Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes.

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aß42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.

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

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

The role of nutrition in the prevention of cognitive decline.

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

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

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

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

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

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

BACKGROUND: In older adults, physical activity (PA) is important in maintaining physical performance. Data on the effectiveness of public open-access community-based programs on physical performance and fall prevention are scarce. METHODS: Prospective observational controlled study in community centers providing an open-access public prevention program. Retirees aged ≥60 years who chose to participate in weekly PA workshops for 3 months were compared to those who chose the cognitive stimulation (CS) workshops. Collected data: handgrip strength, five times sit-to-stand, single-leg stance, Timed Up and Go tests, gait speed, short physical performance battery (SPPB) and frailty status at baseline (M0) and at 3 months (M3). The proportion of participants reporting a history of falls was assessed at baseline and using follow-up telephone interviews (F-Up). RESULTS: Two hundred eighty-eight participants (age 73.8 years, 87% women) were included. The sit-to-stand test, single-leg stance and SPPB scores improved significantly between M0 and M3 in both groups. A greater SPPB increase was observed in the PA than in the CS group (+0.39 vs. +0.32 points, P = 0.02) after adjustment for age, sex, number of sessions attended, fall history and SPPB at baseline. During F-Up (median 22 months), the proportion of participants reporting at least one fall decreased from 55% to 31% (P = 0.01) in the PA group and from 27% to 19% (P = 0.12) in the CS group. CONCLUSION: In a public open-access community-based program participants improved physical performance and reduced fall incidence when participating in the PA or the CS workshops. Older adults may benefit most from multifaceted prevention programs.

Associations among hypertension, dementia biomarkers, and cognition: The MEMENTO cohort.

INTRODUCTION: Approximately 40% of dementia cases could be delayed or prevented acting on modifiable risk factors including hypertension. However, the mechanisms underlying the hypertension-dementia association are still poorly understood. METHODS: We conducted a cross-sectional analysis in 2048 patients from the MEMENTO cohort, a French multicenter clinic-based study of outpatients with either isolated cognitive complaints or mild cognitive impairment. Exposure to hypertension was defined as a combination of high blood pressure (BP) status and antihypertensive treatment intake. Pathway associations were examined through structural equation modeling integrating extensive collection of neuroimaging biomarkers and clinical data. RESULTS: Participants treated with high BP had significantly lower cognition compared to the others. This association was mediated by higher neurodegeneration and higher white matter hyperintensities load but not by Alzheimer's disease (AD) biomarkers. DISCUSSION: These results highlight the importance of controlling hypertension for prevention of cognitive decline and offer new insights on mechanisms underlying the hypertension-dementia association. HIGHLIGHTS: Paths of hypertension-cognition association were assessed by structural equation models. The hypertension-cognition association is not mediated by Alzheimer's disease biomarkers. The hypertension-cognition association is mediated by neurodegeneration and leukoaraiosis. Lower cognition was limited to participants treated with uncontrolled blood pressure. Blood pressure control could contribute to promote healthier brain aging.

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

Neurofilament light chain (NfL) is a potential diagnostic and prognostic plasma biomarker for numerous neurological diseases including Alzheimer's disease (AD). In this study, we investigated the relationship between baseline plasma concentration of Nfl and Mild Cognitive Impairment in participants who did and did not have a clinically determined diagnosis of dementia by the end of the three-year study. Additionally, we explored the connection between baseline plasma concentration of NfL and AD dementia patients, considering their demographics, clinical features, and cognitive profiles. A total of 350 participants from the Biomarker of AmyLoid pepTide and AlZheimer's diseAse Risk (BALTAZAR) multicenter prospective study were investigated: 161 AD dementia participants and 189 MCI participants (of which 141 had amnestic MCI and 48 non-amnestic MCI). Plasma biomarkers were measured at baseline and the progression of clinical and cognitive profiles was followed over the three years of follow-up. Baseline plasma NfL concentration increased across the Alzheimer's disease continuum with a mean NfL value of 17.1 ng/mL [SD = 6.1] in non-amnestic MCI, 20.7 ng/mL [SD = 12.0] in amnestic MCI, and 23.1 ng/mL [SD = 22.7] in AD dementia patients. Plasma NfL concentration correlated with age, body mass index (BMI), and global cognitive performance and decline, as measured by the Mini-Mental State Examination (MMSE). MMSE scores decreased in parallel with increasing plasma NfL concentration, independently of age and BMI. However, NfL concentration did not predict MCI participants' conversion to dementia within three years. Discussion: Baseline plasma NfL concentration is associated with cognitive status along the AD continuum, suggesting its usefulness as a potential informative biomarker for cognitive decline follow-up in patients.

COVID-19 Outbreaks in Nursing Homes Despite Full Vaccination with BNT162b2 of a Majority of Residents.

BACKGROUND: It is not known if widespread vaccination can prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in subpopulations at high risk, like older adults in nursing homes (NH). OBJECTIVE: The objective of the study was to know if coronavirus disease 2019 (COVID-19) outbreaks can occur in NH with high vaccination coverage among its residents. METHODS: We identified, using national professional networks, NH that suffered COVID-19 outbreaks despite having completed a vaccination campaign, and asked them to send data, using predefined collecting forms, on the number of residents exposed, their vaccination status and the number, characteristics, and evolution of patients infected. The main outcome was to identify outbreaks occurring in NH with high vaccine coverage. Secondary outcomes were residents' risk of being infected, developing severe disease, or dying from COVID-19 during the outbreak. SARS-CoV-2 infection was defined by a positive reverse transcriptase-polymerase chain reaction. All residents were serially tested whenever cases appeared in a facility. Unadjusted secondary attack rates, relative risks, and vaccine effectiveness during the outbreak were estimated. RESULTS: We identified 31 NH suffering an outbreak during March-April 2021, of which 27 sent data, cumulating 1,768 residents (mean age 88.4, 73.4% women, 78.2% fully vaccinated). BNT162b2 was the vaccine employed in all NH. There were 365 cases of SARS-CoV-2 infection. Median secondary attack rates were 20.0% (IQR 4.4%-50.0%) among unvaccinated residents and 16.7% (IQR 9.5%-29.2%) among fully vaccinated ones. Severe cases developed in 42 of 80 (52.5%) unvaccinated patients, compared with 56 of 248 (22.6%) fully vaccinated ones (relative risks [RR] 4.17, 95% CI: 2.43-7.17). Twenty of the unvaccinated patients (25.0%) and 16 of fully vaccinated ones (6.5%) died from COVID-19 (RR 5.11, 95% CI: 2.49-10.5). Estimated vaccine effectiveness during the outbreak was 34.5% (95% CI: 18.5-47.3) for preventing SARS-CoV-2 infection, 71.8% (58.8-80.7) for preventing severe disease, and 83.1% (67.8-91.1) for preventing death. CONCLUSIONS: Outbreaks of COVID-19, including severe cases and deaths, can still occur in NH despite full vaccination of a majority of residents. Vaccine remains highly effective, however, for preventing severe disease and death. Prevention and control measures for SARS-CoV-2 should be maintained in NH at periods of high incidence in the community.

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

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

Diagnostic Performance of the 4-Item Geriatric Depression Scale for Depression Screening in Older Patients with Cancer: The ELCAPA Cohort Study.

BACKGROUND: In older patients with cancer, depression is difficult to assess because of its heterogeneous clinical expression. The 4-item version of the Geriatric Depression Scale (GDS-4) is quick and easy to administer but has not been validated in this population. The present study was designed to test the diagnostic performance of the GDS-4 in a French cohort of older patients with cancer before treatment. MATERIALS AND METHODS: Our cross-sectional analysis of data from the Elderly Cancer Patient cohort covered all patients with cancer aged ≥70 years and referred for geriatric assessment at two centers in France between 2007 and 2018. The GDS-4's psychometric properties were evaluated against three different measures of depression: the geriatrician's clinical diagnosis (based on a semistructured interview), the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders, and a cluster analysis. The scale's sensitivity, specificity, positive and negative likelihood ratios, and area under the receiver operating characteristic curve (AUROC) were calculated. RESULTS: In a sample of 2,293 patients (median age, 81 years; women, 46%), the GDS-4's sensitivity and specificity for detecting physician-diagnosed depression were, respectively, 90% and 89%. The positive and negative likelihood ratios were 8.2 and 0.11, and the AUROC was 92%. When considering the subset of patients with data on all measures of depression, the sensitivity and specificity values were, respectively, ≥90% and ≥72%, the positive and negative likelihood ratios were, respectively, ≥3.4 and ≤ 0.11, and the AUROC was ≥91%. CONCLUSION: The GDS-4 appears to be a clinically relevant, easy-to-use tool for routine depression screening in older patients with cancer. IMPLICATIONS FOR PRACTICE: Considering the overlap between symptoms of cancer and symptoms of depression, depression is particularly difficult to assess in older geriatric oncology and is associated with poor outcomes; there is a need for a routine psychological screening. Self-report instruments like the 4-item version of the Geriatric Depression Scale appears to be a clinically relevant, easy-to-use tool for routine depression screening in older patients with cancer. Asking four questions might enable physicians to screen older patients with cancer for depression and then guide them toward further clinical evaluation and appropriate care if required.

Investigating the association between cancer and the risk of dementia: Results from the Memento cohort.

INTRODUCTION: Studies on the association of cancer and risk of dementia are inconclusive due to result heterogeneity and concerns of survivor bias and unmeasured confounding. METHODS: This study uses data from the Memento cohort, a French multicenter cohort following persons with either mild or isolated cognitive complaints for a median of 5 years. Illness-death models (IDMs) were used to estimate transition-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for incident cancer in relation to dementia from time since study entry. RESULTS: The analytical sample (N = 2258) excluded 65 individuals without follow-up information. At the end of follow-up, 286 individuals were diagnosed with dementia, 166 with incident cancer, and 95 died. Incident cancer was associated with a reduced risk of dementia (HR = 0.58, 95% CI = 0.35-0.97), with a corresponding E-value of 2.84 (lower CI = 1.21). DISCUSSION: This study supports a protective relationship between incident cancer and dementia, encouraging further investigations to understand potential underlying mechanisms.

Clinical relevance of brain atrophy subtypes categorization in memory clinics.

INTRODUCTION: The clinical relevance of brain atrophy subtypes categorization in non-demented persons without a priori knowledge regarding their amyloid status or clinical presentation is unknown. METHODS: A total of 2083 outpatients with either subjective cognitive complaint or mild cognitive impairment at study entry were followed during 4 years (MEMENTO cohort). Atrophy subtypes were defined using baseline magnetic resonance imaging (MRI) and previously described algorithms. RESULTS: Typical/diffuse atrophy was associated with faster cognitive decline and the highest risk of developing dementia and Alzheimer's disease (AD) over time, both in the whole analytic sample and in amyloid-positive participants. Hippocampal-sparing and limbic-predominant atrophy were also associated with incident dementia, with faster cognitive decline in the limbic predominant atrophy group. Lewy body dementia was more frequent in the hippocampal-sparing and minimal/no atrophy groups. DISCUSSION: Atrophy subtypes categorization predicted different subsequent patterns of cognitive decline and rates of conversion to distinct etiologies of dementia in persons attending memory clinics.

Comparative Safety and Effectiveness of Oral Anticoagulants in Nonvalvular Atrial Fibrillation: The NAXOS Study.

BACKGROUND AND PURPOSE: The effects of direct oral anticoagulants in nonvalvular atrial fibrillation should be assessed in actual conditions of use. France has near-universal healthcare coverage with a unified healthcare information system, allowing large population-based analyses. NAXOS (Evaluation of Apixaban in Stroke and Systemic Embolism Prevention in Patients With Nonvalvular Atrial Fibrillation) aimed to compare the safety, effectiveness, and mortality of apixaban with vitamin K antagonists (VKAs), rivaroxaban, and dabigatran, in oral anticoagulant-naive patients with nonvalvular atrial fibrillation. METHODS: This was an observational study using French National Health System claims data and including all adults with nonvalvular atrial fibrillation who initiated oral anticoagulant between 2014 and 2016. Outcomes of interest were major bleeding events leading to hospitalization (safety), stroke and systemic thromboembolic events (effectiveness), and all-cause mortality. Four approaches were used for comparative analyses: matching on propensity score (PS; 1:n); as a sensitivity analysis, matching on high-dimensional PS; adjustment on PS; and adjustment on known confounders. For each outcome, cumulative incidence rates accounting for competing risks of death were estimated. RESULTS: Overall, 321 501 patients were analyzed, of whom 35.0%, 27.2%, 31.1%, and 6.6% initiated VKAs, apixaban, rivaroxaban, and dabigatran, respectively. Apixaban was associated with a lower PS-matched risk of major bleeding compared with VKAs (hazard ratio [HR], 0.43 [95% CI, 0.40-0.46]) and rivaroxaban (HR, 0.67 [95% CI, 0.63-0.72]), but not dabigatran (HR, 0.93 [95% CI, 0.81-1.08]). Apixaban was associated with a lower risk of stroke and systemic thromboembolic event compared with VKAs (HR, 0.60 [95% CI, 0.56-0.65]), but not rivaroxaban (HR, 1.05 [95% CI, 0.97-1.15]) or dabigatran (HR, 0.93 [95% CI, 0.78-1.11]). All-cause mortality was lower with apixaban than with VKAs, but not lower than with rivaroxaban or dabigatran. CONCLUSIONS: Apixaban was associated with superior safety, effectiveness, and lower mortality than VKAs; with superior safety than rivaroxaban and similar safety to dabigatran; and with similar effectiveness when compared with rivaroxaban or dabigatran. These observational data suggest potentially important differences in outcomes between direct oral anticoagulants, which should be explored in randomized trials.

In Vivo Large-Scale Mapping of Protein Turnover in Human Cerebrospinal Fluid.

The extraction of accurate physiological parameters from clinical samples provides a unique perspective to understand disease etiology and evolution, including under therapy. We introduce a new methodologic framework to map patient proteome dynamics in vivo, either proteome-wide or in large targeted panels. We applied it to ventricular cerebrospinal fluid (CSF) and could determine the turnover parameters of almost 200 proteins, whereas a handful were known previously. We covered a large number of neuron biology- and immune system-related proteins, including many biomarkers and drug targets. This first large data set unraveled a significant relationship between turnover and protein origin that relates to our ability to investigate organ physiology with protein-labeling strategy specifics. Our data constitute the first draft of CSF proteome dynamics as well as a repertoire of peptides for the community to design new analyses. The disclosed methods apply to other fluids or tissues provided sequential sample collection can be performed. We show that the proposed mathematical modeling applies to other analytical methods in the field.

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

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

Hyperglycaemia is associated with cancer-related but not non-cancer-related deaths: evidence from the IPC cohort.

AIMS/HYPOTHESIS: Hyperglycaemia has been associated with the incidence of all and specific types of cancer, distinct from the risks related to diabetes. The relationships between blood glucose and mortality rates related to all and specific cancers were analysed in comparison with all-cause or non-cancer-related mortality rates in a large, general primary care population in France. METHODS: Between January 1991 and December 2008, 301,948 participants (193,221 men and 108,727 women), aged 16-95 years (mean ± SD 44.8 ± 12.0 years for men and 45.1 ± 14.2 years for women), had a health check at the IPC Centre. All data collected in standard conditions during the health checks-up were used for statistical analysis All examinations were performed under fasting conditions and included a blood glucose measurement. Participants with known diabetes (<9%) were excluded from the analysis. Participants were classified into quintiles based on their blood glucose measurement and were followed for a maximum of 17 years (mean ± SD 9.2 ± 4.7 years) to assess all-cause, cancer and non-cancer mortality rates. RESULTS: A non-linear relationship was observed between cancer mortality rates and blood glucose quintile after adjustment for age and sex. There was a significant association between the group with the highest blood glucose level and cancer-related death (multivariate Cox model, HR [95% CI] 1.17 [1.03, 1.34]), while the group with normoglycaemia showed no association with cancer-related deaths. We did not observe a relationship between blood glucose and all-cause or non-cancer mortality rates. An excess risk of death was observed in the highest blood glucose quintile for gastrointestinal cancer and leukaemia. Adjustments for diabetes and aspirin use did not modify the results. However, this excess risk disappeared with use of glucose-lowering agents (HR [95% CI] 1.03 [0.74, 1.43]). CONCLUSIONS/INTERPRETATION: Hyperglycaemia is associated with significantly higher rates of cancer-related deaths, particularly in gastrointestinal cancer and leukaemia, but not with non-cancer-related deaths. The association is retained when taking into account confounding factors, including chronic aspirin treatment.

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

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

Smoking and the Association Between Depressive Symptoms and Absolute Neutrophil Count in the Investigations Préventives et Cliniques Cohort Study.

OBJECTIVES: Depressive symptoms have been associated with chronic low-grade inflammation, including elevated neutrophil count. Smokers often have both high neutrophil count and depressive symptoms. Thus, smoking could explain the cross-sectional association between depressive symptoms and neutrophil count. METHODS: Total white blood cell count and subtypes, including absolute neutrophil, lymphocyte, monocyte, basophil, and eosinophil counts, were measured in 44,806 participants (28,534 men; mean [standard deviation] age = 38.9 [11.4] years), without a history of chronic disease or current medication. Depressive symptoms were assessed with the Questionnaire of Depression, Second Version, Abridged. Smoking status was self-reported and categorized in five classes. Sex, age, alcohol intake, self-rated health, body mass index, glycemia, physical activity, household composition, occupational status, and education were included as covariates. Associations were examined with general linear models and causal mediation analyses. RESULTS: After adjustment for all covariates except smoking, depressive symptoms were positively associated with neutrophil count only (ß = 5.83, standard error [SE] = 2.41, p = .014). After further adjustment for a semiquantitative measure of smoking, this association was no longer significant (ß = 2.40, SE = 2.36, p = .30). Causal mediation analyses revealed that smoking mediated the association (p < .001), accounting for 57% of its total variance. In contrast, depressive symptoms were negatively associated with lymphocyte count in fully adjusted model only (ß = -3.21, SE = 1.11, p = .004). CONCLUSIONS: Smoking may confound or mediate the association between depressive symptoms and neutrophil count. These results advocate for including an accurate measure of smoking in future studies addressing this association. When considering the link between depression and inflammation, one should not overlook the noxious effects of smoking.