Associated Factors to Efficacy and Tolerance of Immunotherapy in Older Patients with Cancer Aged 70 Years and Over: Impact of Coprescriptions.

BACKGROUND: Immunotherapy with immune checkpoint blockers (ICB) significantly improves the prognosis for an increasing number of cancers. However, data on geriatric populations taking ICB are rare. OBJECTIVE: This study aimed to identify factors associated with the efficacy and tolerance of ICB in an older population. PATIENTS AND METHODS: This retrospective monocentric study included consecutive patients aged ≥ 70 years with solid cancer who received ICB between January 2018 and December 2019. Efficacy was assessed by progression-free survival (PFS) and tolerance was defined as cessation of immunotherapy due to the occurrence of any adverse event. RESULTS: One hundred and five patients (65.7% men) were included, mainly at the metastatic stage (95.2%); 50.5% had lung cancer. Most (80%) patients were treated with anti-PD1 (nivolumab, pembrolizumab), 19.1% with anti-PD-L1 (atezolizumab, durvalumab, and avelumab) and 0.9% with anti-CTLA4 ICB (ipilimumab). Median PFS was 3.7 months [95% confidence interval (CI) (2.75-5.70)]. PFS was shorter in univariate analysis when ICB was taken concomitantly with an antiplatelet agent (AP) [hazard ratio (HR) = 1.93; 95% CI (1.22-3.04); p = 0.005]. Tolerance was lower in univariate analysis for lung cancer [odds ratio (OR) = 3.03; 95% CI (1.07-8.56), p < 0.05] and in patients taking proton pump inhibitors (PPI) [OR = 5.50; 95% CI (1.96-15.42), p < 0.001]. There was a trend toward poorer tolerance among patients living alone [OR = 2.26; 95% CI (0.76-6.72); p = 0.14]. CONCLUSIONS: In older patients taking ICB for solid cancers, concomitant AP may influence efficacy and concomitant PPI may influence tolerance. Further studies are needed to confirm these results.

7ß-Hydroxycholesterol and 7-ketocholesterol: New oxidative stress biomarkers of sarcopenia inducing cytotoxic effects on myoblasts and myotubes.

Aging is a complex biological process which can be associated with skeletal muscle degradation leading to sarcopenia. The aim of this study consisted i) to determine the oxidative and inflammatory status of sarcopenic patients and ii) to clarify the impact of oxidative stress on myoblasts and myotubes. To this end, various biomarkers of inflammation (C-reactive protein (CRP), TNF-α, IL-6, IL-8, leukotriene B4 (LTB4)) and oxidative stress (malondialdehyde, conjugated dienes, carbonylated proteins and antioxidant enzymes: catalase, superoxide dismutase, glutathione peroxidase) as well as oxidized derivatives of cholesterol formed by cholesterol autoxidation (7-ketocholesterol, 7ß-hydroxycholesterol), were analyzed. Apelin, a myokine which contributes to muscle strength, was also quantified. To this end, a case-control study was conducted to evaluate the RedOx and inflammatory status in 45 elderly subjects (23 non-sarcopenic; 22 sarcopenic) from 65 years old and higher. SARCopenia-Formular (SARC-F) and Timed Up and Go (TUG) tests were used to distinguish between sarcopenic and non-sarcopenic subjects. By using red blood cells, plasma and/or serum, we observed in sarcopenic patients an increased activity of major antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase) associated with lipid peroxidation and protein carbonylation (increased level of malondialdehyde, conjugated dienes and carbonylated proteins). Higher levels of 7-ketocholesterol and 7ß-hydroxycholesterol were also observed in the plasma of sarcopenic patients. Significant differences were only observed with 7ß-hydroxycholesterol. In sarcopenic patients comparatively to non-sarcopenic subjects, significant increase of CRP, LTB4 and apelin were observed whereas similar levels of TNF-α, IL-6 and IL-8 were found. The increased plasma level of 7-ketocholesterol and 7ß-hydroxycholesterol in sarcopenic patients led us to study the cytotoxic effect of these oxysterols on undifferentiated (myoblasts) and differentiated (myotubes) murine C2C12 cells. With the fluorescein diacetate and sulforhodamine 101 assays, an induction of cell death was observed both on undifferentiated and differentiated cells: the cytotoxic effects were less pronounced with 7-ketocholesterol. In addition, IL-6 secretion was never detected whatever the culture conditions, TNF-α secretion was significantly increased on undifferentiated and differentiated C2C12 cells treated with 7-ketocholesterol- and 7ß-hydroxycholesterol, and IL-8 secretion was increased on differentiated cells. 7-ketocholesterol- and 7ß-hydroxycholesterol-induced cell death was strongly attenuated by α-tocopherol and Pistacia lentiscus L. seed oil both on myoblasts and/or myotubes. TNF-α and/or IL-8 secretions were reduced by α-tocopherol and Pistacia lentiscus L. seed oil. Our data support the hypothesis that the enhancement of oxidative stress observed in sarcopenic patients could contribute, especially via 7ß-hydroxycholesterol, to skeletal muscle atrophy and inflammation via cytotoxic effects on myoblasts and myotubes. These data bring new elements to understand the pathophysiology of sarcopenia and open new perspectives for the treatment of this frequent age-related disease.

Interest of individual breast cancer screening by mammography in women aged over 75 years / Intérêt du dépistage individuel du cancer du sein par mammographie chez la femme âgée de plus de 75 ans

Organized breast cancer screening in France is recommended for women up to 74 years of age, while the frequency and severity of this cancer increases after 75 years. The aim of this work is to assess the potential benefits of extending organized screening. Methodology: Retrospective study of a continuous monocentric series of women over 75 having undergone surgery for breast cancer. The following variables were studied: addressing after screening or not, age at diagnosis, UICC stage and therapeutic measures (surgery by lumpectomy or mastectomy, lymph node dissection, adjuvant treatment with chemotherapy, radiotherapy or hormone therapy). Results: 185 women aged 82.8 ± 5.2 years [extreme ages 75 to 95] were included in the study. 136 (73.5%) breast cancers were discovered after palpation and 49 (26.5%) after screening mammography. The distribution by stage was: I - 38.8%, II - 39.5%, III - 15.1% and stage IV - 7%. 164 (87.7%), patients received surgical treatment: 115 lumpectomies (61.2%) and 49 mastectomies (26.5%). 51 (27.6%) patients underwent lymph node dissection. The distribution of adjuvant treatments was: chemotherapy 21.1%, radiotherapy 68.6%, or hormone therapy (79.5%), sometimes combined. Women not screened are older than women screened (84 ± 5.3 versus 79.5 ± 3.6 years; p < 0.0001). Cancers are diagnosed at a more advanced stage in non-screened patients compared to screened patients (p < 0.0001). While there is a higher proportion of stage I among screened patients (75.5%), stage II is the most frequent in women not screened (47%). Stage I and II are the majority in the latter (72%). In multivariate analysis with adjustment for age, screening made it possible to make a diagnosis at a less advanced stage (stage I-II vs II-IV: OR = 5.593; 95% CI [1.575­19.866]; p = 0.0078) and to have conservative surgery more often (lumpectomy vs mastectomy: OR = 2.645; 95% CI [1.079­6.493]; p = 0.0333) without more recourse to surgery (OR = 1.856 95% CI [0.207­16.612]; p = 0.58). After adjusting for age and stage, screening was no longer a determining factor in the choice of type of surgery (OR = 1.934; 95% CI [0.753­4.975]; p = 0.170). Conclusion: At the age when organized breast cancer screening in France stopped, there was a decrease in survival, a diagnosis at a higher stage and an increase in co-morbidities. Our study shows a change in management with heavier treatment, more complications and a greater loss of autonomy without screening. This pleads for a continuation beyond 75 years of the practice of mammography screening for breast cancer in elderly women.

Le dépistage du cancer du sein par mammographie est recommandé jusqu'à 74 ans alors que fréquence et gravité de ce cancer augmentent après 75 ans. Le but de ce travail est d'évaluer les bénéfices potentiels de l'extension du dépistage individuel par mammographie. Méthodologie: Étude rétrospective d'une série continue monocentrique de femmes de plus de 75 ans ayant consulté pour cancer du sein. Résultats: Cent-quatre-vingt-cinq femmes âgées (82,8 ± 5,2 ans [75-95]) ont été inclues. Cent-soixante-quatre (87,7 %) patientes ont bénéficié d'une chirurgie (115 tumorectomies (61,2 %), 49 mastectomies (26,5 %) et 51 curages ganglionnaires (27,6 %) avec traitement adjuvant (chimiothérapie 21,1 % ; radiothérapie 68,6 % ; ou hormonothérapie 79,5 %). Quarante-neuf cancers du sein ont été découverts après dépistage individuel par mammographie (26,5 %) chez des femmes moins âgées (79,5 ± 3,6 vs 84 ± 5,3 ans ; p < 0,0001), à un stade moins avancé (stade I-II vs III-IV : OR = 5,6 [1,5­19,8] ; p = 0,0078) avec une chirurgie plus conservatrice (tumorectomie vs mastectomie : OR = 2,6 [1,1­6,5] ; p = 0,0333). Conclusion: Le dépistage individuel du cancer du sein par mammographie permet une prise en charge moins lourde, à un stade moins avancé et devrait être poursuivi après 75 ans.

Assessment of Prescriptions in Elderly Patients Hospitalized in Medicine Departments.

Drug-related iatrogenesis is an important issue in the elderly population, and preventing iatrogenic accidents helps to reduce hospitalizations. Our study's objective was to evaluate prescriptions in the geriatric population of our establishment. The study conducted is a targeted clinical audit. Ten criteria were tested on the hospital prescriptions of people over 75 years old in 11 medical departments, before and after improvement actions. The non-compliance threshold was set at 10% of prescriptions for each criterion. In each phase, 165 patients were included. Four criteria were non-compliant (NC) in the first phase: the presence of Potentially Inappropriate Medications for the Elderly (PIMs) (NC = 57.6%), the adaptation of the medication to renal clearance (NC = 24.9%), the presence of illogical combination (NC = 9.7%), and the total anti-cholinergic score of the prescription (NC = 12.1%). After the implementation of improvement actions, the number of non-compliant criteria decreased between the two phases, from four to two. We obtained a significant improvement for three of the four criteria found to be non-compliant in the first phase. The criterion adaptation to renal function is close to compliance (NC = 10.1%) and the PIMs criterion remained non-compliant after reassessment (NC = 32.1%). Vigilance must be ongoing in order to limit drug iatrogeny, particularly in frail elderly patients.

Level of Medical Intervention in Geriatric Settings: Decision Factors and Correlation With Mortality.

OBJECTIVES: Level of medical intervention (LMI) has to be adapted to each patient in geriatric care. LMI scales intend to help nonintensive care (NIC) decisions, giving priority to patient choice and collegial discussion. In the present study, we aimed to assess the parameters associated with the NIC decision and whether these parameters differ from those associated with in-hospital mortality. DESIGN: Prospective observational study. SETTING AND PARTICIPANTS: All consecutive patients from a French 62-bed acute geriatric unit over 1 year. METHODS: Factors from the geriatric assessment associated with the decision of NIC were compared with those associated with in-hospital and 1-year mortality, in univariate and multivariate analyses. RESULTS: In total, 1654 consecutive patients (median age 87 years) were included. Collegial reflection led to NIC decision for 532 patients (32%). In-hospital and 1-year mortality were 22% and 54% in the NIC group vs 2% and 27% in the rest of the cohort (P < .001 for both). In multivariable analysis, high Charlson Comorbidity Index [odds ratio (OR) 1.15, 95% confidence interval (CI) 1.06-1.23, per point], severe neurocognitive disorders (OR 2.78, 95% CI 1.67-4.55), dependence (OR 1.92, 95% CI 1.45-2.59), and nursing home residence (OR 2.38, 95% CI 1.85-3.13) were highly associated with NIC decision but not with in-hospital mortality. Conversely, acute diseases had little impact on LMI despite their high short-term prognostic burden. CONCLUSIONS AND IMPLICATIONS: Neurocognitive disorders and dependence were strongly associated with NIC decision, even though they were not significantly associated with in-hospital mortality. The decision-making process of LMI therefore seems to go beyond the notion of short-term survival.

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

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

Impact of Age, Multimorbidity and Frailty on the Prescription of Preventive Antiplatelet Therapy in Older Population.

Platelet aggregation inhibitors (PAI) have widely proven their efficiency for the prevention of ischemic cardiovascular events. We aimed to describe PAI prescription in an elderly multimorbid population and to determine the factors that influence their prescription, including the impact of age, comorbidities and frailty, evaluated through a comprehensive geriatric assessment. This cross-sectional study included all patients admitted to the acute geriatric department of a university hospital from November 2016 to January 2017. We included 304 consecutive hospitalized patients aged 88.7 ± 5.5 years. One third of the population was treated with PAI. A total of 133 (43.8%) patients had a history of cardiovascular disease, 77 of whom were on PAI. For 16 patients, no indication was identified. The prescription or the absence of PAI were consistent with medical history in 61.8% of patients. In the multivariate analysis, among the 187 patients with an indication for PAI, neither age (odds ratio (OR) = 1.00; 95% confidence interval (CI): [0.91-1.08], per year of age), nor comorbidities (OR = 0.97; 95% CI: [0.75-1.26], per point of Charlson comorbidity index), nor cognitive disorders (OR = 0.98; 95% CI [0.91-1.06] per point of Mini Mental State Examination), nor malnutrition (OR = 1.07; 95% CI [0.96-1.18], per g/L of albumin) were significantly associated with the therapeutic decision. PAI were less prescribed in primary prevention situations, in patients taking anticoagulants and in patients with a history of bleeding. In conclusion, a third of our older comorbid population of inpatients was taking PAI. PAI prescription was consistent with medical history for 61.8% of patients. Age, multimorbidity and frailty do not appear to have a significant influence on therapeutic decision-making. Further research is needed to confirm such a persistence of cardiovascular preventive strategies in frail older patients from other settings and to assess whether these strategies are associated with a clinical benefit in this specific population.

[Anticoagulant treatment in elderly patients with atrial fibrillation: position paper]. / Traitement par anticoagulants chez les patients atteints de fibrillation atriale : un consensus.

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.

[Osteoporosis treatment in patients over 75 years old with fractures living in nursing home]. / Prise en charge de l'ostéoporose fracturaire chez les patients de plus de 75 ans vivant en institution.

OBJECTIVE: Recommendations for the management of major fractures in institutionalized patients over 75 years old were updated by the GRIO (French group for research and information on osteoporosis) in 2012 and in 2018. This study is an evaluation of practices in osteoporosis management in institutionalized old patients. METHODS: Evaluation of diagnostic and therapeutic management in medical observations of all residents over 75 years old with a history of major fracture in 4 nursing homes. RESULTS: 105 residents were included with the prevalence of osteoporosis fracture of 32.1%. The most common fractures were hip fractures (60.9%) and vertebral fracture (45.8%). Treatments were: calcium supplementation (14.3% of residents), vitamin D (52.4%), rehabilitation (70.5%) and specific treatment (biphosphonates 11.4%). Complete management (calcium supplementation, vitamin D, physical activity and osteoporosis treatment) was found in 5 residents (4.7%). Few factors were related to complete treatment initiation. Residents initially managed in medicine departments were more treated than those in surgical wards (25.0 vs 6.5%; p = 0.0144) rather than those managed by specialists (rheumatologist or geriatrician: 8 vs 4; p < 0.001). Creatinine clearance was significantly higher in residents with calcium supplementation (52.7 ± 27.9 vs 39.1 ± 9.6; p = 0.0505). Regimen number tend to be higher in residents receiving vitamin D (8.9 ± 2.7 vs 6.7 ± 3.4; p = 0.0753). CONCLUSION: This evaluation of professional practices showed that only a minority of residents received complete anti-osteoporotic treatment despite their risk factor for fracture recurrence. Such an evaluation should be systematic at the entry in nursing home, given the number of falling residents.

[Quality and determinants of anticoagulation therapy by AVK in elderly subjects: study of a continuous series of 155 patients hospitalized in geriatric medicine]. / Qualité et déterminants de l'équilibre de l'anticoagulation par AVK des sujets âgés : étude d'une série continue de 155 patients hospitalisés en gériatrie aiguë.

AVK could be prescribed in elderly patients over 75 years for the prevention of thromboembolic complications of atrial fibrillation (AF). The objective of this study was to study the quality of the anticoagulation balance by AVK and its determinants. Inclusion of all patients ≥ 75 years of age treated with AVK for an AF hospitalized in the acute geriatric department of the University hospital of Dijon. The balance of the AVK treatment was determined by the input INR and the calculation of the TTR. The last four INRs prior to admission were retrospectively collected for its calculation. Each patient had a standardized geriatric evaluation (EGS): lifestyle, MMSE, nutritional status (albumin), polypathology (Charlson), level of dependence (ADL-IADL). Bleeding complication were collected. 155 patients aged over 75 years (87±5.6 years, 88 women and 67 men) were included. The mean TTR was 55.4±31.2%. Only 46% of patients had a correct TTR (≥ 75%). The balance was significantly worse in women than in men (49.3±29.5 vs 60.1±31.8%; p=0.0326), and in case of haematological pathology (41.7±27.1 vs 57.2± 9.8; p=0.047) but better with high BMI (r=0.416, p=0.001). No EGS parameters were associated with the quality of anticoagulation. The control of AVK therapy is insufficient in geriatric elderly subjects. No modifiable explicative geriatric factor has been identified. If AVK remains a therapeutic option, direct oral anticoaulants should be considered as the first choice.

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

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.

In geriatric patients, delirium symptoms are related to the anticholinergic burden.

AIM: Anticholinergic drugs are widely prescribed for elderly patients and could induce several neuropsychological disorders, especially delirium. The aim of the present study was to evaluate the relationship between anticholinergic burden and delirium symptoms. METHODS: A total of 102 patients aged over 75 years (86.3 ± 5.8 years, 53 women and 49 men) hospitalized in a geriatric medicine department were included in this prospective study. Anticholinergic burden was assessed by classifying drug use into three levels (low, medium or high). An overall, weighted score was established. Delirium symptoms were measured with the Confusion Assessment Method on days 1, 3, 5, 8, 15 and 21. Covariates studied were comorbidities (Charlson), health status, activities of daily living, nutrition (albumin), cognition, length of stay and mortality. RESULTS: A total of 51.6% of the patients were taking anticholinergic drugs at home (2.13 ± 1.34). Length of stay was 14.5 ± 9.9 days. Prevalence of delirium symptoms ranged on days between 34.8 and 60%. Anticholinergic burden was correlated with the appearance of delirium symptoms. Delirium symptoms were associated with greater mortality (16.1 and 3.7 % in patients with and without delirium symptoms; P = 0.049), a longer hospital stay (18.09 ± 11.34 vs 11.75 ± 7.80 days, P = 0.001), greater dependence on discharge (activities of daily living score: 1.57 ± 1.56 vs 3.41 ± 1.45, P < 0.0001) and worse health status on discharge (5.3 ± 2.7 vs 7.0 ± 1.7, P = 0.0008). CONCLUSION: Anticholinergic burden appears as a risk factor for both delirium symptoms and mortality. Prevention of delirium symptoms requires its reduction.

[Fragility assessment in primary care: which tools for predicting what?]. / Évaluation de la fragilité en soins primaires : quels outils pour quelle prédiction ?

Frailty is a geriatric syndrome associated with high risk for falls, disability, hospitalization, and mortality. The aim of this study is to assess the prevalence of frailty to the Fried's criteria in primary care and its evolution and the outcome of the patients at 1 year. Descriptive prospective study of patients over 75 years coming consult three general practitioners, evaluated initially and at 1 year. Frailty was defined by the presence of three criteria including weight loss, weakness (grip strength), self-reported exhaustion, low physical activity and slow walking speed. Of the 55 patients re-evaluated, 10.9% of patients were frail, 56.4% pre-frail and 32.7% were robust. Robust who become frail during the initial assessment, had a lower IADL score (p = 0.004) and a lower grip strength (p = 0.0311) than those who remained robust. Fried tool is difficult to implement in primary care. Grip strength and IADL are interesting for a simple screening tool in general practice to allow early treatment and delay progression to addiction.

Underuse of oral anticoagulation for individuals with atrial fibrillation in a nursing home setting in France: comparisons of resident characteristics and physician attitude.

OBJECTIVES: To describe the characteristics of nursing home residents diagnosed with atrial fibrillation (AF) and eligible for oral anticoagulants who did not receive these drugs and to detail the conditions that physicians who decide not to prescribe anticoagulants take into account. DESIGN: Cross-sectional. SETTING: Nursing home. PARTICIPANTS: Nursing home residents with a history of AF (N = 1,085). MEASUREMENTS: Data were collected on clinical characteristics, geriatric syndromes, and antithrombotic regimen. Multivariate logistic regression was used to identify factors associated with nonprescription of anticoagulants. A standardized questionnaire was submitted to physicians in charge of patients with AF, to detail conditions associated with their medical decision not to prescribe anticoagulants. RESULTS: History of AF was present in 1,085 nursing home residents (10.1%), mean age 87, with a mean CHA2DS2-VASc score of 5.1 ± 1.4. Of these residents with AF, 544 (50.1%) did not receive anticoagulants. Recurrent falls (odds ratio (OR) = 4.9, 95% confidence interval (CI) = 2.4-9.9, P < .001), past history of bleeding (OR = 3.62, 95% CI = 1.54-8.51, P = .003), paroxysmal AF (OR = 3.5, 95% CI = 1.83-6.66, P < .001), and advanced age (OR = 1.1, 95% CI = 1.01-1.17, P = .02) were significantly associated with not prescribing anticoagulants. Recurrent falls (47%), cognitive impairment (22.6%), and advanced age (16.4%) were the main reasons for not prescribing anticoagulants. CONCLUSION: The prevalence of AF in a cohort of very old nursing home residents was 10%. Anticoagulation was prescribed in fewer than 50% of eligible cases despite high individual risk of stroke. Geriatric syndromes, especially falls and cognitive disorders, were the main reported contraindications for prescribing anticoagulants. Physicians caring for those residents wrongly thought that paroxysmal AF caused fewer thromboembolic events than permanent AF, which explains lower rates of anticoagulant prescription in individuals with paroxysmal AF.

Relationship between cerebrospinal fluid flow, ventricles morphology, and DTI properties in internal capsules: differences between Alzheimer's disease and normal-pressure hydrocephalus.

BACKGROUND: Normal-pressure hydrocephalus (NPH) and Alzheimer's disease (AD) have some similar clinical features and both involve white matter and cerebrospinal fluid (CSF) disorders. PURPOSE: To compare putative relationships between ventricular morphology, CSF flow, and white matter diffusion in AD and NPH. MATERIAL AND METHODS: Thirty patients (18 with AD and 12 with suspected NPH) were included in the study. All patients underwent a 3-Tesla MRI scan, which included phase-contrast MRI of the aqueduct (to assess the aqueductal CSF stroke volume) and a DTI session (to calculate the fractional anisotropy [FA] and apparent diffusion coefficient [ADC]) in the internal capsules). RESULTS: FA was correlated with ventricular volume in the suspected NPH population (P < 0.001; rs = 0.88), whereas the ADC was highly correlated with the aqueductal CSF stroke volume in AD (P < 0.001; rs = 0.79). CONCLUSION: Although AD and NPH both involve CSF disorders, the two diseases do not have the same impact on the internal capsules. The magnitude of the ADC is related to the aqueductal CSF stroke volume in AD, whereas FA is related to ventricular volume in NPH.

Insulin-like growth factor-I and insulin-like growth factor binding protein-3 in Alzheimer's disease.

CONTEXT: Few large studies have been conducted to assess the relationship between circulating IGF and late-life cognition. OBJECTIVE: The aim of the study was to assess the relationship between IGF-I and IGF binding protein-3 (IGFBP-3) serum levels and cognitive impairment, including Alzheimer's disease (AD). METHODS: In this multicentric cross-sectional study, 694 elderly subjects (218 men, 476 women; 78.6 ± 6.7 yr old) were included; 481 had memory complaints and were diagnosed, after comprehensive cognitive assessment, with AD (n = 224) or mild cognitive impairment (MCI) (n = 257). The control group was comprised of 213 subjects without memory complaint and with normal cognition (recruited among patients' caregivers). IGF-I and IGFBP-3 serum levels were determined by ELISA. RESULTS: IGF-I and IGFBP-3 serum levels were significantly associated with cognitive status in men (IGF-I, 137 ± 69 ng/ml for AD vs. 178 ± 88 ng/ml for MCI and 172 ± 91 ng/ml for controls, P = 0.01; IGFBP-3, 3675 ± 1542 ng/ml for AD vs. 4143 ± 1828 ng/ml for MCI and 4488 ± 1893 ng/ml for controls, P = 0.04). In women, IGFBP-3 was significantly associated with cognitive status (3781 ± 1351 ng/ml for AD vs. 4190 ± 1408 ng/ml for MCI and 4390 ± 1552 ng/ml for controls; P < 0.001), but no significant differences between groups for IGF-I occurred. After adjustment for confounding variables (age, educational level, body mass index, diabetes, apolipoprotein E ε4 status), logistic regression indicated that IGF-I [odds ratio (95% confidence interval) = 0.48 (0.26-0.88)] and IGFBP-3 [odds ratio (95% confidence interval) = 0.71 (0.52-0.97)] serum levels were independently associated with AD in men, but not in women. CONCLUSIONS: We report a significant association between low IGF-I and IGFBP-3 serum levels and AD in men, but not in women.

A possible role for CSF turnover and choroid plexus in the pathogenesis of late onset Alzheimer's disease.

According to the amyloid theory, the appearance of amyloid-ß (Aß) deposits represents a pivotal event in late onset Alzheimer's disease (LOAD). Physiologically, Aß42 monomers are cleaned by capillary resorption, enzymatic catabolism, and cerebrospinal fluid (CSF) transport. Factors that promote the oligomerization of Aß42 must be specified. In vitro, these monomers spontaneously form neurotoxic oligomers whose rate increases with time suggesting that the stasis of CSF favors the oligomerization. In animals, experimental hydrocephalus generates CSF stasis followed by the appearance of amyloid deposits. In normal pressure hydrocephalus, amyloid deposits are common, especially in elderly patients, and the turnover decline has the same order of magnitude as in AD. In this disease, the effects of CSF stasis are potentiated by the decline in the ability of CSF to inhibit the formation of oligomers. CSF originates from choroid plexus (CP). In LOAD, the functions of secretion, synthesis, and transport of CP are impaired and this is related to morphological modifications. These impairments favor the decrease of CSF turnover, the diminished levels of transthyretin, a sequestering protein synthesized by CP, and the oligomerization of Aß42. They are potentiated by a reduced enzymatic catabolism and a decreased capillary reabsorption of Aß42, both alterations being related to age.

Reduced CSF turnover and decreased ventricular Aß42 levels are related.

BACKGROUND: The appearance of Aß42 peptide deposits is admitted to be a key event in the pathogenesis of Alzheimer's disease, although amyloid deposits also occur in aged non-demented subjects. Aß42 is a degradation product of the amyloid protein precursor (APP). It can be catabolized by several enzymes, reabsorbed by capillaries or cleared into cerebrospinal fluid (CSF). The possible involvement of a decrease in CSF turnover in A4ß2 deposit formation is up to now poorly known. We therefore investigated a possible relationship between a reduced CSF turnover and the CSF levels of the A4ß2 peptide.To this aim, CSF of 31 patients with decreased CSF turnover were studied. These patients presented chronic hydrocephalus communicating or obstructive, which required surgery (ventriculostomy or ventriculo-peritoneal shunt). Nine subjects had idiopathic normal pressure hydrocephalus (iNPH), and the other 22 chronic hydrocephalus from other origins (oCH).The Aß42 peptide concentration was measured by an ELISA test in 31 ventricular CSF samples and in 5 lumbar CSF samples from patients with communicating hydrocephalus. RESULTS: The 5 patients with lumbar CSF analysis had similar levels of lumbar and ventricular Aß42. A significant reduction in Aß42 ventricular levels was observed in 24 / 31 patients with hydrocephalus. The values were lower than 300 pg/ml in 5 out of 9 subjects with iNPH, and in 15 out of 22 subjects with oCH. CONCLUSION: The decrease of CSF Aß42 seems to occur independently of the surgical hydrocephalus aetiology. This suggests that a CSF reduced turnover may play an important role in the decrease of CSF Aß42 concentration.

[Which brakes upon severe dementia clinical research?]. / Quels freins à la recherche clinique sur la démence sévère ?

Publications devoted to severe dementia remain limited, whereas several authors underline the need to carry on clinical research in the field. The aim of this paper is to analyze the various technical, psychological and sociological factors that slow down the development of clinical research in severe dementia. To reduce these obstacles seems of main interest considering the economic, medical and human issues related to the severe stage of dementia.