[show abstract][hide abstract] ABSTRACT: To develop an informant-based instrument that would provide a valid estimate of premorbid cognitive abilities in low-educated populations.
A questionnaire was drafted by focusing on the premorbid period with a 10-year time frame. The initial pool of items was submitted to classical test theory and a factorial analysis. The resulting instrument, named the Premorbid Cognitive Abilities Scale (PCAS), is composed of questions addressing educational attainment, major lifetime occupation, reading abilities, reading habits, writing abilities, calculation abilities, use of widely available technology, and the ability to search for specific information. The validation sample was composed of 132 older Brazilian adults from the following three demographically matched groups: normal cognitive aging (n = 72), mild cognitive impairment (n = 33), and mild dementia (n = 27). The scores of a reading test and a neuropsychological battery were adopted as construct criteria. Post-mortem inter-informant reliability was tested in a sub-study with two relatives from each deceased individual.
All items presented good discriminative power, with corrected item-total correlation varying from 0.35 to 0.74. The summed score of the instrument presented high correlation coefficients with global cognitive function (r = 0.73) and reading skills (r = 0.82). Cronbach's alpha was 0.90, showing optimal internal consistency without redundancy. The scores did not decrease across the progressive levels of cognitive impairment, suggesting that the goal of evaluating the premorbid state was achieved. The intraclass correlation coefficient was 0.96, indicating excellent inter-informant reliability.
The instrument developed in this study has shown good properties and can be used as a valid estimate of premorbid cognitive abilities in low-educated populations. The applicability of the PCAS, both as an estimate of premorbid intelligence and cognitive reserve, is discussed.
PLoS ONE 01/2013; 8(3):e60084. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: The human prefrontal cortex has been considered different in several aspects and relatively enlarged compared to the rest of the cortical areas. Here we determine whether the white and gray matter of the prefrontal portion of the human cerebral cortex have similar or different cellular compositions relative to the rest of the cortical regions by applying the Isotropic Fractionator to analyze the distribution of neurons along the entire anteroposterior axis of the cortex, and its relationship with the degree of gyrification, number of neurons under the cortical surface, and other parameters. The prefrontal region shares with the remainder of the cerebral cortex (except for occipital cortex) the same relationship between cortical volume and number of neurons. In contrast, both occipital and prefrontal areas vary from other cortical areas in their connectivity through the white matter, with a systematic reduction of cortical connectivity through the white matter and an increase of the mean axon caliber along the anteroposterior axis. These two parameters explain local differences in the distribution of neurons underneath the cortical surface. We also show that local variations in cortical folding are neither a function of local numbers of neurons nor of cortical thickness, but correlate with properties of the white matter, and are best explained by the folding of the white matter surface. Our results suggest that the human cerebral cortex is divided in two zones (occipital and non-occipital) that differ in how neurons are distributed across their gray matter volume and in three zones (prefrontal, occipital, and non-occipital) that differ in how neurons are connected through the white matter. Thus, the human prefrontal cortex has the largest fraction of neuronal connectivity through the white matter and the smallest average axonal caliber in the white matter within the cortex, although its neuronal composition fits the pattern found for other, non-occipital areas.
Frontiers in Neuroanatomy 01/2013; 7:28. · 4.06 Impact Factor
[show abstract][hide abstract] ABSTRACT: To assess the distribution of dementia subtypes in Brazil using a population-based clinicopathological study.
Brains from deceased individuals aged ≥50 years old were collected after the next of kin signed an informed consent form and provided information through standardized questionnaires. Post-mortem clinical diagnoses were established in consensus meetings, and only cases with moderate or severe dementia or without cognitive impairment were included in the analysis. Immunohistochemical neuropathological examinations were performed following the universally accepted guidelines. A diagnosis of Alzheimer's disease was made when there were at least both a moderate density of neuritic plaques (Consortium to Establish a Register for Alzheimer's disease B or C) and Braak stage III for neurofibrillary tangle distribution. For the diagnosis of vascular dementia, at least three zones or strategic areas had to be affected by infarcts, lacunae, or microinfarcts.
From 1,291 subjects, 113 cases were classified as having moderate or severe dementia, and 972 cases were free of cognitive impairment. The neuropathological diagnoses of the dementia sub-group were Alzheimer's disease (35.4%), vascular dementia (21.2%), Alzheimer's disease plus vascular dementia (13.3%), and other causes of dementia (30.1%). Small-vessel disease, which alone was not considered sufficient for a vascular dementia diagnosis, was present in 38.9% of all of the dementia cases and in 16.8% of the group without cognitive impairment (odds ratio = 2.91; 95% confidence interval, 1.53-5.51), adjusted for age, sex, and education.
The relatively high frequencies of vascular dementia and small-vessel disease in the dementia sub-group constitute relevant findings for public health initiatives because control of vascular risk factors could decrease the prevalence of dementia in developing countries.
Clinics (São Paulo, Brazil) 01/2013; 68(8):1140-5. · 1.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: To determine the frequency of medical adverse events in elderly patients admitted to an acute care geriatric unit, the predictive factors of occurrence, and the correlation between adverse events and hospital mortality rates.
This prospective study included 171 admissions of patients aged 60 years and older in the acute care geriatric unit in a teaching hospital in Brazil between 2007 and 2008. The following variables were assessed at admission: the patient age, gender, number of prescription drugs, geriatric syndromes (e.g., immobility, postural instability, dementia, depression, delirium, and incontinence), comorbidities, functional status (evaluated with the Katz Index of Independence in Activities of Daily Living), and severity of illness (evaluated with the Simplified Acute Physiology Score Il). The incidence of delirium, infection, mortality, and the prescription of potentially inappropriate medications (based on the Beers criteria) were assessed during hospitalization. An observer who was uninvolved in patient care reported the adverse events.
The mean age of the sample was 78.12 years. A total of 187 medical adverse events occurred in 94 admissions (55%). The predictors of medical adverse events were undetermined. Compared with the patients with no adverse events, the patients with medical adverse events had a significantly longer hospital stay (21.41 ± 15.08 days versus 10.91 ± 7.21 days) and a higher mortality rate (39 deaths [41.5%] versus 17 deaths [22.1%]). Mortality was significantly predicted by the Simplified Acute Physiology Score II score (odds ratio [OR] = 1.13, confidence interval [CI] 95%, 1.07 to 1.20), the Katz score (OR=1.47, CI 95%, 1.18 to 1.83), and medical adverse events (OR = 3.59, CI 95%, 1.55 to 8.30).
Medical adverse events should be monitored in every elderly hospitalized patient because there is no risk profile for susceptible patients, and the consequences of adverse events are serious, sometimes leading to longer hospital stays or even death.
Clinics (São Paulo, Brazil) 11/2012; 67(11):1247-52. · 1.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: Alzheimer's disease (AD) is the most common cause of dementia in the human population, characterized by a spectrum of neuropathological abnormalities that results in memory impairment and loss of other cognitive processes as well as the presence of non-cognitive symptoms. Transcriptomic analyses provide an important approach to elucidating the pathogenesis of complex diseases like AD, helping to figure out both pre-clinical markers to identify susceptible patients and the early pathogenic mechanisms to serve as therapeutic targets. This study provides the gene expression profile of postmortem brain tissue from subjects with clinic-pathological AD (Braak IV, V, or V and CERAD B or C; and CDR ≥1), preclinical AD (Braak IV, V, or VI and CERAD B or C; and CDR = 0), and healthy older individuals (Braak ≤ II and CERAD 0 or A; and CDR = 0) in order to establish genes related to both AD neuropathology and clinical emergence of dementia. Based on differential gene expression, hierarchical clustering and network analysis, genes involved in energy metabolism, oxidative stress, DNA damage/repair, senescence, and transcriptional regulation were implicated with the neuropathology of AD; a transcriptional profile related to clinical manifestation of AD could not be detected with reliability using differential gene expression analysis, although genes involved in synaptic plasticity, and cell cycle seems to have a role revealed by gene classifier. In conclusion, the present data suggest gene expression profile changes secondary to the development of AD-related pathology and some genes that appear to be related to the clinical manifestation of dementia in subjects with significant AD pathology, making necessary further investigations to better understand these transcriptional findings on the pathogenesis and clinical emergence of AD.
PLoS ONE 01/2012; 7(11):e48751. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.Molecular Psychiatry advance online publication, 8 November 2011; doi:10.1038/mp.2011.136.
[show abstract][hide abstract] ABSTRACT: Previous ultrasound-based studies have shown an association between carotid artery atherosclerosis and dementia. Our aim was to investigate this association using postmortem examination.
Postmortem morphometric measurements of carotid stenosis and intima-media thickness were performed in individuals with dementia (n=112) and control subjects (n=577). Multivariate logistic regression models were applied.
High-grade left internal carotid stenosis (≥70%) was associated with increased odds for dementia (OR, 2.30; 95% CI, 1.14-4.74; P=0.02). Intima-media thickness was not associated with dementia.
The likelihood of dementia is increased with high-grade left internal carotid artery atherosclerosis after adjusting for demographic and cardiovascular risk factors.
[show abstract][hide abstract] ABSTRACT: To determine the impact of delirium on post-discharge mortality in hospitalized older patients.
Delirium is frequent in hospitalized older patients and correlates with high hospital mortality. There are only a few studies about its impact on post-discharge mortality.
This is a prospective study of patients over 60 years old who were hospitalized in the Geriatric Unit at Hospital das Clínicas of São Paulo between May 2006 and March 2007. Upon admission, demographics, comorbidities, number of drugs taken, and serum albumin concentration were evaluated for each patient. Delirium was diagnosed according to the DSM-IV criteria. Patients were divided into group A (with delirium) and group B (without delirium). One year after discharge, the patients or their caregivers were contacted to assess days of survival.
The sample included 199 patients, 66 (33%) of whom developed delirium (Group A). After one year, 33 (50%) group A patients had died, and 45 (33.8%) group B patients had died (p = 0.03). There was a significant statistical difference in average age (p = 0.001) and immobility (p <0.001) between groups A and B. There were no statistically significant differences between groups A and B in number of drugs taken greater than four (p = 0.62), sex (p = 0.54) and number of diagnoses greater than four (p = 0.21). According to a multivariate analysis, delirium was not an independent predictor of post-discharge mortality. The predictors of post-discharge mortality were age > or = 80 years (p = 0.029), albumin concentration < 3.5 g/dl (p = 0.001) and immobility (p = 0.007).
Delirium is associated with higher post-discharge mortality as a dependent predictor.
Clinics (São Paulo, Brazil) 03/2010; 65(3):251-5. · 1.59 Impact Factor