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Background Few data are available on the prognosis of older patients who received corticosteroids for COVID-19. We aimed to compare the in-hospital mortality of geriatric patients hospitalized for COVID-19 who received corticosteroids or not. Methods We conducted a multicentric retrospective cohort study in 15 acute COVID-19 geriatric wards in the Paris area from March to April 2020 and November 2020 to May 2021. We included all consecutive patients aged 70 years and older who were hospitalized with confirmed COVID-19 in these wards. Propensity score and multivariate analyses were used. Results Of the 1 579 patients included (535 received corticosteroids), the median age was 86 (interquartile range 81–91) years, 56% of patients were female, the median Charlson Comorbidity Index (CCI) was 2.6 (interquartile range 1–4), and 64% of patients were frail (Clinical Frailty Score 5–9). The propensity score analysis paired 984 patients (492 with and without corticosteroids). The in-hospital mortality was 32.3% in the matched cohort. On multivariate analysis, the probability of in-hospital mortality was increased with corticosteroid use (odds ratio [OR] = 2.61 [95% confidence interval (CI) 1.63–4.20]). Other factors associated with in-hospital mortality were age (OR = 1.04 [1.01–1.07], CCI (OR = 1.18 [1.07–1.29], activities of daily living (OR = 0.85 [0.75–0.95], oxygen saturation < 90% on room air (OR = 2.15 [1.45–3.17], C-reactive protein level (OR = 2.06 [1.69–2.51], and lowest lymphocyte count (OR = 0.49 [0.38–0.63]). Among the 535 patients who received corticosteroids, 68.3% had at least one corticosteroid side effect, including delirium (32.9%), secondary infections (32.7%), and decompensated diabetes (14.4%). Conclusions In this multicentric matched-cohort study of geriatric patients hospitalized for COVID-19, the use of corticosteroids was significantly associated with in-hospital mortality.

BACKGROUND While randomized clinical trials have shown the benefit of thrombolysis and endovascular thrombectomy (EVT) in patients with acute ischemic stroke (AIS), we aimed to describe in a real-life study the differences between older (>80 years old) and younger patients treated for AIS. METHODS Thousand patients treated with thrombolysis and/or EVT were consecutively included in a prospective monocentric database (admitted from December 2015 to May 2019 in our comprehensive stroke center). Demographic data with detailed history, baseline physical examinations and treatments, laboratory and imaging data, prestroke functional status, and outcome 3 months after stroke were analyzed. RESULTS Older patients (n = 357) had more baseline comorbidities and lower levels of prestroke independence (modified Rankin scale ≤2; 67.2% vs. 96.1%) and more severe strokes (median National Institute of Health Stroke Score [NIHSS] 15 vs. 12; p

Resume Le risque d’encephalopathie metabolique est rarement decrit dans les effets indesirables potentiels du lacosamide. Nous decrivons ici le cas d’une patiente de 84 ans qui a presente un tableau d’encephalopathie sous l’association levetiracetam et lacosamide regressif a l’arret du lacosamide, faisant suspecter son implication. Parmi les traitements pouvant provoquer une encephalopathie metabolique, les antiepileptiques sont cites dans la litterature mais peu souvent le lacosamide.

Background: Biological COVID-19 abnormalities are varied (lymphopenia, high levels of blood inflammatory markers, …). Regarding physiological immune responses, eosinophils were for a long time thought to be mainly against extra-cellular pathogen like helminthes. It has recently been pointed out that they appear to play a part in recognition of virus and to have the capacity to perform direct action against viruses. This study aimed to seek for an association between eosinophils count < 10 /mm3 and mortality in an older adults suffering from COVID-19 hospitalized in a specific geriatric ward. Methods: This observational retrospective study was conducted in a French geriatric ward from March 17 to April 18, 2020. All 118 patients hospitalized for COVID-19 over 70 yo in acute stay care were enrolled. Patients with a treatment or a condition which could interfere with eosinophil count were excluded. Results: No statistical difference was found between surviving or deceased patient regarding age (mean age (SD): 87 years (7)) and sex (34% of males). Differences for the most frequent acute events were statically different: Quick Sepsis-related Organ Failure Assessment (qSOFA) score was ≥ 2 at admission for 23% in the survivor group vs 72% in the deceased (p < .001); acute kidney injury concerned 17% of the survivors vs. 69% of the decease (p< .001). Eosinophil count < 10/mm3 was significantly associated with mortality (OR (95% CI)) = 3.54 (1.23-11.4) after adjustment on age, gender, and activity of daily living.Conclusion: Low eosinophil count (< 10/mm3) seems to be associated with mortality on older adults. Due to the specific physiological ageing process of the immune system, this calls to explore more globally the impact of inflammaging and immunosenescence on SARS-CoV-2 infection in this population.

BackgroundIt is unclear whether olfactory deficits improve after remission in depressed patients. Therefore, we aimed to assess in drug-free patients the olfactory performance of patients with major depressive episodes (MDE) and its change after antidepressant treatment.MethodsIn the DEP-ARREST-CLIN study, 69 drug-free patients with a current MDE in the context of major depressive disorder (MDD) were assessed for their olfactory performances and depression severity, before and after 1 (M1) and 3 (M3) months of venlafaxine antidepressant treatment. They were compared to 32 age- and sex-matched healthy controls (HCs). Olfaction was assessed with a psychophysical test, the Sniffin’ Sticks test (Threshold: T score; Discrimination: D score; Identification: I score; total score: T + D + I = TDI score) and Pleasantness (pleasantness score: p score; neutral score: N score; unpleasantness score: U score).ResultsAs compared to HCs, depressed patients had lower TDI olfactory scores [mean (s.d.) 30.0(4.5) v. 33.3(4.2), p < 0.001], T scores [5.6(2.6) v. 7.4(2.6), p < 0.01], p scores [7.5(3.0) v. 9.8(2.8), p < 0.001)] and higher N scores [3.5(2.6) v. 2.1(1.8), p < 0.01]. T, p and N scores at baseline were independent from depression and anhedonia severity. After venlafaxine treatment, significant increases of T scores [M1: 7.0(2.6) and M3: 6.8(3.1), p < 0.01] and p scores [M1: 8.1(3.0) and M3: 8.4(3.3), p < 0.05] were evidenced, in remitters only (T: p < 0.01; P: p < 0.01). Olfaction improvement was mediated by depression improvement.ConclusionsThe olfactory signature of MDE is restored after venlafaxine treatment. This olfaction improvement is mediated by depression improvement.

BACKGROUND Orthostatic hypotension (OH) measurement reproducibility is poor. Our objectives were to assess feasibility of self-detection home-measured OH (HOH) and HOH determinants. METHODS Subjects older than 65 years, attending a geriatric outpatient clinic, able to understand the HOH protocol: 3 blood pressure (BP) measures after 5 minutes of seating and BP measures after 1 and 3 minutes of standing, each morning and evening for 3 consecutive days were lent a validated digital automatic sphygmomanometer. Reports containing at least 4 correct measurements were deemed a success. Factors associated with HOH were studied. RESULTS HOH feasibility was 82.8% (241 subjects) with no difference between participants who failed or succeeded. Among the 241 subjects (mean age (SD) = 78.0 (8.3) years old; 62.1% of women), 139 were free of HOH, 70 had 1 HOH episode and 32 had 2 or more HOH episodes. Hypertension, dementia, atrial fibrillation, diabetes, and heart failure were found in 70.0%, 10.4%, 9.4%, 8.8%, and 3.4% of cases, respectively. Subjects were treated with antihypertensive, benzodiazepine, statin medication in 47.3%, 9.3%, 7.4% of cases, respectively, and 42.4% experienced polypharmacy. HOH episodes were associated with dementia (P = 0.01), presence of OH during the geriatric outpatient clinic assessment (P = 0.0002), statin therapy (P = 0.04), and polypharmacy (P = 0.0002). In multivariate analysis, benzodiazepine (OR (95% CI) = 2.59 (1.10–6.08) and statin medication (OR (95% CI) = 1.92 (1.10–3.33)) remained significantly associated with HOH. CONCLUSIONS HOH had a good feasibility and relevant determinants. A study to address the predictive value of HOH will be conducted.

Background: This study aimed to seek for an association between absolute eosinopenia (eosinophils count < 10 /mm3) and mortality in an older adults suffering from COVID-19 hospitalized in a specific geriatric ward. Methods: This observational retrospective study was conducted in a French geriatric ward from March 17 to April 18, 2020. All 118 patients hospitalized for COVID-19 over 70 yo in acute stay care were enrolled. Patients with a treatment or a pathology which could interfere with eosinophil count were excluded. Results: No statistical difference was found between surviving or deceased patient regarding age (mean age (SD): 87 years (7)) and sex (34% of males). Differences for the most frequent acute events were statically different: Quick Sepsis-related Organ Failure Assessment (qSOFA) score was ≥ 2 at admission for 23% in the survivor group vs. 23 (72%) in the deceased (p < .001); acute kidney injury concerned 17% of the survivors vs. 69% of the decease (p< .001). Eosinopenia < 10/mm3 was significantly associated with mortality (OR (CI95%)) = 3.5 (1.2-11.4) after adjustment on age, gender, and activity of daily living. Conclusion: Absolute eosinopenia was associated with in hospital mortality in older adults. This result, if confirmed in other study, may help to predict the outcome of a SARS-COV-2 infection on geriatric patients and calls for immunologist to explore more globally the impact of inflammaging on the SARS-CoV-2 infection.

Objective The role of treatment with renin-angiotensin-aldosterone system blockers at the onset of COVID-19 infection is not known in geriatric population. The aim of this study was to assess the relationship between angiotensin receptor blockers (ARB) and an ACE inhibitor (ACEI) use and in-hospital mortality in geriatric patients hospitalized for COVID-19. Design This observational retrospective study was conducted in a French geriatric department. Patients were included between March 17 and April 18, 2020. Setting and Participants: All consecutive 201 patients hospitalized for COVID-19 (confirmed by RT-PCR methods) were included. All non-deceased patients had 30 days of follow-up and no patient was lost to follow-up. Methods Demographic, clinical, biological data and medications were collected. In-hospital mortality of patients treated or not by ACEI/ARB was analyzed using multivariate Cox models. Results Mean age of the population was 86.3 (8.0) years old, 62.7% of patients were institutionalized, 88.6% had dementia and 53.5% had severe disability (ADL score < 2). Sixty-three patients were treated with ACEI/ARB and 138 were not. Mean follow-up was 23.4 (10.0) days, 66 (33.8%) patients died after an average of 10.0 days (6.0). Lower mortality rate was observed in patients treated with ACEI/ARB compared with patients not treated with ARB nor ACEI (22.2% (14) vs. 37.7% (52), HR = 0.54 (95% CI = 0.30-0.97), p=0.03). In a multivariate Cox regression model including age, sex, ADL score, Charlson index, renal function, dyspnea, CRP and white blood cells count, use of ACEI/ARB was significantly associated with lower in-hospital mortality (HR = 0.52 (0.27−0.99), p=0.048). Conclusion and Implications In very old subjects hospitalized in geriatric settings for COVID-19, mortality was significantly lower in subjects treated with ARB or ACEI prior to the onset of infection. The continuation of ACEI/ARB therapy should be encouraged during periods of coronavirus outbreak in older subjects., In very old subjects hospitalized for COVID-19 in geriatric settings, mortality was significantly lower in those treated with ARB or ACEI prior to the onset of infection.

Background There is limited information describing the characteristics and outcomes of hospitalized older patients with confirmed coronavirus disease 2019 (COVID-19). Method We conducted a multicentric retrospective cohort study in 13 acute COVID-19 geriatric wards, from March 13 to April 15, 2020, in Paris area. All consecutive patients aged 70 years and older, with confirmed COVID-19, were enrolled. Results Of the 821 patients included in the study, the mean (SD) age was 86 (7) years; 58% were female; 85% had ≥2 comorbidities; 29% lived in an institution; and the median [interquartile range] Activities of Daily Living scale (ADL) score was 4 [2–6]. The most common symptoms at COVID-19 onset were asthenia (63%), fever (55%), dyspnea (45%), dry cough (45%), and delirium (25%). The in-hospital mortality was 31% (95% confidence interval [CI] 27–33). On multivariate analysis, at COVID-19 onset, the probability of in-hospital mortality was increased with male gender (odds ratio [OR] 1.85; 95% CI 1.30–2.63), ADL score Conclusions This study provides new information about older patients with COVID-19 who are hospitalized. A quick bedside evaluation at admission of sex, functional status, systolic arterial pressure, consciousness, respiratory rate, and asthenia can identify older patients at risk of unfavorable outcomes.

OBJECTIVE Caregivers do not usually use services that could alleviate their burden. The objectives were to determine the refusal's prevalence and the reasons why informal caregivers of demented patients refuse clinic medico-psycho-social assessment in the first day care hospital dedicated to caregivers in France. METHODS Caregivers of patients hospitalized in geriatric ward were prospectively asked to fill in a questionnaire (demographic data, risk for depression and caregiver burden (Zarit scale) about their willingness to benefit from a clinic checkup. If caregivers refused eleven close questions were asked. Characteristics of the caregivers were compared according to the caregivers' agreement or refusal to the clinic checkup. RESULTS Seventy-seven caregivers (mean age (standard deviation): 68.2 (11.5)) were included: 68.8% of women, 51.9% of children and 35.1% of spouses, mean Zarit scale score was 32.8 (8.8)/88. Clinic checkup was accepted by 28 caregivers. Agreement was associated with exhaustion (p

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

Dementia is a worldwide health concern, which leads to loss of autonomy. To date no curative treatment is available so focus on modifiable risk factors is of particular interest. Hypertension, particularly midlife high blood pressure, has been associated with an increased risk for cognitive decline and dementia including vascular dementia (VAD) and Alzheimer disease (AD). In this context, antihypertensive treatments might have a preventive effect. The objective of this review was to examine the relationship between antihypertensive therapy and cognitive decline or dementia. Areas covered: A literature search was conducted using PUBMED and the COCHRANE LIBRARY for publications from 1990 onwards mentioning cognitive decline, AD, Vad, mixed dementia, vascular cognitive impairment, hypertension and antihypertensive therapy. Thirty-nine relevant publications including 20 longitudinal studies, 10 randomized-controlled trials and 9 meta-analyses were taken into account. Expert opinion: Most observational studies have suggested a potential preventive effect of antihypertensive therapies on cognitive decline and dementia, particularly calcium channel blockers and renin-angiotensin system blockers. Randomized clinical trials and meta-analyses provided more conflicting results potentially due to methodological issues. In conclusion, antihypertensive therapies may reduce cognitive decline and incidence of dementia. Further randomized clinical trials conducted in populations at higher risk of cognitive decline, with longer periods of follow-up and cognition as the primary outcome are still needed.

Alzheimer’s disease (AD) is the most common form of dementia in the elderly population. The pathophysiological mechanisms of AD involves intraneuronal protein clusters of hyperphosphorylated tau pr...

International audience; A combination of low cerebrospinal fluid (CSF) Amyloid β1–42 (Aβ1–42) and high Total-Tau (T-Tau) and Phosphorylated-Tau (P-Tau) occurs at a prodromal stage of Alzheimer’s disease (AD) and recent findings suggest that network abnormalities and interneurons dysfunction contribute to cognitive deficits. Somatostatin (SOM) and Neuropeptide Y (NPY) are two neuropeptides which are expressed in GABAergic interneurons with different fates in AD the former only being markedly affected. The aim of this study was to analyze CSF SOM, NPY and CSF Aβ1–42; T-Tau, P-Tau relationships in 43 elderly mild cognitively impairment (MCI) participants from the Biomarker of AmyLoïd pepTide and AlZheimer’s disease Risk (BALTAZAR) cohort. In these samples, CSF SOM and CSF Aβ1–42 on the one hand, and CSF NPY and CSF T-Tau and P-Tau on the other hand are positively correlated. CSF SOM and NPY concentrations should be further investigated to determine if they can stand for early AD biomarkers.Clinical Trial Registration: www.ClinicalTrials.gov, identifier #NCT01315639.

ObjectivesNew diagnostic criteria for Alzheimer’s disease (AD) include cerebrospinal fluid (CSF) biomarkers that allow diagnosis at the stage of mild cognitive impairment (MCI). However, the impact of CSF biomarkers in MCI populations in clinical practice has been poorly evaluated. The objective of this study is to assess the use and impact in clinical practice of AD CSF biomarkers in French memory clinics.DesignWe performed a nation-wide, prospective survey between March 2012 and September 2014. Data over the same period was extracted from the French National Database (Banque Nationale Alzheimer, BNA) and compared with the results of the survey.Setting29 secondary and tertiary memory clinics in France.ParticipantsClinicians prescribing lumbar puncture (LP) in order to measure AD CSF biomarkers. Clinicians completed a two-part questionnaire for each of their patients undergoing LP.Primary and secondary outcome measuresAssessment of diagnosis, level of confidence before and after CSF biomarkers and impact on management in patients who underwent LP for CSF AD biomarkers in clinical routine.Results977 questionnaires were completed, of which 61 were excluded because of unknown initial/final diagnosis or non-contributory CSF results. Of 916 patients reported, 153 (16.7%) had MCI as the initial diagnosis, of which 51 (33.3%) displayed an AD profile. CSF biomarkers resulted in a change in diagnosis in 44 patients (28.8%). Confidence level significantly increased after LP (8.3±1.4vs 6.73±1.18, pConclusionThis nation-wide survey, reflecting clinical practice in French memory clinics, describes the impact of CSF AD biomarkers in patients with MCI in clinical practice.

International audience; 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 Aβ42 and Aβ40 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 Aβ1-42 and Aβ1-40 were lower in AD (36.9 [11.7] and 263 [80] pg/mL) than in amnestic MCI (38.2 [11.9] and 269 [68] pg/mL) than in nonamnestic MCI (39.7 [10.5] and 272 [52] pg/mL), respectively (P = .01 for overall difference between groups for Aβ1-42 and P = .04 for Aβ1-40). Globally, plasma Aβ1-42 correlated with age, Mini-Mental State Examination, and APOE ε4 allele. Plasma Aβ1-42 correlated with all CSF biomarkers in MCI but only with CSF Aβ42 in AD.DISCUSSION:Plasma Aβ was associated with cognitive status and CSF biomarkers, suggesting the interest of plasma amyloid biomarkers for diagnosis purpose.Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

The mini mental state examination (MMSE) is a validated tool to assess global cognitive function. Training is required before scoring. Inaccurate scoring can lead to inappropriate medical decisions. In France, MMSE is usually scored by medical students. To assess if medical French students know how to properly score a mini mental state examination. Two « physician-patient » role playings performed by 2 specialized physicians, were performed in front of University Paris V medical students. Role playing A: Scoring of a MMSE according to a script containing five tricks; Role playing B: Find the 5 errors committed in a pre-filled MMSE form, according to the second script. One hundred and five students (64.4% of women, 49.5% in fifth medical school year) anonymously participated. Eighty percent of students had already scored a MMSE and 40% had been previously trained to MMSE scoring. Forty five percent of students previously scored an MMSE, without previously being trained. In test A, 16% of students did not commit any errors, 45.7% one error and 38.1% two errors. In test B, the proportion of students who provided 0, 1, 2, 3, 4 and 5 good answers was 3.3%, 29.7%, 29.7%, 25.3%, 7.7% and 4.4% respectively. No association between medical school year, previous training to MMSE scoring and performances at both tests were found. French students do not properly score MMSE. MMSE scoring is not enough or accurately taught (by specialists). The university will provide on line the tests and a short filmed teaching course performed by neuropsychological specialists.

Chantier qualité GA; International audience; Objective: Since a reduction of the insulin/IGF-1 signaling cascade extends life span in many species and IGF-1 signaling might partly mediate the effects of caloric restriction (CR), an experimental intervention for increasing longevity, the purpose of the present study was to use quantitative trait loci (QTL) analysis, an unbiased genetic approach, to identify particular regions of the genome influencing plasma IGF-1 levels in an F2 intercross between F344 and LOU/C rats; the latter being an inbred strain of Wistar origin, considered as a model of healthy aging since it resists to age (and diet)-induced obesity. Design: F1 hybrids were obtained by crossbreeding LOU/C with F344 rats, and then F1 were bred inter se to obtain the F2 population, of which 93 males and 94 females were studied. Total plasma IGF-1 levels were determined by radioimmunoassay. A genome scan of the F2 population was made with 100 microsatellite markers) selected for their polymorphism between LOU/C and F344 strains (and by covering evenly the whole genome. Results: By simple interval mapping sex-dependent QTLs were found on chromosome 17 in males and on chromosome 18 in females. By multiple interval mapping, additional QTLs were found on chromosomes 1, 4, 5, 6, 12, 15 and 19 in males and on chromosomes 3, 5, 6, 12 and 17 in females. Only the markers D1Rat196 and D12Mgh5 were found in both males and females. The majority of QTLs corresponded to metabolic syndrome (cardiac function: n = 45 (30%), obesity/diabetes: n = 22 (15%), inflammation: n = 19 (13%) and only a limited number to body weight: n = 13 (9%), proliferation (n = 10 (7%) or ossification: n = 7 (5%). Ninety-six candidate genes were located on the different QTLs. A significant proportion of these genes are connected to IGF-1 production and receptor pathways (n = 18) or metabolic syndrome (n = 11). Conclusions: Subsequent studies are necessary to determine whether the genetic networks underscored are also involved in age-associated obesity, diabetes and inflammation as well as cardiovascular impairments.

OBJECTIVES Hypertension is a risk factor for cognitive impairment and dementia. Arterial stiffness could be involved in the mechanisms of vascular cognitive impairment and in Alzheimer's disease. We examined the association between arterial stiffness, assessed by carotid-femoral pulse wave velocity (PWV), and medial temporal lobe (MTL) atrophy, a biomarker of Alzheimer's disease. METHODS Elderly community-dwelling study participants (n = 149) with memory complaints were diagnosed with Alzheimer's disease (n = 62) or mild cognitive impairment (n = 87) at a memory clinic. PWV, peripheral and central blood pressure (SBP), and pulse pressure (PP) were measured. MTL was graded on MRI according to the Scheltens' scale. RESULTS Mean age was 79.5 (SD = 5) years old, 36% of study participants were men. MTL was absent or discrete in 23.5%, moderate in 53.0% and severe in 23.5% of study participants. PWV was 9.3 (2.2) m/s in none or discrete, 11.1 (2.8) in moderate and 13.5 (4.0) in severe MTL atrophy (P

Background The aim of this volumetric study was to explore the neuroanatomical correlates of the Free and Cued Selective Reminding Test (FCSRT) and the Delayed Matching-to-Sample—48 items (DMS-48), two tests widely used in France to assess verbal and visual anterograde memory. We wanted to determine to what extent the two tests rely on the medial temporal lobe, and could therefore be predictive of Alzheimer’s disease, in which pathological changes typically start in this region. Methods We analysed data from a cohort of 138 patients with mild cognitive impairment participating in a longitudinal multicentre clinical research study. Verbal memory was assessed using the FCSRT and visual recognition memory was evaluated using the DMS-48. Performances on these two tests were correlated to local grey matter atrophy via structural MRI using voxel-based morphometry. Results Our results confirm the existence of a positive correlation between the volume of the medial temporal lobe and the performance on the FCSRT, prominently on the left, and the performance on the DMS-48, on the right, for the whole group of patients (family-wise error, P Conclusions The two tests are able to detect an amnestic profile of the medial temporal type, under the condition that the scores remain deficient after the cued recall of the FCSRT or decline on the delayed recognition trial of the DMS-48. Strategic retrieval as well as perceptual/attentional processes, supported by prefrontal and temporo-parietal cortices, were also found to have an impact on the performances. Finally, the implication of the hippocampus appears time dependent, triggered by a longer delay than the parahippocampus, rather than determined by the sense of recollection or the encoding strength associated with the memory trace.

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

International audience; PURPOSE: To retrospectively determine whether blood oxygen level-dependent functional magnetic resonance (MR) imaging can aid prediction of postoperative memory changes in epileptic patients after temporal lobe surgery. MATERIALS AND METHODS: This study was approved by the local ethics committee, and informed consent was obtained from all patients. Data were analyzed from 25 patients (12 women, 13 men; age range, 19-52 years) with refractory epilepsy in whom temporal lobe surgery was performed after they underwent preoperative functional MR imaging, the Wada test, and neuropsychological testing. The functional MR imaging protocol included three different memory tasks (24-hour delayed recognition, encoding, and immediate recognition). Individual activations were measured in medial temporal lobe (MTL) regions of both hemispheres. The prognostic accuracy of functional MR imaging for prediction of postoperative memory changes was compared with the accuracy of the Wada test and preoperative neuropsychological testing by using a backward multiple regression analysis. RESULTS: An equation that was based on left functional MR imaging MTL activation during delayed recognition, side of the epileptic focus, and preoperative global verbal memory score was used to correctly predict worsening of verbal memory in 90% of patients. The right functional MR imaging MTL activation did not substantially correlate with the nonverbal memory outcome, which was only predicted by using the preoperative nonverbal global score. Wada test data were not good predictors of changes in either verbal or nonverbal memory. CONCLUSION: Findings suggest that functional MR imaging activation during a delayed-recognition task is a better predictor of individual postoperative verbal memory outcome than is the Wada test.

OBJECTIVES: To compare the accuracy of the two most popular creatinine clearance (CrCl) estimation formulae (Cockcroft-Gault (CG) and Modification Diet in Renal Disease (MDRD)) in older hospitalized patients. DESIGN: Prospective, cross-sectional, observational study. SETTING: Two hospital geriatric wards. PARTICIPANTS: Consecutive patients aged 70 and older with an indwelling urinary catheter for the purpose of care. MEASUREMENTS: CrCl was determined according to three methods: measured CrCl from plasma and urine creatinine and 24-hour urine volume, CG (CG-CrCl), and MDRD (MDRD-CrCl). Results were expressed as median and interquartile range (IQR). Moderate and severe renal impairment were defined as a CrCl between 30.0 and 59.9 mL/min and less than 30.0 mL/min, respectively. RESULTS: One hundred twenty-one patients were included (46% male). Mean age was 86.1±6.7 (range 72–100). Median measured CrCl was 43.8 mL/min (IQR 33.6–61.1 mL/min), CG-CrCl was 40.9 mL/min (IQR 31.0–52.6 mL/min), and MDRD-CrCl was 61.3 mL/min (IQR 49.4–77.0 mL/min). The biases of CG-CrCl and MDRD were −3.5±22.5 and 20.1±28.2, respectively (P

BACKGROUND Therapeutic trials concerning the effect of antihypertensive therapy on cognition have produced controversial findings. Our objective was to evaluate the impact of antihypertensive therapy on the cognitive function in subjects already diagnosed with Alzheimer's disease (AD). METHODS We conducted an observational study in a memory clinic assessing outpatients suffering from AD. A total of 321 patients were included. Cognitive function was assessed yearly by the Mini-Mental State Examination (MMSE; score/30). RESULTS The mean age of patients was 78.1 +/- 6 years, 54% of them received antihypertensive therapy and the mean MMSE scores were similar in both groups (patients taking antihypertensive therapy and patient without antihypertensive therapy). The mean follow-up was 34.1 +/- 6 months. MMSE means were significantly higher among patients using antihypertensive therapy compared to those without antihypertensive therapy (MMSE scores = 21.9 +/- 4.9 vs. 21.2 +/- 5.1 at 1 year (P = 0.001); 20.8 +/- 5.5 vs. 19.4 +/- 5.7 at 2 years (P < 0.001); 19.0 +/- 6.7 vs. 17.5 +/- 6.4 at 3 years (P < 0.001)), after adjustment for age, gender, education level, systolic blood pressure (SBP), and diastolic blood pressure (DBP) at baseline, MMSE at baseline, coronary heart disease, statins, and antiplatelet agents' consumption. Furthermore, the use of antihypertensive therapy was associated with a lower estimated risk of cognitive decline (as defined by a decrease of at least one point in MMSE score over time) (hazard ratio = 0.61; 95% confidence interval = 0.45-0.81) after adjustment for the same factors. CONCLUSIONS These results suggest an association between antihypertensive therapy, a lower decrease in mean MMSE and a lower cognitive decline over time in AD.

E Duron, Olivier HanonBroca Hospital, Paris, FranceAbstract: Dementia is one of the most important neurological disorders in the elderly. Aging is associated with a large increase in the prevalence and incidence of degenerative (Alzheimer’s disease) and vascular dementia, leading to a devastating loss of autonomy. In view of the increasing longevity of populations worldwide, prevention of dementia has turned into a major public health challenge. In the past decade, several vascular risk factors have been found to be associated with vascular dementia but also Alzheimer’s disease. Some longitudinal studies, have found significant associations between hypertension, diabetus mellitus, and metabolic syndrome, assessed at middle age, and dementia. Studies assessing the link between hypercholesterolemia, atrial fibrillation, smoking, and dementia have given more conflicting results. Furthermore, some studies have highlighted the possible protective effect of antihypertensive therapy on cognition and some trials are evaluating the effects of statins and treatments for insulin resistance. Vascular risk factors and their treatments are a promising avenue of research for prevention of dementia, and further long-term, placebo-controlled, randomized studies, need to be performed.Keywords: dementia, hypertension, diabetus mellitus, hypercholesterolemia, metabolic syndrome

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

Background Insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3) are involved in oxidative stress and atherosclerosis; however, the relationship between the IGF-I system and atrial fibrillation (AF) is not known. The objective of this analysis was to assess, the relationship between IGF-I and IGFBP-3 serum levels and AF among elderly participants. Methods In this cross-sectional study, 719 participants (mean age [SD] years: 78.2 [6.8]; 31.8% men) were evaluated during an outpatient geriatric assessment. AF was determined by electrocardiogram or medical record. Participants were classified into two groups: Participants with AF (n = 91) or without AF (n = 628). IGF-I and IGFBP-3 serum levels were determined by enzyme linked immunosorbent assay. Results After adjusting for age and sex, the mean IGF-I and IGFBP-3 serum levels were significantly lower among AF participants than among non-AF participants (mean IGF-I ng/mL [SD] = 133.8 [66.6] vs 157.9 [80.0], p = .02; mean IGFBP-3 ng/mL [SD] = 3,653 [1,393] vs 4,151 [1,583], p = .03, respectively). After adjusting for confounding factors (age, gender, beta blocker medication, heart rate, hypertension, stroke, and chronic heart failure), low IGF-I serum level (OR [95% CI] = 0.66 [0.49-0.87]) and low IGFBP-3 serum level (0.71 [0.54-0.93]) remained independent determinants of AF. Conclusions Low IGF-I and low IGFBP-3 serum levels were independently associated with AF in this elderly population. This result should be confirmed in a longitudinal study to evaluate whether IGF-I and/or IGFBP-3 serum levels are predictive of incident AF.

Some studies have highlighted the difficulty for physicians to evaluate patient's ability to consent to bio-medical research in the elderly population. The University of California Brief Assessment of Capacity to Consent (UBACC) is a rapid questionnaire to assess the ability to consent, previously validated among schizophrenic patients.To evaluate the accuracy of the UBACC scale, French version, to determine the capacity to consent to biomedical studies of older people with normal cognition, mild cognitive impairment (MCI) or Alzheimer Disease (AD).A prospective validation study between September 2008 to November 2011.A Memory clinic.We included 61 subjects in a memory clinic who had already consented to participate to a biomedical research and had signed a consent form. Those subjects, who had memory impairment, had a comprehensive neuro-psychological (including Mini Mental State Examination (MMSE)/30), clinical, biological assessment and brain imagery during day-care hospital. They were classified as MCI or AD patients. Control group included patients' caregivers without memory complaints and a normal comprehensive neuro-psychological assessment.The consent form was once again explained to the subjects by a physician who subjectively evaluated if subjects had understood the study. Then, the 10 questions of the French version of the UBACC scale (max score 20) were asked to the participants. This scale evaluates the understanding of the study's aim, risks and benefits. A comparison was made between subjective assessment and the UBACC score.The physician considered that 18/61 patients (2 MCI and 16 AD) had not understood. These ones had a lower UBACC score (Score/20 (SD) [range]: 7.56 (3.03) [0-12] versus 17.72 (2.68) [13-28], p0.001), a lower MMSE (Score/ 30 (SD): 21.1 (5.9) versus 27.3 (2.9); p0.001) and were older (age (years old) 80.8 versus 76.6. p0.0001) compared to those who had understood. Moreover, all the patients who had not understood had an UBACC score ≤ 12. The administration time was accurate in this population (10 minutes).The UBACC scale, in its French version, was accurate to assess capacity to consent in an older, cognitively impaired population.

International audience; 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.TRIAL REGISTRATION: ClinicalTrials.gov NCT00647478.

Objectifs Determiner la faisabilite et la pertinence de en auto-mesure ou auto-mesure aidee de l'hypotension orthostatique (HO) au domicile chez de sujets âges ambulatoires. Methodes 185 patients evalues en hopital de jour (HDJ) d'evaluation geriatrique, âges de plus de 60 ans, ayant un MMSE>25 ou un aidant naturel pouvant effectuer les mesures et pouvant tenir debout au moins 3 minutes, ont ete inclus. L'HO etait mesuree a 1 et 3 minutes lors de la consultation Les participants ou leur aidant principal ont recu une information detaillee sur les modalites de la recherche d'HO a domicile. Un tensiometre automatique (OMRON M6) leur a ete prete. La pression arterielle etait mesuree en position assise puis apres 1 et 3 minutes d'orthostatisme, le matin et le soir pendant trois jours consecutifs a domicile. Les participants rendaient une feuille de recueil. La pertinence de l'auto-mesure a ete evaluee sur la nature des facteurs associes (determinants) et la concordance HO en auto mesure -HO en consultation. Resultats L'âge moyen etait 79.3 (7.9) ans, 62,7 % de femmes. Le MMSE moyen etait 24.4 (5.4)/30. La prevalence de l'HO en consultation etait de 14.8 %. L'HO en consultation etait associee aux antecedents de chute (65.2 % vs 30.4 %) (p = 0.03) et a la presence de symptomes d'HO (69.6 % vs 35.3 %, p = 0.004. Centre trente- neuf sujets (75,1 %) ont reussi a realiser la recherche d'HO a domicile (auto-mesure dans 59 % des cas, mesure par un aidant dans 41 %). Seul le sexe masculin etait associe a une plus grande reussite des mesures (p = 0.05). La prevalence cumulee de l'HO a domicile etait de 46 % : Les participants faisaient respectivement 1, 2, 3, 4, 5,6 episodes d'HO dans 25.9 ; 9.4 ; 5 ; 3.6 ; 1.4 ; 0.7 % des cas. Les determinants de l'HO a domicile etaient : l'insuffisance cardiaque (3.81 % vs 0 %, p = 0.02), la prise de plus de 4 medicaments (48.4 % vs 30.7 % ; p = 0,04), une albuminemie plus basse (39.8 (2.2) vs 40,8 g/l (2.7), p = 0.02) et un force de prehension plus faible (19 (9.5) vs 23.7 (11.2) kg, p = 0.002). L'HO en auto mesure etait marginalement associee a l'HO en consultation (23.4 % vs 10.7 %). Conclusion Les resultats indiquent une prevalence tres importante de l'HO a domicile chez le sujet âge. La pertinence de cette mesure est a evaluer de facon prospective afin de determiner si elle est associee a la survenue d'evenements defavorables (chutes, morbi-mortalite cardio-vasculaire).

Background: To determine the relationship between orthostatic hypotension (OH) and cognitive function in elderly subjects with memory complaints. Methods: We studied the association between cognitive function and OH in 495 consecutive elderly outpatients attending a memory centre. Blood pressure (BP) was measured in a sitting and standing position.We examined cognitive function using a validated comprehensive battery of neuropsychological tests, the cognitive efficiency profile (CEP) assessing the main cognitive areas. Subjects were classified into 4 categories according to their cognitive status: normal cognitive function, mild cognitive impairment (MCI), Alzheimer’s disease (AD) or vascular dementia (VD).Results: In this population, 7668 years of age (women 72%), 18% had normal cognitive function, 28% had MCI, 47% AD, and 7% VD. Hypertension was observed in 74% of patients. OH was present in 14% of subjects (n1⁄469). After adjustment for age, education level, systolic BP, diastolic BP, weight, and antihypertensive drugs, subjects with OH had worse cognitive function than those without OH (CEP score 50624 vs 56622, p < 0.05). Moreover, a significant relationship was observed between OH and cognitive status (normal cognitive function, MCI, AD, or VD). OH was present in 22% in VD subjects, 15% in AD subjects, 12% in MCI subjects and 4% in normal control subjects (p< 0.01 for overall test).Conclusions:Our results showed an association between OH and cognitive impairment or dementia and emphasize the need for longitudinal studies designed to evaluate the nature of the relationship between OH and cognitive decline.

OBJECTIVE: To identify the mortality risk factors of elderly patients (>/=65 years old) during major digestive surgery, as defined according to the complexity of the operation. BACKGROUND: In the aging populations of developed countries, the incidence rate of major digestive surgery is currently on the rise and is associated with a high mortality rate. Consequently, validated indicators must be developed to improve elderly patients' surgical care and outcomes. METHODS: We acquired data from a multicenter prospective cohort that included 3322 consecutive patients undergoing major digestive surgery across 47 different facilities. We assessed 27 pre-, intra-, and postoperative demographic and clinical variables. A multivariate analysis was used to identify the independent risk factors of mortality in elderly patients (n = 1796). Young patients were used as a control group, and the end-point was defined as 30-day postoperative mortality. RESULTS: In the entire cohort, postoperative mortality increased significantly among patients aged 65-74 years, and an age >/=65 years was by itself an independent risk factor for mortality (odds ratio [OR], 2.21; 95% confidence interval [CI], 1.36-3.59; P = 0.001). The mortality rate among elderly patients was 10.6%. Six independent risk factors of mortality were characteristic of the elderly patients: age >/=85 years (OR, 2.62; 95% CI, 1.08-6.31; P = 0.032), emergency (OR, 3.42; 95% CI, 1.67-6.99; P = 0.001), anemia (OR, 1.80; 95% CI, 1.02-3.17; P = 0.041), white cell count > 10,000/mm(3) (OR, 1.90; 95% CI, 1.08-3.35; P = 0.024), ASA class IV (OR, 9.86; 95% CI, 1.77-54.7; P = 0.009) and a palliative cancer operation (OR, 4.03; 95% CI, 1.99-8.19; P < 0.001). CONCLUSION: Characterization of independent validated risk indicators for mortality in elderly patients undergoing major digestive surgery is essential and may lead to an efficient specific workup, which constitutes a necessary step to developing a dedicated score for elderly patients.

Atrial fibrillation (AF), which prevalence increases with age, is a growing public health problem and a well known risk factor for stroke. On the other hand, dementia is one of the most important neurological disorders in the elderly, and with aging of the population in developed countries, the number of demented patients will increase in absence of prevention. In the past decade, several vascular risk factors (hypertension, obesity and metabolic syndrome, hypercholesterolemia) have been found, with various degree of evidence, to be associated with vascular dementia but also, surprisingly, with Alzheimer's disease. This review is devoted to the links between atrial fibrillation, cognitive decline and dementia. Globally, transversal studies showed a significant association between atrial fibrillation, cognitive decline and dementia. However, these studies are particularly sensitive to various biases. In this context, recent longitudinal studies of higher level of evidence have been conducted to assess the link between AF and dementia. One study disclosed a high incidence of dementia among patients suffering from atrial fibrillation during a 4.6 years follow-up. Similarly another study showed that atrial fibrillation was significantly associated with conversion from mild cognitive impairment to dementia during a 3 years follow-up. Nevertheless two other longitudinal studies did not find any significant association between AF and dementia, but this discrepancy should be interpreted taking into account that the comparability of all these studies is moderate because they were using different methodologies (population, cognitive testing, and mean follow-up). Possible explanatory mechanisms for the association between AF and the risk of dementia are proposed, such as thrombo-embolic ischemic damage and cerebral hypo perfusion due to fluctuations in the cardiac output. Thus, there is some evidence that FA could be associated with cognitive decline and dementia but this link should be supported by more powerful long term longitudinal studies.

To determine the relationship between orthostatic hypotension (OH) and cognitive function in elderly subjects with memory complaints.We studied the association between cognitive function and OH in 495 consecutive elderly outpatients attending a memory centre. Blood pressure (BP) was measured in a sitting and standing position. We examined cognitive function using a validated comprehensive battery of neuropsychological tests, the cognitive efficiency profile (CEP) assessing the main cognitive areas. Subjects were classified into 4 categories according to their cognitive status: normal cognitive function, mild cognitive impairment (MCI), Alzheimer's disease (AD) or vascular dementia (VaD).In this population, 76±8 years of age (women 72%), 18% had normal cognitive function, 28% had MCI, 47% AD, and 7% VaD. Hypertension was observed in 74% of patients. OH was present in 14% of subjects (n=69). After adjustment for age, education level, systolic BP, diastolic BP, weight, and antihypertensive drugs, subjects with OH had worse cognitive function than those without OH (CEP score 50±24 vs 56±22, p0.05). Moreover, a significant relationship was observed between OH and cognitive status (normal cognitive function, MCI, AD, or VaD). OH was present in 22% in VaD subjects, 15% in AD subjects, 12% in MCI subjects and 4% in normal control subjects (p0.01 for overall test).Our results showed an association between OH and cognitive impairment and emphasize the need for longitudinal studies designed to evaluate the nature of the relationship between OH and cognitive decline.