved by the French National Agency for Medicines and Health Products Safety and the Sud-Est I French Ethics Committee (2017-A00946-47). Results will be published in peer-reviewed journals.

Trial Registration Number: NCT03138018.
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http://dx.doi.org/10.1136/bmjopen-2019-032265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797355PMC
October 2019

[Interest of the multidimensional prognostic index (MPI) as an assessment tool in hospitalized patients in geriatrics].

Geriatr Psychol Neuropsychiatr Vieil 2019 12;17(4):386-392

Service de gériatrie, CHU La Milétrie, Poitiers, France, Centre d'investigation clinique, CIC Inserm 1402, CHU La Milétrie, Poitiers, France.

The collection of prognostic information in the elderly is essential. The main objective was to perform a replication of the multidimensional prognostic index (MPI), to predict mortality at one-year in patients hospitalized in geriatric wards. Secondary objectives were to evaluate if the MPI was predictive of the length of hospital stay, and of rehospitalization in the following year.

Methods: Prospective study conducted from February 2015 to November 2016 at the University Hospital of Poitiers (Geriatrics department). A comprehensive geriatric assessment (number of treatment, lifestyle, autonomy, comorbidities, risk of pressure sore, nutritional and cognitive status) was used to calculate the MPI score and to categorize patients into three groups: low (MPI-1), moderate (MPI-2) and high (MPI-3) risk of mortality.

Results: 153 patients were included, with mean age 85.9 ± 5.4 years. Twenty-one patients (13.7%) belonged to MPI-1 group, 98 (64.1%) to MPI-2 group, and 34 (22.2%) to MPI-3 group. The number of deaths at one-year according to the MPI group was different (p < 0.01). The one-year prognostic performance of MPI was good (AUC at 0.76). MPI was also predictive of hospital length stay (p < 0.05).

Conclusion: MPI appears to be a relevant prognostic tool in the stratification of one-year mortality risk in elderly patients hospitalized in geriatrics.
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http://dx.doi.org/10.1684/pnv.2019.0823DOI Listing
December 2019

Older women are frailer, but less often die then men: a prospective study of older hospitalized people.

Maturitas 2019 Oct 3;128:81-86. Epub 2019 Aug 3.

Department of Geriatric Care, Orthogeriatrics and Rehabilitation, E.O. Galliera Hospital, Geriatric Unit, National Relevance & High Specialization Hospital, Genoa, Italy; Department of Interdisciplinary Medicine, 'Aldo Moro' University of Bari, Italy. Electronic address:

Objectives: The association between frailty, mortality and sex is complex, but a limited literature is available on this topic, particularly for older hospitalized patients. Therefore, the objective of our study was to prospectively evaluate sex differences in frailty, assessed by the Multidimensional Prognostic Index (MPI) and mortality, institutionalization, and re-hospitalization in an international cohort of older people admitted to hospital.

Study Design: We used data from nine public hospitals in Europe and Australia, to evaluate sex differences in mortality, frailty and the risk of institutionalization and re-hospitalization, during one year of follow-up.

Main Outcome Measures: People aged 65 years or more admitted to hospital for an acute medical condition or for a relapse of a chronic disease were included. A standardized comprehensive geriatric assessment, which evaluated functional, nutritional, and cognitive status, risk of pressure sores, comorbidities, medications and co-habitation status, was used to calculate the MPI to measure frailty in all hospitalized older people. Data regarding mortality, institutionalization and re-hospitalization were also recorded for one year.

Results: Altogether, 1140 hospitalized patients (mean age = 84.2 years; 694 women = 60.9%) were included. The one-year mortality rate was 33.2%. In multivariate analysis, adjusted for age, MPI score, centre and diagnosis at baseline, although women had higher MPI scores than men, the latter had higher in-hospital (odds ratio, OR = 2.26; 95% confidence intervals, CI = 1.27-4.01) and one-year post-discharge mortality (OR = 2.04; 95%CI = 1.50-2.79). Furthermore, men were less frequently institutionalized in a care home than female patients (OR = 0.55; 95%CI: 0.34-0.91), but they were also more frequently re-hospitalized (OR = 1.42; 95%CI: 1.06-1.91) during the year after hospital discharge.

Conclusion: Older hospitalized men were less frail, but experienced higher in-hospital and one-year mortality than women. Women were admitted more frequently to nursing homes and experienced a lower risk of re-hospitalization. These findings suggest important differences between the sexes and extends the 'male-female health-survival paradox' to acutely ill patient groups.
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http://dx.doi.org/10.1016/j.maturitas.2019.07.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461698PMC
October 2019

Acute Clostridioides difficile Infection in Hospitalized Persons Aged 75 and Older: 30-Day Prognosis and Risk Factors for Mortality.

J Am Med Dir Assoc 2020 01 17;21(1):110-114. Epub 2019 Sep 17.

Pôle de Gériatrie, Centre Hospitalier Universitaire de Poitiers, Université de Poitiers, Poitiers, France; Centre d'Investigation Clinique CIC 1402, INSERM, Centre Hospitalier Universitaire de Poitiers, Université de Poitiers, Poitiers, France.

Objectives: To assess the 30-day mortality predictive markers in the oldest patients with Clostridioides difficile infection (CDI) and to analyze the accuracy of the European severity risk markers in this population.

Design: Observational prospective multicenter cohort study conducted by the French Infectious Diseases Society and Geriatrics Society networks. An electronic questionnaire was sent to members of both societies regarding their participation. Each investigator used an online survey to gather the data.

Setting And Participants: Patients aged ≥75 years hospitalized in French geriatric or infectious wards with confirmed diagnosis of CDI between March 1, 2016 and May 1, 2017.

Methods: Clinical and laboratory parameters included medical history and comorbidities with the Cumulative Illness Rating Scale (CIRS). Criteria increasing the risk of severe disease were recorded as listed in the European guidelines. Therapeutic management, recurrence, and mortality rates were assessed at day 30 after diagnosis.

Results: Included patients numbered 247; mean age was 87.2 years (SD 5.4). Most of the CDI incidences (66.4%) were health care-associated infections, with 81% diagnosed within 30 days of hospitalization; CIRS mean score was 16.6 (SD 6.6). Markers of severity ≥3 included 97 patients (39.3%). Metronidazole was the main initial treatment (51.0%). C difficile infection in the older adult was associated with a 30-day mortality of 12.6%. Multivariate analysis showed that baseline CIRS score [hazard ratio (HR) 1.06 per 1-point increase, 95% confidence interval (CI) 1.00-1.12] and evidence of cardiac, respiratory, or renal decompensation (HR 3.04, 95% CI 1.40-6.59) were significantly associated with mortality.

Conclusions And Implications: European severity markers are adequate in the oldest old. Organ failure and comorbidities appeared to be the main markers of prognosis, and these should raise the awareness of practitioners. Although antibiotic treatment was not predictive of mortality, our results point out the lack of adherence to current guidelines in this population.
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http://dx.doi.org/10.1016/j.jamda.2019.07.002DOI Listing
January 2020

Characteristics and management of giant cell arteritis in France: a study based on national health insurance claims data.

Rheumatology (Oxford) 2020 01;59(1):120-128

Internal Medicine and Clinical Immunology, CHU Lille, University Lille, LIRIC, INSERM, Lille, France.

Objective: Few data are available on the epidemiology and management of GCA in real life. We aimed to address this situation by using health insurance claims data for France.

Methods: This retrospective study used the Echantillon Généraliste de Bénéficiaires (EGB) database, a 1% representative sample of the French national health insurance system. The EGB contains anonymous data on long-term disease status, hospitalizations and reimbursement claims for 752 717 people. Data were collected between 2007 and 2015. The index date was defined as the date of the first occurrence of a GCA code. Demographics, comorbidities, diagnostic tests and therapies were analysed. Annual incidence rates were calculated, and incident and overall GCA cases were studied.

Results: We identified 241 patients with GCA. The annual incidence was 7-10/100 000 people ⩾50 years old. Among the 117 patients with incident GCA, 74.4% were females, with mean age 77.6 years and mean follow-up 2.2 years. After the index date, 51.3% underwent temporal artery biopsy and 29.1% high-resolution Doppler ultrasonography. Among the whole cohort, 84.3% used only glucocorticoids. The most-prescribed glucocorticoid-sparing agent was methotrexate (12.0%).

Conclusion: The incidence of GCA in France is 7-10/100 000 people ⩾ 50 years old. Adjunct agents, mainly methotrexate, are given to only a few patients. The use of temporal artery biopsy in only half of the patients might reflect a shift toward the use of imaging techniques to diagnose GCA.
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http://dx.doi.org/10.1093/rheumatology/kez251DOI Listing
January 2020

Enteral tube feeding and mortality in hospitalized older patients: A multicenter longitudinal study.

Clin Nutr 2020 05 22;39(5):1608-1612. Epub 2019 Jul 22.

Department of Geriatric Care, Orthogeriatrics and Rehabilitation, Geriatric Unit, E.O. Galliera Hospital, Genova, Italy; Department of Interdisciplinary Medicine, 'Aldo Moro' University of Bari, Italy.

Background & Aims: The literature regarding enteral nutrition and mortality in older frail people is limited and still conflicting. Moreover, the potential role of comprehensive geriatric assessment is poorly explored. We therefore aimed to investigate whether the Multidimensional Prognostic Index (MPI), an established tool that assesses measures of frailty and predicts mortality, may help physicians in identifying patients in whom ETF (enteral tube feeding) is effective in terms of reduced mortality.

Methods: Observational, longitudinal, multicenter study with one year of follow-up. Data regarding ETF were recorded through medical records. A standardized comprehensive geriatric assessment was used to calculate the MPI. Participants were divided in low (MPI-1), moderate (MPI-2) or severe (MPI-3) risk of mortality. Data regarding mortality were recorded through administrative information.

Results: 1064 patients were included, with 79 (13 in MPI 1-2 and 66 in MPI-3 class) receiving ETF. In multivariable analysis, patients receiving ETF experienced a higher risk of death (odds ratio, OR = 2.00; 95% confidence intervals, CI: 1.19-3.38). However, after stratifying for their MPI at admission, mortality was higher in MPI-3 class patients (OR = 2.03; 95%CI: 1.09-3.76), but not in MPI 1-2 class patients (OR = 1.51; 95%CI: 0.44-5.25). The use of propensity score confirmed these findings.

Conclusions: ETF is associated with a higher risk of death. However, this is limited to more frail patients, suggesting the importance of the MPI in the prognostic evaluation of ETF.
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http://dx.doi.org/10.1016/j.clnu.2019.07.011DOI Listing
May 2020

Impact of time to surgery in upper femoral fracture in orthogeriatrics.

Orthop Traumatol Surg Res 2019 09 10;105(5):975-978. Epub 2019 Jul 10.

Service de Chirurgie Orthopédique et Traumatologie, CHU de Poitiers, 2, rue de la Milétrie, Poitiers, 86000 France; Laboratoire PRISMATICS, CHU de Poitiers, 2, rue de la Milétrie, Poitiers 86000, France.

Introduction: Treatment of hip fracture in the elderly is a major public health issue. Orthogeriatric departments have been developed for these patients at high risk of complications. Time to surgery seems to be an important factor in the care pathway, but remains controversial.

Objectives: The aim of this study was to assess the impact of less than 24 hours' time to surgery on 1-year morbidity and mortality in patients managed in our orthogeriatric department.

Hypothesis: The study hypothesis was that<24 hours' time to surgery decreases mortality in elderly patients with upper femoral fracture.

Materials And Methods: A retrospective cohort study from September 2015 to July 2016 included patients aged 75 years and older, eligible for orthogeriatric management of upper femoral fracture. Patients with comorbidities were prioritized for admission and for access to the operating room. Time to surgery was defined as time between the arrival in A&E and transfer to the operating room. The primary endpoint was 1-year survival. Comorbidities were assessed on Charlson score. ROC curve analysis determined the optimal cut-off for time to surgery. Variables significantly associated with mortality were included in a Cox regression model to estimate the adjusted effect of time to surgery on mortality.

Results: One hundred and eight patients were included; mean age, 87±6.2 years; 26 male (24.1%), 82 female (75.9%). One-year mortality was 24.1% (26/108). Mean time to surgery was 14.1±30.9hours. ROC curve analysis showed a rise in mortality after a cut-off of 22hours 37minutes (p<0.0001).

Conclusion: Within a dedicated orthogeriatric department, time to surgery is a significant factor in the management of hip fractures in the elderly. Patients should be prioritized for theater and ideally receive "early" surgery within 24hours of admission to A&E. The potential benefit of "ultra-early" surgery (time to surgery<6hours) requires robust assessment.

Level Of Evidence: IV, Retrospective cohort study.
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http://dx.doi.org/10.1016/j.otsr.2019.04.018DOI Listing
September 2019

How many patients are eligible for disease-modifying treatment in Alzheimer's disease? A French national observational study over 5 years.

BMJ Open 2019 06 24;9(6):e029663. Epub 2019 Jun 24.

Neurology, CHU de la Pitiè Salpêtrière-AP-HP, Paris, France.

Objective: We aimed to study the epidemiology of the prodromal and mild stages of Alzheimer's disease (AD) patients who are eligible for clinical trials with disease-modifying therapies.

Settings: We analysed two large complementary databases to study the incidence and characteristics of this population on a nationwide scope in France from 2014 to 2018. The National Alzheimer Database contains data from 357 memory centres and 90 private neurologists. Data from 2014 to 2018 have been analysed.

Participants: Patients, 50-85 years old, diagnosed with AD who had an Mini-Mental State Exam (MMSE) score of ≥20 were included. We excluded patients with mixed and non-AD neurocognitive disorders.

Primary Outcome Measure: Descriptive statistics of the population of interest was the primary measure.

Results: In the National Alzheimer Database, 550 198 patients were assessed. Among them, 72 174 (13.1%) were diagnosed with AD and had an MMSE ≥20. Using corrections for specificity of clinical diagnosis of AD, we estimated that about 50 000 (9.1%) had a prodromal or mild AD. In the combined electronic clinical records database of 11 French expert memory centres, a diagnosis of prodromal or mild AD, certified by the use of cerebrospinal fluid AD biomarkers, could be established in 195 (1.3%) out of 14 596 patients.

Conclusions: AD was not frequently diagnosed at a prodromal or mild dementia stage in France in 2014 to 2018. Diagnosis rarely relied on a pathophysiological marker even in expert memory centres. National databases will be valuable to monitor early stage AD diagnosis efficacy in memory centres when a disease-modifying treatment becomes available.
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http://dx.doi.org/10.1136/bmjopen-2019-029663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597622PMC
June 2019

[Non-programmed hospitalization of elderly patients with cancer: Which care pathway?]

Bull Cancer 2019 Apr 1;106(4):293-303. Epub 2019 Mar 1.

CHU La Milétrie, pôle de gériatrie, 2, rue de La Milétrie, 86021 Poitiers cedex, France.

Introduction: Management of elderly patients with cancer is challenging worldwide. Improvement of their care pathway should focus on unplanned hospitalizations. This study aimed to compare the geriatric and oncologic profiles of elderly patients with cancer, hospitalized for an acute pathology either in medical oncology or acute geriatric medicine units.

Methods: Epidemiological, analytical, monocentric, transversal study performed in the geriatric and oncological short-stay units of the university hospital of Poitiers (France) from 07/01/2014 to 06/30/2015. Only patients with diagnosed cancer prior to hospitalization were included. The geriatric, oncological and hospitalization data were collected and analyzed.

Results: In total, 230 patients were included (156 in geriatrics, 74 in oncology). Alteration of the general condition was the most frequent reason for admission. In multivariate age-adjusted analyses, factors associated with admission to a geriatric unit were co-morbidities (OR=0.18 [95% CI: 0.07-0.46], P<0.01) and dependence (OR=0.07 [95% CI: 0.01-0.36], P<0.01). Ongoing antineoplastic treatment (OR=2.60 [95%CI: 1.14-5.89], P=0.02) and metastatic cancer (OR=2.63 [95%CI: 1.18-5.86], P=0.02) influenced hospitalization in the oncology unit. During the hospital stay there was more frequent psychological support in oncology (OR=45.59 [95%CI: 9.79-212.23], P<0.01) and social support in Geriatrics (OR=0.13 [95% CI: 0.04-0.40], P<0.01).

Conclusion: This first comparative study showed a significant difference in profiles of elderly patients with cancer hospitalized for an acute problem, depending on the hospital unit. This finding paves the way of improvement of care pathway by formalizing links between these two departments to optimize care and referrals to the most appropriate care unit, according to patients condition, in case of unscheduled hospitalization.
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http://dx.doi.org/10.1016/j.bulcan.2018.12.012DOI Listing
April 2019

Trans ε viniferin decreases amyloid deposits and inflammation in a mouse transgenic Alzheimer model.

PLoS One 2019 20;14(2):e0212663. Epub 2019 Feb 20.

University of Poitiers, EA3808 Neurovascular Unit and Cognitive Disorders, Pôle Biologie Santé, POITIERS, France.

As Alzheimer's disease (AD) induces several cellular and molecular damages, it could be interesting to use multi-target molecules for therapeutics. We previously published that trans ε-viniferin induced the disaggregation of Aβ42 peptide and inhibited the inflammatory response in primary cellular model of AD. Here, effects of this stilbenoid were evaluated in transgenic APPswePS1dE9 mice. We report that trans ε-viniferin could go through the blood brain barrier, reduces size and density of amyloid deposits and decreases reactivity of astrocytes and microglia, after a weekly intraperitoneal injection at 10 mg/kg from 3 to 6 months of age.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0212663PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382128PMC
November 2019

Prognosis of geriatric patients with severe kidney disease.

Geriatr Psychol Neuropsychiatr Vieil 2018 Dec;16(4):376-382

Pôle de gériatrie, CHU de Poitiers, Poitiers, France, Inserm, CIC1402, CHU de Poitiers, France.

Over three million French people present a severe chronic kidney disease, among which there is a high prevalence of elder subjects. We conducted a prospective monocentric study in a geriatric acute care ward. The aims were to determine the short-term prognosis of patients with severe chronic kidney disease and to determine the factors associated with mortality at six-months.

Methods: Patients 75 years of age and older, with an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m (chronic kidney disease epidemiology CKD-EPI) were recruited. A comprehensive geriatric assessment was performed at hospital discharge. Comprehensive geriatric assessment was performed: Activities of daily livings and Instrumental activities of daily livings scores, of the risk of pressure sore with Exton-Smith scale, the cognitive status with MMSE score, nutritional status according to Mini-nutritional assessment short form and albuminemia, comorbidities with Cumulative illness rating scale, number of drugs in presciption and living status. Six months follow-up was performed to assess vital status and evolution of the eGFR.

Results: Sixty-seven patients were included, mean age 88.6±4.82 years with a mean eGFR of 21.3±6 mL/min. Mortality rate at six months was 36%. Multivariate analysis showed that a high CIRS score (RR=1.52; IC 95% 1.05-2.19) and a decline of creatinine clearance≥ 2 mL/min (4.72; 1.27-17.52) were predictive of mortality. On the opposite, a high MNA-SF score was protective (0.76; 0.62-0.94).

Conclusion: Prognosis of geriatric patients with severe chronic kidney disease is poor. Comprehensive geriatric assessment helps to assess short-term prognosis, in a focus of person-centered care.
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http://dx.doi.org/10.1684/pnv.2018.0756DOI Listing
December 2018

Study protocol on Alzheimer's disease and related disorders: focus on clinical and imaging predictive markers in co-existing lesions.

BMC Geriatr 2018 11 14;18(1):280. Epub 2018 Nov 14.

Clinical and Research Memory Centre of Lyon, Hospital of Charpennes, Hospices Civils de Lyon, Lyon, France.

Background: One of the crucial challenges for the future of therapeutic approaches to Alzheimer's disease (AD) is to target the main pathological processes responsible for disability and dependency. However, a progressive cognitive impairment occurring after the age of 70, the main population affected by dementia, is often related to mixed lesions of neurodegenerative and vascular origins. Whereas young patients are mostly affected by pure lesions, ageing favours the occurrence of co-lesions of AD, cerebrovascular disease (CVD) and Lewy body dementia (LBD). Most of clinical studies report on functional and clinical disabilities in patients with presumed pure pathologies. But, the weight of co-morbid processes involved in the transition from an independent functional status to disability in the elderly with co-lesions still remains to be elucidated. Neuropathological examination often performed at late stages cannot answer this question at mild or moderate stages of cognitive disorders. Brain MRI, Single Photon Emission Computed Tomography (SPECT) with DaTscan®, amyloid Positron Emission Tomography (PET) and CerebroSpinal Fluid (CSF) AD biomarkers routinely help in performing the diagnosis of underlying lesions. The combination of these measures seems to be of incremental value for the diagnosis of mixed profiles of AD, CVD and LBD. The aim is to determine the clinical, neuropsychological, neuroradiological and biological features the most predictive of cognitive, behavioral and functional impairment at 2 years in patients with co-existing lesions.

Methods: A multicentre and prospective cohort study with clinical, neuro-imaging and biological markers assessment will recruit 214 patients over 70 years old with a cognitive disorder of AD, cerebrovascular and Lewy body type or with coexisting lesions of two or three of these pathologies and fulfilling the diagnostic criteria for dementia at a mild to moderate stage. Patients will be followed every 6 months (clinical, neuropsychological and imaging examination and collection of cognitive, behavioural and functional impairment) for 24 months.

Discussion: This study aims at identifying the best combination of markers (clinical, neuropsychological, MRI, SPECT-DaTscan®, PET and CSF) to predict disability progression in elderly patients presenting coexisting patterns.

Trial Registration: NCT02052947 .
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http://dx.doi.org/10.1186/s12877-018-0949-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236893PMC
November 2018

Prevalence of cancer and management in elderly nursing home residents. A descriptive study in 45 French nursing homes.

Eur J Cancer Care (Engl) 2019 Mar 29;28(2):e12957. Epub 2018 Oct 29.

Department of Geriatrics, Poitiers University Hospital, Poitiers, France.

This study aimed to determine cancer prevalence occurring after the age of 75 in 45 French nursing homes (NH), as well as residents' characteristics and parameters associated with cancer-specific management. Descriptive retrospective study including 214 residents (mean age, 89.7 years) with cancer diagnosed after age 75. The studied parameters were sociodemographic, functional, nutritional and cognitive data; comorbidity assessment; date of tumoral diagnosis; cancer type; tumoral stage; treatment plan; multidisciplinary staff decision and oncologic follow-up. Our results showed that cancer prevalence in NH was 8.4 ± 1.1%, diagnosed before admission in 63% of cases. The most common tumoral sites were skin (26%), digestive tract and breast (18% for both); 12% had metastasis. Cognitive impairment was the most common comorbidity (42%), and 44% of the residents were highly dependent. Multivariate analysis showed that therapeutic decisions were associated with age. Older patients had less staging exploration (odd ratios [ORs], 0.90, 95% confidence interval [CI], 0.85-0.97) and underwent less cancer-specific treatment (ORs, 0.92; 95%CI, 0.86-0.99). Oncologic follow-up was more frequent in younger patients (ORs, 0.90; 95%CI, 0.81-0.99) and those with recent diagnosis (ORs, 0.37; 95%CI, 0.23-0.61). This study identified factors associated with substandard neoplastic management in elderly NH residents. It highlights needs for information, education and training in cancer detection to improve cancer consideration and care in NH.
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http://dx.doi.org/10.1111/ecc.12957DOI Listing
March 2019

Using the Multidimensional Prognostic Index to Predict Clinical Outcomes of Hospitalized Older Persons: A Prospective, Multicenter, International Study.

J Gerontol A Biol Sci Med Sci 2019 09;74(10):1643-1649

National Institute on Aging, Baltimore, Maryland.

Background: Multidimensional Prognostic Index (MPI) is useful as a prognostic tool in hospitalized older patients, but our knowledge is derived from retrospective studies. We therefore aimed to evaluate in a multicenter, longitudinal, cohort study whether the MPI at hospital admission is useful to identify groups with different mortality risk and whether MPI at discharge may predict institutionalization, rehospitalization, and use of home care services during 12 months.

Methods: This longitudinal study, carried out between February 2015 and August 2017, included nine public hospitals in Europe and Australia. A standardized comprehensive geriatric assessment including information on functional, nutritional, cognitive status, risk of pressure sores, comorbidities, medications, and cohabitation status was used to calculate the MPI and to categorize participants in low, moderate, and severe risk of mortality. Data regarding mortality, institutionalization, rehospitalization, and use of home care services were recorded through administrative information.

Results: Altogether, 1,140 hospitalized patients (mean age 84.1 years, women = 60.8%) were included. In the multivariable analysis, compared to patients with low risk group at admission, patients in moderate (odds ratio [OR] = 3.32; 95% CI: 1.79-6.17; p < .001) and severe risk (OR = 10.72, 95% CI: 5.70-20.18, p < .0001) groups were at higher risk of overall mortality. Among the 984 older patients with follow-up data available, those in the severe-risk group experienced a higher risk of overall mortality, institutionalization, rehospitalization, and access to home care services.

Conclusions: In this cohort of hospitalized older adults, higher MPI values are associated with higher mortality and other negative outcomes. Multidimensional assessment of older people admitted to hospital may facilitate appropriate clinical and postdischarge management.
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http://dx.doi.org/10.1093/gerona/gly239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940980PMC
September 2019

Positive perception of aging is a key predictor of quality-of-life in aging people.

PLoS One 2018 3;13(10):e0204044. Epub 2018 Oct 3.

Pôle Biologie, Pharmacie et Santé Publique, Centre Hospitalier Universitaire de Poitiers, Université de Poitiers, Poitiers, France.

Objective: We conducted a cross-sectional survey in France in a cohort over 55 years of age to characterize the impact of psychological dimensions on quality-of-life (QoL).

Methods: The predictors of QoL in relation with aging were studied using an adapted quality-of-life model, based on emotional, cognitive and physical symptoms, functional status, and general health perception. Adding psychological dimensions such as self-esteem, psychological distress, perceptions of ageing and coping, was hypothesized to improve the QoL model. Responses were analyzed using structural equation modeling and path analysis.

Results: The study involved 258 participants, mean age 66.9±7.9 years. Psychological distress and positive perception of aging exhibited the strongest direct impact on QoL (p<0.0001). Psychological distress also appeared to be mediator on QoL for perceived health status, self-esteem and negative perception of aging. Coping centred on emotion exhibited direct impact on self-esteem and so, indirect impact on QoL (p = 0.0002). Perception of personal financial situation (p = 0.0007) and coping centred on social support (p = 0.02) appeared as direct mediators influencing QoL.

Conclusions: Psychological dimensions are predictors of QOL and have to be taken into account to maximize the resources with a view to successful aging. Further interventions targeting successful aging should focus on positive perception aging.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0204044PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169874PMC
April 2019

Differential chemokine expression under the control of peripheral blood mononuclear cells issued from Alzheimer's patients in a human blood brain barrier model.

PLoS One 2018 9;13(8):e0201232. Epub 2018 Aug 9.

EA3808, molecular Targets and Therapeutics of Alzheimer's disease, University of Poitiers, Poitiers, France.

Growing evidence highlights the peripheral blood mononuclear cells (PBMCs) role and the chemokine involvement in the Alzheimer's disease (AD) physiopathology. However, few data are available about the impact of AD PBMCs in the chemokine signature in a brain with AD phenotype. Therefore, this study analyzed the chemokine levels in a human blood brain barrier model. A human endothelial cell line from the immortalized cerebral microvascular endothelial cell line (hCMEC/D3) and a human glioblastoma U-87 MG cell line, both with no AD phenotype were used while PBMCs came from AD at mild or moderate stage and control patients. PBMCs from moderate AD patients decreased CCL2 and CCL5 levels in endothelial, and also CXCL10 in abluminal compartments and in PBMCs compared to PBMCs from mild AD patients. The CX3CL1 expression increased in endothelial and abluminal compartments with PBMCs from mild AD patients compared to controls. AD PBMCs can convert the chemokine signature towards that found in AD brain, targeting some chemokines as new biomarkers in AD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0201232PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6084889PMC
February 2019

Blood Inflammatory Mediators and Cognitive Decline in Alzheimer's Disease: A Two Years Longitudinal Study.

J Alzheimers Dis 2018 ;63(1):87-92

Poitiers University Hospital, Centre Mémoire de Ressources et de Recherche, France.

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.
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http://dx.doi.org/10.3233/JAD-171131DOI Listing
August 2019

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

Alzheimers Dement 2018 07 17;14(7):858-868. Epub 2018 Feb 17.

Memory Resource and Research Centre of de Paris-Broca-Ile de France, Hopital Broca, APHP, Paris, France; EA 4468, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

Introduction: Diagnostic relevance of plasma amyloid β (Aβ) for Alzheimer's disease (AD) process yields conflicting results. The objective of the study was to assess plasma levels of Aβ and Aβ 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 Aβ and Aβ 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 Aβ and P = .04 for Aβ). Globally, plasma Aβ correlated with age, Mini-Mental State Examination, and APOE ε4 allele. Plasma Aβ correlated with all CSF biomarkers in MCI but only with CSF Aβ in AD.

Discussion: Plasma Aβ was associated with cognitive status and CSF biomarkers, suggesting the interest of plasma amyloid biomarkers for diagnosis purpose.
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http://dx.doi.org/10.1016/j.jalz.2018.01.004DOI Listing
July 2018

Trans ε-viniferin is an amyloid-β disaggregating and anti-inflammatory drug in a mouse primary cellular model of Alzheimer's disease.

Mol Cell Neurosci 2018 04 7;88:1-6. Epub 2017 Dec 7.

University of Poitiers, EA3808 Molecular Targets and Therapeutics of Alzheimer's Disease, Pôle Biologie Santé, 1 Rue Georges Bonnet, TSA 51106, 86073 Poitiers Cedex 9, France. Electronic address:

Alzheimer's disease (AD) is marked by several cellular and molecular damage. Therefore, the therapeutic interest of multi-target molecules is increasingly justified. Polyphenols presenting multiple pharmacological effects would be more efficient. In this study, beneficial effects of trans ε-viniferin, a natural polyphenol were thus evaluated. This study reported that this stilbenoid (1) induced the disaggregation of amyloid β (Aβ) peptide and (2) rescued inflammation in murine primary neuronal cultures. These both effects are higher than those of resveratrol, and so, trans ε-viniferin could be a good therapeutic multi-target candidate.
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http://dx.doi.org/10.1016/j.mcn.2017.12.003DOI Listing
April 2018

Cognitive and imaging markers in non-demented subjects attending a memory clinic: study design and baseline findings of the MEMENTO cohort.

Alzheimers Res Ther 2017 Aug 29;9(1):67. Epub 2017 Aug 29.

Memory Resource and Research Centre of Besançon, CHU de Besançon, Hôpital Jean Minjoz, Hôpital Saint-Jacques, F-25000, Besançon, France.

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 F-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.

Trial Registration: Clinicaltrials.gov, NCT01926249 . Registered on 16 August 2013.
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http://dx.doi.org/10.1186/s13195-017-0288-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576287PMC
August 2017

Peripheral Blood Mononuclear Cells of Alzheimer's Disease Patients Control CCL4 and CXCL10 Levels in a Human Blood Brain Barrier Model.

Curr Alzheimer Res 2017 ;14(11):1215-1228

EA3808 molecular Targets and Therapeutics of Alzheimer's disease, University of Poitiers, 86073 Poitiers, France.

Background: Alzheimer's disease (AD) is accompanied by a neuroinflammation triggering chemoattractant signals towards peripheral blood mononuclear cells (PBMCs), which in turn could reduce amyloid plaques after transmigration through the blood brain barrier (BBB). But the chemotactic environment remains unclear.

Objective: To analyze five chemokines known to be involved in AD in three different cellular models to better understand the cellular and molecular interactions in the BBB.

Method: Chemokines (CCL-2, 4 and 5, CXCL10 and CX3CL1) were measured in isolated cells, a BBB model without PBMCs (H4 and hCMEC/D3 cells, a neuroglioma and human endothelial cells, respectively) and in a complete BBB model with PBMCs from AD patients at a moderate stage. In one set of experiments, H4 cells were treated with Aβ42.

Results: CCL2 and CCL5 significantly increased in hCMEC/D3 and H4 cells in the complete BBB model. In turn, the rate of CCL2 increased in PBMCs whereas for CCL5, it decreased. CXCL10 increased in all cellular actors in the complete BBB model, compared to isolated cells. For CCL4, PBMCs induced a robust increase in H4 and hCMEC/D3. In turn, the level of CCL4 decreased in PBMCs. Furthermore, PBMCs triggered a significant increase in CX3CL1 in hCMEC/D3. Surprisingly, no effect of Aβ42 was observed in the complete BBB model.

Conclusion: These findings highlight the interest of a BBB model in order to explore chemokine production. For the first time, results showed that PBMCs from patients with AD can control the production of CCL4 and CXCL10 in a human BBB model.
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http://dx.doi.org/10.2174/1567205014666170417110337DOI Listing
June 2018

Using a multidimensional prognostic index (MPI) based on comprehensive geriatric assessment (CGA) to predict mortality in elderly undergoing transcatheter aortic valve implantation.

Int J Cardiol 2017 Jun 16;236:381-386. Epub 2017 Feb 16.

Pôle de Gériatrie, Centre Hospitalier Universitaire de Poitiers, Université de Poitiers, Poitiers, France; INSERM, CIC-P 1402, Centre Hospitalier Universitaire de Poitiers, Université de Poitiers, Poitiers, France.

Background: Selection of appropriate elderly who can benefit from transcatheter aortic valve implantation (TAVI) is challenging. We evaluated the prognosis of this procedure according to the comprehensive geriatric assessment (CGA) based on the multidimensional prognostic index (MPI).

Methods: Prospective observational monocentric study from January 2013 to December 2015. Consecutive patients aged ≥75 who underwent TAVI and a complete CGA were included. Baseline demographic, geriatric and cardiologic data were collected. CGA was used to calculate the MPI score that is divided in three groups according to the mortality risk. Follow up was performed until December 2016 and mortality rate was assessed at one, six and 12months.

Results: 116 patients were included. Mean age was 86.2±4.2years, mean European system for cardiac operative risk evaluation (EuroSCORE) was 19.2±11.3%, mean MPI score was 0.39±0.13. Forty-five (38.8%) patients belonged to MPI-1 group, 68 (58.6%) to MPI-2 group and three to MPI-3 group. MPI score and Euroscore were moderately correlated (Spearman correlation coefficient r=0.27, p=0.0035). Mortality rate was significantly different between MPI groups at six and 12months (p=0.040 and p=0.022). Kaplan Meier survival estimates at one year stratified by MPI groups was significantly different (hazard ratio HR=2.83, 95%confidence interval (CI) 1.38-5.82, p=0.004). Among variables retained to perform logistic regression analysis, the score of instrumental activities of daily living appeared the most relevant (p<0.001).

Conclusion: This study indicates that CGA based on MPI tool is accurate to predict prognosis in elderly patients undergoing TAVI procedure.
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http://dx.doi.org/10.1016/j.ijcard.2017.02.048DOI Listing
June 2017
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