Calculating Route: Functional Trajectories and Long-Term Outcomes in Survivors of Severe COVID-19.

OBJECTIVES: We investigated functional trajectories after severe COVID-19 and estimated their associations with adverse outcomes (falls, rehospitalizations, institutionalization, or death), cognition and post COVID-19 condition within 1-year of hospital discharge. DESIGN: Prospective cohort study. SETTING: A large academic medical center in Sao Paulo, Brazil. PARTICIPANTS: Survivors of COVID-19 admissions to an intensive care unit. INTERVENTIONS: None. MEASUREMENTS: We evaluated participants' disability status before hospital admission and three, six, nine, and twelve months after discharge using 15 activities of daily living. During follow-up, cognition and post COVID-19 condition (defined as persistent symptoms with duration ≥2 months) were assessed. A latent class growth analysis was performed to investigate functional trajectories after discharge. RESULTS: We included 422 participants (median age 63 years, 13.5% were frail before COVID-19). Four distinct functional trajectories could be identified: "minimal disability trajectory" (37.4% of participants), "mild disability trajectory" (37.9%), "moderate disability trajectory" (16.8%), and "severe disability trajectory" (7.8%). Compared with minimal disability trajectory, the odds ratios (95% confidence interval) for 1-year adverse outcomes were 2.28 (1.38-3.76) for minor disability trajectory; 4.21 (2.10-8.42) for moderate disability trajectory; and 4.16 (1.51-11.46) for severe disability trajectory, even after adjustments. The occurrence of post COVID-19 condition was 67.5% and associated with functional trajectories (p=0.004). Cognition was also associated with functional trajectories. CONCLUSION: Severe COVID-19 survivors can experience diverse functional trajectories, with those presenting higher levels of disability at increased risk for long-term adverse outcomes. Further investigations are essential to confirm our findings and assess the effectiveness of rehabilitation interventions, aiming to improve health outcomes in those who survived severe COVID-19 and other causes of sepsis.

Prolonged heart rate recovery time after 6-minute walk test is an independent risk factor for cardiac events in heart failure: a prospective cohort study

OBJECTIVES: To determine whether the time for peak exercise heart rate to return to resting heart rate after the 6-minute walk test (6MWT) can predict cardiac events in patients with heart failure (HF) within 2 years. DESIGN: Prospective cohort study. SETTING: HF outpatient facility at a tertiary teaching hospital. PARTICIPANTS: Seventy-six patients with HF, New York Heart Association functional classification II and III, and left ventricular ejection fraction <50% MAIN OUTCOME MEASURES: Patients used a heart rate monitor to measure the time for peak exercise heart rate to return to resting heart rate after the 6MWT. Data were analysed using Polar Pro-Trainer 5 software (Kempele, Finland). Patients were followed for >2 years for cardiac events (hospitalisations and death). RESULTS: Thirty-four patients had cardiac events during the 2-year follow-up period. There was a significant difference in time to return to resting heart rate between the groups with and without cardiac events {with 3.6 [standard deviation (SD) A] vs without 2.8 (SD B) minutes; mean difference C; 95% confidence interval (CI) of the difference D to E; P=0.003}. No significant differences between patients with and without cardiac events were found for mean walking distance, mean heart rate recovery at 1 minute and mean heart rate recovery at 2 minutes. The receiver operating curve discriminated between patients with and without cardiac events (área under the curve 0.71, 95% CI 0.61 to 0.81; P< 0.001). Using logistic regression analysis, prolonged time to return to resting heart rate (≥3 minutes) independently increased the risk for cardiac events 6.9-fold (95% CI 2.34 to 20.12; P< 0.001). The Kaplan­Meier curve showed more cardiac events in patients with prolonged time to return to resting heart rate (P=0.028). CONCLUSIONS: Prolonged time to return to resting heart rate (≥3 minutes) after the 6MWT was an independent predictor of cardiac events in patients with HF.

Prolonged heart rate recovery time after 6-minute walk test is an independent risk factor for cardiac events in heart failure: A prospective cohort study.

OBJECTIVES: To determine whether the time for peak exercise heart rate to return to resting heart rate after the 6-minute walk test (6MWT) can predict cardiac events in patients with heart failure (HF) within 2 years. DESIGN: Prospective cohort study. SETTING: HF outpatient facility at a tertiary teaching hospital. PARTICIPANTS: Seventy-six patients with HF, New York Heart Association functional classification II and III, and left ventricular ejection fraction <50%. MAIN OUTCOME MEASURES: Patients used a heart rate monitor to measure the time for peak exercise heart rate to return to resting heart rate after the 6MWT. Data were analysed using Polar Pro-Trainer 5 software (Kempele, Finland). Patients were followed for >2 years for cardiac events (hospitalisations and death). RESULTS: Thirty-four patients had cardiac events during the 2-year follow-up period. However, there was a significant difference in the time to return to resting heart rate between the groups with and without cardiac events {with 3.6 (SD 1.1) vs without 2.8 (SD 1.1) minutes; mean difference of 0.79 (95% confidence interval (CI) of the difference 0.28 to 1.28; P=0.003}. No significant differences between patients with and without cardiac events were found for mean walking distance, mean heart rate recovery at 1minute and mean heart rate recovery at 2minutes. The receiver operating curve discriminated between patients with and without cardiac events (área under the curve 0.71, 95% CI 0.61 to 0.81; P<0.001). Using logistic regression analysis, prolonged time to return to resting heart rate (≥3minutes) independently increased the risk for cardiac events 6.9-fold (95% CI 2.34 to 20.12; P<0.001). The Kaplan-Meier curve showed more cardiac events in patients with prolonged time to return to resting heart rate (P=0.028). CONCLUSIONS: Prolonged time to return to resting heart rate (≥3minutes) after the 6MWT was an independent predictor of cardiac events in patients with HF.

The Impact of Frailty on the Relationship between Life-Space Mobility and Quality of Life in Older Adults during the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic has led to abrupt restrictions of life-space mobility. The impact of shelter-in-place orders on older adults' health and well-being is still unclear. OBJECTIVE: To investigate the relationship between life-space mobility and quality of life (QoL) in older adults with and without frailty during the COVID-19 pandemic. DESIGN: Multicenter prospective cohort study based on structured telephone interviews. SETTING: Four geriatric outpatient clinics in the metropolitan area of Sao Paulo, Brazil. PARTICIPANTS: 557 community-dwelling adults aged 60 years and older. MEASUREMENTS: The Life-Space Assessment was used to measure community mobility before and during the COVID-19 pandemic, and a previously validated decrease of ≥ 5 points defined restricted life-space mobility. Frailty was assessed through the FRAIL (fatigue, resistance, ambulation, illnesses, and loss of weight) scale. The impact of shelter-in-place orders on QoL was evaluated with the question «How is the COVID-19 pandemic affecting your QoL?¼, to which participants could respond «not at all¼, «to some extent¼, or «to a great extent¼. We used ordinal logistic regressions to investigate the relationship between restricted life-space mobility and impact on QoL, adjusting our analyses for demographics, frailty, comorbidities, cognition, functionality, loneliness, depression, and anxiety. We explored whether frailty modified the association between life-space mobility and impact on QoL. RESULTS: Participants were on average 80±8 years old, 65% were women, and 33% were frail. The COVID-19 quarantine led to a restriction of community mobility in 79% of participants and affected the QoL for 77% of participants. We found that restricted life-space mobility was associated with impact on QoL in older adults during the pandemic, although frailty modified the magnitude of the association (P-value for interaction=0.03). Frail participants who experienced restricted life-space mobility had twice the odds of reporting an impact on QoL when compared with non-frail individuals, with respective adjusted odds ratios of 4.20 (95% CI=2.36-7.50) and 2.18 (95% CI=1.33-3.58). CONCLUSION: Older adults experienced substantial decreases in life-space mobility during the COVID-19 pandemic, and this unexpected change impacted their QoL. Providers should be particularly watchful for the consequences of abrupt life-space restrictions on frail individuals.

Role of Gait Speed, Strength, and Balance in Predicting Adverse Outcomes of Acutely Ill Older Outpatients.

AIM: To evaluate the ability of the Short Physical Performance Battery (SPPB) for predicting 1-year adverse outcomes of acutely ill older outpatients. METHODS: Prospective study with 512 acutely ill older outpatients (79.4±8.3 years, 63% female) in an acute care day hospital. The SPPB was administered at admission. Participants were classified as low (0-4 points), intermediate (5-8 points), or high (9-12 points) performance. Primary outcomes were new dependence in basic activities of daily living (ADL), hospitalization, and death at 1 year. Cox models tested whether the SPPB predicted outcomes after adjustment for sociodemographic factors, comorbidities and well-known geriatric conditions. We also estimated whether the chair-stand and balance tests improve the SPPB's ability to identify patients at high risk of adverse outcomes. RESULTS: Patients with intermediate or low SPPB performance were at higher risk of 1-year new ADL dependence (32% vs 13%: adjusted hazard ratio [aHR]=2.00; 95%CI=1.18-3.37; 58% vs 13%: aHR=3.40; 95%CI=2.00-5.85, respectively), hospitalization (43% vs 29%: aHR=1.56; 95%CI=1.04-2.33; 44% vs 29%: aHR=1.80; 95%CI=1.15-2.82), and death (18% vs 6%: aHR=2.54; 95%CI=1.17-5.53; 21% vs 6%: aHR=2.70; 95%CI=1.17-6.21). Use of all three components (versus gait speed alone) improved predictions of new ADL dependence (Harrell's C=0.73 vs 0.70;P=0.01), hospitalization (Harrell's C=0.60 vs 0.57;P=0.04), and death (Harrell's C=0.67 vs 0.62;P=0.04). CONCLUSIONS: The SPPB is as a powerful tool for identifying acutely ill older outpatients at high-risk of adverse outcomes. The combination of the three components of the SPPB resulted in better predictive performance than gait speed alone.

A 10-min Targeted Geriatric Assessment Predicts Mortality in Fast-Paced Acute Care Settings: A Prospective Cohort Study.

OBJECTIVES: To estimate whether a 10-minute Targeted Geriatric Assessment (10-TaGA) adds utility to sociodemographic characteristics and comorbidities in predicting one-year mortality in busy acute care settings. We have also compared the performance of 10-TaGA with the Identification of Seniors at Risk (ISAR) scale. DESIGN: Prospective cohort study. SETTING: Geriatric day hospital specializing in acute care in Brazil. PARTICIPANTS: 751 older adults aged 79.4 ± 8.4 years (64% female), presenting non-surgical, medical illness requiring hospital-level care (e.g., intravenous therapy, laboratory test, radiology) for ≤ 12 hours. MEASUREMENTS: The 10-TaGA, an easy-to-administer screening tool based on the comprehensive geriatric assessment (CGA), provided a measure of cumulative deficits ranging from 0 (no deficits) to 1 (highest deficit) on admission. Standard risk factors, including sociodemographics (age, gender, ethnicity, income) and the Charlson comorbidity index, were evaluated. The ISAR, a well-validated screening tool, was used for comparison. RESULTS: During one year of follow-up, 130 (17%) participants died. Compared to the ISAR, 10-TaGA offered better accuracy in identifying older patients at risk of death (area under the receiver operating characteristic curve: [AUC] 0.70 vs 0.65; P = 0.03). In a Cox regression model adjusted for sociodemographics and comorbidities, each 0.1 increment in the 10-TaGA score (range 0-1) was associated with increased mortality (hazard ratio = 1.42, 95% confidence interval 1.27-1.59). The addition of 10-TaGA markedly improved the discrimination of the model, which already incorporated standard risk factors (AUC 0.76 vs 0.71; P = 0.005); adding ISAR (AUC 0.73 vs 0.71; P = 0.09) did not have this marked effect. CONCLUSION: The 10-TaGA is an independent predictor of one-year mortality in acute care patients. This multidimensional screening tool offers better accuracy than ISAR when differentiating between older people at low and high risk of death in healthcare settings where providers have limited time and resources.

Prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy in cognitively normal older adults: systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis on the prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy in cognitively normal older adults. METHODS: We systematically reviewed and performed a meta-analysis on the prevalence of TDP-43 proteinopathy in older adults with normal cognition, evaluated by the Mini-Mental State Examination or the Clinical Dementia Rating. We estimated the overall prevalence of TDP-43 using random-effect models, and stratified by age, sex, sample size, study quality, antibody used to assess TDP-43 aggregates, analysed brain regions, Braak stage, Consortium to Establish a Registry for Alzheimer's Disease score, hippocampal sclerosis and geographic location. RESULTS: A total of 505 articles were identified in the systematic review, and 7 were included in the meta-analysis with 1196 cognitively normal older adults. We found an overall prevalence of TDP-43 proteinopathy of 24%. Prevalence of TDP-43 proteinopathy varied widely across geographic location (North America: 37%, Asia: 29%, Europe: 14%, and Latin America: 11%). Estimated prevalence of TDP-43 proteinopathy also varied according to study quality (quality score >7: 22% vs. quality score <7: 42%), antibody used to assess TDP-43 proteinopathy (native: 18% vs. hyperphosphorylated: 24%) and presence of hippocampal sclerosis (without 24% vs. with hippocampal sclerosis: 48%). Other stratified analyses by age, sex, analysed brain regions, sample size and severity of AD neuropathology showed similar pooled TDP-43 prevalence. CONCLUSIONS: Different methodology to access TDP-43, and also differences in lifestyle and genetic factors across different populations could explain our results. Standardization of TDP-43 measurement, and future studies about the impact of genetic and lifestyle characteristics on the development of neurodegenerative diseases are needed.

Quantifying the accretion of hyperphosphorylated tau in the locus coeruleus and dorsal raphe nucleus: the pathological building blocks of early Alzheimer's disease.

AIMS: Hyperphosphorylated tau neuronal cytoplasmic inclusions (ht-NCI) are the best protein correlate of clinical decline in Alzheimer's disease (AD). Qualitative evidence identifies ht-NCI accumulating in the isodendritic core before the entorhinal cortex. Here, we used unbiased stereology to quantify ht-NCI burden in the locus coeruleus (LC) and dorsal raphe nucleus (DRN), aiming to characterize the impact of AD pathology in these nuclei with a focus on early stages. METHODS: We utilized unbiased stereology in a sample of 48 well-characterized subjects enriched for controls and early AD stages. ht-NCI counts were estimated in 60-µm-thick sections immunostained for p-tau throughout LC and DRN. Data were integrated with unbiased estimates of LC and DRN neuronal population for a subset of cases. RESULTS: In Braak stage 0, 7.9% and 2.6% of neurons in LC and DRN, respectively, harbour ht-NCIs. Although the number of ht-NCI+ neurons significantly increased by about 1.9× between Braak stages 0 to I in LC (P = 0.02), we failed to detect any significant difference between Braak stage I and II. Also, the number of ht-NCI+ neurons remained stable in DRN between all stages 0 and II. Finally, the differential susceptibility to tau inclusions among nuclear subdivisions was more notable in LC than in DRN. CONCLUSIONS: LC and DRN neurons exhibited ht-NCI during AD precortical stages. The ht-NCI increases along AD progression on both nuclei, but quantitative changes in LC precede DRN changes.

d-serine levels in Alzheimer's disease: implications for novel biomarker development.

Alzheimer's disease (AD) is a severe neurodegenerative disorder still in search of effective methods of diagnosis. Altered levels of the NMDA receptor co-agonist, d-serine, have been associated with neurological disorders, including schizophrenia and epilepsy. However, whether d-serine levels are deregulated in AD remains elusive. Here, we first measured D-serine levels in post-mortem hippocampal and cortical samples from nondemented subjects (n=8) and AD patients (n=14). We next determined d-serine levels in experimental models of AD, including wild-type rats and mice that received intracerebroventricular injections of amyloid-ß oligomers, and APP/PS1 transgenic mice. Finally, we assessed d-serine levels in the cerebrospinal fluid (CSF) of 21 patients with a diagnosis of probable AD, as compared with patients with normal pressure hydrocephalus (n=9), major depression (n=9) and healthy controls (n=10), and results were contrasted with CSF amyloid-ß/tau AD biomarkers. d-serine levels were higher in the hippocampus and parietal cortex of AD patients than in control subjects. Levels of both d-serine and serine racemase, the enzyme responsible for d-serine production, were elevated in experimental models of AD. Significantly, d-serine levels were higher in the CSF of probable AD patients than in non-cognitively impaired subject groups. Combining d-serine levels to the amyloid/tau index remarkably increased the sensitivity and specificity of diagnosis of probable AD in our cohort. Our results show that increased brain and CSF d-serine levels are associated with AD. CSF d-serine levels discriminated between nondemented and AD patients in our cohort and might constitute a novel candidate biomarker for early AD diagnosis.

Sensorial differences according to sex and ages.

OBJECTIVE: To investigate age and sex differences in orofacial sensory detection. METHODS: One hundred and twenty-six (126) healthy subjects were divided into five groups according to their ages. They were assessed with a quantitative sensory testing protocol for gustative, olfactory, thermal (cold/warm), mechanical (tactile/vibration/electric), and pain (deep/superficial) detection thresholds. The corneal reflex was also evaluated. Data were analyzed with the one-way ANOVA, chi-squared, Fisher's exact, Mann-Whitney, and Kruskal-Wallis tests. RESULTS: The groups of subjects over 61 years old had higher olfactory (P < 0.001), gustative (sweet P = 0.004, salty P = 0.007, sour P = 0.006), thermal (warm P < 0.001, cold P < 0.001), and tactile (P < 0.001) detection thresholds than the others. The vibration detection threshold was high only for subjects over 75 years old (P < 0.001). The electric and deep pain detection thresholds were different for the 61-75 years old group (P ≤ 0.001). Women in all age groups had lower gustative (sweet P = 0.020, salty P = 0.002, sour P < 0.001, and bitter P = 0.002), olfactory (P = 0.010), warm (P < 0.001) and deep (P < 0.001), and superficial pain (P = 0.008) detection thresholds than men, and men from all age groups had lower vibratory detection thresholds (P = 0.006) than women. CONCLUSION: High sensory detection thresholds were observed in subjects over the 6th decade of life, and women had a more accurate sensory perception than men.

Combined enrichment of neuromelanin granules and synaptosomes from human substantia nigra pars compacta tissue for proteomic analysis.

This article gives a detailed description of a protocol using density gradient centrifugation for the enrichment of neuromelanin granules and synaptosomes from low amounts (≥0.15g) of human substantia nigra pars compacta tissue. This has a great advantage compared to already existing methods as it allows for the first time (i) a combined enrichment of neuromelanin granules and synaptosomes and (ii) just minimal amounts of tissue necessary to enable donor specific analysis. Individual specimens were classified as control or diseased according to clinical evaluation and neuropathological examination. For the enrichment of synaptosomes and neuromelanin granules from the same tissue sample density gradient centrifugations using Percoll® and Iodixanol were performed. The purity of resulting fractions was checked by transmission electron microscopy. We were able to establish a reproducible and easy to handle protocol combining two different density gradient centrifugations: using an Iodixanol gradient neuromelanin granules were enriched and in parallel, from the same sample, a fraction of synaptosomes with high purity using a Percoll® gradient was obtained. Our subfractionation strategy will enable a subsequent in depth proteomic characterization of neurodegenerative processes in the substantia nigra pars compacta in patients with Parkinson's disease and dementia with Lewy bodies compared to appropriate controls. BIOLOGICAL SIGNIFICANCE: Key features of Parkinson's disease are the degeneration of dopaminergic neurons in the substantia nigra pars compacta, an associated loss of the brain pigment neuromelanin and a resulting impairment of the neuronal network. The accumulation of iron binding neuromelanin granules is age- and disease-dependent and disease specific alterations could affect the neuronal iron homeostasis leading to oxidative stress induced cell death. The focus of the described method is the analysis of neuromelanin granules as well as axonal cell-endings of nerve cells (synaptosomes) of individual donors (control and diseased). It is the basis for the identification of disease-relevant changes in the iron homeostasis and the generation of new insight into altered protein compositions or regulations which might lead to disturbed communications between nerve cells resulting in pathogenic processes.

African ancestry protects against Alzheimer's disease-related neuropathology.

Previous studies in dementia epidemiology have reported higher Alzheimer's disease rates in African-Americans when compared with White Americans. To determine whether genetically determined African ancestry is associated with neuropathological changes commonly associated with dementia, we analyzed a population-based brain bank in the highly admixed city of São Paulo, Brazil. African ancestry was estimated through the use of previously described ancestry-informative markers. Risk of presence of neuritic plaques, neurofibrillary tangles, small vessel disease, brain infarcts and Lewy bodies in subjects with significant African ancestry versus those without was determined. Results were adjusted for multiple environmental risk factors, demographic variables and apolipoprotein E genotype. African ancestry was inversely correlated with neuritic plaques (P=0.03). Subjects with significant African ancestry (n=112, 55.4%) showed lower prevalence of neuritic plaques in the univariate analysis (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.55-0.95, P=0.01) and when adjusted for age, sex, APOE genotype and environmental risk factors (OR 0.43, 95% CI 0.21-0.89, P=0.02). There were no significant differences for the presence of other neuropathological alterations. We show for the first time, using genetically determined ancestry, that African ancestry may be highly protective of Alzheimer's disease neuropathology, functioning through either genetic variants or unknown environmental factors. Epidemiological studies correlating African-American race/ethnicity with increased Alzheimer's disease rates should not be interpreted as surrogates of genetic ancestry or considered to represent African-derived populations from the developing nations such as Brazil.

Brazilian psychiatric brain bank: a new contribution tool to network studies.

There is an urgent need for expanding the number of brain banks serving psychiatric research. We describe here the Psychiatric Disorders arm of the Brain Bank of the Brazilian Aging Brain Study Group (Psy-BBBABSG), which is focused in bipolar disorder (BD) and obsessive compulsive disorder (OCD). Our protocol was designed to minimize limitations faced by previous initiatives, and to enable design-based neurostereological analyses. The Psy-BBBABSG first milestone is the collection of 10 brains each of BD and OCD patients, and matched controls. The brains are sourced from a population-based autopsy service. The clinical and psychiatric assessments were done by an expert team including psychiatrists, through an informant. One hemisphere was perfused-fixed to render an optimal fixation for conducting neurostereological studies. The other hemisphere was comprehensively dissected and frozen for molecular studies. In 20 months, we collected 36 brains. A final report was completed for 14 cases: 3 BDs, 4 major depressive disorders, 1 substance use disorder, 1 mood disorder NOS, 3 obsessive compulsive spectrum symptoms, 1 OCD and 1 schizophrenia. The majority were male (64%), and the average age at death was 67.2 ± 9.0 years. The average postmortem interval was 16 h. Three matched controls were collected. The pilot stage confirmed that the protocols are well fitted to reach our goals. Our unique autopsy source makes possible to collect a fairly number of high quality cases in a short time. Such a collection offers an additional to the international research community to advance the understanding on neuropsychiatric diseases.

Treadmill test is limited in elderly patients with peripheral arterial disease.

BACKGROUND: To describe the applicability and the performance of the treadmill test in elderly patients with peripheral arterial disease (PAD) and without PAD (non-PAD). PATIENTS AND METHODS: Fifty consecutive PAD and non-PAD elderly patients performed a progressive treadmill test. The proportion of patients who were unable to perform the test and the maximal walking distance were obtained. RESULTS: The proportion of patients who were unable to perform the treadmill test was similar between PAD (16.6 %) and non-PAD patients (12.5 %), P = .57. Maximal walking time for patients who performed the treadmill test was not different between PAD (232 +/- 218 s) and non-PAD patients (308 +/- 289 s), P = .37. CONCLUSIONS: The treadmill test is limited in almost 20 % of elderly patients with PAD and non-PAD. These results highlight the need for other forms of exercise stress tests in order to assess the peripheral limitation of patients with PAD.

The dorsal raphe nucleus shows phospho-tau neurofibrillary changes before the transentorhinal region in Alzheimer's disease. A precocious onset?

AIMS: Alzheimer's disease (AD) is a progressive and irreversible disease. There is strong evidence that the progression of the phospho-tau neurofibrillary cytoskeletal changes, rather than the beta-amyloid burden, is crucial in determining the severity of the dementia in AD. The Braak and Braak staging system (BB) focuses mainly on the cortical cytoskeletal pathology and classifies this progressive pathology into six stages, spreading from the transentorhinal region to primary cortices. Although it is reported elsewhere that the midbrain's dorsal raphe nucleus (DR), which is connected with those areas of the cerebral cortex undergoing early changes during BB I and II, exhibits AD-related cytoskeletal pathology, this nucleus has not been considered by the BB. METHODS: To determine during which BB stage and how frequently the DR is affected by AD-related neurofibrillary changes, we studied the DR of 118 well-characterized individuals of the Brain Bank of the Brazilian Aging Brain Study Group categorized according to the BB. Thirty-eight of these individuals were staged as BB = 0, and 80 as BB >or= 1. RESULTS: In all of the BB >or= 1 individuals (cortical neurofibrillary changes were present at least in the transentorhinal region) and in more than 1/5 of the BB = 0 individuals neurofibrillary changes were detected in the supratrochlear subnucleus of the DR. CONCLUSIONS: These observations: (i) support the hypothesis of transneuronal spread of neurofibrillary changes from the DR to its interconnected cortical brain areas; and (ii) indicate that the supratrochlear subnucleus of the DR is affected by neurofibrillary changes before the transentorhinal cortex during the disease process underlying AD.

Immunogenicity of a 23-valent pneumococcal polysaccharide vaccine in Brazilian elderly.

Serum antibodies specific for the capsular polysaccharides of Streptococcus pneumoniae provide protection against invasive pneumococcal infection. In Brazil, this vaccine has been used for people over 65 years with clinical risk to develop pneumococcal infection since 1999. We evaluated the immune response of 102 elderly subjects (75.5% females and 24.5% males) with a mean age of 71 years, and 19 young healthy adults (63.2% females and 36.8% males) with a mean age of 27 years. The elderly study group consisted of outpatients who received follow-up care in the Geriatric Department of General Hospital, Faculty of Medicine, University of São Paulo. None had acute illness at the time of vaccination. Both groups were immunized with one intra-deltoid injection with 0.5 ml of a 23-valent pneumococcal polysaccharide vaccine. The total IgG specific antibody concentrations to capsular polysaccharides 1, 3, 5, 6B, 8, and 14 were determined against pre- and 1-month post-vaccination sera. All samples were analyzed according to the second-generation pneumococcal polysaccharide ELISA protocol. We observed that the pneumococcal polysaccharide vaccine evoked consistent antibody increase for serotypes 1, 5, 6B, 8, and 14 (geometric mean concentration increase of 2.46 in the elderly and 2.84 in the young adults). Otherwise, we observed no increase in antibody concentration for serotype 3 in both groups.

Immunogenicity of a 23-valent pneumococcal polysaccharide vaccine in Brazilian elderly

Serum antibodies specific for the capsular polysaccharides of Streptococcus pneumoniae provide protection against invasive pneumococcal infection. In Brazil, this vaccine has been used for people over 65 years with clinical risk to develop pneumococcal infection since 1999. We evaluated the immune response of 102 elderly subjects (75.5 percent females and 24.5 percent males) with a mean age of 71 years, and 19 young healthy adults (63.2 percent females and 36.8 percent males) with a mean age of 27 years. The elderly study group consisted of outpatients who received follow-up care in the Geriatric Department of General Hospital, Faculty of Medicine, University of São Paulo. None had acute illness at the time of vaccination. Both groups were immunized with one intra-deltoid injection with 0.5 ml of a 23-valent pneumococcal polysaccharide vaccine. The total IgG specific antibody concentrations to capsular polysaccharides 1, 3, 5, 6B, 8, and 14 were determined against pre- and 1-month post-vaccination sera. All samples were analyzed according to the second-generation pneumococcal polysaccharide ELISA protocol. We observed that the pneumococcal polysaccharide vaccine evoked consistent antibody increase for serotypes 1, 5, 6B, 8, and 14 (geometric mean concentration increase of 2.46 in the elderly and 2.84 in the young adults). Otherwise, we observed no increase in antibody concentration for serotype 3 in both groups.

[Comparison of body fat using anthropometry bioelectrical impedance and DEXA in elderly women]. / Comparação da gordura corporal de mulheres idosas segundo antropometria, bioimpedância e DEXA.

Verify correspondence and compare percentage body fat (%BF) estimates by skinfold thickness (SKT), bioelectrical impedance analysis (BIA) and DEXA. Twenty voluntaries women (aged 62-79 yr) were assessed. The body fat was estimated using two different equations of SKT(Jackson (19); Durning and Womersley, (20)), BIA using two-predictions formulas (23) and DEXA. To compare mean values of %BF was used analysis of variance for repeated measures (ANOVA--Bonferroni), the correlation of the inter-method was verified by Pearson correlation coefficients (r), and correspondence between prediction formulas was tested by using the approach by Bland and Altman (25). The %BF assessed by BIA (23) shown poor correlation (r < 0.5) with two SKT equations. The %BF ranged from 31.5 +/- 5.5 to 41.2 +/- 6.1 (mean +/- SD) for Jackson (19) e DEXA, respectively. The analysis of variance shown no significant differences (p > 0.05) between methods and/or equations by BIA (RJL-CompCorp) vs. DC-Jackson (19). There were observed significant differences (p < 0.001) between all comparisons. The correspondence between RJL-CompCorp vs. Deurenberg (23) was good and the same was observed for DEXA vs. Durning and Womersley (20). Although the methods and/or equations used in this study have been commonly utilized to estimate BF in elderly subjects, they neither must be used as a standard method. Each method has limitations and the comparison can be useful for interpretation of results.

Does the secretion of cytokines in the periphery reflect their role in bone metabolic diseases?

Much interest has been focused on the role of the immune system in bone remodeling. Here, we compare the production of Interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) by peripheral blood mononuclear cells (PBMC) in elderly Paget's patients, elderly osteoporotic patients and in normal elderly subjects. We studied Paget's patients (71.00 +/- 3.74 years), 7 osteoporotic patients (71.86 +/- 3.23 years), age and sex matched, and 5 elderly healthy control subjects (74.20 +/- 4.10 years) An ELISA test was used to quantify IL-1 beta and IL-6 in the supernatant culture of PBMC stimulated by phytohemagglutinin (PHA). IL-1 beta and IL-6 production from Paget's patients (IL-1 beta, 651.43 +/- 95.92 pg/ml; IL-6, 1402.85 +/- 148.11 pg/ml) was not statistically different from the production observed in the osteoporotic patients (IL-1 beta, 552.57 +/- 79.04 pg/ml; IL-6, 1458.85 +/- 118.35 pg/ml) and in the healthy elderly group (IL-1 beta, 717.60 +/- 131.34 pg/ml; IL-6, 1502.40 +/- 211.90 pg/ml). Although IL-1 and IL-6 can be involved in the bone remodeling process, we did not find any difference when we compared their production by PBMC in elderly normal, elderly osteoporotic and elderly Paget's patients.