The influence of age and sex on the absolute cell numbers of the human brain cerebral cortex.

The human cerebral cortex is one of the most evolved regions of the brain, responsible for most higher-order neural functions. Since nerve cells (together with synapses) are the processing units underlying cortical physiology and morphology, we studied how the human neocortex is composed regarding the number of cells as a function of sex and age. We used the isotropic fractionator for cell quantification of immunocytochemically labeled nuclei from the cerebral cortex donated by 43 cognitively healthy subjects aged 25-87 years old. In addition to previously reported sexual dimorphism in the medial temporal lobe, we found more neurons in the occipital lobe of men, higher neuronal density in women's frontal lobe, but no sex differences in the number and density of cells in the other lobes and the whole neocortex. On average, the neocortex has ~10.2 billion neurons, 34% in the frontal lobe and the remaining 66% uniformly distributed among the other 3 lobes. Along typical aging, there is a loss of non-neuronal cells in the frontal lobe and the preservation of the number of neurons in the cortex. Our study made possible to determine the different degrees of modulation that sex and age evoke on cortical cellularity.

Role of Nutritional Supplements on Gut-Muscle Axis Across Age: a Mini-Review.

Sarcopenia is a progressive skeletal muscle disorder associated with aging, resulting in loss of muscle mass and function. It has been linked to inflammation, oxidative stress, insulin resistance, hormonal changes (i.e. alterations in the levels or activity of hormones which can occur due to a variety of factors, including aging, stress, disease, medication, and environmental factors), and impaired muscle satellite cell activation. The gut microbiome is also essential for muscle health, and supplements such as probiotics, prebiotics, protein, creatine, and betaalanine can support muscle growth and function while also promoting gut health. Chronic low-grade inflammation is a leading cause of sarcopenia, which can activate signaling pathways that lead to muscle wasting and reduce muscle protein synthesis. Insulin resistance, hormonal changes, and impaired muscle satellite cell activation contribute to sarcopenia, and high levels of fat mass also play a role in the pathogenesis of sarcopenia. Resistance exercise and dietary supplementation have been shown to be effective treatments for sarcopenia. In addition, a combination of resistance exercise and supplementation has been shown to have a more significant beneficial effect on anthropometric and muscle function parameters, leading to a decrease in sarcopenic state. Thus, understanding the relationship between the gut microbiome and muscle metabolism is crucial for developing new treatments for sarcopenia across age groups.

Global and local ancestry modulate APOE association with Alzheimer's neuropathology and cognitive outcomes in an admixed sample.

Dementia is more prevalent in Blacks than in Whites, likely due to a combination of environmental and biological factors. Paradoxically, clinical studies suggest an attenuation of APOE ε4 risk of dementia in African ancestry (AFR), but a dearth of neuropathological data preclude the interpretation of the biological factors underlying these findings, including the association between APOE ε4 risk and Alzheimer's disease (AD) pathology, the most frequent cause of dementia. We investigated the interaction between African ancestry, AD-related neuropathology, APOE genotype, and functional cognition in a postmortem sample of 400 individuals with a range of AD pathology severity and lack of comorbid neuropathology from a cohort of community-dwelling, admixed Brazilians. Increasing proportions of African ancestry (AFR) correlated with a lower burden of neuritic plaques (NP). However, for individuals with a severe burden of NP and neurofibrillary tangles (NFT), AFR proportion was associated with worse Clinical Dementia Rating sum of boxes (CDR-SOB). Among APOE ε4 carriers, the association between AFR proportion and CDR-SOB disappeared. APOE local ancestry inference of a subset of 309 individuals revealed that, in APOE ε4 noncarriers, non-European APOE background correlated with lower NP burden and, also, worse cognitive outcomes than European APOE when adjusting by NP burden. Finally, APOE ε4 was associated with worse AD neuropathological burden only in a European APOE background. APOE genotype and its association with AD neuropathology and clinical pattern are highly influenced by ancestry, with AFR associated with lower NP burden and attenuated APOE ε4 risk compared to European ancestry.

Neuropathological correlates of neuropsychiatric symptoms in dementia.

INTRODUCTION: Neuropsychiatric symptoms (NPS) are common in Lewy body disease (LBD), but their etiology is poorly understood. METHODS: In a population-based post mortem study neuropathological data was collected for Lewy body (LB) neuropathology, neurofibrillary tangles (NFT), amyloid beta burden, TDP-43, lacunar infarcts, cerebral amyloid angiopathy (CAA), and hyaline atherosclerosis. Post mortem interviews collected systematic information regarding NPS and cognitive status. A total of 1038 cases were included: no pathology (NP; n = 761), Alzheimer's disease (AD; n = 189), LBD (n = 60), and AD+LBD (n = 28). RESULTS: Hallucinations were associated with higher LB Braak stages, while higher NFT Braak staging was associated with depression, agitation, and greater number of symptoms in the Neuropsychiatric Inventory. Cases with dual AD+LBD pathology had the highest risk of hallucinations, agitation, apathy, and total symptoms but a multiplicative interaction between these pathologies was not significant. DISCUSSION: LB and AD pathology contribute differentially to NPS likely with an additive process contributing to the increased burden of NPS.

Dissipating the fog: Cognitive trajectories and risk factors 1 year after COVID-19 hospitalization.

INTRODUCTION: Cognitive impairment is common after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, associations between post-hospital discharge risk factors and cognitive trajectories have not been explored. METHODS: A total of 1105 adults (mean age ± SD 64.9 ± 9.9 years, 44% women, 63% White) with severe coronavirus disease 2019 (COVID-19) were evaluated for cognitive function 1 year after hospital discharge. Scores from cognitive tests were harmonized, and clusters of cognitive impairment were defined using sequential analysis. RESULTS: Three groups of cognitive trajectories were observed during the follow-up: no cognitive impairment, initial short-term cognitive impairment, and long-term cognitive impairment. Predictors of cognitive decline after COVID-19 were older age (ß = -0.013, 95% CI = -0.023;-0.003), female sex (ß = -0.230, 95% CI = -0.413;-0.047), previous dementia diagnosis or substantial memory complaints (ß = -0.606, 95% CI = -0.877;-0.335), frailty before hospitalization (ß = -0.191, 95% CI = -0.264;-0.119), higher platelet count (ß = -0.101, 95% CI = -0.185;-0.018), and delirium (ß = -0.483, 95% CI = -0.724;-0.244). Post-discharge predictors included hospital readmissions and frailty. DISCUSSION: Cognitive impairment was common and the patterns of cognitive trajectories depended on sociodemographic, in-hospital, and post-hospitalization predictors. HIGHLIGHTS: Cognitive impairment after coronavirus disease 2019 (COVID-19) hospital discharge was associated with higher age, less education, delirium during hospitalization, a higher number of hospitalizations post discharge, and frailty before and after hospitalization. Frequent cognitive evaluations for 12-month post-COVID-19 hospitalization showed three possible cognitive trajectories: no cognitive impairment, initial short-term impairment, and long-term impairment. This study highlights the importance of frequent cognitive testing to determine patterns of COVID-19 cognitive impairment, given the high frequency of incident cognitive impairment 1 year after hospitalization.

Apolipoprotein E ε2 allele is associated with lower risk of carotid artery obstruction in a population-based autopsy study.

INTRODUCTION: Apolipoprotein E (APOE) ε4 allele has been associated with higher carotid atherosclerosis risk, while the APOE-ε2 seems to decrease this risk. Data from autopsy studies, where carotid arteries can be evaluated in their full extension, is scarce. Therefore, we investigated the association between APOE alleles and direct morphometric measurements of carotid atherosclerosis in an autopsy study with an admixed sample. METHODS: We measured the intima-media thickness (IMT) and stenosis of the common (CCA) and internal carotid (ICA) arteries. The APOE polymorphisms were determined by real-time polymerase chain reaction. Participants were classified into three groups according to the APOE alleles (ε2, ε3, and ε4). We evaluated the association between APOE groups and carotid atherosclerosis using adjusted regression models and included interaction terms of APOE alleles with age, sex, and race. RESULTS: We evaluated 1,850 carotid artery samples from 185 participants (mean age=75±12 years old, 55% female, and 71% White). The APOE-ε2 group (n=17) had a lower carotid obstruction and a lower number of severe stenoses (≥ 70%). Having at least one ε4 allele (n=51) was not associated with carotid atherosclerosis. APOE alleles were also not associated with carotid IMT. Age, sex, and race did not modify these relationships. CONCLUSION: APOE-ε2 carriers had a lower percentage of carotid obstruction and less severe stenosis. APOE-ε4 was not related to a higher risk of carotid atherosclerosis in this cross-sectional population-based autopsy study.

Patient-Centered Outcomes Following COVID-19: Frailty and Disability Transitions in Critical Care Survivors.

OBJECTIVES: As the pandemic advances, the interest in the long-lasting consequences of COVID-19 increases. However, a few studies have explored patient-centered outcomes in critical care survivors. We aimed to investigate frailty and disability transitions in COVID-19 patients admitted to ICUs. DESIGN: Prospective cohort study. SETTING: University hospital in Sao Paulo. PATIENTS: Survivors of COVID-19 ICU admissions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We assessed frailty using the Clinical Frailty Scale (CFS). We also evaluated 15 basic, instrumental, and mobility activities. Baseline frailty and disability were defined by clinical conditions 2-4 weeks before COVID-19, and post-COVID-19 was characterized 90 days (day 90) after hospital discharge. We used alluvial flow diagrams to visualize transitions in frailty status, Venn diagrams to describe the overlap between frailty and disabilities in activities of daily living, and linear mixed models to explore the occurrence of new disabilities following critical care in COVID-19. We included 428 participants with a mean age of 64 years, 57% males, and a median Simplified Acute Physiology Score-3 score of 59. Overall, 14% were frail at baseline. We found that 124/394 participants (31%) were frail at day 90, 70% of whom were previously non-frail. The number of disabilities also increased (mean difference, 2.46; 95% CI, 2.06-2.86), mainly in participants who were non-frail before COVID-19. Higher pre-COVID-19 CFS scores were independently associated with new-onset disabilities. At day 90, 135 patients (34%) were either frail or disabled. CONCLUSIONS: Frailty and disability were more frequent 90 days after hospital discharge compared with baseline in COVID-19 patients admitted to the ICU. Our results show that most COVID-19 critical care survivors transition to poorer health status, highlighting the importance of long-term medical follow-up for this population.

Increased levels of TAR DNA-binding protein 43 in the hippocampus of subjects with bipolar disorder: a postmortem study.

Bipolar disorder shares symptoms and pathological pathways with other neurodegenerative diseases, including frontotemporal dementia (FTD). Since TAR DNA-binding protein 43 (TDP-43) is a neuropathological marker of frontotemporal dementia and it is involved in synaptic transmission, we explored the role of TDP-43 as a molecular feature of bipolar disorder (BD). Homogenates were acquired from frozen hippocampus of postmortem brains of bipolar disorder subjects. TDP-43 levels were quantified using an ELISA-sandwich method and compared between the postmortem brains of bipolar disorder subjects and age-matched control group. We found higher levels of TDP-43 protein in the hippocampus of BD (n = 15) subjects, when compared to controls (n = 15). We did not find associations of TDP-43 with age at death, postmortem interval, or age of disease onset. Our results suggest that protein TDP-43 may be potentially implicated in behavioral abnormalities seen in BD. Further investigation is needed to validate these findings and to examine the role of this protein during the disease course and mood states.

Cause of Death Determined by Full-body Autopsy in Neuropathologically Diagnosed Dementias: The Biobank for Aging Studies of the University of Sao Paulo (BAS-USP), Brazil.

OBJECTIVE: This study aimed to compare causes of death in the most prevalent neuropathologically diagnosed dementias. METHODS: We analyzed causes of death in a community-based cohort of participants aged 50 or older, submitted to full-body autopsy and a comprehensive neuropathologic examination of the brain. Individuals with Alzheimer disease (AD), vascular dementia (VaD), mixed dementia (AD+VaD), or dementia with Lewy bodies (DLBs) were compared with individuals with no dementia. RESULTS: In a sample of 920 individuals, 456 had no dementia, 147 had AD, 120 had VaD, 53 had DLB, and 37 had AD+VaD. Pneumonia as the cause of death was more frequent in the AD (P=0.023), AD+VaD (P=0.046), and DLB (P=0.043) groups. In addition, VaD (P=0.041) and AD+VaD (P=0.028) groups had a higher frequency of atherosclerosis as detected by full-body autopsy. CONCLUSION: Our findings highlight the importance of preventive measures regarding atherosclerosis and pneumonia in patients with dementia. Moreover, because of cognitive impairment, these patients may not fully account for symptoms to make early detection and diagnosis possible. These results confirm findings from previous studies that were based on clinical data, with added accuracy provided by neuropathologic diagnosis and full-body autopsy reports.

Decision-making executive function profile and performance in older adults with major depression: a case-control study.

OBJECTIVES: Decision making (DM) is a component of executive functioning, essential for choosing appropriate decisions. Executive dysfunctioning is particularly common in late-life depression, however the literature is scarce on DM. This case-control study aimed to evaluate the DM profile and performance in participants with and without unipolar major depression. METHOD: The DM profile and performance were assessed by the Melbourne Decision Making Questionnaire and the Iowa Gambling Task (IGT), respectively, in three groups of older adults from a university-based geriatric psychiatry clinic, i.e. current depression (n = 30), remitted depression (n = 43) and healthy controls (n = 59). The Hamilton Depression scale (HAM-D) 21 items, the Hamilton Anxiety scale, and the Mini-Mental State Examination were used to access depressive symptoms, anxiety symptoms, and cognitive impairment, respectively. Multinomial, nominal and binary logistic regression was used to evaluate the associations between depression, depressive symptomatology and DM. RESULTS: In comparison to the control group, patients with current depression presented higher scores in buck-passing and proscratination DM profiles. In the hypervigilance profile, there was a significant difference between current and remitted depression groups. A higher value ​in the HAM-D scale increased the probability of disadvantageous DM profiles. Depressive patients showed a tendency of a higher mean score in both disadvantageous decks (A and B) of IGT. Patients with current depression showed a worse performance compared to the remitted depression group in the IGT netscore. CONCLUSION: Older adults with current depression showed DM profiles considered maladaptive or disadvantageous compared to both remitted depression and healthy controls groups.

Education, but not occupation, is associated with cognitive impairment: The role of cognitive reserve in a sample from a low-to-middle-income country.

INTRODUCTION: Education, and less frequently occupation, has been associated with lower dementia risk in studies from high-income countries. We aimed to investigate the association of cognitive impairment with education and occupation in a low-middle-income country sample. METHODS: In this cross-sectional study, cognitive function was assessed by the Clinical Dementia Rating sum of boxes (CDR-SOB). We investigated the association of occupation complexity and education with CDR-SOB using adjusted linear regression models for age, sex, and neuropathological lesions. RESULTS: In 1023 participants, 77% had < 5 years of education, and 56% unskilled occupations. Compared to the group without education, those with formal education had lower CDR-SOB (1-4 years: ß $\beta \;$ = -0.99, 95% confidence interval [CI] = -1.85; -0.14, P = .02; ≥5 years: ß $\beta \;$ = -1.42, 95% CI = -2.47; -0.38, P = .008). Occupation complexity and demands were unrelated to cognition. DISCUSSION: Education, but not occupation, was related to better cognitive abilities independent of the presence of neuropathological insults.

Alcohol Use Disorder is Associated with Upregulation of MicroRNA-34a and MicroRNA-34c in Hippocampal Postmortem Tissue.

BACKGROUND: To investigate epigenetic mechanisms potentially involved in the cognitive decline associated with chronic alcohol intake, we evaluated the expressions of three micro-RNAs (miR-34a, -34b, and -34c) highly expressed in the hippocampus and involved in neuronal physiology and pathology. MiR-34a participates in functioning and survival of mature neurons; miR-34b is associated with Alzheimer-like disorders; and miR-34c is implicated in the memory impairment of Alzheimer disease in rodents and humans. METHODS: A total of 69 cases were selected from the Biobank for Aging Studies and categorized according to the absence (n = 50) or presence (n = 19) of alcohol use disorder (AUD). Cases presenting with neuropathological diagnoses of dementias were excluded. Total RNA was extracted from hippocampal paraffinized slices, complementary DNA was synthesized from miRs, and RT-qPCR was performed with TaqMan® assays. RESULTS: Higher expressions of miR-34a and miR-34c, but not of miR-34b, were found in the group with AUD in comparison with the group without AUD after adjustment for potential confounders (age, sex, body mass index, presence of hypertension, diabetes mellitus, smoking, and physical inactivity). CONCLUSIONS: Hippocampal upregulation of miR-34a and miR-34c may be involved in the cognitive decline associated with chronic alcohol consumption.

Usefulness of ECG criteria to rule out left ventricular hypertrophy in older individuals with true left bundle branch block: an observational study.

BACKGROUND: Advanced age is associated with both left bundle branch block (LBBB) and hypertension and the usefulness of ECG criteria to detect left ventricular hypertrophy (LVH) in patients with LBBB is still unclear. The diagnostic performance and clinical applicability of ECG-based LVH criteria in patients with LBBB defined by stricter ECG criteria is unknown. The aim of this study was to compare diagnostic accuracy and clinical utility of ECG criteria in patients with advanced age and strict LBBB criteria. METHODS: Retrospective single-center study conducted from Jan/2017 to Mar/2018. Patients undergoing both ECG and echocardiogram examinations were included. Ten criteria for ECG-based LVH were compared using LVH defined by the echocardiogram as the gold standard. Sensitivity, specificity, predictive values, likelihood ratios, AUC, and the Brier score were used to compare diagnostic performance and a decision curve analysis was performed. RESULTS: From 4621 screened patients, 68 were included, median age was 78.4 years, (IQR 73.3-83.4), 73.5% with hypertension. All ECG criteria failed to provide accurate discrimination of LVH with AUC range between 0.54 and 0.67, and no ECG criteria had a balanced tradeoff between sensitivity and specificity. No ECG criteria consistently improved the net benefit compared to the strategy of performing routine echocardiogram in all patients in the decision curve analysis within the 10-60% probability threshold range. CONCLUSION: ECG-based criteria for LVH in patients with advanced age and true LBBB lack diagnostic accuracy or clinical usefulness and should not be routinely assessed.

A fuller picture of COVID-19 prognosis: the added value of vulnerability measures to predict mortality in hospitalised older adults.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) disproportionally affects older adults, the use of conventional triage tools in acute care settings ignores the key aspects of vulnerability. OBJECTIVE: This study aimed to determine the usefulness of adding a rapid vulnerability screening to an illness acuity tool to predict mortality in hospitalised COVID-19 patients. DESIGN: Cohort study. SETTING: Large university hospital dedicated to providing COVID-19 care. PARTICIPANTS: Participants included are 1,428 consecutive inpatients aged ≥50 years. METHODS: Vulnerability was assessed using the modified version of PRO-AGE score (0-7; higher = worse), a validated and easy-to-administer tool that rates physical impairment, recent hospitalisation, acute mental change, weight loss and fatigue. The baseline covariates included age, sex, Charlson comorbidity score and the National Early Warning Score (NEWS), a well-known illness acuity tool. Our outcome was time-to-death within 60 days of admission. RESULTS: The patients had a median age of 66 years, and 58% were male. The incidence of 60-day mortality ranged from 22% to 69% across the quartiles of modified PRO-AGE. In adjusted analysis, compared with modified PRO-AGE scores 0-1 ('lowest quartile'), the hazard ratios (95% confidence interval) for 60-day mortality for modified PRO-AGE scores 2-3, 4 and 5-7 were 1.4 (1.1-1.9), 2.0 (1.5-2.7) and 2.8 (2.1-3.8), respectively. The modified PRO-AGE predicted different mortality risk levels within each stratum of NEWS and improved the discrimination of mortality prediction models. CONCLUSIONS: Adding vulnerability to illness acuity improved accuracy of predicting mortality in hospitalised COVID-19 patients. Combining tools such as PRO-AGE and NEWS may help stratify the risk of mortality from COVID-19.

Serotonin receptor inhibitor is associated with falls independent of frailty in older adults.

OBJECTIVES: To evaluate whether fall risk in older adults is associated with the use of selective serotonin receptor inhibitor (SSRI) monotherapy among geriatric outpatients, and whether this association is moderated by the presence of depressive disorder and/or frailty. METHODS: Prospective cohort study with a 12-month follow-up and including 811 community-dwelling adults aged 60 or older from a university-based Geriatric Outpatient Unit. Major depressive disorder (MDD) was diagnosed according to DSM-5 criteria; subsyndromal depression as not meeting MDD criteria, but a Geriatric Depression Scale 15-item score ≥ 6 points. Frailty was evaluated with the FRAIL questionnaire. The association between SSRI use, depression, or both as well as the association between SSRI use, frailty, or both with falls were estimated through a generalized estimating equation (GEE) adjusted for relevant confounders. RESULTS: At baseline, 297 patients (36.6%) used a SSRI (82 without remitted depression) and 306 (37.7%) were classified as physically frail. Frailty was more prevalent among SSRI users (44.8% versus 33.7%, p =.004). After 12 months, 179 participants had at least one fall (22.1%). SSRI use, depression as well as frailty were all independently associated with falls during follow-up. Nonetheless, patients with concurrent of SSRI usage and non-remitted depression had no higher risk compared to either remitted SSRI users or depressed patients without SSRIs. In contrast, concurrence of SSRI use and frailty increases the risk of falling substantially above those by SSRI usage or frailty alone. CONCLUSION: SSRI usage was independently associated with falls. Especially in frail-depressed patients, treatment strategies for depression other than SSRIs should be considered.

Evaluation of the Diaphragm Muscle Remodeling, Inflammation, Oxidative Stress and Vascularization in Smokers: An Autopsy Study.

BACKGROUND/AIMS: Cigarette smoking is a key factor in systemic inflammation and oxidative stress, and it has also been associated with the loss of muscle strength and an elevated risk of pulmonary diseases. Thus, this study aimed to analyze the effects of cigarette smoking on the diaphragm muscle structure of postmortem samples. METHODS: Immunohistochemical techniques were used for muscle remodeling (metalloproteinases 2 and 9), inflammation (cyclooxygenase-2), oxidative stress (8-hydroxy-2'-deoxyguanosine), and vascularization (vascular endothelial growth factor). Hematoxylin and eosin stain was used for histopathological analysis and Picrosirius stain was used to highlight the collagen fibers. RESULTS: Cigarette smokers had an increase of diaphragm muscle remodeling, oxidative stress, inflammation, and vascularization compared to non-smokers. CONCLUSION: Diaphragm muscle structure may be negatively affected by cigarette smoking.

Prospective GERiatric Observational (ProGERO) study: cohort design and preliminary results.

BACKGROUND: The demographic changes in Brazil as a result of population aging is one of the fastest in the world. The far-reaching new challenges that come with a large older population are particularly disquieting in low- and middle-income countries (LMICs). Longitudinal studies must be completed in LMICs to investigate the social and biological determinants of aging and the consequences of such demographic changes in their context. Therefore, we designed the Prospective GERiatric Observational (ProGERO) study, a longitudinal study of outpatient older adults in São Paulo, Brazil, to collect data both on aging and chronic diseases, and investigate characteristics associated with adverse outcomes in this population. METHODS: The ProGERO study takes place in a geriatric outpatient clinic in the largest academic medical center in Latin America. We performed baseline health examinations in 2017 and will complete subsequent in-person visits every 3 years when new participants will also be recruited. We will use periodic telephone interviews to collect information on the outcomes of interest between in-person visits. The baseline evaluation included data on demographics, medical history, physical examination, and comprehensive geriatric assessment (CGA; including multimorbidity, medications, social support, functional status, cognition, depressive symptoms, nutritional status, pain assessment, frailty, gait speed, handgrip strength, and chair-stands test). We used a previously validated CGA-based model to rank participants according to mortality risk (low, medium, high). Our selected outcomes were falls, disability, health services utilization (emergency room visits and hospital admissions), institutionalization, and death. We will follow participants for at least 10 years. RESULTS: We included 1336 participants with a mean age of 82 ± 8 years old. Overall, 70% were women, 31% were frail, and 43% had a Charlson comorbidity index score ≥ 3. According to our CGA-based model, the incidence of death in 1 year varied significantly across categories (low-risk = 0.6%; medium-risk = 7.4%; high-risk = 17.5%; P < 0.001). CONCLUSION: The ProGERO study will provide detailed clinical data and explore the late-life trajectories of outpatient older patients during a follow-up period of at least 10 years. Moreover, the study will substantially contribute to new information on the predictors of aging, senescence, and senility, particularly in frail and pre-frail outpatients from an LMIC city.

AMPI-AB validity and reliability: a multidimensional tool in resource-limited primary care settings.

BACKGROUND: The early identification of individuals at high risk for adverse outcomes by a Comprehensive Geriatric Assessment (CGA) in resource-limited primary care settings enables tailored treatments, however, the evidence concerning its benefits are still controversial. The main objective of this study was to examine the validity and reliability of the "Multidimensional Assessment of Older People in Primary Care (AMPI-AB)", a CGA for primary care in resource-limited settings. METHODS: Longitudinal study, with median follow-up time of 16 months. Older adults from a public primary care unit in São Paulo, Brazil, were consecutively admitted. Reliability was tested in a sample from a public geriatric outpatient clinic. Participants were classified by the AMPI-AB score as requiring a low, intermediate or high complexity of care. The Physical Frailty Phenotype was used to explore the AMPI-AB's concurrent validity. Predictive validity was assessed with mortality, worsening of the functional status, hospitalizations, emergency room (ER) visits and falls. The area under the ROC curve and logistic regression were calculated for binary outcomes, and a Cox proportional hazards model was used for survival analysis. RESULTS: Older adults (n = 317) with a median age of 80 (74-86) years, 67% female, were consecutively admitted. At the follow-up, 7.1% of participants had died, and increased dependency on basic and instrumental activities of daily living was detected in 8.9 and 41.1% of the participants, respectively. The AMPI-AB score was accurate in detecting frailty (area under the ROC curve = 0.851), predicted mortality (HR = 1.25, 95%CI = 1.13-1.39) and increased dependency on basic (OR = 1.26, 95%CI = 1.10-1.46) and instrumental (OR = 1.22, 95%CI = 1.12-1.34) activities of daily living, hospitalizations (OR = 2.05, 95%CI = 1.04-1.26), ER visits (OR = 1.20, 95%CI = 1.10-1.31) and falls (OR = 1.10, 95%CI = 1.01-1.20), all models adjusted for sex and years of schooling. Reliability was tested in a sample of 52 older adults with a median age of 72 (85-64) years, 63.5% female. The AMPI-AB also had good interrater (ICC = 0.87, 95%CI = 0.78-0.92), test-retest (ICC = 0.86, 95%CI = 0.76-0.93) and proxy reliability (ICC = 0.84, 95%CI = 0.67-0.93). The Cronbach's alpha was 0.69, and the mean AMPI-AB administration time was 05:44 ± 02:42 min. CONCLUSION: The AMPI-AB is a valid and reliable tool for managing older adults in resource-limited primary care settings.

Design and methodology of the Aging Nephropathy Study (AGNES): a prospective cohort study of elderly patients with chronic kidney disease.

BACKGROUND: Renal replacement therapy (RRT) is usually indicated for patients with chronic kidney disease (CKD) with glomerular filtration rate below 10 ml/ml/min/1.73m2. However, the need for RRT and timing of dialysis initiation are debatable for patients aged 70 years or older. We here describe the study design and methodology of the Aging Nephropathy Study (AGNES) protocol that aims at evaluating to what extent geriatric-related conditions such as frailty, cognitive dysfunction, and presence of comorbidities have an impact on survival and RRT initiation in this group of patients. In this manuscript we provide detailed information about the AGNES study design and methodology. METHODS: AGNES is a prospective observational cohort that aim to investigate clinical, biochemical and demographic factors associated with RRT initiation and mortality of patients with CKD stage 4 or 5 who are aged 70 years and older. We plan to include 200 patients over 5 years. Clinically stable outpatients on conservative management for at least 6 months will be recruited from the Nephrogeriatric Clinic at the Hospital das Clinicas da Universidade de Sao Paulo, Brazil. Eligible patients are submitted to a full clinical examination, geriatric assessment, and blood test at baseline. Following the baseline visit the patients are being monitored during an observational follow up period of at least 12 months during which patients will be contacted in the clinic at their regular follow up or by phone until either RRT initiation or death occurs. This cohort includes evaluation of cognition by the education-adjusted 10-point Cognitive Screener (10-CS), frailty by Fried index score, a complete nutritional assessment (by body composition assessment, global subjective assessment and dietary intake), comorbidities by Charlson comorbidity index and biochemical markers including FGF-23 and Klotho. DISCUSSION: The AGNES cohort, a real-world study of current clinical practice in elderly patients with advanced CKD prior to dialysis initiation, will shed light into progression of CKD and its complications, indications of RRT and factors determining survival. This investigation will elucidate to what extent geriatric conditions, nutritional status and clinical factors are associated with survival, quality of life and RRT initiation in elderly CKD patients not yet on dialysis. TRIAL REGISTRATION: Registered on ClinicalTrials.gov on 18 October 2019 ( NCT04132492 ).

The growing impact of older patients in the emergency department: a 5-year retrospective analysis in Brazil.

BACKGROUND: The average age of the global population is rising at an increasing rate. There is a disproportional increase in Emergency Department (ED) visits by older people worldwide. In the Brazilian health system, complex and severely ill patients and those requiring specialized urgent procedures are referred to tertiary level care. As far as we know, no other study in Latin America has analyzed the impact of demographic changes in tertiary ED attendance. AIM: To describe the sociodemographic characteristics and outcomes of tertiary Brazilian ED users. METHODS: Design: Observational cross-sectional analytic study. SETTING: Emergency Department, tertiary university hospital, São Paulo, Brazil. PARTICIPANTS: patients aged 18 years or older attending a tertiary ED (2009-2013). The primary outcomes were hospitalization and mortality; the secondary outcome was ICU admission. Age was categorized as 'young adults' (18-39y), 'adults' (40-59y), 'young-older adults' (60-79y), and 'old-older adults' (80-109y). Other variables included sex, reason for attendance, time of ED visit, mode of presentation, type of hospitalization, main procedure, length of hospital stay (LOS) and length of ICU stay (ICU-LOS). We calculated descriptive statistics, built generalized linear mixed models for each outcome and estimated Odds Ratios (95% CI) for the independent categorical variables. The significance level was 5% with Bonferroni correction. RESULTS: Older age-groups represented 26.6% of 333,028 ED visits, 40.7% of admissions, 42.7% of ICU admissions and 58% of all deaths. Old-older patients accounted for 5.1% of ED visits, 9.5% of admissions and 10.1% of ICU admissions. Hospitalization, ICU admission and mortality rates increased with older age in both sexes. LOS and ICU-LOS were similar across age-groups. The proportions of visits and admissions attributed to young adults decreased annually, while those of people aged 60 or over increased. The ORs for hospitalization, ICU admission and mortality associated with the old-older group were 3.49 (95% CI = 3.15-3.87), 1.27 (1.15-1.39) and 5.93 (5.29-6.66) respectively, with young adults as the reference. CONCLUSIONS: In tertiary ED, age is an important risk factor for hospitalization and mortality, but not for ICU admission. Old-older people are at the greatest risk and demand further subgroup stratification.