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"Nitrini, Ricardo"
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Cognitive decline following acute viral infections: literature review and projections for post-COVID-19
by
Furlan, Damiano Rodolfo
,
Constantino, Miguel Eurípedes
,
Castro Luiz Henrique Martins
in
Alzheimer's disease
,
Cognition & reasoning
,
Cognitive ability
2022
Recently, much attention has been drawn to the importance of the impact of infectious disease on human cognition. Several theories have been proposed, to explain the cognitive decline following an infection as well as to understand better the pathogenesis of human dementia, especially Alzheimer’s disease. This article aims to review the state of the art regarding the knowledge about the impact of acute viral infections on human cognition, laying a foundation to explore the possible cognitive decline followed coronavirus disease 2019 (COVID-19). To reach this goal, we conducted a narrative review systematizing six acute viral infections as well as the current knowledge about COVID-19 and its impact on human cognition. Recent findings suggest probable short- and long-term COVID-19 impacts in cognition, even in asymptomatic individuals, which could be accounted for by direct and indirect pathways to brain dysfunction. Understanding this scenario might help clinicians and health leaders to deal better with a wave of neuropsychiatric issues that may arise following COVID-19 pandemic as well as with other acute viral infections, to alleviate the cognitive sequelae of these infections around the world.
Journal Article
Understanding brain resilience in superagers: a systematic review
by
Studart-Neto, Adalberto
,
da Costa Leite, Claudia
,
Alves, Cesar Augusto Pinheiro Ferreira
in
Adults
,
Aging
,
Amyloid
2021
Purpose
Superagers are older adults presenting excellent memory performance that may reflect resilience to the conventional pathways of aging. Our contribution aims to shape the evidence body of the known distinctive biomarkers of superagers and their connections with the Brain and Cognitive Reserve and Brain Maintenance concepts.
Methods
We performed a systematic literature search in PubMed and ScienceDirect with no limit on publication date for studies that evaluated potential biomarkers in superagers classified by validated neuropsychological tests. Methodological quality was assessed using the QUADAS-2 tool.
Results
Twenty-one studies were included, the majority in neuroimaging, followed by histological, genetic, cognition, and a single one on blood plasma analysis. Superagers exhibited specific regions of cortical preservation, rather than global cortical maintenance, standing out the anterior cingulate and hippocampus regions. Both superagers and controls showed similar levels of amyloid deposition. Moreover, the functional oscillation patterns in superagers resembled those described in young adults. Most of the quality assessment for the included studies showed medium risks of bias.
Conclusion
This systematic review supports selective cortical preservation in superagers, comprehending regions of the default mode, and salience networks, overlapped by stronger functional connectivity. In this context, the anterior cingulate cortex is highlighted as an imaging and histologic signature of these subjects. Besides, the biomarkers included pointed out that the Brain and Cognitive Reserve and Brain Maintenance concepts are independent and complementary in the superagers’ setting.
Journal Article
Neuropathological diagnoses and clinical correlates in older adults in Brazil: A cross-sectional study
by
Grinberg, Lea T.
,
Brucki, Sonia M. D.
,
Farfel, Jose M.
in
Acetylation
,
Aged
,
Aged, 80 and over
2017
Clinicopathological studies are important in determining the brain lesions underlying dementia. Although almost 60% of individuals with dementia live in developing countries, few clinicopathological studies focus on these individuals. We investigated the frequency of neurodegenerative and vascular-related neuropathological lesions in 1,092 Brazilian admixed older adults, their correlation with cognitive and neuropsychiatric symptoms, and the accuracy of dementia subtype diagnosis.
In this cross-sectional study, we describe clinical and neuropathological variables related to cognitive impairment in 1,092 participants (mean age = 74 y, 49% male, 69% white, and mean education = 4 y). Cognitive function was investigated using the Clinical Dementia Rating (CDR) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE); neuropsychiatric symptoms were evaluated using the Neuropsychiatric Inventory (NPI). Associations between neuropathological lesions and cognitive impairment were investigated using ordinal logistic regression. We developed a neuropathological comorbidity (NPC) score and compared it to CDR, IQCODE, and NPI scores. We also described and compared the frequency of neuropathological diagnosis to clinical diagnosis of dementia subtype. Forty-four percent of the sample met criteria for neuropathological diagnosis. Among these participants, 50% had neuropathological diagnoses of Alzheimer disease (AD), and 35% of vascular dementia (VaD). Neurofibrillary tangles (NFTs), hippocampal sclerosis, lacunar infarcts, hyaline atherosclerosis, siderocalcinosis, and Lewy body disease were independently associated with cognitive impairment. Higher NPC scores were associated with worse scores in the CDR sum of boxes (β = 1.33, 95% CI 1.20-1.46), IQCODE (β = 0.14, 95% CI 0.13-0.16), and NPI (β = 1.74, 95% CI = 1.33-2.16). Compared to neuropathological diagnoses, clinical diagnosis had high sensitivity to AD and high specificity to dementia with Lewy body/Parkinson dementia. The major limitation of our study is the lack of clinical follow-up of participants during life.
NFT deposition, vascular lesions, and high NPC scorewere associated with cognitive impairment in a unique Brazilian sample with low education. Our results confirm the high prevalence of neuropathological diagnosis in older adults and the mismatch between clinical and neuropathological diagnoses.
Journal Article
An assessment of direct and indirect costs of dementia in Brazil
by
Ferreira, Fernando F.
,
Brucki, Sonia M. D.
,
Sarti, Flávia M.
in
Analysis
,
Care and treatment
,
Dementia
2018
To analyze costs associated with dementia based on a cross-sectional study in the Brazilian health system.
Direct and indirect costs were estimated by conducting comprehensive interviews on the use of resources in a sample of 156 patients with dementia treated at an outpatient memory clinic of a tertiary hospital. A regression model was used to determine the main determinants of costs associated with dementia.
Global costs of dementia were US$1,012.35; US$1,683.18 and US$1,372.30 per patient/month for mild, moderate and severe stages, respectively. Indirect costs ranged from US$536.62 to US$545.17 according to severity. Dementia costs were influenced by medication, FAST score, and educational level of caregiver.
The study represents an original contribution toward establishing direct and indirect costs of dementia in Brazil. Results indicate significant economic impacts, including projection of annual costs of US$16,548.24 per patient.
Journal Article
Updates in the Diagnosis and Treatment of Paraneoplastic Neurologic Syndromes
by
Ronnyson Susano Grativvol
,
Martins Castro, Luiz Henrique
,
Mateus, Mistieri Simabukuro
in
Acids
,
Antibodies
,
Antigens
2018
The disorders of the central nervous system associated with cancer by remote immune-mediated mechanisms are a heterogeneous group. These disorders encompass the classic paraneoplastic disorders and the recently recognized autoimmune encephalitis associated with antibodies against neuronal cell surface or synaptic proteins that occur with or without cancer association. In the last decade, the new surge of interest in neuronal diseases associated with anti-neuronal antibodies led to the rapid discovery of new forms of disease that have different manifestations and were not previously suspected to be immune mediated. The recognition of these syndromes is important because it may lead to early detection of an underlying malignancy and prompt initiation of treatment, improving chances for a better outcome.
Journal Article
Bearded capuchin monkeys as a model for Alzheimer’s disease
2024
The absence of a natural animal model is one of the main challenges in Alzheimer’s disease research. Despite the challenges of using nonhuman primates in studies, these animals can bridge mouse models and humans, as nonhuman primates are phylogenetically closer to humans and can spontaneously develop AD-type pathology. The capuchin monkey, a New World primate, has recently attracted attention due to its skill in creating and using instruments. We analyzed one capuchin brain using structural 7 T MRI and performed a neuropathological evaluation of three animals. Alzheimer-type pathology was found in the two of the capuchins. Widespread β-amyloid pathology was observed, mainly in focal deposits with variable morphology and a high density of mature plaques. Notably, plaque-associated dystrophic neurites associated with disruption of axonal transport and early cytoskeletal alteration were frequently found. Unlike in other species of New World monkeys, cerebral arterial angiopathy was not the predominant form of β-amyloid pathology. Additionally, abnormal aggregates of hyperphosphorylated tau, resembling neurofibrillary pathology, were observed in the temporal and frontal cortex. Astrocyte hypertrophy surrounding plaques was found, suggesting a neuroinflammatory response. These findings indicate that aged capuchin monkeys can spontaneously develop Alzheimer-type pathology, indicating that they may be an advantageous animal model for research in Alzheimer’s disease.
Journal Article
Effects of dabigatran versus warfarin on 2-year cognitive outcomes in old patients with atrial fibrillation: results from the GIRAF randomized clinical trial
by
Rodrigues, Ana Carolina O.
,
Caramelli, Paulo
,
Brucki, Sonia M. D.
in
Aged patients
,
Anticoagulants
,
Atrial fibrillation
2022
Background
Observational studies support a role for oral anticoagulation to reduce the risk of dementia in atrial fibrillation patients, but conclusive data are lacking. Since dabigatran offers a more stable anticoagulation, we hypothesized it would reduce cognitive decline when compared to warfarin in old patients with atrial fibrillation.
Methods
The GIRAF trial was a 24-month, randomized, parallel-group, controlled, open-label, hypothesis generating trial. The trial was done in six centers including a geriatric care unit, secondary and tertiary care cardiology hospitals in São Paulo, Brazil. We included patients aged ≥ 70 years and CHA2DS2-VASc score > 1. The primary endpoint was the absolute difference in cognitive performance at 2 years. Patients were assigned 1:1 to take dabigatran (110 or 150 mg twice daily) or warfarin, controlled by INR and followed for 24 months. Patients were evaluated at baseline and at 2 years with a comprehensive and thorough cognitive evaluation protocol of tests for different cognitive domains including the Montreal Cognitive Assessment (MoCA), Mini-Mental State Exam (MMSE), a composite neuropsychological test battery (NTB), and computer-generated tests (CGNT).
Results
Between 2014 and 2019, 5523 participants were screened and 200 were assigned to dabigatran (
N
= 99) or warfarin (
N
= 101) treatment. After adjustment for age, log of years of education, and raw baseline score, the difference between the mean change from baseline in the dabigatran group minus warfarin group was − 0.12 for MMSE (95% confidence interval [CI] − 0.88 to 0.63;
P
= 0.75), 0.05 (95% CI − 0.07 to 0.18;
P
= 0.40) for NTB, − 0.15 (95% CI − 0.30 to 0.01;
P
= 0.06) for CGNT, and − 0.96 (95% CI − 1.80 to 0.13;
P
= 0.02) for MoCA, with higher values suggesting less cognitive decline in the warfarin group.
Conclusions
For elderly patients with atrial fibrillation, and without cognitive compromise at baseline that did not have stroke and were adequately treated with warfarin (TTR of 70%) or dabigatran for 2 years, there was no statistical difference at 5% significance level in any of the cognitive outcomes after adjusting for multiple comparisons.
Trial registration
Cognitive Impairment Related to Atrial Fibrillation Prevention Trial (GIRAF),
NCT01994265
.
Journal Article
Current trends and challenges on dementia management and research in Latin America
by
Caramelli, Paulo
,
Barbosa, Maira Tonidandel
,
Yassuda, Mônica Sanches
in
Biomedical Research - trends
,
Cardiovascular diseases
,
Dementia
2020
In these studies, incidence was similar [17,19] or higher in LA countries than in Western countries [18]. Besides age, other risk factors included markers of low cognitive reserve [18], poor cardiovascular health [20], and being a carrier of at least one APOE-ϵ 4 allele [19]. Joint efforts of clinicians and epidemiologists would be essential to improve the quality of epidemiological data on dementia in LA. Besides the high overall prevalence of dementia reported in most studies, prevalence among younger elderly (ie, 65-69 years) was found to be 2.4%, exactly twice the rate reported by a systematic review of 21 studies conducted in Europe [8]. [...]low education might increase dementia risk by limiting adequate diagnosis and treatment of comorbidities, particularly cardiovascular diseases and diabetes mellitus, as well as being commonly associated with impaired nutritional status. [...]low educational attainment is also associated with low cognitive reserve [21], thus possibly leading to the earlier manifestation of dementia symptoms. [...]the illiteracy rate among the elderly population is high, currently at 21%. [...]at least in Brazil, there is an unequal distribution of literacy rates, with lower figures in specific regions (North and Northeast) and rural areas of the country.
Journal Article
Memory complaints after COVID-19: a potential indicator of primary cognitive impairment or a correlate of psychiatric symptoms?
by
Guedes, Bruno Fukelmann
,
Busatto Filho, Geraldo
,
Serafim, Antonio de Pádua
in
631/378/1595
,
692/699/476
,
Adult
2024
Cognitive impairment and symptoms of psychiatric disorders have been reported frequently as features of post-acute sequelae of SARS-CoV-2 infection. This study aims to investigate subjective memory complaints in COVID-19 survivors and determine if these are more strongly associated with objective cognitive impairment related to sequelae of SARS-CoV-2 infection or with symptoms of psychiatric conditions. A total of 608 COVID-19 survivors were evaluated in-person 6–11 months after hospitalization, with 377 patients assigned to a “no subjective memory complaint (SMC)” group and 231 patients assigned to an SMC group based on their Memory Complaint Scale scores. Follow-up evaluations included an objective cognitive battery and scale-based assessments of anxiety, depression, and post-traumatic stress symptoms. We found the perception of memory impairment in COVID-19 survivors to be more strongly associated to core symptoms of psychiatric conditions rather than to primary objective cognitive impairment. Univariate analysis indicated significant differences between the “no SMC” and SMC groups, both for the psychiatric symptom evaluations and for the cognitive evaluations (p < 0.05); however, the psychiatric symptoms all had large partial eta-squared values (ranging from 0.181 to 0.213), whereas the cognitive variables had small/medium partial eta-squared values (ranging from 0.002 to 0.024). Additionally, multiple regression analysis indicated that only female sex and depressive and post-traumatic stress symptoms were predictors of subjective memory complaints. These findings may help guide clinical evaluations for COVID-19 survivors presenting with memory complaints while also serving to expand our growing understanding of the relationship between COVID-19, subjective memory complaints, and the risk of cognitive decline.
Journal Article
FC30: Bridging the gap: an estimate of undetected dementia in Brazil and differences between genders, age groups and regions
by
Caramelli, Paulo
,
Suemoto, Claudia Kimie
,
Brucki, Sonia
in
Age differences
,
Age groups
,
Aging
2024
Objectives: Despite the increasing number of people with dementia (PWD), detection remains low worldwide. In Brazil, PWD is expected to triple by 2050, and diagnosis can be challenging, contributing to high and growing rates of underdiagnosis. At the moment, there is no national estimate of the under detection or characteristics of its distribution according to gender, age and region. We aimed to estimate the proportion of PWD not diagnosed in relation to the estimated number of PWD. Methods: The number of diagnosed individuals were estimated based on national records of the prescription of anticholinesterases drugs (AChE) in 2022 for the treatment of mild and moderate stages of Alzheimer’s Disease (AD) held by the Unified Health System (SUS). Data were obtained from ftp://ftp.datasus.gov.br and drugs were dispensed according to the national clinical protocol. Studies from the national literature were consulted to estimate: (i) the number of people currently diagnosed with mild and moderate AD; (ii) the proportion of those who obtain AChE from SUS; (iii) the proportion of those who do not take AChE; and (iv) the proportion of AD related to other dementias. We assumed that the under-detection rate of AD would be similar to other dementias and 70% of the diagnosed AD individuals obtain AChE from SUS. Results: More than 80% of the PWD 60+ are undetected (88.7%, 95% CI = 88.6–88.7). The poorest regions had higher rates (94.6% 95%, CI = 94.5–94.6) than the richest (84.8%, 95% CI = 84.7–84.8). Men had higher rates (89.8%, 95% CI = 89.7–89.9) than women (87.4%, 95% CI = 87.4–87.5). The youngest age group (60-64) had the highest rate (94.6%, 95% CI = 94.5–94.7) which decreased until 85–89 (84.3%, 95% CI = 84.2–84.4), before increasing again to 91.1% (95% CI = 91.0–91.2) among 90+. Conclusions: Dementia under detection in Brazil is among the highest in the world. Fast populational aging and the highest rates among the youngest individuals are of concern as it may be related to late diagnosis. Gender and regional disparities also need to be considered when developing health policies.
Journal Article