Wilson Jacob-Filho

• Principal Investigator at University of São Paulo

Introduction: An increased blood pressure variability (BPV) is associated with a high risk of cardiovascular events in the general population. This concept was scarcely tested in patients with chronic kidney disease. We investigated the behavior of BPV parameters in a large cohort of older patients with CKD. Methods: This retrospective cohort study...

Background: Oral infections are prevalent in the adult population. Their impact includes the implication as a risk factor for Alzheimer’s disease (AD), altering its progression. One of the potential mechanisms involves immune mediators such as circulating cytokines. Objective: The goal of the present study was to investigate the prevalence of oral...

Background The Neuromodulatory Subcortical System (NSS) consists of nuclei exhibiting early vulnerability to tauopathies, including Alzheimer’s Disease (AD). Within the NSS, there is a spectrum of vulnerability that becomes apparent in the earliest stages of AD, offering a chance to probe factors underlying vulnerability to AD. Method In this stud...

Background Frailty, characterized by increased physical vulnerability, is associated with a higher incidence and severity of cognitive impairment and also a higher burden of neurodegenerative and cerebrovascular diseases. This study investigates the association between frailty and neurodegenerative and cerebrovascular pathologies. Method Cross‐sec...

Background Racial differences in dementia prevalence and incidence were found with higher dementia burden in African descendants. Previous neuropathological studies were conducted mostly in white participants in convenience samples. Further studies in diverse populations are important to foster the understanding of race differences in dementia path...

Background Hypertension is a midlife modifiable risk factor for dementia. Uncontrolled hypertension is related to brain damage that could result in cognitive impairment, and one way of evaluating uncontrolled hypertension through life is assessing left ventricular hypertrophy (LVH). Previous imaging studies have shown a relationship between LVH and...

Background Dementia is characterized by a chronic and progressive loss of cognitive function in the absence of a fluctuating level of consciousness. Alzheimer’s disease is the main etiology of dementia, presenting insidiously and causing progressive cognitive impairment with increasing severity over the years. Given the immense complexity of managi...

Skeletal muscle aging, or sarcopenia, involves progressive muscle mass and function loss, which limits mobility and independence in the aged populations. This decline is driven by chronic inflammation, oxidative stress, and insulin resistance, all of which impair muscle regeneration and accelerate protein breakdown. Mineralocorticoid receptors (MRs...

Background Nitric oxide (NO) is involved in synaptic transmission and cerebral plasticity, playing a role in the memory process. However, in states of brain inflammation, hypoxia, or ischemia, there is induction of inducible nitric oxide synthase (iNOS) expression by astrocytes and pyramidal cells in the brain. Under conditions of chronic activatio...

Background Previous studies suggest an association between Alzheimer’s disease and carotid artery atherosclerosis. However, the association between atherosclerotic carotid plaque composition and Alzheimer’s disease pathology (neuritic plaques and neurofibrillary tangles) has not been explored yet. Method Carotid arteries were dissected and the seg...

Background Alzheimer’s Disease(AD) patients experience circadian rhythm disorder. The circadian rhythm is synchronized by a master clock, the suprachiasmatic nucleus(SCN), which is spatially well‐conserved but a tiny nucleus in the hypothalamus. Little is known about the molecular and pathological changes that occur in the SCN during AD progression...

Background Transactive DNA‐binding protein 43 (TDP‐43) proteinopathy is associated with neurodegeneration, including LATE and linked to cognitive deterioration. While some research suggests a higher prevalence of TDP‐43 in women, no differences have been identified among racial groups. Nonetheless, the influence of gender on cognition within the co...

Background The atherosclerotic plaque in carotid arteries has been associated with dementia. Clinic radiological studies in older adults suggest that the composition of atherosclerotic plaque in the carotid artery can predict vascular dementia (VD) or mixed dementia. The proposed study aims to assess components of atherosclerotic plaques in the car...

Background Excessive daytime sleepiness is a common and early symptom of Alzheimer’s disease (AD). The subcortical wake‐promoting neurons in the lateral hypothalamic area, tuberomammillary nucleus (TMN), and locus coeruleus synchronize to maintain wakefulness/arousal. Although significant neuronal decline occurs in wake‐promoting regions, the TMN h...

Background Lewy body disease (LBD) is a neurodegenerative condition marked by the accumulation of neuronal alpha‐synuclein, leading to both Parkinson’s disease and Lewy body dementia. It is regarded as the second most common neurodegenerative disease associated with aging. However, there is limited knowledge of LBD prevalence in the general populat...

Background The study of dementia and its differences between the sexes is widely investigated, mainly in Alzheimer’s disease. However, most studies on dementia are not carried out in a multiethnic population. Here we analyze demographic data, clinical symptoms, and neuropathological characteristics of a large mixed Brazilian sample. Method The Bio...

Background Prior research investigating sex and racial differences in amyloid pathology burden has yielded inconsistent findings. We examined the impact of sex and other confounding factors on neuritic plaque burden and cognitive outcomes. Method This study included 1,857 individuals, with post‐mortem brain tissues, from the Biobank for Aging Stud...

Background Clinicopathological studies suggest a role of minor cerebrovascular changes in the cognitive decline of individuals with a low neurodegenerative burden. However, it remains unclear whether small vascular brain lesions can impact cognition in middle aging individuals. Additionally, recent clinicopathological studies have shown that even a...

Background Although sleep duration and sleep-related breathing disorders were associated with dementia previously, few studies examined the association between circadian rhythm association and cognitive status. Objective We aimed to investigate the association of rest and activity rhythm with cognitive performance in older people with cognitive co...

Inclusão digital e idosos ativos O envelhecimento populacional ativo torna-se importante na promoção da saúde do idoso. A inclusão digital das pessoas idosas colabora para a promoção da saúde, e deve ser realizada de forma a atender as especificidades desta população. O grupo de idosos GAMIA (Grupo de Assistência Multidisciplinar ao Idoso Ambulator...

Background The association of moderate and severe dementia with low body mass index (BMI) is well described, but weight decline seems to also occur in individuals with preclinical neuropathologies. Considering that up to one-fifth of individuals with normal cognition meet the criteria for a dementia-related neuropathological diagnosis, autopsy stud...

Importance Race differences in dementia prevalence and incidence have previously been reported, with higher dementia burden in Black decedents. However, previous neuropathological studies were conducted mostly in convenience samples with White participants; conducting clinicopathological studies across populations is crucial for understanding the u...

Context Vehicle driving depends on the integration of motor, visual, and cognitive skills to respond appropriately to different situations that occur in traffic. Objectives To analyze a model of performance predictor for braking time in the driving simulator, using a battery of tests divided by gender. Methods: Selected were 100 male drivers with...

Sarcopenia screening tools have a low capacity to predict adverse outcomes that are consequences of sarcopenia in the elderly population. This study aimed to evaluate the ability of a new sarcopenia screening tool SARC-GLOBAL to predict negative clinical outcomes in the elderly. A total of 395 individuals were evaluated in a 42-month period. The sc...

Sarcopenia is associated with clinical complications, which increase mortality. Effective sarcopenia risk screening in the elderly should be grounded in a comprehensive assessment, encompassing both nutritional status and medication use. Current screening tools, while emphasizing muscular per-formance, exhibit limited sensitivity in identifying eld...

Background: Sleep-wake dysfunction is an early and common event in Alzheimers disease (AD). The lateral hypothalamic area (LHA) regulates the sleep and wake cycle through wake-promoting orexinergic and sleep-promoting melanin-concentrating hormone (MCH) neurons. These neurons share close anatomical proximity with functional reciprocity. This study...

Individuals with Alzheimers Disease (AD) experience circadian rhythm disorder. The circadian rhythm is synchronized by a master clock, the suprachiasmatic nucleus (SCN), which is a tiny hypothalamic nucleus. Little is known about the molecular and pathological changes that occur in the SCN during AD progression. We examined postmortem brains of 12...

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 e...

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. Prospective cohort study. A large academic medical center in Sao Paulo, Brazil. Survivors of COVI...

Atypical Alzheimer's disease shares similar neuropathological changes with amnestic AD, i.e., accumulation of extracellular amyloid-beta plaques and aggregation of intracellular tau tangles; however, atypical AD presents different symptoms and patterns of brain atrophy. Thus, contrasting amnestic and atypical AD provides a unique framework to inves...

Silymarin, derived from Silybum marianum , has recently demonstrated its potential to improve health in conditions such as obesity and metabolic disturbances. Understanding the impact of nutraceuticals on intestinal morphology is crucial for developing supplements that promote a higher quality of life. Therefore, this study aimed to investigate the...

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 i...

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...

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 m...

We aimed to investigate associations between sleep quality with selected quantitative and qualitative parameters of health in older individuals with obesity. Cross-sectional assessment (n = 95 men/women; ≥ 65 years; BMI ≥ 30 kg/m²) of sleep quality, body composition, handgrip strength, quality-of-life, anxiety/depression. Mean PSQI score was 6.3. P...

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-base...

Background Neuropsychiatric symptoms (NPS) are very common in Lewy body dementias (LBD), but their aetiology is poorly understood. In a post‐mortem study we aimed to characterise the contribution of neuropathological substrates to some of the most common NPS in dementia. Method Participants who passed away between 2004 and 2021 underwent comprehen...

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 divid...

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...

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, m...

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. W...

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...

Introduction: The expansion of higher education in Brazil is recent. In the medical field, with the advent of the “Mais Médicos” Program, this expansion became feasible and culminated with the publication of new National Curricular Guidelines (DCN, Diretrizes Curriculares Nacionais) for undergraduate medical courses. The Pedagogical Course Project...

Resumo: Introdução: A ampliação da educação superior no Brasil é recente. Na área médica, com o advento do Programa Mais Médicos, essa expansão tornou-se viável e culminou com a publicação de novas Diretrizes Curriculares Nacionais (DCN) para o curso de graduação em Medicina. O projeto pedagógico do curso (PPC) traduz o que se realiza no curso e fu...

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 coronav...

Objectives To compare variables of access to healthcare between the LGBT+ population aged 50 and over and those non-LGBT+. Methods A cross-sectional study was carried out in Brazil through a confidential online questionnaire. The use of the health system was characterized by the number of preventive tests performed and measured by the PCATool-Bras...

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...

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 dist...

Background Frailty is associated with several adverse outcomes in older adults, including functional dependency, hospitalizations, and death. However, it has not been determined whether older LGBT + individuals are at a higher risk of frailty than the overall population. Therefore, we aimed to investigate the prevalence of frailty in older LGBT + a...

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 kno...

Dementia affects more Black individuals, likely due to a combination of environmental and biological factors1,2,3. APOE ε4 allele risk of dementia is different between individuals with European (EUR) and African (AFR) ancestries4,5,6. It is unclear what drives these differences in Alzheimer’s disease (AD) neuropathology among patients with cognitiv...

Background Most people with dementia already live in low‐ to middle‐income countries (LMIC). However, most evidence regarding dementia prevention comes from high‐income countries that have different socioeconomic status (SES) and risk factors prevalence than LMIC. In this session, we will present results on risk and protective factors for dementia...

Objective We examined the impact of loss of skeletal muscle mass in post-acute sequelae of SARS-CoV-2 (PASC) infection, hospital readmission rate, self-perception of health, and health care costs in a cohort of COVID-19 survivors. Design Prospective observational study. Setting and Participants Tertiary Clinical Hospital. Eighty COVID-19 survivor...

Rationale: Recent reports suggest patients with severe coronavirus disease 2019 (COVID-19) often experience long-term consequences of the infection. However, studies on intensive care unit (ICU) survivors are underrepresented. Objectives: We aimed to explore 12-month clinical outcomes after critical COVID-19, describing the longitudinal progress...

Introduction: Neuropsychiatric symptoms (NPS) are common in Lewy body disease (LBD), but their etiology is poorly understood. Methods: In a population-based post mortem study neuropathological data was collected for Lewy body (LB) neuropathology, neurofibrillary tangles (NFT), amyloid beta burden, TDP-43, lacunar infarcts, cerebral amyloid angio...

In the last decades, improvements in the average life expectancy in the world population have been associated with a significant increase in the proportion of elderly people, in parallel with a higher prevalence of non-communicable diseases, such as hypertension and diabetes. As the kidney is a common target organ of a variety of diseases, an adequ...

Dementia is more prevalent in Blacks than in Whites, likely due to a combination of environmental and biological factors. Paradoxically, clinical studies suggest an attenuation of APOE ε4 risk of dementia in African ancestry (AFR), but a dearth of neuropathological data preclude the interpretation of the biological factors underlying these findings...

Background : Apolipoprotein E gene (APOE) ε4 allele is associated with a higher risk of carotid atherosclerosis, but less is known about the association of APOE with intracranial atherosclerotic disease (IAD). We aimed to investigate the association of APOE alleles with IAD in a cross-sectional autopsy study. Methods : We measured the stenosis in...

Objective: To examine associations between potentially inappropriate medication, use and the risk of falls, unplanned hospitalization and death in older patients receiving initial care in a geriatric day hospital due to acute conditions. Methods: Cohort study with older adults referred to a geriatric day hospital from 2014 to 2017 due to acute c...

Objective: The decline in physical capacity in humans occurs as a consequence of ageing. It is well established that oxidative mechanisms play a role in ageing process, leading to oxidative accumulation in tissue damage. Regular physical exercise can minimize the physiological changes that occur during aging and also contribute to improving the in...

Objective: To establish a microcephaly cut-off size in adults using head circumference as an indirect measure of brain size, as well as to explore factors associated with microcephaly via data mining. Methods: In autopsy studies, head circumference was measured with an inelastic tape placed around the skull. Total brain volume was also directly...

OBJECTIVES:. Few studies have explored the effect of frailty on the long-term survival of COVID-19 patients after ICU admission. Furthermore, the Clinical Frailty Scale (CFS) validity in critical care patients remains debated. We investigated the association between frailty and 6-month survival in critically ill COVID-19 patients. We also explored...

Associations between age-related neuropathological lesions and adult-onset lifetime major depressive disorder (a-MDD), late-life MDD (LLD), or depressive symptoms close to death (DS) were examined in a large community sample of non-demented older adults. 741 individuals (age at death=72.2±11.7 years) from the Biobank for Aging Studies were analyzed...

Dementia is more prevalent in Blacks than in Whites, likely due to a combination of environmental and biological factors. Paradoxically, clinical studies suggest an attenuation of APOE ϵ4 risk of dementia in African ancestry (AFR), but lack of neuropathological data preclude the interpretation of the biological factors underlying these findings, in...

Objectives: As the pandemic advances, the interest in the long-lasting consequences of COVID-19 increases. However, a few studies have explored patient-centered outcomes in critical care survivors. We aimed to investigate frailty and disability transitions in COVID-19 patients admitted to ICUs. Design: Prospective cohort study. Setting: Univer...

Objective: This study aimed to compare causes of death in the most prevalent neuropathologically diagnosed dementias. Methods: We analyzed causes of death in a community-based cohort of participants aged 50 or older, submitted to full-body autopsy and a comprehensive neuropathologic examination of the brain. Individuals with Alzheimer disease (A...

Introduction: Education, and less frequently occupation, has been associated with lower dementia risk in studies from high-income countries. We aimed to investigate the association of cognitive impairment with education and occupation in a low-middle-income country sample. Methods: In this cross-sectional study, cognitive function was assessed b...

Introduction: Both obesity and sarcopenia are associated with poor sleep quality. It is, therefore, plausible to speculate that the coexistence of both conditions (i.e., sarcopenic obesity) could potentiate their negative effects on sleep quality. Objective: To investigate whether elderly with sarcopenic obesity have a worse sleep quality than non-...

Objectives Frailty is a risk factor for poor cognitive performance in older adults. However, few studies have evaluated the association of cognitive performance with frailty in a low- to middle-income country (LMIC). This study aimed to investigate an association between cognitive performance and frailty in older adults with memory complaints in Br...

The increase in senescent cells in tissues, including the brain, is a general feature of normal aging and age-related pathologies. Senescent cells exhibit a specific phenotype, which includes an altered nuclear morphology and transcriptomic changes. Astrocytes undergo senescence in vitro and in age-associated neurodegenerative diseases, but little...

Background Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive actions, that presents the involvement of the cortico-striatal areas. The contribution of environmental risk factors to OCD development suggests that epigenetic mechanisms may contribute to its pathophysiology. DNA methylation changes and gene expre...

Background Clinical Dementia Rating Scale (CDR) is one of the most used assessment scales in the care of dementia but it still lacks a detailed analysis of construct validity. We aimed to analyze evidences of construct validity of the CDR to assess the level of cognitive decline by informants. Method We analyzed 650 records of elderly subjects bel...

Background Advanced age is associated with both left bundle branch block (LBBB) and hypertension and the usefulness of ECG criteria to detect left ventricular hypertrophy (LVH) in patients with LBBB is still unclear. The diagnostic performance and clinical applicability of ECG-based LVH criteria in patients with LBBB defined by stricter ECG criteri...

BACKGROUND Usefulness of ECG criteria to detect left ventricular hypertrophy (LVH) in patients with left bundle branch block (LBBB) is still unclear. LVH is a relevant prognostic marker both at baseline and as an evolving change over time. The diagnostic performance and clinical applicability of ECG-based LVH criteria in patients with LBBB defined...

Background Strength and muscle mass are predictors of relevant clinical outcomes in critically ill patients, but in hospitalized patients with COVID-19, it remains to be determined. In this prospective observational study, we investigated whether muscle strength or muscle mass are predictive of hospital length of stay (LOS) in patients with moderat...

The elderly spend more of their daily time indoors, especially at home, and due to this, air quality measurements where they live are extremely important. Thus, this study was conducted to evaluate indoor/outdoor size-segregated particulate matter (PM) mass concentrations, followed by black carbon (rBC) and trace elements analysis and health risk a...

Objectives Decision making (DM) is a component of executive functioning, essential for choosing appropriate decisions. Executive dysfunctioning is particularly common in late-life depression, however the literature is scarce on DM. This case-control study aimed to evaluate the DM profile and performance in participants with and without unipolar maj...

Objectives The primary aim of this study was to evaluate the effect of a multidimensional program including home-based standing exercises, health education, and telephone support for the reduction of sedentary behavior in community-dwelling frail older adults. The secondary aim of this study was to evaluate the safety and adherence of the program....

Recently, a new ECG criterion, the Peguero-Lo Presti (PLP), improved overall accuracy in the diagnosis of left ventricular hypertrophy (LVH)—compared to traditional ECG criteria, but with few patients with advanced age. We analyzed patients with older age and examined which ECG criteria would have better overall performance. A total of 592 patients...

Background: Body mass index (BMI) in midlife is associated with dementia. However, the association between BMI and late-life obesity is controversial. Few studies have investigated the association between BMI and cognitive performance near the time of death using data from autopsy examination. We aimed to investigate the association between BMI and...

The increase in senescent cells in tissues, including the brain, is a general feature of normal aging and age-related pathologies. Senescent cells exhibit a specific phenotype, which includes an altered nuclear morphology and transcriptomic changes. Astrocytes undergo senescence in vitro and in age-associated neurodegenerative diseases, but little...

Background: Frailty screening using the Clinical Frailty Scale (CFS) has been proposed to guide resource allocation in acute care settings during the pandemic. However, the association between frailty and coronavirus disease 2019 (COVID-19) prognosis remains unclear. Objectives: To investigate the association between frailty and mortality over 6...

Objective To verify the effects of the Pilates compared to Resistance method on autonomic modulation of heart rate of older women. Design and method Twenty-four older women (60 to 80 y.o.) submitted to resistance training, W (RT, n = 12) or Pilates (PT, n = 12) for 12 weeks, twice a week, one hour per session. Physical evaluation was performed at...

Importance: Strength and muscle mass are predictors of relevant clinical outcomes in critically ill patients, but in hospitalized patients with COVID-19 remains to be determined. Objective: To investigate whether muscle strength or muscle mass are predictive of hospital length of stay (LOS) in patients with moderate to severe COVID-19. Design: Pros...

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...