Optimal cardiovascular health is associated with slower cognitive decline.

BACKGROUND: Life's Simple 7, a lifestyle and cardiovascular index associated with cognition, has been updated to Life's Essential 8 (LE8) to include sleep. LE8 has been related to cardiovascular outcomes but its association with cognition is unclear. METHODS: In this longitudinal analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), LE8 score was based on health behaviors (diet, physical activity, nicotine exposure, and sleep health) as well as health-related factors (body mass index, blood lipids, blood glucose, and blood pressure). Cognition was assessed in three waves, 4 years apart, using the Consortium to Establish a Registry for Alzheimer's Disease - Word List, semantic and phonemic verbal fluency, the Trail-Making Test B (TMT-B), and a global composite score. We used linear mixed-model analysis, inverse probability weighting, and interaction analysis. RESULTS: At baseline, the mean age of the study cohort was 51.4 ± 8.9 years, 56% were women, and 53% were White. Higher baseline LE8 scores were associated with slower decline in global cognition (ß = 0.001, 95% confidence interval [CI] 0.001, 0.002; p < 0.001), memory (ß = 0.001, 95% CI 0.000, 0.002; p = 0.013), verbal fluency (ß = 0.001, 95% CI 0.000, 0.002; p = 0.003), and TMT-B (ß = 0.004, 95% CI 0.003, 0.005; p < 0.001). This association was mainly driven by LE8 health factors, particularly blood glucose and blood pressure. Age, sex, and race were modifiers of the association between LE8 and global cognitive decline (p < 0.001), suggesting it was more pronounced in older, male, and Black participants. CONCLUSIONS: Higher baseline LE8 scores were associated with slower global and domain-specific cognitive decline during 8 years of follow-up, mainly due to health factors such as blood glucose and blood pressure. Sociodemographic factors were modifiers of this association.

Causes of death in individuals with lifetime major depression: a comprehensive machine learning analysis from a community-based autopsy center.

BACKGROUND: Depression can be associated with increased mortality and morbidity, but no studies have investigated the specific causes of death based on autopsy reports. Autopsy studies can yield valuable and detailed information on pathological ailments or underreported conditions. This study aimed to compare autopsy-confirmed causes of death (CoD) between individuals diagnosed with major depressive disorder (MDD) and matched controls. We also analyzed subgroups within our MDD sample, including late-life depression and recurrent depression. We further investigated whether machine learning (ML) algorithms could distinguish MDD and each subgroup from controls based on their CoD. METHODS: We conducted a comprehensive analysis of CoD in individuals who died from nontraumatic causes. The diagnosis of lifetime MDD was ascertained based on the DSM-5 criteria using information from a structured interview with a knowledgeable informant. Eleven established ML algorithms were used to differentiate MDD individuals from controls by simultaneously analyzing different disease category groups to account for multiple tests. The McNemar test was further used to compare paired nominal data. RESULTS: The initial dataset included records of 1,102 individuals, among whom 232 (21.1%) had a lifetime diagnosis of MDD. Each MDD individual was strictly paired with a control non-psychiatric counterpart. In the MDD group, the most common CoD were circulatory (67.2%), respiratory (13.4%), digestive (6.0%), and cancer (5.6%). Despite employing a range of ML models, we could not find distinctive CoD patterns that could reliably distinguish individuals with MDD from individuals in the control group (average accuracy: 50.6%; accuracy range: 39-59%). These findings were consistent even when considering factors within the MDD group, such as late-life or recurrent MDD. When comparing groups with paired nominal tests, no differences were found for circulatory (p=0.450), respiratory (p=0.790), digestive (p=1.000), or cancer (p=0.855) CoD. CONCLUSIONS: Our analysis revealed that autopsy-confirmed CoD exhibited remarkable similarity between individuals with depression and their matched controls, underscoring the existing heterogeneity in the literature. Future research should prioritize more severe manifestations of depression and larger sample sizes, particularly in the context of CoD related to cancer.

Clinical characteristics and outcomes of COVID-19 patients with preexisting dementia: a large multicenter propensity-matched Brazilian cohort study.

BACKGROUND: Although dementia has emerged as an important risk factor for severe SARS-CoV-2 infection, results on COVID-19-related complications and mortality are not consistent. We examined the clinical presentations and outcomes of COVID-19 in a multicentre cohort of in-hospital patients, comparing those with and without dementia. METHODS: This retrospective observational study comprises COVID-19 laboratory-confirmed patients aged ≥ 60 years admitted to 38 hospitals from 19 cities in Brazil. Data were obtained from electronic hospital records. A propensity score analysis was used to match patients with and without dementia (up to 3:1) according to age, sex, comorbidities, year, and hospital of admission. Our primary outcome was in-hospital mortality. We also assessed admission to the intensive care unit (ICU), invasive mechanical ventilation (IMV), kidney replacement therapy (KRT), sepsis, nosocomial infection, and thromboembolic events. RESULTS: Among 1,556 patients included in the study, 405 (4.5%) had a diagnosis of dementia and 1,151 were matched controls. When compared to matched controls, patients with dementia had a lower frequency of dyspnoea, cough, myalgia, headache, ageusia, and anosmia; and higher frequency of fever and delirium. They also had a lower frequency of ICU admission (32.7% vs. 47.1%, p < 0.001) and shorter ICU length of stay (7 vs. 9 days, p < 0.026), and a lower frequency of sepsis (17% vs. 24%, p = 0.005), KRT (6.4% vs. 13%, p < 0.001), and IVM (4.6% vs. 9.8%, p = 0.002). There were no differences in hospital mortality between groups. CONCLUSION: Clinical manifestations of COVID-19 differ between older inpatients with and without dementia. We observed that dementia alone could not explain the higher short-term mortality following severe COVID-19. Therefore, clinicians should consider other risk factors such as acute morbidity severity and baseline frailty when evaluating the prognosis of older adults with dementia hospitalised with COVID-19.

Advancements in dementia research, diagnostics, and care in Latin America: Highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico City.

INTRODUCTION: While Latin America (LatAm) is facing an increasing burden of dementia due to the rapid aging of the population, it remains underrepresented in dementia research, diagnostics, and care. METHODS: In 2023, the Alzheimer's Association hosted its eighth satellite symposium in Mexico, highlighting emerging dementia research, priorities, and challenges within LatAm. RESULTS: Significant initiatives in the region, including intracountry support, showcased their efforts in fostering national and international collaborations; genetic studies unveiled the unique genetic admixture in LatAm; researchers conducting emerging clinical trials discussed ongoing culturally specific interventions; and the urgent need to harmonize practices and studies, improve diagnosis and care, and use affordable biomarkers in the region was highlighted. DISCUSSION: The myriad of topics discussed at the 2023 AAIC satellite symposium highlighted the growing research efforts in LatAm, providing valuable insights into dementia biology, genetics, epidemiology, treatment, and care.

Potentially inappropriate medications and cognitive performance: cross-sectional results from the ELSA-Brasil study.

OBJECTIVES: Potentially inappropriate medications (PIM), especially those with potential effects on the central nervous system, can increase the risk of cognitive impairment. We investigated the association of the use of PIM and PIM that may impair cognition (PIM-Cog) with cognitive performance among older adults. METHODS: In this cross-sectional study with 2,626 participants, PIM and PIM-Cog were defined by the 2019 American Geriatrics Society Beers criteria. We calculated global cognition and memory, verbal fluency, and Trail Making Test B version (TMT-B) z-scores. Linear regression models adjusted for sociodemographic and clinical variables were used to investigate the association between PIM and cognition. RESULTS: 27% and 7% of the sample (mean age = 65.1 ± 4.1 years old, 54% women, and 61% White) used at least one PIM and PIM-cog, respectively. PIM was associated with poor performance in the TMT-B (ß = -0.17, 95% Cl = -0.29; -0.05, p = 0.007). PIM-Cog was also associated with poor TMT-B performance (ß = -0.08, 95% Cl = -0.15; -0.01, p = 0.025). CONCLUSION: The use of PIM and PIM-Cog was associated with poor executive function among older adults. The review of PIM use and the deprescription of these drugs may be an effective way to improve cognitive function.

The association of hearing loss with depressive symptoms and cognitive function among older people: Results from the Brazilian Longitudinal Study of Aging.

OBJECTIVES: Hearing loss, depression, and cognitive decline are common among older people. We investigated the association of hearing loss with depressive symptoms and cognitive function in a nationally representative sample of people aged 50+ in Brazil. METHODS: Data from the Brazilian Longitudinal Study of Aging (ELSI-Brazil) included information on self-reported hearing loss, hearing aid use (effective or not effective), depressive symptoms (CES-D-8), and a global cognitive score (composed of immediate and late recall, verbal fluency, orientation and prospective memory) in a sample of 9412 individuals. Multiple linear regression was used to estimate the association of hearing loss and hearing aid use with both depressive symptoms and cognitive performance. The analyses were conducted with 7837 participants with complete data, and then repeated with data from the whole sample after multiple imputation. RESULTS: Compared to those without hearing loss, those with hearing loss were more likely to have a higher number of depressive symptoms (ß: 0.53 (0.40-0.67) p < 0.001) but not worse cognitive performance (ß: -0.01 (-0.03 to 0.19) p = 0.631). Among those with hearing loss, the use of hearing aid was neither associated with cognitive performance (ß: -0.08 (-0.19 to 0.03) p = 0.169) or depressive symptoms (ß: -0.42 (-0.98 to 0.14) p = 0.143); its effective use was associated with less depressive symptoms (ß: -0.62 (-1.23 to -0.01) p = 0.045) but not worse cognitive performance (ß: -0.15 (-0.030 to 0.03) p = 0.057). Sensitivity analyses revealed that hearing loss is associated with a worse performance in two non-amnestic cognitive domains. CONCLUSIONS: Hearing loss may negatively affect specific cognitive domains and depressive symptoms among older people, and the use of a hearing aid may mitigate the association with depressive symptoms.

Association between carotid intima-media thickness and cognitive decline differs by race.

INTRODUCTION: Common carotid intima-media thickness (cIMT) is a marker of subclinical atherosclerosis and is associated with cognitive decline. Although carotid atherosclerosis is more frequent in White than in Black participants, little is known whether race modifies the association between cIMT and cognitive decline. METHODS: In this longitudinal analysis of the ELSA-Brasil, we assessed cIMT using ultrasound and cognitive performance using different domain tests. We used linear mixed models, interaction analysis, and race stratified analyses. RESULTS: Baseline high IMT values were associated with memory (p < 0.001), verbal fluency (p < 0.001), TMT-B (p < 0.001)), and global cognitive decline (p < 0.001). Race was an effect modifier in the association between IMT and global cognitive decline (0.043), with stronger association in White (p < 0.001) than in Black (p = 0.009) participants. DISCUSSION: Baseline IMT was associated with global and domain-specific cognitive decline and race modified this relationship, with stronger associations in White participants. HIGHLIGHTS: Carotid intima-media thickness (cIMT) was associated with cognitive decline. cIMT and cognitive decline association was stronger in White than in Black participants. We used inverse probability weighting to address attrition bias.

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.

Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS): Study design and harmonization.

INTRODUCTION: Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS) is the first non-pharmacological multicenter randomized clinical trial (RCT) to prevent cognitive impairment in Latin America (LA). Our aim is to present the study design and discuss the strategies used for multicultural harmonization. METHODS: This 1-year RCT (working on a 1-year extension) investigates the feasibility of a multi-domain lifestyle intervention in LA and the efficacy of the intervention, primarily on cognitive function. An external harmonization process was carried out to follow the FINGER model, and an internal harmonization was performed to ensure this study was feasible and comparable across the 12 participating LA countries. RESULTS: Currently, 1549 participants have been screened, and 815 randomized. Participants are ethnically diverse (56% are Nestizo) and have high cardiovascular risk (39% have metabolic syndrome). DISCUSSION: LatAm-FINGERS overcame a significant challenge to combine the region's diversity into a multi-domain risk reduction intervention feasible across LA while preserving the original FINGER design.

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.

Sex differences in the association between alcohol intake and cognitive decline over 4 years in a middle-aged cohort: The Brazilian Longitudinal Study of Adult Health.

BACKGROUND AND PURPOSE: The association between alcohol intake and cognitive decline has been widely studied. Sex differences and cognitive domains affected by alcohol intake patterns make this topic complex. The objective of this study was to investigate the effect of alcohol intake on cognition in middle-aged participants in the Brazilian Longitudinal Study of Adult Health by sex during 4 years of follow-up. METHODS: A total of 7595 participants (55% women) aged between 50 and 75 years at baseline were assessed. Semantic and phonemic fluency, memory, and executive functions were assessed at baseline (2008-2010) and repeated during Visit 2. Linear mixed models were used to investigate the association between cognition and current abstainers, never drinkers, light drinkers, moderate drinkers, and heavy drinkers. RESULTS: Heavy alcohol intake accentuated the decline in executive functions for men (ß = -0.01, p < 0.05), and in semantic fluency (ß = -0.02, p < 0.05) and memory (ß = -0.02, p < 0.05) for women. Never drinker men also showed an accentuated decline in semantic fluency (ß = -0.02, p < 0.01). Moderate alcohol intake slowed cognitive decline in phonemic fluency for men (ß = 0.02, p < 0.01) and women (ß = 0.01, p < 0.01), and in executive functions (ß = 0.01, p < 0.05) for women. CONCLUSIONS: Having more than 14 drinks per week can impact executive functions in men and memory in women. In addition, alcohol consumption of seven to 14 drinks per week may have a protective effect on gender-specific cognitive functions. These findings should be considered in public health policies and guidelines on alcohol and cognitive aging.

Anticholinergic burden and cognitive performance: cross-sectional results from the ELSA-Brasil study.

OBJECTIVES: Using multiple drugs with anticholinergic properties is common and might lead to cumulative anticholinergic toxicity and increased risk of cognitive impairment. Therefore, we sought to investigate the association between the Anticholinergic Cognitive Burden (ACB) Scale and cognitive performance among middle-aged and older adults. METHODS: In this cross-sectional study with 13,065 participants from the baseline visit of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), mean age was 51.7 ± 9.0 years old, 55% women, and 53% white. The ACB was calculated based on the medications in use. We investigated the association of ACB with global cognition and memory, verbal fluency (VF), and trail-making test version B (TMT-B) z-scores, using multiple linear regression models adjusted for sociodemographic and clinical variables. RESULTS: Overall, 16% of participants had an ACB score greater than 0. ACB was associated with poor cognitive performance in all tests in crude analysis. After adjustment for sociodemographic characteristics, the association remained significant for the global cognitive score, as well as the memory and the TMT-B z-scores. However, after further adjustments for clinical variables, only trend associations of ACB with poor memory (ß = - 0.02, 95% Cl = - 0.05, 0.00, p = 0.056) and the TMT-B z-scores (ß = - 0.02, 95% Cl = - 0.04, 0.00, p = 0.054) were found. In stratified analyses by age groups, ACB was associated with poor cognitive performance on the TMT-B (ß = - 0.03, 95% Cl = - 0.05, - 0.01, p = 0.005) in individuals aged less than 65 years old. CONCLUSION: Although the ACB was associated with poor executive function only among middle-aged adults in adjusted analysis, residual confounding may partly explain our results.

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.

Dementia in Latin America: Paving the way toward a regional action plan.

Across Latin American and Caribbean countries (LACs), the fight against dementia faces pressing challenges, such as heterogeneity, diversity, political instability, and socioeconomic disparities. These can be addressed more effectively in a collaborative setting that fosters open exchange of knowledge. In this work, the Latin American and Caribbean Consortium on Dementia (LAC-CD) proposes an agenda for integration to deliver a Knowledge to Action Framework (KtAF). First, we summarize evidence-based strategies (epidemiology, genetics, biomarkers, clinical trials, nonpharmacological interventions, networking, and translational research) and align them to current global strategies to translate regional knowledge into transformative actions. Then we characterize key sources of complexity (genetic isolates, admixture in populations, environmental factors, and barriers to effective interventions), map them to the above challenges, and provide the basic mosaics of knowledge toward a KtAF. Finally, we describe strategies supporting the knowledge creation stage that underpins the translational impact of KtAF.

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.

Microgliosis is associated with visual memory decline in patients with temporal lobe epilepsy and hippocampal sclerosis: A clinicopathologic study.

Hippocampal sclerosis (HS) is characterized by neuronal loss and gliosis. The intensity and distribution of these histopathological findings over the Cornu Ammonis (CA) subfields are important for the classification of HS and prognostication of patients with temporal lobe epilepsy (TLE). Several studies have associated the neuronal density reduction in the hippocampus with cognitive decline in patients with TLE. The current study aimed at investigating whether the expression of glial proteins in sclerotic hippocampi is associated with presurgical memory performance of patients with TLE. Before amygdalohippocampectomy, patients were submitted to memory tests. Immunohistochemical and morphometric analyses with glial fibrillary acidic protein (GFAP) for astrogliosis and human leucocyte antigen DR (HLA-DR) for microgliosis were performed in paraffin-embedded HS and control hippocampi. Sclerotic hippocampi exhibited increased gliosis in comparison with controls. In patients with TLE, the area and intensity of staining for HLA-DR were associated with worse performance in the memory tests. Glial fibrillary acidic protein was neither associated nor correlated with memory test performance. Our data suggest association between microgliosis, but not astrogliosis, with visual memory decline in patients with TLE.

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.

Cigarette Smoking Impairs the Diaphragm Muscle Structure of Patients without Respiratory Pathologies: An Autopsy Study.

BACKGROUND/AIMS: Smoking is a major risk factor for several cardiovascular and pulmonary diseases, and it has also been associated with the loss of skeletal muscle mass and strength leading to sarcopenia. The aim of this is study is to analyze the effects of cigarette smoking on the diaphragm muscle histopathology of postmortem samples from patients without respiratory diseases. METHODS: Diaphragm samples were stained with hematoxylin and eosin for histopathological analysis. Picrosirius stain was used to highlight the collagen fibers. RESULTS: Cigarette smokers had an increase of histopathological alterations as abnormal cytoplasm, abnormal fiber size and shape, and central nucleus. Additionally, smokers had an increase of collagen fibers on diaphragm muscle. CONCLUSION: Smoking may influence in a negatively fashion the diaphragm musculature.

Depression is associated with self-rated frailty in older adults from an outpatient clinic: a prospective study.

ABSTRACTObjectives:The aim of the present study was to evaluate the association between depression and SSRI monotherapy and frailty both baseline and prospectively in older adults. DESIGN: Prospective cohort study, 12-month follow-up. SETTING: Geriatric outpatient clinic in São Paulo, Brazil. PARTICIPANTS: A total of 811 elderly adults aged 60 or older. MEASUREMENTS: Depression was diagnosed as follows: (1) a diagnosis of major depression disorder (MDD) according to DSM-5; or (2) an incomplete diagnosis of MDD, referred to as minor or subsyndromic depression, plus Geriatric Depression Scale 15-itens ≥ 6 points, and social or functional impairment secondary to depressive symptoms and observed by relatives. Frailty evaluation was performed through the FRAIL questionnaire, which is a self-rated scale. Trained investigators blinded to the baseline assessment conducted telephone calls to evaluate frailty after 12-month follow-up. The association between depression and the use of SSRI with frailty was estimated through a generalized estimating equation adjusted for age, gender, total drugs, and number of comorbidities. RESULTS: Depression with SSRI use was associated with frailty at baseline (OR 2.82, 95% CI = 1.69-4.69) and after 12 months (OR 2.75, 95% CI = 1.84-4.11). Additionally, depression with SSRI monotherapy was also associated with FRAIL subdomains Physical Performance (OR 1.99, 95% CI = 1.29-3.07) and Health Status (OR 4.64, 95% CI = 2.11-10.21). SSRI use, without significant depressive symptoms, was associated with subdomain Health Status (OR 1.52, 95% CI = 1.04-2.23). CONCLUSION: It appears that depression with SSRI is associated to frailty, and this association cannot be explained only by antidepressant use.

Migraine and cognitive function: Baseline findings from the Brazilian Longitudinal Study of Adult Health: ELSA-Brasil.

Background The association between migraine and cognitive performance is unclear. We analyzed whether migraine is associated with cognitive performance among participants of the Brazilian Longitudinal Study of Adult Health, ELSA-Brasil. Methods Cross-sectional analysis, including participants with complete information about migraine and aura at baseline. Headache status (no headaches, non-migraine headaches, migraine without aura and migraine with aura), based on the International Headache Society classification, was used as the dependent variable in the multilinear regression models, using the category "no headache" as reference. Cognitive performance was measured with the Consortium to Establish a Registry for Alzheimer's Disease word list memory test (CERAD-WLMT), the semantic fluency test (SFT), and the Trail Making Test version B (TMTB). Z-scores for each cognitive test and a composite global score were created and analyzed as dependent variables. Multivariate models were adjusted for age, gender, education, race, coronary heart disease, heart failure, hypertension, diabetes, dyslipidemia, body mass index, smoking, alcohol use, physical activity, depression, and anxiety. In women, the models were further adjusted for hormone replacement therapy. Results We analyzed 4208 participants. Of these, 19% presented migraine without aura and 10.3% presented migraine with aura. All migraine headaches were associated with poor cognitive performance (linear coefficient ß; 95% CI) at TMTB -0.083 (-0.160; -0.008) and poorer global z-score -0.077 (-0.152; -0.002). Also, migraine without aura was associated with poor cognitive performance at TMTB -0.084 (-0.160, -0.008 and global z-score -0.077 (-0.152; -0.002). Conclusion In participants of the ELSA-study, all migraine headaches and migraine without aura were significantly and independently associated with poorer cognitive performance.