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Background: Given the increasing number of people with dementia in Brazil, there is an urgency for health and social systems to plan strategies to meet the needs of this population and their families. Therefore, research on dementia costs is essential. This study estimated direct and indirect costs related to dementia in Brazil., Methods: We employed the cost of illness study methodology to estimate dementia-related costs. Moreover, we used household interview data from the ReNaDe project and public, free-of-charge national databases to collect service use and values information. The societal and the SUS (Brazilian Universal Health System) perspectives were adopted., Results: The monthly cost of dementia per individual increases with the syndrome's progression from US$ 843.04 in the initial stage to US$ 1,317.81 in the intermediate stage, peaking at US$ 1,576.15 in the advanced stage. Indirect costs constitute at least 73% of total expenses. When considering the costs for Brazil, it is in the intermediate stage of dementia that the country's total expenses are the highest., Conclusions: Family caregivers shoulder at least 73% of the health-related costs of dementia in Brazil, highlighting the need to improve and create supporting strategies for people with dementia and their families., Competing Interests: The authors report no conflicts of interest.

Introduction: Alzheimer's disease and other dementia have a higher incidence among women and that risk factors specific to the female sex could be involved. Few studies looked into female reproductive factors and their association with dementia in low-and middle-income countries., Materials and Methods: We analyzed the baseline data from the Brazilian Longitudinal Study of Aging (ELSI-Brazil) and included data from 2594 women aged 60 years and older. We used an algorithm approach to determine dementia status and performed logistic regressions using as predictors the self-reported total length of the reproductive period, total parity and use of hormonal replacement therapy. We also analyzed the effects of hormonal replacement therapy use for different age groups and the effects of number of living children., Results: Reproductive period length, hormonal replacement therapy use and parity as a continuous measure were not significantly associated with dementia status. When compared with 0 births, the group with 5-8 had more dementia while the other groups displayed no differences. For the number of living children, but a higher occurrence of dementia was found among women with more children., Conclusions: We did not find any association between continuous parity, reproductive period length or hormonal replacement therapy use and dementia. Social factors of motherhood appear to play an important role, and group specific effects of parity and hormonal replacement therapy require further study., (© 2024 John Wiley & Sons Ltd.)

The Cd40l -/- mouse is a well-established model of X-linked hyper-immunoglobulin M (IgM) syndrome, an immunodeficiency disorder of human beings characterized by the lack of expression of the CD40 ligand (CD40L) on activated T-cells, predisposing to infections with opportunistic pathogens like Pneumocystis jirovecii . The aim of our study was to describe the pulmonary lesions in Cd40l -/- mice experimentally infected with Pneumocystis murina , in comparison with naturally infected severe combined immunodeficient (SCID) mice. Formalin-fixed paraffin-embedded lungs from 26 Cd40l -/- , 11 SCID, and 5 uninfected Cd40l -/- mice were examined by histology and immunohistochemistry for the presence of the pathogen and for leukocyte populations (CD3, CD4, CD45R/B220, CD8a, Iba-1, Ly-6G, CD206, MHC II, and NKp46/NCR1). Infection was confirmed by immunohistochemistry in 18/26 (69%) Cd40l -/- mice and in 11/11 (100%) SCID mice. Fourteen out of 26 (54%) Cd40l -/- mice had interstitial pneumonia. Twenty-three out of 26 (88%) Cd40l -/- mice had peribronchiolar/perivascular lymphoplasmacytic infiltrates, rich in B-cells and Mott cells. Acidophilic macrophage pneumonia was additionally found in 20/26 (77%) Cd40l -/- mice. Only 4/11 (36%) SCID mice had interstitial pneumonia, but no peribronchiolar/perivascular infiltrates or acidophilic macrophage pneumonia were observed in this strain. This study represents the first description of pulmonary histopathological lesions in Cd40l -/- mice infected with P. murina . We speculate that the singular characteristics of the inflammatory infiltrates observed in Cd40l -/- mice could be explained by the specific immune phenotype of the model., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Cutaneous and subcutaneous mast cell tumors (MCTs) are common canine neoplasms characterized by variable biological behavior. Tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs) can be effective prognostic markers in numerous human neoplasms and are increasingly investigated in dogs. The aim of this study was to characterize immune cells in canine MCTs and their relationship with histological location (cutaneous, subcutaneous) and histologic nodal metastatic status (HN0-3). Thirty-eight MCTs (26 cutaneous, 12 subcutaneous) from 33 dogs with known sentinel lymph node (SLN) metastatic status were immunolabeled for Iba1 (macrophages), CD20 (B cells), CD3 (T cells), and Foxp3 (regulatory T cells). Semiquantitative scoring of interstitial and perivascular CD3+, CD20+, and Foxp3+ cells and morphological evaluation of Iba1+ cells were performed. For each marker, the percent immunopositive area was evaluated by image analysis. All MCTs were diffusely infiltrated by Iba1+ cells and variably infiltrated by CD20+, CD3+, and rare Foxp3+ cells. Stellate/spindle Iba1+ cells were associated with HN2 and HN3 SLNs. Perivascular Foxp3+ cells, CD3+ cells, and percent CD3+ areas were increased in subcutaneous MCTs. Interstitial CD3+ cells were increased in cutaneous MCTs with HN0 SLNs. No differences in CD20+ cells were identified between cutaneous and subcutaneous MCTs and among SLN classes. MCTs were markedly infiltrated by TAMs and variably infiltrated by TILs. Stellate/spindle morphology of TAMs associated with HN2 and HN3 SLNs is suggestive of a pro-tumoral (M2) phenotype. Cutaneous and subcutaneous MCTs have different tumor-immune microenvironments, and T-cell infiltration might contribute to prevention of nodal metastatic spread of cutaneous MCTs., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: People with dementia have several unmet needs during the syndrome progression. More unmet needs are related to hospitalizations, injuries, and death. Little is known about the care needs for people living with dementia in Brazil. This study aims to translate and adapt the Johns Hopkins Dementia Care Needs Assessment (JHDCNA 2.0), a tool design to identify the dementia-related needs of people with dementia and their caregivers, to Brazilian Portuguese, and to verify psychometric properties., Method: JHDCNA 2.0 underwent a translation, back-translation, and cultural adaptation. Preliminary psychometric testing of the Brazilian version (JHDCNA-Br 2.0) included pilot testing and experts' assessment, analyses of reliability, evidence based on test content and relations to other variables. We conducted 140 in-home interviews to assess several sociodemographic and health aspects and to be able to complete the JHDCNA-Br 2.0., Results: The JHDCNA-Br 2.0 is reliable and has evidence based on test content and on relations to other variables for people living with dementia and caregivers. Preliminary results suggest high prevalence of unmet needs., Conclusion: JHDCNA-Br 2.0 is a reliable and valid tool. The availability of this tool brings new opportunities to the study of dementia care, taking into consideration cultural aspects and may help inform future approaches to dementia care delivery to support persons and families affected by these conditions.

We conducted two studies to evaluate the construct validity, short term test-retest reliability, and sensitivity to mental fatigue of the Stroop task when used with older adults. In Study 1, 40 participants visited our lab on two separate days. On the first visit, they took five screening scales, and we measured their height and body mass. On the second visit, they completed the Stroop task twice with a 30-minute interval between assessments. In Study 2, 15 different participants took a 30-minute Flanker/Reverse Flanker task during the interval between the two administrations of the Stroop tasks and they gave subjective ratings of their mental fatigue on the Visual Analogue Scale (VAS) prior to taking either of the Stroop tasks. In Study 1, participants showed a ceiling effect on the Stroop accuracy measure, there was strong concurrent validity for the Stroop with significant score differences between the Stroop's congruent and incongruent conditions ( p < .001), and there was excellent response time reliability (ICC = 0.926) on day two when participants took the Stroop twice within a 30-minute inter-test interval. However, there were significant test-retest performance differences with respect to cognitive inhibition ( p < .001). In Study 2, mental fatigue from the Flanker/Reverse Flanker test resulted in a significantly worse second Stroop performance ( p = .045). We concluded that the Stroop task demonstrated strong concurrent validity and response time reliability among older adults, but it showed sensitivity to mental fatigue, and repeated administrations within the short 30-minute test-retest interval revealed that the most important Stroop measure (cognitive inhibition) was unreliable. We discuss the implications of these findings., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The prevalence of cognitive impairment no dementia (CIND) and dementia appears to be higher in low- and middle-income countries (LMICs) compared to high-income economies. Yet few nationally representative studies from Latin American LMICs have investigated life-course socioeconomic factors associated with the susceptibility to these two cognitive conditions. Hence, the present study aimed to examine the associations of early- (education and food insecurity), mid- (employment stability), and late-life (personal income and household per capita income) socioeconomic determinants of CIND and dementia among older adults from Brazil, while simultaneously exploring whether sex plays an effect-modifier role on these associations., Methods: This population-based study comprised a nationally representative sample of older adults (N = 5,249) aged 60 years and over from the Brazilian Longitudinal Study of Aging (ELSI-Brazil). We fitted multinomial regressions and estimated odds ratios with the respective 95% confidence intervals (CIs)., Results: In multivariate analyses, participants with more years of early-life education (0.89, 95% CI [0.81, 0.97]) and mid-life employment stability (0.97, 95% CI [0.96, 0.99]) and higher late-life household per capita income (0.70, 95% CI [0.51, 0.95) were less likely to have dementia. Regarding CIND, more years of mid-life employment stability (0.97, 95% CI [0.96, 0.98]) was the only determinant to confer protection. Notably, secondary sex-based analyses showed the higher the early-life educational attainment, the lower the odds of dementia in women (0.81, 95% CI [0.75, 0.87]) but not in men (1.00, 95% CI [0.86, 1.16])., Conclusions: These findings may have implications for population health and health policy by advancing our understanding of socioeconomic determinants of CIND and dementia, especially in Latin America., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

An 8-month-old intact male domestic shorthair cat was referred to the Emergency Service of the Veterinary Teaching Hospital (VTH) of the Department of Veterinary Science of the University of Parma (Italy) from the Parma municipal multi-cat shelter, during the winter season (January 2023), for lethargy, anorexia, hypothermia, and hypoglycemia. At the VTH, upon cardiologic examination, an increase in heart rate, under normal blood pressure conditions, was detected. Signalment, clinical history, basal metabolic panel (BMP), ultrasound investigations, and cytological findings were all consistent with a diagnosis of feline infectious peritonitis (FIP). FIP was confirmed in the effusive abdominal fluid by a molecular genetic test (real-time PCR for feline coronavirus RNA). The molecular genetic investigation also detected an FCoV S gene single-nucleotide mutation: biotype M1058L. At necropsy, an effusive collection was recorded in the abdomen, thoracic cavity, and pericardium sac. White parenchymal nodules, of about 1 mm diameter, were found on the surface and deep in the lungs, liver, kidneys, and heart. Histopathology revealed the typical FIP pyogranulomatous vasculitis and IHC confirmed the presence of the FIP virus (FIPV) antigen. The most relevant histopathological finding was the myocarditis/myocardial necrosis associated with the presence of the S gene-mutated FCoV (M1058L biotype). This is the first case of myocarditis in a cat positive for the FCoV/FIP M1058L biotype. Further studies are necessary to support the mutated FCoV M1058L biotype, as an uncommon, but possible, causative pathogen of myocarditis in FCoV/FIP-positive cats. Studies including several FCoV/FIP M1058L-positive cases could allow us to make a correlation with heart gross pathology, histopathology, and immunolocalization of the FCoV/FIP M1058L biotype in the myocardium. The investigation will potentially allow us to determine the effective tropism of the FCoV/FIP M1058L biotype for myocardiocytes or whether myocardiocyte lesions are evident in the presence of concomitant causes related to the patient, its poor condition, or external environmental distress such as cold season, and whether the aforementioned concomitant events are correlated.

Job insecurity is now one of the major stressors affecting well-being at work. In academia, researchers appear to be in the most precarious position. To explore the relationship between job insecurity and well-being at work, we analyzed a sample of research fellows belonging to STEM disciplines in Italy. Using a latent profile approach, we identified three "hidden" subgroups: "Safe & Sound"; "Safe not so Sound" and "Neither Safe or Sound." Compared to previous studies, our results show that even within a population of STEM researchers that tends to have good levels of employability and mobility, there are subgroups of people characterized by greater job insecurity and low work commitment, who suffer from emotional exhaustion and cynicism at work level, i.e., more exposed to the risk of burnout., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bacci, Viotti, Bertola, Converso and Loera.)

Background: Subjective memory complaints (SMCs) are a possible prodrome of cognitive decline but are understudied in low- and middle-income countries (LMIC). We aimed to estimate the prevalence of SMCs in a large, nationally representative sample of older adults from Brazil and to identify sociodemographic and health-related factors that are associated with SMCs independently of objective memory., Methods: Baseline data (n = 7831) from the ELSI-Brazil study, a national representative sample of adults aged 50 and over. They were asked to rate their memory and then divided into two groups - having or not having SMCs. Logistic regression models were used to estimate the association of demographic characteristics, health related factors, objective memory performance and disability in basic (b-ADL), instrumental (i-ADL), and advanced (a-ADL) activities of daily living associated with SMCs. Whether sex was an effect modifier of the association between age and objective memory performance and SMCs was also tested., Results: Of the sample, 42% (95% CI; 39.9-43.9) had SMCs, and it was higher among women (46.9%) than men (35.9%). SMC prevalence decreased with age among women and increased among men, and for both it decreased with better cognitive performance. Fully adjusted logistic regression model showed that older age, higher education, higher b-ADL scores, and better cognitive performance were associated with decreased SMCs, while being female, with higher number of chronic conditions, higher i-ADL scores, worst self-rated health, and an increased number of depressive symptoms were associated with increased SMCs. However, the interaction test (p < 0.001) confirmed that increased age was associated with decreased SMCs only among women, and that better objective memory performance was associated with decreased SMCs only among men., Conclusions: SMCs are common in the Brazilian older population and are associated with health and sociodemographic factors, with different patterns between men and women. There is a need for future studies looking at the cognitive trajectory and dementia risk in older adults with subjective cognitive complaints., (© 2023 John Wiley & Sons Ltd.)

Objectives: Rural residents are exposed to many risk factors for poor diet quality, such as low socioeconomic status and food insecurity. However, the differences between urban and rural residents regarding the association of fruit and vegetable consumption with cognitive performance have not been explored. The aim of this study was to investigate the association of fruit and vegetable consumption with cognitive performance in urban and rural areas in a nationally representative sample of Brazilian older adults., Methods: The sample included 9,412 adults aged 50 years or older from the Brazilian Longitudinal Study of Aging (Estudo Longitudinal da Saúde dos Idosos Brasileiros [ELSI]). The association between consumption of fruits and vegetables and cognitive performance was evaluated using linear regression., Results: In 8,158 participants (mean age 61.6 ± 9.3 years, 54% women, 44% White, and 15% from rural areas), the mean frequency of fruit and vegetable consumption was 2.0 ± 1.3 times a day. Higher intake of fruits and vegetables was associated with better memory (ß = 0.031, 95%CI 0.014-0.049), verbal fluency (ß = 0.030, 95%CI 0.004-0.056), and global cognition (ß = 0.035, 95%CI 0.015-0.055) performance in urban, but not rural residents (p for interaction = 0.036)., Conclusions: Higher frequency of fruit and vegetable intake was associated with better cognitive performance in urban, but not in rural areas in Brazil., Competing Interests: The authors report no conflicts of interest.

Education is protective against cognitive impairment. We used nationally representative data from Mexico and Brazil to assess the association between education and cognitive function. The sample included adults ≥ 50 years from the Brazilian Longitudinal Study of Aging (ELSI) and the Mexican Health and Aging Study (MHAS). Participants were classified as cognitively impaired or not impaired. We used logistic regression models to estimate the association between education and cognitive function. Education level was higher in MHAS than in ELSI. Participants with at least 1 year of education were less likely to have cognitive impairment than those with no formal education in both cohorts. Men in ELSI had higher odds for cognitive impairment compared to men in MHAS. In both cohorts, higher educational level was associated with lower odds of cognitive impairment compared to no formal education. Sex was an effect modifier in MHAS but not in ELSI., Highlights: Cognitive test batteries were harmonized using a regression-based approach.Even very low levels of education were associated with reduced odds of cognitive impairment compared to no formal education.Brazilians were more likely to have cognitive impairment than Mexicans given the same education level.The differences in the association of education with cognition between Brazil and Mexico were only observed among men., Competing Interests: The authors report no conflicts of interest. Author disclosures are available in the supporting information., (© 2023 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: The Brazilian population in the United States (U.S.), a Latinx subgroup, is rapidly growing and aging but remains underrepresented in U.S. health research. In addition to group-specific genetic and environmental risks, Brazilian immigrants and their offspring in the U.S. likely have cumulative risks for health inequities.It is estimated that 71% of Brazilian immigrants in the U.S. are undocumented, which may limit healthcare access/utilization. Furthermore, mental health is reported as a health priority by Brazilian immigrants in the U.S., and there is a lack of research on Alzheimer's disease and related dementia (AD/ADRD) in this population., Methods: We reviewed the scientific literature using traditional (e.g., PubMed) sources and databases generated by U.S. and Brazilian governments, as well as international organizations, and press articles., Results: This perspective review lists recommendations for researchers, health providers, and policymakers to promote greater inclusion of U.S. Brazilian populations in health research and care. The review identifies research areas in need of attention to address health inequities and promote mental/brain health in Brazilian immigrants and their offspring living in the U.S. These research areas are: 1) epidemiological studies to map the prevalence and incidence of mental/brain health conditions; 2) research on aging and AD/ADRD risk factors among Brazilian populations in the U.S.; and 3) the need for greater representation of U.S-residing Brazilian population in other relevant research areas involving genetics, neuropathology, and clinical trials., Conclusions: The recommendation and research efforts proposed should help to pave the way for the development of community-engagement research and to promote mental/brain health education, improvement of mental/brain health and AD/ADRD services, and the development of culturally-informed intervention to the U.S.-residing Brazilian communities., Highlights: The Brazilian population in the United States is growing but is underrepresented in U.S. health research.Approximately 71% of Brazilian immigrants in the United States are undocumented, with an increased risk for health inequities.Mental health is reported as a central health priority by Brazilian immigrants in the United States.There is a lack of research on Alzheimer's disease and other dementias (ADRD) in Brazilian immigrants in the United States.Epidemiological research is needed to map the prevalence/incidence of mental health conditions and ADRD risk factors among Brazilian immigrants in the United States., Competing Interests: The authors have no competing interests to declare., (© 2023 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

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 (β = -0.013, 95% CI = -0.023;-0.003), female sex (β = -0.230, 95% CI = -0.413;-0.047), previous dementia diagnosis or substantial memory complaints (β = -0.606, 95% CI = -0.877;-0.335), frailty before hospitalization (β = -0.191, 95% CI = -0.264;-0.119), higher platelet count (β = -0.101, 95% CI = -0.185;-0.018), and delirium (β = -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., (© 2023 the Alzheimer's Association.)

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., (© 2023 the Alzheimer's Association.)

Background: The association between social isolation and cognitive performance has been less investigated in low-to-middle-income countries (LMIC) and the presence of depression as a moderator on this association has not been examined. The authors examined the associations of social isolation and perceived loneliness with cognitive performance in the Brazilian Longitudinal Study of Aging., Methods: In this cross-sectional analysis, social isolation was evaluated by a composite score including marital status, social contact, and social support. The dependent variable was global cognitive performance, which considered memory, verbal fluency, and temporal orientation tests. Linear and logistic regressions were adjusted for sociodemographic and clinical variables. The authors added interaction terms of depressive symptoms with social isolation and loneliness to examine whether depression, measured through the Center for Epidemiologic Studies-Depression Scale, modified these associations., Results: Among 6,986 participants (mean age = 62.1 ± 9.2 years), higher levels of social connections were associated with better global cognitive performance (B = 0.02, 95%CI: 0.02; 0.04). Perceived loneliness was associated with worse cognition (B = -0.26, 95%CI = -0.34; -0.18). Interactions of depressive symptoms with social connections scores were found on memory z-score and with loneliness on global and memory z-scores, suggesting a weaker association between social isolation or loneliness and cognition among those with depressive symptoms., Conclusion: In a large sample from an LMIC, social isolation and loneliness were associated with worse cognitive performance. Surprisingly, depressive symptoms decrease the strength of these associations. Future longitudinal studies are important to assess the direction of the association between social isolation and cognitive performance., (Copyright © 2023. Published by Elsevier Inc.)

Several studies evaluating Ki67 in canine cutaneous mast cell tumors (cMCTs) have reported its prognostic value when tumors of all histological grades are included. This study aims to evaluate whether the Ki67 index has a predictive value in a homogeneous cohort of G2/LG cMCTs with HN2 lymph nodes (LNs) and to describe the clinical outcome. The second goal was to explore the correlation between the Ki67 index and MC. The medical databases of three institutions were retrospectively searched for dogs undergoing surgical treatment for cMCT and LN extirpation, with a histological diagnosis of G2/LG with HN2 LNs. Information about histological margins, MC, Ki67 index, local recurrence, nodal relapse, distant metastasis, de novo cMCT occurrence and date and cause of death were included. A total of 39 cases were identified. None of these developed local and nodal relapse or metastatic distant disease. Median MC was 1 (0-2). Median Ki67 index was 3.5 (0.7-14.3). Ki67 and MC were not significantly correlated. At the end of the study, 32 (82%) dogs were alive, 7 (18%) dogs were dead from unrelated causes and 4 (10.2%) dogs were lost to follow-up. The median ST was not reached, and the mean was 893 days (104-2241 days). Considering the strict inclusion criteria, dogs affected by G2/LG with HN2 LNs treated with surgery alone may have a good oncologic outcome; the Ki67 index does not have prognostic impact.

Background: Malignant Pleural Mesothelioma (MPM) is an aggressive cancer of the mesothelial lining associated with exposure to airborne non-degradable asbestos fibers. Its poor response to currently available treatments prompted us to explore the biological mechanisms involved in its progression. MPM is characterized by chronic non-resolving inflammation; in this study we investigated which inflammatory mediators are mostly expressed in biological tumor samples from MPM patients, with a focus on inflammatory cytokines, chemokines and matrix components., Methods: Expression and quantification of Osteopontin (OPN) was detected in tumor and plasma samples of MPM patients by mRNA, immunohistochemistry and ELISA. The functional role of OPN was investigated in mouse MPM cell lines in vivo using an orthotopic syngeneic mouse model., Results: In patients with MPM, the protein OPN was significantly more expressed in tumors than in normal pleural tissues and predominantly produced by mesothelioma cells; plasma levels were elevated in patients and associated with poor prognosis. However, modulation of OPN levels was not significantly different in a series of 18 MPM patients receiving immunotherapy with durvalumab alone or with pembrolizumab in combination with chemotherapy, some of whom achieved a partial clinical response. Two established murine mesothelioma cell lines: AB1 and AB22 of sarcomatoid and epithelioid histology, respectively, spontaneously produced high levels of OPN. Silencing of the OPN gene ( Spp1 ) dramatically inhibited tumor growth in vivo in an orthotopic model, indicating that OPN has an important promoting role in the proliferation of MPM cells. Treatment of mice with anti-CD44 mAb, blocking a major OPN receptor, significantly reduced tumor growth in vivo ., Conclusion: These results demonstrate that OPN is an endogenous growth factor for mesothelial cells and inhibition of its signaling may be helpful to restrain tumor progression in vivo . These findings have translational potential to improve the therapeutic response of human MPM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor CP declared a past co-authorship with the author ME., (Copyright © 2023 Digifico, Erreni, Mannarino, Marchini, Ummarino, Anfray, Bertola, Recordati, Pistillo, Roncalli, Bossi, Zucali, D’Incalci, Belgiovine and Allavena.)

Background: Approximately 77% of older adults with dementia in Brazil have not been diagnosed, indicating a major public health issue. Previous epidemiological dementia studies in Brazil were based on data from 1 geopolitical region., Methods: We aimed to estimate the general and subgroup-specific (age, education, and sex) prevalence of dementia and cognitive impairment no dementia (CIND) classification using data from 5 249 participants aged 60 years and older from the ELSI-Brazil, a large nationally representative sample. Participants were classified as having normal cognitive function, CIND, or dementia based on a combination of the individual's cognitive and functional status., Results: We found a general prevalence of 5.8% (95% CI = 4.7-7.2) for dementia and 8.1% (95% CI = 6.8-9.5) for CIND. Dementia prevalence ranged from 3.2% (60-64 years old) to 42.8% (≥90 years old) by age, and from 2.1% (college level or higher) to 16.5% (illiterates) by education. Females had a higher dementia prevalence (6.8%) than males (4.6%). CIND prevalence was similar across age, sex, and education., Conclusions: The estimated dementia prevalence is lower than that in previous Brazilian epidemiological studies, but is in line with other Latin American studies. Only 1.2% of the ELSI-Brazil participants reported having a previous diagnosis of dementia, revealing that underdiagnosis is rampant and a common reality. Based on our results and national statistics projections, we estimate that in 2019, there were 1 757 480 people aged 60 years and older living with dementia in Brazil and, at least, another 2 271 314 having to deal with some form of cognitive impairment., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Gastrointestinal graft-versus-host disease (GvHD) is a major cause of mortality and morbidity following allogeneic bone marrow transplantation (allo-BMT). Chemerin is a chemotactic protein that recruits leukocytes to inflamed tissues by interacting with ChemR23/CMKLR1, a chemotactic receptor expressed by leukocytes, including macrophages. During acute GvHD, chemerin plasma levels were strongly increased in allo-BM-transplanted mice. The role of the chemerin/CMKLR1 axis in GvHD was investigated using Cmklr1-KO mice. WT mice transplanted with an allogeneic graft from Cmklr1-KO donors (t-KO) had worse survival and more severe GvHD. Histological analysis demonstrated that the gastrointestinal tract was the organ mostly affected by GvHD in t-KO mice. The severe colitis of t-KO mice was characterized by massive neutrophil infiltration and tissue damage associated with bacterial translocation and exacerbated inflammation. Similarly, Cmklr1-KO recipient mice showed increased intestinal pathology in both allogeneic transplant and dextran sulfate sodium-induced colitis. Notably, the adoptive transfer of WT monocytes into t-KO mice mitigated GvHD manifestations by decreasing gut inflammation and T cell activation. In patients, higher chemerin serum levels were predictive of GvHD development. Overall, these results suggest that CMKLR1/chemerin may be a protective pathway for the control of intestinal inflammation and tissue damage in GvHD.

The systematic assessment of cognitive performance of older people without cognitive complaints is controversial and unfeasible. Identifying individuals at higher risk of cognitive impairment could optimize resource allocation. We aimed to develop and test machine learning models to predict cognitive impairment using variables obtainable in primary care settings. In this cross-sectional study, we included 8,291 participants of the baseline assessment of the ELSA-Brasil study, who were aged between 50 and 74 years and were free of dementia. Cognitive performance was assessed with a neuropsychological battery and cognitive impairment was defined as global cognitive z-score below 2 standard deviations. Variables used as input to the prediction models included demographics, social determinants, clinical conditions, family history, lifestyle, and laboratory tests. We developed machine learning models using logistic regression, neural networks, and gradient boosted trees. Participants' mean age was 58.3±6.2 years, 55% were female. Cognitive impairment was present in 328 individuals (4%). Machine learning algorithms presented fair to good discrimination (areas under the ROC curve between 0.801 and 0.873). Extreme Gradient Boosting presented the highest discrimination, high specificity (97%), and negative predictive value (97%). Seventy-six percent of the individuals with cognitive impairment were included among the highest ranked individuals by this algorithm. In conclusion, we developed and tested a machine learning model to predict cognitive impairment based on primary care data that presented good discrimination and high specificity. These characteristics could support the detection of patients who would not benefit from cognitive assessment, facilitating the allocation of human and economic resources.

Mucosal vaccination is regarded as a promising alternative to classical, intramuscular vaccine delivery. However, only a limited number of vaccines have been licensed for mucosal administration in humans. Here we propose Leishmania tarentolae, a protozoan parasite, as a potential antigen vehicle for mucosal vaccination, for administration via the rectal or oral routes. To test this hypothesis, we exploited L. tarentolae for the production and delivery of SARS-CoV-2 antigens. Two antigens were assayed in BALB/c mice: Lt-spike, a L. tarentolae clone engineered for the surface expression of the SARS-CoV-2 spike protein; RBD-SD1, a purified portion of the spike protein, produced by another engineered clone of the protozoon. Immune response parameters were then determined at different time points. Both antigens, administered either separately or in combination (Lt-spike + RBD-SD1, hereafter LeCoVax-2), determined significant IgG seroconversion and production of neutralizing antibodies after subcutaneous administration, but only in the presence of adjuvants. After rectal administration, the purified RBD-SD1 antigen did not induce any detectable immune response, in comparison with the intense response observed after administration of LeCoVax-2 or Lt-spike alone. In rectal administration, LeCoVax-2 was also effective when administered without adjuvant. Our results show that L. tarentolae is an efficient and safe scaffold for production and delivery of viral antigens, to be used as vaccines. In addition, rectal vaccination experiments prove that L. tarentolae is suitable as a vaccine vehicle and adjuvant for enteral vaccination. Finally, the combined preparation LeCoVax-2 can be considered as a promising candidate vaccine against SARS-CoV-2, worthy of further investigation., Competing Interests: Declaration of Competing Interest The candidate vaccine Lt-spike and its potential application have been described in the PCT/IB2022/051585 (23 February 2022). The antigen Lt-RBD and its potential application have been described in the patent application no. IT 02021000004160 (23 February 2021). A.M., F.D., M.M., and I.R. are employed by VisMederi Srl; M.L. is employed by VisMederi Research Srl; E.M. is the President and Founder of VisMederi Group. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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: β $\beta \;$ = -0.99, 95% confidence interval [CI] = -1.85; -0.14, P = .02; ≥5 years: β $\beta \;$ = -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., (© 2021 the Alzheimer's Association.)

A 5-year-old female Springer Spaniel dog was submitted for necropsy after sudden death following vaccination against Leptospira spp. Gross examination revealed a diffuse dark red discolouration of skeletal musculature, severe diffuse congestion of all the abdominal organs and a contracted spleen. Severe dilation and reduction in wall width was seen in the right ventricle and histological examination revealed multifocal replacement of the right ventricular myocardium by a large amount of fibrofatty tissue. Pathological changes were consistent with post-vaccinal anaphylactic shock in a dog with arrhythmogenic right ventricular cardiomyopathy (ARVC), a rare condition typical of Boxer dogs but not previously reported in Springer Spaniels. Canine vaccine-associated adverse events are discussed and ARVC is compared with the corresponding human cardiac condition., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: While efforts have been made to validate intrinsic capacity (IC) as a multidimensional indicator of healthy aging in high-income countries, we still need evidence from lower-income countries. We examined associations of IC with wide ranges of activities of daily living in a nationally representative sample of Brazilians aged≥50 years., Methods: This cross-sectional analysis included 7175 participants from the Brazilian Longitudinal Study of Aging. IC domains (cognitive, psychological, sensory, locomotor, and vitality) were determined using self-reported and physical performance measures. IC was operationalized through factorial analysis. We investigated associations of IC and its domains with functional ability in basic, instrumental, and advanced activities of daily living (ADL, IADL, and AADL) using logistic regressions adjusted for sociodemographic, clinical, and modifiable risk factors., Findings: The IC bi-factorial model revealed satisfactory goodness-of-fit. Preserved ability in ADL and IADL, respectively, ranged from 69% and 29% to 89% and 74% across IC quartiles. In adjusted analyses, every standard deviation increment in IC composite score was associated with almost twice the odds of preserved ADL (OR=1·72; 95%CI=1·54-1·93), preserved IADL (OR=1·95; 95%CI=1·77-2·16), and high performance in AADL (OR=1·79; 95%CI=1·59-2·00). Similar results were reported using the IC domains as predictors. Although age, race/ethnicity, and education did not modify associations of IC with functional ability, we found sex differences with stronger relationships of IC with preserved ADL or IADL in females., Interpretation: Our results support IC validity and reliability to measure healthy aging in diverse socioeconomic and cultural settings. Incorporating IC in routine practices can promote holistic and person-centered care approaches in aging societies., Funding: The Brazilian Ministry of Health and Ministry of Science, Technology, Innovation, and Communication., Competing Interests: The authors have no competing interests., (© 2022 The Author(s).)

Background: Previous phylogeographic studies of the lion (Panthera leo) have improved our insight into the distribution of genetic variation, as well as a revised taxonomy which now recognizes a northern (Panthera leo leo) and a southern (Panthera leo melanochaita) subspecies. However, existing whole range phylogeographic studies on lions either consist of very limited numbers of samples, or are focused on mitochondrial DNA and/or a limited set of microsatellites. The geographic extent of genetic lineages and their phylogenetic relationships remain uncertain, clouded by massive sampling gaps, sex-biased dispersal and incomplete lineage sorting., Results: In this study we present results of low depth whole genome sequencing and subsequent variant calling in ten lions sampled throughout the geographic range, resulting in the discovery of >150,000 Single Nucleotide Polymorphisms (SNPs). Phylogenetic analyses revealed the same basal split between northern and southern populations, as well as four population clusters on a more local scale. Further, we designed a SNP panel, including 125 autosomal and 14 mitochondrial SNPs, which was tested on >200 lions from across their range. Results allow us to assign individuals to one of these four major clades (West & Central Africa, India, East Africa, or Southern Africa) and delineate these clades in more detail., Conclusions: The results presented here, particularly the validated SNP panel, have important applications, not only for studying populations on a local geographic scale, but also for tracing samples of unknown origin for forensic purposes, and for guiding conservation management of ex situ populations. Thus, these genomic resources not only contribute to our understanding of the evolutionary history of the lion, but may also play a crucial role in conservation efforts aimed at protecting the species in its full diversity., (© 2022. The Author(s).)

Repeated cognitive assessment in longitudinal studies favors the occurrence of retest effects, usually increasing the scores obtained at the follow-up assessments when compared to baseline. Therefore, retest effects can compromise the evaluation of cognitive decline in older adults., Objectives: We aimed to verify the occurrence of the retest effect and the impact of sociodemographic characteristics on the follow-up scores in a sample of 5,592 participants with a diverse sociodemographic profile, who were assessed twice during 4 years of follow-up., Methods: We tested two possible approaches to correct the retest effect and calculated the Reliable Change Index., Results: We observed increased scores at the follow-up assessment after 4 years, but the results indicate a modest occurrence of retest effects. The regression difference correction successfully generated follow-up corrected scores, while the mean difference did not provide effective corrections. Sociodemographic characteristics had a minor impact on the retest., Conclusions: We recommend the regression difference correction for retest effects. The absence of this methodological approach might lead to biased results using longitudinal cognitive scores., Competing Interests: Disclosure: The authors report no conflicts of interest.

Background: As global populations age, cross-national comparisons of cognitive health and dementia risk are increasingly valuable. It remains unclear, however, whether country-level differences in cognitive function are attributable to population differences or bias due to incommensurate measurement. To demonstrate an effective method for cross-national comparison studies, we aimed to statistically harmonize measures of episodic memory and language function across two population-based cohorts of older adults in the United States (HRS HCAP) and India (LASI-DAD)., Methods: Data for 3,496 HRS HCAP (≥65 years) and 3,152 LASI-DAD (≥60 years) participants were statistically harmonized for episodic memory and language performance using confirmatory factor analysis (CFA) methods. Episodic memory and language factor variables were investigated for differential item functioning (DIF) and precision., Results: CFA models estimating episodic memory and language domains based on a priori adjudication of comparable items fit the data well. DIF analyses revealed that four out of ten episodic memory items and five out of twelve language items measured the underlying construct comparably across samples. DIF-modified episodic memory and language factor scores showed comparable patterns of precision across the range of the latent trait for each sample., Conclusions: Harmonization of cognitive measures will facilitate future investigation of cross-national differences in cognitive performance and differential effects of risk factors, policies, and treatments, reducing study-level measurement and administrative influences. As international aging studies become more widely available, advanced statistical methods such as those described in this study will become increasingly central to making universal generalizations and drawing valid conclusions about cognitive aging of the global population., Competing Interests: The authors have declared that no competing interests exist.

Background and Objectives: To investigate sociodemographic and medical predictors of incident mild cognitive impairment (MCI) and subsequent course of MCI at follow-up, including sustained MCI diagnosis, classification as cognitively normal, and progression to dementia., Methods: Within a community-based cohort, diagnoses of MCI were made with a published algorithm. Diagnosis of dementia was based on clinical consensus. Cox regressions estimated hazard ratios of incident MCI associated with several predictors. Modified Poisson regressions estimated relative risks associated with predictors of diagnostic status at follow-up after incidence., Results: Among 2,903 cognitively normal participants at baseline, 752 developed MCI over an average of 6.3 (SD 4.5) years (incidence rate 56 per 1,000 person-years). Presence of APOE ε4 and higher medical burden increased risk of incident MCI, while more years of education, more leisure activities, and higher income decreased this risk. Of the incident MCI cases, after an average of 2.4 years of follow-up, 12.9% progressed to dementia, 9.6% declined in functioning and did not meet the algorithmic criteria for MCI but did not meet the clinical criteria for dementia, 29.6% continued to meet MCI criteria, and 47.9% no longer met MCI criteria. Multidomain MCI, presence of APOE ε4 , depressive symptoms, and antidepressant use increased the risk of progression to dementia., Discussion: This community-based study showed that almost half of the individuals with incident MCI diagnoses were classified as cognitively normal at follow-up. Predictors of incident MCI demonstrably differed from those of subsequent MCI course; these findings can refine expectations for cognitive and functional course of those presenting with MCI., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background and Purpose: Early life socioeconomic status (SES) may impact cognitive performance later in life. We investigated the effect on cognitive performance of early life SES, education, and late life SES in the Brazilian Longitudinal Study of Adult Health., Methods: Path analysis was used to decompose associations between SES measures across the lifespan and cognition. The model included direct paths to cognition from early life SES, education, and late life SES, and indirect paths from early life passing through education and late life SES. We investigated whether the effects of early life SES are similar across middle-aged and older adults., Results: In 13,395 adults, the mean age was 51.5 (8.9) years, 54% were female, 53% were white, and 56% had at least college education. The direct path from early life SES remained significant in the presence of mediation paths through education, late life SES, or both, contributing to cognitive performance in both middle-aged and older adults. The indirect and total effect of early life SES was smaller for middle-aged compared to older adults. Early life SES continues to impact cognitive performance later in life independently of educational attainment and late life SES. The higher percent of mediation through education suggests that education may improve later life cognition even in the presence of low early life SES., Conclusions: Our results highlight the importance of public health initiatives to improve early life SES and education to foster cognitive aging in low- and middle-income countries., (© 2021 European Academy of Neurology.)

Glaucoma, cataracts, and cognitive decline are most common in older ages. Although cross-sectional studies showed that these disorders are associated, follow-up studies are lacking. To investigate this issue, baseline and follow-up data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) were employed. We evaluated participants ≥ 55 years-old at follow-up without diagnosis of dementia, stroke, and other eye conditions except for glaucoma and cataracts. Cognition was evaluated using delayed word recall, verbal fluency, and trail making (version B) tests. Regression models were employed to investigate associations between glaucoma and cognition, adjusted by several confounders. Out of 3,867 participants, 379 and 118 presented cataracts and glaucoma, respectively. Only glaucoma was apredictor of lower verbal fluency (B = -0.23, 95% CI -035 to -012, p< 0.001). Other associations were not significant (ps>0.57). Our results suggest that glaucoma may be related to declining cognition.

Objectives: Telomeres are structures at the extremity of chromosomes that prevents genomic instability, and its shortening seems to be a hallmark of cellular aging. Past studies have shown contradictory results of telomere length (TL) in major depression, and are a few studies in late-life depression (LLD). This explores the association between TL as a molecular marker of aging and diagnosis of LLD, the severity of depressive symptoms, and cognitive performance in older adults., Methods/design: We included 78 older adults (45 with LLD and 33 nondepressed controls, according to DSM-V criteria), aged 60-90 years. TL was measured in leukocytes by a quantitative polymerase chain reaction, determining the relative ratio (T/S) between the telomere region copy number (T) and a single copy gene (S), using a relative standard curve., Results: TL was significantly shorter in the LLD compared with control participants (p = .039). Comparing groups through the severity of depressive symptoms, we found a negative correlation with the severity of depressive symptoms (Hamilton Depression Rating Scale-21, r = -0.325, p = .004) and medical burden (r = -0.271, p = .038). There was no significant correlation between TL and cognitive performance (Mattis Dementia Rating Scale, r = 0.152, p = .21)., Conclusions: We found that older adults with LLD have shorter telomere than healthy controls, especially those with a more severe depressive episode. Our findings suggest that shorter TL can be a marker of the severity of depressive episodes in older adults and indicate that these individuals may be at higher risk of age-associated adverse outcomes linked to depression., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Objective: Longitudinal measurement invariance analyses are an important way to assess a test's ability to estimate the underlying construct over time, ensuring that cognitive scores across visits represent a similar underlying construct, and that changes in test performance are attributable to individual change in cognitive abilities. We aimed to evaluate longitudinal measurement invariance in a large, social and culturally diverse sample over time., Methods: A total of 5,949 participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) were included, whose cognition was reassessed after four years. Longitudinal measurement invariance analysis was performed by comparing a nested series of multiple-group confirmatory factor analysis models (for memory and executive function factors)., Results: Configural, metric, scalar and strict invariance were tested and supported over time., Conclusion: Cognitive temporal changes in this sample are more likely to be due to normal and/or pathological aging. Testing longitudinal measurement invariance is essential for diverse samples at high risk of dementia, such as in low- and middle-income countries.

Objectives: Normative data should consider sociodemographic diversity for the accurate diagnosis of cognitive impairment. This study aims to provide normative data for a brief neuropsychological battery and present diagnostic criteria for cognitive impairment that could be used in primary care settings., Methods: We selected 9618 Brazilian middle-aged and older adults after detailed exclusion criteria to avoid subtle cognitive impairment. We analyzed age, sex, and education influence on cognitive performance. To verify the evidence of criterion validity, we compared the cognitive performance of subjects with and without a depressive episode. Additionally, we verified the percentage of spurious scores under three different cutoffs., Results: Age and education had the greatest impact on cognition. Normative scores were provided according to age and education groups. Participants with a depressive episode performed poorer than control subjects. The clinical cutoff of at least two scores below the 7th percentile revealed the adequate percentage of spurious and possible clinical performance., Conclusions: The Longitudinal Study on Adult Health (ELSA-Brasil) provided normative data based on a unique selected set of cognitively normal subjects. Normative groups were selected based on age and education, and the battery was sensitive to the presence of a depressive episode. We suggested clinical cutoffs for the tests in this battery that could be used in primary care settings to improve the accurate diagnosis of cognitive impairment.

Background: DNA oxidative damage is a marker of increased oxidative stress activity. Elevated DNA oxidative damage has been associated with major depressive disorder in young adults, but there is no information about DNA oxidative damage in late-life depression. This study aims to evaluate whether older adults with late-life depression (LLD) has increased DNA oxidative damage compared to healthy older adults., Methods: We included 92 participants (57 with LLD [73.2 ± 7.7 years-old] and 35 non-depressed subjects (Controls) [70.5 ± 7.4 years-old]). We analyzed the plasma 8‑hydroxy-2'-deoxyguanosine (8-oxo-dG), a marker of DNA oxidation, using a commercially-available ELISA assay., Results: LLD participants had significantly higher 8-oxo-DG levels compared to controls (P<0.001). 8-oxo-dG levels were significantly correlated with depressive symptoms as assessed by the Hamilton Depression Rating Scale (rho=0.34, p<0.001). The plasma levels of 8-OHdG were not significantly correlated with other clinical, neurocognitive, and demographic variables., Limitations: Our current results are limited by the relatively small sample size, cross-sectional design, and the recruitment of participants in tertiary center for assessment and treatment of LLD., Conclusions: Older adults with LLD have increased DNA oxidative damage. Our findings provide additional evidence for elevated oxidative stress activity in LLD and the possible activation of age-related biological pathways and enhanced biological aging changes in LLD., (Copyright © 2020. Published by Elsevier B.V.)

Background: Subtle thyroid alterations have a controversial role in cognition., Objective: We investigated the longitudinal association of baseline thyroid function, thyrotropin (TSH), and thyroxine (FT4) levels with cognitive performance after 4 years of follow-up in middle-aged and older adults without overt thyroid dysfunction., Methods: We included 4,473 individuals, age≥55 years at the second study wave, without overt thyroid dysfunction at baseline. Individuals were divided according to thyroid function and TSH and FT4 tertiles. Cognition was assessed at baseline and after 4 years of follow-up by the word recall (DWR), semantic verbal fluency (SVF), and trail making (TMT) tests. The longitudinal association of thyroid function and TSH and FT4 tertiles with cognitive performance was investigated using generalized estimating equations adjusted for sociodemographic characteristics, lifestyle, cardiovascular risk factors and depression., Results: There was no longitudinal association of thyroid function and TSH and FT4 baseline levels with performance on the cognitive tests. However, there was a baseline cross-sectional U-shaped association of FT4 tertiles with poorer performance in the SVF (first FT4 tertile: β= -0.11, 95% CI = -0.17; -0.04; third FT4 tertile: β= -0.10, 95% CI = -0.17; -0.04) and of the third FT4 tertile with poorer performance in the DWR (β= -0.09, 95% CI = -0.16; -0.02)., Conclusion: Thyroid function and hormone levels were not associated with cognitive decline during 4 years of follow-up in middle-aged and older adults without overt thyroid dysfunction. Future studies with longer follow-up could clarify the implications of subtle thyroid alterations in cognition.

Background and Purpose: Most evidence for the association between ideal vascular health (IVH) and cognitive performance comes from high income countries. The aim was to investigate this association in the Brazilian Longitudinal Study of Adult Health., Methods: Cognition was assessed using the word list, verbal fluency and trail making tests. The IVH score included ideal metrics for body mass index, smoking, physical activity, diet, blood pressure, fasting glucose and total cholesterol. Poor, intermediate and optimal health were characterized in those presenting 0-2, 3-4, 5-7 ideal metrics, respectively. To determine the association between IVH score and cognitive performance, linear regression models adjusted for age, sex, education, race, alcohol use, depression and thyroid function were used., Results: In 12 271 participants, the mean age was 51.3 ± 8.9 years, 54% were women, 57% White and 53% had poor vascular health. Participants with intermediate (β = 0.064, 95% confidence interval 0.033; 0.096) and optimal health (β = 0.108, 95% confidence interval 0.052; 0.164) had better global cognitive Z-scores. In addition, interactions of IVH score with age, education and race were found, suggesting a better cognitive performance with higher IVH in older adults, Black/Brown participants and those with lower levels of education., Conclusion: Ideal vascular health was associated with better cognitive performance. Older, Black/Brown and low-educated participants had better cognition in the presence of higher IVH scores., (© 2020 European Academy of Neurology.)

Recent evidence suggests that glaucoma and Alzheimer's disease are neurodegenerative diseases sharing common pathophysiological and etiological features, although findings are inconclusive. We sought to investigate whether self-reported glaucoma patients without dementia present poorer cognitive performance, an issue that has been less investigated. We employed cross-sectional data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) and included participants ≥50 years of age without a known diagnosis of dementia and a self-reported glaucoma diagnosis. We excluded those with previous stroke, other eye conditions, and using drugs that could impair cognition. We evaluated cognition using delayed word recall, phonemic verbal fluency, and trail making (version B) tests. We used multinomial linear regression models to investigate associations between self-reported glaucoma with cognition, adjusted by several sociodemographic and clinical variables. Out of 4,331 participants, 139 reported glaucoma. Fully-adjusted models showed that self-reported glaucoma patients presented poorer performance in the verbal fluency test (β=-0.39, 95%CI=-0.64 to -0.14, P=0.002), but not in the other cognitive assessments. Thus, our results support the hypothesis that self-reported glaucoma is associated with poor cognitive performance; however, longitudinal data are necessary to corroborate our findings.

Background: Cognitive deficits in major depressive disorder (MDD) are associated with low quality of life and higher suicide risk. Antidepressant drugs have modest to null effects in improving such deficits. Therefore, we investigated the cognitive effects of transcranial direct current stimulation (tDCS), which is a promising antidepressant non-pharmacological intervention, in MDD., Methods: An exploratory analysis on cognitive performance was conducted in 243 depressed patients from the Escitalopram vs. Electric Current Therapy for Treating Depression Clinical Study (ELECT-TDCS), a sham-controlled study comparing the efficacy of tDCS vs. escitalopram. A neuropsychological battery was applied at baseline and endpoint (10 weeks of treatment) to create composite cognitive scores (processing speed, working memory, and verbal fluency). Linear mixed regression models were used to evaluate changes according to intervention groups, adjusted for confounding variables (age, years of schooling, gender, and benzodiazepine use) and depression improvement., Results: No cognitive deterioration was observed in any group. Patients receiving tDCS presented reduced practice gains compared to placebo in processing speed. In patients receiving escitalopram vs. placebo and in the subgroup of clinical responders (>50% depression improvement from baseline), those receiving tDCS vs. placebo presented increased performance in verbal fluency. No significant differences between tDCS and escitalopram groups were detected., Limitations: Absence of healthy controls., Conclusion: Prefrontal tDCS did not lead to cognitive deficits in depressed patients, although it reduced practice effects in processing speed. tDCS responders presented increased performance in verbal fluency. Further investigation of tDCS cognitive effects in depression is warranted., Competing Interests: Declaration of Competing Interest F.P. has received speaker's honoraria and support with equipment from Mag&More GmbH, Munich, Germany and the neuroCare Group, Munich, Germany as well as from Brainsway Inc., Jerusalem, Israel., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: Neuropsychological tests are often used in aging studies to compare distinct groups regarding diagnosis and prognosis. Because sociodemographic characteristics can influence cognitive scores, measurement of invariance is useful to assess the tests' ability to estimate the underlying constructs equally across groups and thus prevent biased interpretation. This study aims to verify measurement invariance in a large and socioculturally diverse sample., Method: Middle-aged and older adults ( N = 13,395) from the ELSA-Brasil study were evaluated regarding health status and cognition. Mean age was 51.5 ± 8.9 years, 54% were female, 52% were white, and 10% had lower education. Measurement invariance was analyzed using multiple-group confirmatory factor analysis for a two-factor model (memory and executive function). Configural, metric, and scalar invariance were tested across age, sex, race, and education groups., Results: The 2-factor model had a good fit to the entire dataset and for each group. Configural, metric, and scalar invariance confirmed that cognitive measures had the same structure and the items had similar relationships with the latent factors. Strict invariance was not achieved in most group comparison., Conclusions: The 2-factor model was appropriate for estimating cognitive performance in participants without measurement error by age, sex, race, and education. These results suggest that differences in cognitive outcomes are likely to indicate true differences. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Objective: Aging studies regularly assume that years of education are a protective factor for baseline cognition. In developing countries with specific sociocultural issues, this relationship may not work as expected, and an unmet need remains for alternative resilience factors. This study aimed to analyze different moderators for the relationship between aging and general cognition that could reflect better protective factors., Methods: One hundred and fourteen Brazilian older adults, deemed healthy by global cognition, absence of psychiatric symptoms, or neurological history, participated in this cross-sectional study. Moderators for the relationship between age and global cognition included education, intelligence, and occupational factors. Semantic memory was added as a protective factor reflecting culturally acquired conceptual knowledge., Results: As expected, age alone is a predictor of global cognitive scores; surprisingly, however, education, intelligence, and occupation were not moderators of the association. Semantic memory was a significant moderator (p = 0.007), indicating that knowledge acquired during life may be a protective factor., Conclusion: In developing countries, the use of resilience factors based only on years of education may be misleading. Sociocultural issues influence the educational system and achievement and, consequently, affect the use of this simple measure. Resilience-factor studies should consider using crystallized abilities when studying populations with sociocultural particularities.

Objectives: Low educational attainment is a risk factor for more rapid cognitive aging, but there is substantial variability in cognitive trajectories within educational groups. The aim of this study was to determine the factors that confer resilience to memory decline within educational strata., Methods: We selected 2573 initially nondemented White, African American, and Hispanic participants from the longitudinal community-based Washington Heights/Inwood Columbia Aging Project who had at least two visits. We estimated initial memory (intercept) and the rate of memory decline (slope) using up to five occasions of measurement. We classified groups according to the educational attainment groups as low (≤5 years), medium (6-11 years), and high (≥12 years). We used a multiple-group latent growth model to identify the baseline predictors of initial memory performance and rate of memory decline across groups. The model specification considered the influence of demographic, socioeconomic, biomedical, and cognitive variables on the intercept and the slope of memory trajectory., Results: Our results indicated that the three educational groups do not benefit from the same factors. When allowed to differ across groups, the predictors were related to cognitive outcomes in the highly educated group, but we found no unique predictor of cognition for the low educated older adults., Conclusions: These findings highlight that memory-protective factors may differ across older adults with distinct educational backgrounds, and the need to evaluate a broader range of potential resilience factors for older adults with few years of school.

Bengal tigers (Panthera tigris tigris) serve a pivotal role as an apex predator in forest ecosystems. To increase our knowledge on factors impacting the viability and health of this endangered species, we studied the gut microbiota in 32 individual Bengal tigers from three geographically separated areas (Chitwan National Park (CNP), Bardia National Park (BNP) and Suklaphanta Wildlife Reserve (SWR)) in Nepal, using noninvasive genetic sampling methods. Gut microbiota influence the immune system, impact various physiological functions, and modulates metabolic reactions, that ultimately impact the host health, behavior and development. Across the tiger populations in Nepal, we found significant differences in the composition of microbial communities based on their geographic locations. Specifically, we detected significant differences between CNP and the other two protected areas (CNP vs BNP: pseudo t = 1.944, P = 0.006; CNP vs SWR: pseudo t = 1.9942, P = 0.0071), but no differences between BNP and SWR. This mirrors what has been found for tiger gene flow in the same populations, suggesting gut microbiota composition and host gene flow may be linked. Furthermore, predictive metagenome functional content analysis (PICRUSt) revealed a higher functional enrichment and diversity for significant gut microbiota in the Chitwan tiger population and the lowest enrichment and diversity in Suklaphanta. The CNP tiger population contained higher proportions of microbiota that are associated with predicted functions relevant for metabolism of amino acid, lipid, xenobiotics biodegradation, terpenoides and polyketides than the SWR population. We conclude the tiger population structure, gut microbiota profile and associated functional metabolic categories are correlated, with geographically most separated CNP and SWR tiger population having the most distinct and different host genotype and microbiota profiles. Our work dramatically expands the understanding of tiger microbiota in wild populations and provides a valuable case study on how to investigate genetic diversity at different hierarchical levels, including hosts as well as their microbial communities., Competing Interests: The authors have declared that no competing interests exist.

Changes in microRNAs (miRNAs) expression have been described in major depressive disorder in young and middle-aged adults. However, no study has evaluated miRNA expression in older adults with major depression (or late-life depression [LLD]). Our primary aim was to evaluate the expression of miRNAs in subjects with LLD. We first evaluated the miRNA expression using next-generation sequencing (NGS) and then we validated the miRNAs found in NGS in an independent sample of LLD patients, using RT-qPCR. Drosophila melanogaster model was used to evaluate the impact of changes in miRNA expression on behavior. NGS analysis showed that hsa-miR-184 (log 2 foldchange = -4.21, p = 1.2 × 10 -03 ) and hsa-miR-1-3p (log 2 foldchange = -3.45, p = 1.3 × 10 -02 ) were significantly downregulated in LLD compared to the control group. RT-qPCR validated the downregulation of hsa-miR-184 (p < 0.001), but not for the hsa-miR-1-3p. The knockout flies of the ortholog of hsa-miR-184 showed significantly reduced locomotor activity at 21-24 d.p.e (p = 0.04) and worse memory retention at 21-24 d.p.e (24h post-stimulus, p = 0.02) compared to control flies. Our results demonstrated that subjects with LLD have significant downregulation of hsa-miR-184. Moreover, the knockout of hsa-miR-184 in flies lead to depressive-like behaviors, being more pronounce in older flies., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Epidermal growth factor (EGF) and Fibroblast Growth Factor-2 (FGF-2) are growth factors involved neuronal growth and synaptic plasticity. These markers have been implicated in neuropsychiatric disorders, including major depression. However, no particular studies of EGF and FGF-2 have been conducted in older adults with major depressive disorder (MDD). In this study, we aim to investigate the plasma levels of EGF and FGF-2 in elderly with MDD. We included 89 older adults with MDD and 51 older (healthy control, HC) adults. The cognitive performance was evaluated by the Mattis Dementia Rating Scale (MDRS). The EGF and FGF-2 were measured by using multiplex assay for LUMINEX platform. There were also no significant differences between the patient group in terms of plasma levels of EGF and FGF-2 when compared to the HC group. There were not any significant correlations between plasma levels of EGF or FGF2 and MDRS total or individual scores in patient group and HC. There were significant correlations between plasma levels of EGF and FGF2 in both patient group and HC. Further study on plasma levels of EGF and FGF2 should be implemented in larger samples in elderly with MDD., (Copyright © 2018. Published by Elsevier B.V.)

Background: Oxidative stress has been implicated in the pathophysiology of mood disorders in young adults. However, there is few data to support its role in the elderly. The primary aim of this study was to evaluate whether subjects with late-life depression (LLD) presented with changes in oxidative stress response in comparison with the non-depressed control group. We then explored how oxidative stress markers associated with specific features of LLD, in particular cognitive performance and age of onset of major depressive disorder in these individuals., Methods: We included a convenience sample of 124 individuals, 77 with LLD and 47 non-depressed subjects (Controls). We measure the plasma levels of 6 oxidative stress markers: thiobarbituric acid reactive substances (TBARS), protein carbonil content (PCC), free 8-isoprostane, glutathione peroxidase (GPx) activity, glutathione reductase (GR) activity, and glutathione S-transferase (GST) activity., Results: We found that participants with LLD had significantly higher free 8-isoprostane levels (p = 0.003) and lower glutathione peroxidase activity (p = 0.006) compared to controls. Free 8-isoprostane levels were also significantly correlated with worse scores in the initiation/perseverance (r = -0.24, p = 0.01), conceptualization (r = -0.22, p = 0.02) sub-scores, and the total scores (r = -0.21, p = 0.04) on the DRS., Conclusions: Our study provides robust evidence of the imbalance between oxidative stress damage, in particular lipid peroxidation, and anti-oxidative defenses as a mechanism related to LLD, and cognitive impairment in this population. Interventions aiming to reduce oxidative stress damage can have a potential neuroprotective effect for LLD subjects., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Hip fracture is one of the most common health care problems among elderly people. Literature shows that high self-efficacy expectations and positive affect are some of the key issues in functional recovery after hip fracture. The present investigation tested whether self-narration of such life-breaking event influences self-efficacy and depression during the process of rehabilitation. We designed a Self-Narration Journey (SNJ) to be administered during the in-hospital rehabilitation. In Study 1, we investigated the influence of SNJ on depression and perceived self-efficacy. Study 2 aimed to explore the effect of SNJ, depression, and self-efficacy on functional recovery of independence to perform daily activities during the rehabilitation process. The data showed that the Self-Narration Journey proved effective in increasing the perceived self-efficacy and in lowering the level of depression. The present work highlights a significant effect of the SNJ on the functional recovery process., Competing Interests: Competing Interests: The authors have declared that no competing interests exist.

Background: In Italy, the work-related stress and organizational well-being evaluation is subject to specific norms and regulations. The Italian National Anti-Corruption Authority (Autorità Nazionale Anticorruzione - ANAC) has developed a questionnaire to assess the organizational well-being of the employees in Public Administration Institutions., Objectives: The study aims to analyse, according to the Job Demands-Resources Theory, the relationship between some job demands (workload, discrimination) and job resources (supervisors and colleagues support, job autonomy, fairness, career opportunities, membership), and some outcomes (work-related stress, emotional exhaustion, job satisfaction)., Methods: The research involved a public administration and was conducted through a self-report questionnaire (N=414, 60% of the employees). The ANAC questionnaire was integrated with measures from national and international literature on the topic of well-being and stress at work., Results: Multiple regression analyses highlighted the relationship between outcomes, job demands and resources. Work-related stress showed a positive relation with demands (work load β coefficient=0.22; perceived discrimination β=0.14) and a negative one with some resources (supervisors' support β=-0.21 and membership β=-0.11). Emotional exhaustion had a negative relationship with some job resources, specifically career opportunities (β=-0.14), autonomy (β=-0.21) and membership (β=-0.25). Job satisfaction showed a positive relationship with all job resources considered., Conclusions: The study seeks to integrate the assessment of well-being and work-related stress thus highlighting the importance of linking the different outcomes with job demands and resources. The results identify possible practices to promote well-being in the organization.

Objective: A consistent body of research has confirmed that patients with major depressive disorder (MDD) have increased concentrations of pro-inflammatory cytokines, including IL-6, TNF-α, IL-1β, the soluble IL-2 receptor, and C-reactive protein, compared to controls; however, there is limited information on IL-17A in MDD. Moreover, information about IL-17A in older populations, i.e., patients with late-life depression (LLD), is conspicuously missing from the literature. The purpose of this study was to investigate the role of IL-17A in LLD., Methods: A convenience sample of 129 individuals, 74 with LLD and 55 non-depressed controls, were enrolled in this study. The Mann-Whitney U test was used to compare plasma IL-17A levels between LLD and controls subjects, and Spearman's rank order correlation was used to investigate correlation of these levels with clinical, neuropsychological, and cognitive assessments., Results: Plasma IL-17A levels were not statistically different between LLD patients and controls (p = 0.94). Among all subjects (LLD + control), plasma IL-17A did not correlate significantly with depressive symptoms (rho = -0.009, p = 0.92) but a significant correlation was observed with cognitive assessments (rho = 0.22, p = 0.01)., Conclusion: Our findings do not support an association between plasma IL-17A levels and LLD. Nevertheless, IL-17A may be associated with cognitive impairment in LLD patients. If this finding is confirmed in future longitudinal studies, modulation of the T-helper 17 cell (Th17) immune response may be a treatment target for cognitive impairment in this population.