The relationship of neuropsychiatric symptoms with inflammatory markers in the hippocampus and cingulate cortex of bipolar disorder subjects: A post-mortem study.

Increased levels of inflammation markers have been found in the peripheral tissue of individuals with bipolar disorder (BD), especially during mood episodes. Previous studies found distinctive inflammatory profiles across different brain regions, but potential associations with clinical symptoms are still lacking. This study aims to evaluate the association of neuropsychiatric symptoms with inflammatory markers in the hippocampus and cingulate of individuals with BD. Levels of IL-1ß, IL-6, IL-17A, cortisol, and C-reactive protein (CRP) were measured in the hippocampus and anterior cingulate of 14 BD individuals and their non-psychiatric controls. Neuropsychiatric symptoms present in the three months before death were assessed using the Neuropsychiatric Inventory (NPI). In the BD group, greater NPI scores were associated with higher IL-6 in the hippocampus (p = 0.011) and cingulate (p = 0.038) and higher IL-1ß (p = 0.039) in the hippocampus. After adjusting for age, sex and CDR, IL-1ß and IL-6 were still associated with higher NPI in the hippocampus. In correlation analysis considering both BD and their controls, moderate positive associations were found between NPI and IL-6 and cortisol in the hippocampus (p < 0.001 and p = 0.006) and cingulate (p = 0.024 and p = 0.016), IL-1ß (p < 0.001) and IL-17A in the hippocampus (p = 0.002). No difference in inflammatory markers was found according to type of psychotropic medication used. Hence, in individuals with BD, neuropsychiatric symptoms were differently associated with specific inflammatory cytokines and CRP in the hippocampus and cingulate. These results suggest that the neuroinflammatory changes occurring in BD may be more complex than previously expected and could be associated with clinical manifestations.

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.

Leisure-Time Physical Activity May Attenuate the Impact of Diabetes on Cognitive Decline in Middle-Aged and Older Adults: Findings From the ELSA-Brasil Study.

OBJECTIVE: To assess leisure-time physical activity (LTPA) as a modifier of the diabetes/cognitive decline association in middle-aged and older participants in the Estudo Longitudinal de Saude do Adulto (ELSA-Brasil) study. RESEARCH DESIGN AND METHODS: ELSA-Brasil is a cohort of 15,105 participants (age 35-74 years) enrolled between 2008 and 2010. We evaluated global cognitive function, summing the scores of six standardized tests evaluating memory and verbal fluency, including the Trail-Making Test, at baseline and follow-up. Incident cognitive impairment was defined as a global cognitive function score at follow-up lower than -1 SD from baseline mean. Participants reporting ≥150 min/week of moderate to vigorous LTPA at baseline were classified as physically active. We assessed the association of LTPA with global cognition change in those with diabetes in the context of our overall sample through multivariable regression models. RESULTS: Participants' (N = 12,214) mean age at baseline was 51.4 (SD 8.8) years, and 55.5% were women. During a mean follow-up of 8.1 (SD 0.6) years, 9,345 (76.5%) inactive participants and 1,731 (14.1%) participants with diabetes at baseline experienced faster declines in global cognition than those who were active (ß = -0.003, -0.004, and -0.002) and those without diabetes (ß = -0.004, -0.005, and -0.003), respectively. Diabetes increased the risk of cognitive impairment (hazard ratio [HR] 1.71; 95% Cl 1.22, 2.39) in inactive but not in active adults (HR 1.18; 95% CI 0.73, 1.90). Among participants with diabetes, those who were active showed a delay of 2.73 (95% CI 0.94, 4.51) years in the onset of cognitive impairment. CONCLUSIONS: In adults living with diabetes, LTPA attenuated the deleterious association between diabetes and cognitive function.

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.

Association between APOE-ε4 allele and cognitive function is mediated by Alzheimer's disease pathology: a population-based autopsy study in an admixed sample.

BACKGROUND: Apolipoprotein E ε4 allele (APOE-ε4) is the main genetic risk factor for late-onset Alzheimer's disease (AD) and may impact cognitive function also via other neuropathological lesions. However, there is limited evidence available from diverse populations, as APOE associations with dementia seem to differ by race. Therefore, we aimed to evaluate the pathways linking APOE-ε4 to cognitive abilities through AD and non-AD neuropathology in an autopsy study with an admixed sample. METHODS: Neuropathological lesions were evaluated following international criteria using immunohistochemistry. Participants were classified into APOE-ε4 carriers (at least one ε4 allele) and non-carriers. Cognitive abilities were evaluated by the Clinical Dementia Rating Scale sum of boxes. Mediation analyses were conducted to assess the indirect association of APOE-ε4 with cognition through AD-pathology, lacunar infarcts, hyaline arteriosclerosis, cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), and TAR DNA-binding protein 43 (TDP-43). RESULTS: We included 648 participants (mean age 75 ± 12 years old, mean education 4.4 ± 3.7 years, 52% women, 69% White, and 28% APOE-ε4 carriers). The association between APOE-ε4 and cognitive abilities was mediated by neurofibrillary tangles (ß = 0.88, 95% CI = 0.45; 1.38, p < 0.001) and neuritic plaques (ß = 1.36, 95% CI = 0.86; 1.96, p < 0.001). Lacunar infarcts, hyaline arteriosclerosis, CAA, LBD, and TDP-43 were not mediators in the pathway from APOE-ε4 to cognition. CONCLUSION: The association between APOE-ε4 and cognitive abilities was partially mediated by AD-pathology. On the other hand, cerebrovascular lesions and other neurodegenerative diseases did not mediate the association between APOE-ε4 and cognition.

Rural-urban disparities in fruit and vegetable consumption and cognitive performance in Brazil

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 (β = 0.031, 95%CI 0.014-0.049), verbal fluency (β = 0.030, 95%CI 0.004-0.056), and global cognition (β = 0.035, 95%CI 0.015-0.055) performance in urban, but not rural residents (p for interaction = 0.036). Conclusion: Higher frequency of fruit and vegetable intake was associated with better cognitive performance in urban, but not in rural areas in Brazil.

Rural-urban disparities in fruit and vegetable consumption and cognitive performance in Brazil.

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.

Untangle the relationship of muscle mass and bone mineral content on handgrip strength: Results of ELSA-Brasil.

The study aims to investigate the independent association of muscle mass (MM) and bone mineral content (BMC) in the performance of the handgrip strength (HGS) test and whether there is effect modification by sex and age. In 12,491 participants from the ELSA-Brasil we estimated the associations between MM, BMC and HGS using linear regression models. All the analyses were performed for total population, also stratified for sex and age. For total population an interaction term was included between each explanatory variable of interest with sex and age to verify the presence of effect modification. We observed that the higher quintiles of MM and BMC were associated to an increasing in the mean of HGS compared to the first quintile, with greater magnitudes in men compared to women, also adults compared to elderly. When we estimated the independent effect of each exposure of interest, MM showed stronger effect in HGS in women, men and adults then BMC. In conclusion, we observed that higher amounts of MM and BMC are associated with higher HGS, regardless of sociodemographic characteristics, health conditions and lifestyle, with this effect being greater in men and adults.

Untangle the relationship of muscle mass and bone mineral content on handgrip strength: Results of ELSA-Brasil / Desvendando a relação entre massa muscular e conteúdo mineral ósseo na força de preensão palmar: Resultados do ELSA-Brasil

Abstract The study aims to investigate the independent association of muscle mass (MM) and bone mineral content (BMC) in the performance of the handgrip strength (HGS) test and whether there is effect modification by sex and age. In 12,491 participants from the ELSA-Brasil we estimated the associations between MM, BMC and HGS using linear regression models. All the analyses were performed for total population, also stratified for sex and age. For total population an interaction term was included between each explanatory variable of interest with sex and age to verify the presence of effect modification. We observed that the higher quintiles of MM and BMC were associated to an increasing in the mean of HGS compared to the first quintile, with greater magnitudes in men compared to women, also adults compared to elderly. When we estimated the independent effect of each exposure of interest, MM showed stronger effect in HGS in women, men and adults then BMC. In conclusion, we observed that higher amounts of MM and BMC are associated with higher HGS, regardless of sociodemographic characteristics, health conditions and lifestyle, with this effect being greater in men and adults.

Resumo O estudo tem como objetivo investigar a associação independente da massa muscular (MM) e conteúdo mineral ósseo (CMO) na realização do teste de força de preensão manual (FPM) e se há modificação do efeito por sexo e idade. Em 12.491 participantes do ELSA-Brasil estimamos as associações entre MM, CMO e FPM usando modelos de regressão linear. Todas as análises foram realizadas para a população total, também estratificada por sexo e idade. Para a população total foi incluído um termo de interação entre cada variável explicativa de interesse com sexo e idade para verificar a presença de modificação de efeito. Observamos que os maiores quintis de MM e BMC estiveram associados a um aumento na média da FPM em relação ao primeiro quintil, com maiores magnitudes em homens em relação a mulheres, também em adultos em relação a idosos. Quando estimamos o efeito independente de cada exposição de interesse, MM mostrou efeito mais forte na FPM em mulheres, homens e adultos do que BMC. Em conclusão, observamos que maiores quantidades de MM e BMC estão associadas a maior FPM, independentemente das características sociodemográficas, condições de saúde e estilo de vida, sendo esse efeito maior em homens e adultos.

The (in)visible Brazilians: A perspective review on the need for brain health and dementia research with Brazilian immigrants in the United States.

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.

Education and cognitive function among older adults in Brazil and Mexico.

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.

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.

Smoking Intensity Increases Diaphragm Muscle Injury: A Clinicopathologic Study.

BACKGROUND: Studying the effects of smoking intensity is important to evaluate the risk of tobacco use on a range of illnesses, such as as sarcopenia among the elderly. Thus, this study aimed to analyze the effects of pack-years of cigarette smoking on the diaphragm muscle (DIAm) histopathology of postmortem samples. METHODS: Subjects were divided into three groups: never-smoker (n = 46); less than 30 pack-years of smoking (n = 12); and more than 30 pack-years of smoking (n = 30). Diaphragm samples were stained with Picrosirius red and hematoxylin and eosin stain for general structure. RESULTS: Participants with more than 30 pack-years of cigarette smoking had a significant increase in adipocytes, blood vessels and collagen deposit, as well as an increase in histopathological alterations. CONCLUSIONS: Pack-years of smoking was associated with DIAm injury. However, further clinicopathological studies are needed to confirm our findings.

Smoking intensity increases diaphragm muscle injury: a clinicopathologic study

BACKGROUND: Studying the effects of smoking intensity is important to evaluate the risk of tobacco use on a range of illnesses, such as sarcopenia among the elderly. Thus, this study aimed to analyze the effects of pack-years of cigarette smoking on the diaphragm muscle (DIAm) histopathology of postmortem samples. METHODS: Subjects were divided into three groups: never-smoker (n = 46); less than 30 pack-years of smoking (n = 12); and more than 30 pack-years of smoking (n = 30). Diaphragm samples were stained with Picrosirius red and hematoxylin and eosin stain for general structure. RESULTS: Participants with more than 30 pack-years of cigarette smoking had a significant increase in adipocytes, blood vessels and collagen deposit, as well as an increase in histopathological alterations. CONCLUSIONS: Pack-years of smoking was associated with DIAm injury. However, further clinicopathological studies are needed to confirm our findings.

Postmortem Brains from Subjects with Diabetes Mellitus Display Reduced GLUT4 Expression and Soma Area in Hippocampal Neurons: Potential Involvement of Inflammation.

Diabetes mellitus (DM) is an important risk factor for dementia, which is a common neurodegenerative disorder. DM is known to activate inflammation, oxidative stress, and advanced glycation end products (AGEs) generation, all capable of inducing neuronal dysfunctions, thus participating in the neurodegeneration progress. In that process, disturbed neuronal glucose supply plays a key role, which in hippocampal neurons is controlled by the insulin-sensitive glucose transporter type 4 (GLUT4). We investigated the expression of GLUT4, nuclear factor NF-kappa B subunit p65 [NFKB (p65)], carboxymethyllysine and synapsin1 (immunohistochemistry), and soma area in human postmortem hippocampal samples from control, obese, and obese+DM subjects (41 subjects). Moreover, in human SH-SY5Y neurons, tumor necrosis factor (TNF) and glycated albumin (GA) effects were investigated in GLUT4, synapsin-1 (SYN1), tyrosine hydroxylase (TH), synaptophysin (SYP) proteins, and respective genes; NFKB binding activity in the SLC2A4 promoter; effects of increased histone acetylation grade by histone deacetylase 3 (HDAC3) inhibition. Hippocampal neurons (CA4 area) of obese+DM subjects displayed reduced GLUT4 expression and neuronal soma area, associated with increased expression of NFKB (p65). Challenges with TNF and GA decreased the SLC2A4/GLUT4 expression in SH-SY5Y neurons. TNF decreased SYN1, TH, and SYP mRNAs and respective proteins, and increased NFKB binding activity in the SLC2A4 promoter. Inhibition of HDAC3 increased the SLC2A4 expression and the total neuronal content of CRE-binding proteins (CREB/ICER), and also counterbalanced the repressor effect of TNF upon these parameters. This study revealed reduced postmortem human hippocampal GLUT4 content and neuronal soma area accompanied by increased proinflammatory activity in the brains of DM subjects. In isolated human neurons, inflammatory activation by TNF reduced not only the SLC2A4/GLUT4 expression but also the expression of some genes related to neuronal function (SYN1, TH, SYP). These effects may be related to epigenetic regulations (H3Kac and H4Kac status) since they can be counterbalanced by inhibiting HDAC3. These results uncover the improvement in GLUT4 expression and/or the inhibition of HDAC3 as promising therapeutic targets to fight DM-related neurodegeneration.

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 Potential Role of Selection Bias in the Association Between Coronary Atherosclerosis and Cognitive Impairment.

BACKGROUND: Coronary atherosclerosis assessed in vivo was associated with cognitive impairment; however, conflicting findings have been reported in autopsy samples. OBJECTIVE: Our aims were to assess the association between atherosclerotic stenosis in the coronary arteries and cognitive impairment and to investigate the possibility of selection bias in an autopsy study. METHODS: Coronary arteries were collected, and the largest luminal stenosis was measured. Sociodemographic, clinical, and cognitive information were reported by a reliable next-of-kin. The association was tested using logistic and linear regressions adjusted for sociodemographic and clinical variables. We restricted the sample to individuals that were born in 1935 or earlier and stratified the analysis by cause of death to investigate the role of selection bias. RESULTS: In 253 participants (mean age = 78.0±8.5 years old, 48% male), stenosis was not associated with cognitive impairment (OR = 0.85, 95% CI = 0.69; 1.06, p = 0.15). In individuals who were born before 1936 in the absence of cardiovascular disease as the cause of death, greater stenosis was associated with cognitive impairment (OR = 4.02, 95% CI = 1.39; 11.6, p = 0.01). On the other hand, this association was not present among those born in 1935 or earlier who died of cardiovascular diseases (OR = 0.83, 95% CI = 0.60; 1.16, p = 0.28). CONCLUSION: We found that higher coronary stenosis was associated with cognitive impairment only in individuals born in 1935 or earlier and who had not died from cardiovascular diseases. Selection bias may be an important issue when investigating risk factors for chronic degenerative diseases in older individuals using autopsy samples.

Dietary folate intake and its association with longitudinal changes in cognition function.

BACKGROUND & AIMS: Folate (vitamin B9) is an essential co-factor for one-carbon metabolism. Controversial evidence has emerged regarding the association between folate and cognitive performance. The aim of the study was to investigate the association between baseline dietary folate intake and cognitive decline in a population exposed to mandatory fortification during a median follow-up of 8 years. METHODS: Multicenter, prospective cohort study involving 15,105 public servants aged 35-74 years old, both sexes, from The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Baseline dietary intake was assessed by a Food Frequency Questionnaire (FFQ). Six cognitive tests were performed in the three waves to assess memory, executive function and global cognition. Linear mixed-effects models were used to assess the association between dietary folate intake at baseline and changes in cognition over time. RESULTS: Data from 11,276 participants were analyzed. The mean (SD) age was 51.7 (9) years, 50% were women, 63% were overweight/obese, and 56% had graduated from college or more. Overall dietary folate intake was not associated with cognitive decline; neither vitamin B12 intake was a modifier of this association. General dietary supplements and specifically multivitamins use did not affect these findings. Natural food folate group was associated with a slower rate of global cognitive decline (ß (95% CI): 0.001 (0.000; 0.002), P = 0.015). There was no association between fortified food group and cognition scores. CONCLUSION: Overall dietary folate intake was not associated with cognitive function in this Brazilian population. However, folate naturally occurring in food sources may slow global cognitive decline.