Effectiveness of Multimodal Training Compared to a Uni-Modal Walking Intervention on Postural Control, Strength, Gait Speed and Flexibility in Community-Dwelling Older Adults.

Background: Multimodal training may induce positive effects in different physical domains. Compared to unimodal training, multimodal training allows similar effect sizes at lower overall training volumes. Studies are needed to investigate the potential value of multimodal training with systematic training, especially compared to other exercise-based interventions. This study aimed to compare the effects of a multimodal training with an outdoor walking program, on postural control, muscle strength, and flexibility in community-dwelling older adults. Methods: This study is a pragmatic controlled clinical trial. We compared two real community exercise groups: a multimodal group (n = 53) and an outdoor, overground walking group (n = 45). Both groups participated in 32 sessions of training, twice a week, over 16 weeks. Participants were evaluated using the Mini-Balance Evaluation Systems Test (Mini-BESTest), Handgrip, 5-Times Sit-to-Stand Test, 3-meter Gait Speed Test, and Sit and Reach Test. Results: There was an interaction effect between evaluation and group in the Mini- BESTest with difference between pre and post-intervention only in multimodal group. Regarding gait speed, there was an interaction effect between evaluation and group with difference between pre and post-intervention only in the walking group. In the Sit and Reach Test: there was interaction effect between evaluation and group with difference between pre and post-intervention only in the walking group. Conclusion: The multimodal training improved postural control, while an outdoor walking program improved gait speed and flexibility. Both interventions improved muscle strength without between-group differences.

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.

Ten years of a geriatric oncology service at a public university cancer centre in Brazil.

The implementation of a geriatric oncology service is challenging in both high-income and low-and-middle-income countries. The Octavio Frias de Oliveira Institute of Cancer of Sao Paulo (ICESP) is a tertiary healthcare complex of the Clinics Hospital of the University of Sao Paulo Medical School and is considered a model of excellence in oncology in Latin America. The objective of this manuscript is to describe 10 years of the geriatric oncology service at ICESP and the challenges for its implementation. We performed a narrative description of the ICESP's geriatric oncology service and a general retrospective descriptive analysis of data collected from routine structured medical records of patients referred to the service from 2011 to 2021. This article highlights the different settings in which the service operates (outpatient, pre-operative and hospital follow-up). In this period, 1,700 patients were assessed for preoperative evaluation (median age 83.9, SD 4.95), 468 patients were evaluated for therapeutic decision (median age 79.4, SD 7.38), 968 in general geriatric oncology care outpatient clinics from 2012 to 2021 (median age 78.7, SD 7.91) and 1,391 inpatient evaluations. In the past 10 years, our geriatric oncology team has grown exponentially and changed its characteristics in order to adjust them to the hospital demands, raising awareness among the oncology teams about the benefit of using geriatric assessment and promoting multidisciplinary discussions.

Impact of oral health on frailty syndrome in frail older adults.

OBJECTIVE: This study aimed to correlate oral and general health in frail and non-frail older adults. METHODS: This observational study included 52 older adults, of whom 35 were frail (Frail Group), and 17 were non-frail (Non-Frail Group), according to Fried's self-reported test addressing oral health variables, number of systemic diseases, and medications in use. The geriatric oral health assessment index was used to assess the oral hygiene of the groups. RESULTS: The number of preserved teeth in dentulous older adults was significantly higher in the Non-Frail Group (p=0.048). No significant differences were observed between the two groups in the use of dental prostheses or in the detection of soft tissue lesions. Overall, 74.3% of the Frail Group had a "bad" geriatric oral health index score, which significantly differed from that of the Non-Frail Group (p=0.045). The numbers of systemic diseases and medicines used were higher in the Frail Group than in the Non-Frail Group (p<0.001), demonstrating the pathophysiological characteristics of multimorbidity and polypharmacy in frailty syndrome. CONCLUSION: The results showed a clear correlation between oral and general health conditions and frailty syndrome.

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.

Gene expression alterations in the postmortem hippocampus from older patients with bipolar disorder - A hypothesis generating study.

Bipolar disorder (BD) presents with a progressive course in a subset of patients. However, our knowledge of molecular changes in older BD is limited. In this study, we examined gene expression changes in the hippocampus of BD from the Biobank of Aging Studies to identify genes of interest that warrant further exploration. RNA was extracted from the hippocampus from 11 subjects with BD and 11 age and sex-matched controls. Gene expression data was generated using the SurePrint G3 Human Gene Expression v3 microarray. Rank feature selection was performed to identify a subset of features that can optimally differentiate BD and controls. Genes ranked in the top 0.1% with log2 fold change >1.2 were identified as genes of interest. Average age of the subjects was 64 years old; duration of disease was 21 years and 82% were female. Twenty-five genes were identified, of which all but one was downregulated in BD. Of these, CNTNAP4, MAP4, SLC4A1, COBL, and NEURL4 had been associated with BD and other psychiatric conditions in previous studies. We believe our findings have identified promising targets to inform future studies aiming to understand the pathophysiology of BD in later life.

High Prevalence of Energy and Nutrients Inadequacy among Brazilian Older Adults.

Poor nutrition increases the risk of diseases and adverse health outcomes in older adults. We evaluated the potential inadequacy of nutrient intake among older adults in Brazil and its association with body anthropometry and composition outcomes. Dietary intake was obtained from 295 community-living older adults (>60 years old), of both genders, using a seven-day food record. Nutrient inadequacy was further identified based on the Dietary Reference Intakes and European Guidelines. Skeletal muscle mass (SM), strength and performance, and the diagnosis of sarcopenia were assessed using reference methods. Nutritional inadequacy was high, with energy, dietary fiber, and six micronutrients exhibiting the greatest inadequacy levels (>80%). Energy intake was correlated with SM strength (p = 0.000) and performance (p = 0.001). Inadequate energy, fiber, and protein intakes influenced BMI, while inadequate intake of vitamin B6 directly affected the diagnosis of sarcopenia (p ≤ 0.005). Further research is required to investigate whether these inadequacies can be associated with other clinical health outcomes.

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.

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

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

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.

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

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

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

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

Crash Risk Predictors in Older Drivers: A Cross-Sectional Study Based on a Driving Simulator and Machine Learning Algorithms.

The ability to drive depends on the motor, visual, and cognitive functions, which are necessary to integrate information and respond appropriately to different situations that occur in traffic. The study aimed to evaluate older drivers in a driving simulator and identify motor, cognitive and visual variables that interfere with safe driving through a cluster analysis, and identify the main predictors of traffic crashes. We analyzed the data of older drivers (n = 100, mean age of 72.5 ± 5.7 years) recruited in a hospital in São Paulo, Brazil. The assessments were divided into three domains: motor, visual, and cognitive. The K-Means algorithm was used to identify clusters of individuals with similar characteristics that may be associated with the risk of a traffic crash. The Random Forest algorithm was used to predict road crash in older drivers and identify the predictors (main risk factors) related to the outcome (number of crashes). The analysis identified two clusters, one with 59 participants and another with 41 drivers. There were no differences in the mean of crashes (1.7 vs. 1.8) and infractions (2.6 vs. 2.0) by cluster. However, the drivers allocated in Cluster 1, when compared to Cluster 2, had higher age, driving time, and braking time (p < 0.05). The random forest performed well (r = 0.98, R2 = 0.81) in predicting road crash. Advanced age and the functional reach test were the factors representing the highest risk of road crash. There were no differences in the number of crashes and infractions per cluster. However, the Random Forest model performed well in predicting the number of crashes.

Adaptation to the driving simulator and prediction of the braking time performance, with and without distraction, in older adults and middle-aged adults.

CONTEXT: Many studies show the importance of evaluating the adaptation time of subjects in a virtual driving environment, looking forwards to a response as closest as a possible real vehicle. OBJECTIVES: This study aimed to identify and analyze the adaptation to the driving simulator in older adults and middle-aged adults with and without a distraction, and a secondary aim was to identify predictors of safe performance for older adults' drives. DESIGN: Male and female middle-aged adults (n = 62, age = 30.3 ± 7.1 years) and older adults (n = 102, age = 70.4 ± 5.8 years) were evaluated for braking time performance in a driving simulator; cognition performance assessment included the Mini-Mental State Examination; motor evaluation included ankle flexor muscle strength with the isokinetic dynamometer and handgrip strength; the postural balance was evaluated with Timed Up and Go test, with and without a cognitive distraction task. RESULTS: Older adults (men and women) and middle-aged adult women require more time to adapt to the driving simulator. The distractor increases the adaptation time for all groups. The main predictors of braking time for older women are age, muscle strength, and postural balance associated with distraction, and for older men, muscle strength. CONCLUSIONS: Age, sex, and distractor interfere in the adaptation of the virtual task of driving in a simulator. The evaluation model developed with multi-domains demonstrated the ability to predict which skills are related to braking time with and without the presence of the distractor.

Resilience of Neural Cellularity to the Influence of Low Educational Level.

BACKGROUND: Education is believed to contribute positively to brain structure and function, as well as to cognitive reserve. One of the brain regions most impacted by education is the medial temporal lobe (MTL), a region that houses the hippocampus, which has an important role in learning processes and in consolidation of memories, and is also known to undergo neurogenesis in adulthood. We aimed to investigate the influence of education on the absolute cell numbers of the MTL (comprised by the hippocampal formation, amygdala, and parahippocampal gyrus) of men without cognitive impairment. METHODS: The Isotropic Fractionator technique was used to allow the anisotropic brain tissue to be transformed into an isotropic suspension of nuclei, and therefore assess the absolute cell composition of the MTL. We dissected twenty-six brains from men aged 47 to 64 years, with either low or high education. RESULTS: A significant difference between groups was observed in brain mass, but not in MTL mass. No significant difference was found between groups in the number of total cells, number of neurons, and number of non-neuronal cells. Regression analysis showed that the total number of cells, number of neurons, and number of non-neuronal cells in MTL were not affected by education. CONCLUSIONS: The results indicate a resilience of the absolute cellular composition of the MTL of typical men to low schooling, suggesting that the cellularity of brain regions is not affected by formal education.