La aplicación del saber médico. Hipertensión y daño cognitivo

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Introduction: High blood pressure (HBP) is the leading cause of death from cardiovascular disease. Despite the advances, the percentage of undiagnosed and untreated hypertensive patients is 58.4%. The evaluation of cognitive damage in HBP focuses on preventing stroke, while functional damage is ignored. This inadequate management may be multifactorial. The objective was to analyze the opinions that doctors have about the relationship between high blood pressure and cognitive damage. Methodology: Observational, descriptive, cross-sectional study developed in the period between August 2020 and August 2023. Analysis of data obtained from a self-administered, anonymous and voluntary questionnaire. Revealing information on the professional profile, knowledge of HBP, its link with cognitive impairment (CD), diagnosis and treatment. Results: 222 professionals were included, 215 (96.8%) agree with the existence of a link between HBP and other cardiovascular risk factors in CD, and 218 (98.1%) acknowledge assisting patients at risk of suffering from CD. The CD evaluation is carried out in selected cases by 132 (59.4%) participants and 59 (26.7%) always do it. Of those who perform evaluation, 103 (54%) use the Mini Mental State Examination (MMSE), 10 (5.2%) use the Montreal Cognitive Assessment (MoCA) and 9 (4.7%) use the Clock Drawing Test. Regarding the decrease in blood pressure in elderly patients and the link with risk of CD: 54 (24.3%) do not recognize risk and 65 (29.2%) recognize a moderate-high risk. In reference to the implication of the treatment of cardiovascular disease and CD: 217 (97.7%) recognized a beneficial effect. Discussion: Given the recognition of the link between HBP and CD, it would be expected that CD would be investigated in the vast majority, however only 26.7% always evaluate it. There is no consensus on the method, the MMSE being the most used, with a low application of the MoCA test and/or Clock Drawing Test, the latter being the ones that evaluate executive function, mostly altered in CD linked to HBP. Although the treatment of cardiovascular disease is recognized as beneficial with respect to CD, the control of HBP in older adults is considered risky. A diagnosis is made of a situation where a disparity is evident between what one recognizes as knowing and what one claims to do. Conclusions: The role of vascular disease in functional brain damage is recognized, considering it necessary to know the cognitive status of patients, however there is a low application of screening tests that evaluate executive function. In this context, a gap between medical knowledge and practice is shown.

Introdução: A hipertensão arterial (HA) é a principal causa de morte por doenças cardiovasculares. Apesar dos avanços, o percentual de hipertensos não diagnosticados e não tratados é de 58,4%. A avaliação do dano cognitivo na hipertensão concentra-se na prevenção do acidente vascular cerebral, enquanto o dano funcional é ignorado. Esse manejo inadequado pode ser multifatorial. É objetivo fue analisar a opinião dos médicos sobre a relação entre hipertensão arterial e danos cognitivos. Metodologia: Estudo observacional, descritivo, transversal desenvolvido no período entre agosto de 2020 e agosto de 2023. Análise de dados obtidos a partir de questionário autoaplicável, anônimo e voluntário. Revelar informações sobre o perfil profissional, conhecimento sobre a HA, sua ligação com o comprometimento cognitivo (DC), diagnóstico e tratamento. Resultados: Foram incluídos 222 profissionais, 215 (96,8%) concordam com a existência de ligação entre hipertensão e outros fatores de risco cardiovascular na DC e 218 (98,1%) reconhecem ajudar pacientes com risco de sofrer de D.C. A avaliação da DC é realizada em casos selecionados por 132 (59,4%) participantes e 59 (26,7%) a fazem sempre. Dos que realizam avaliação, 103 (54%) utilizam o Mini Exame do Estado Mental (MEEM), 10 (5,2%) utilizam a Avaliação Cognitiva de Montreal (MoCA) e 9 (4,7%) utilizam o Clock Drawing Test. Em relação à diminuição da pressão arterial em pacientes idosos e a ligação com o risco de DC: 54 (24,3%) não reconhecem risco e 65 (29,2%) reconhecem risco moderado-alto. Em referência à implicação do tratamento de doenças cardiovasculares e DC: 217 (97,7%) reconheceram o efeito benéfico. Discussão: Dado o reconhecimento da ligação entre hipertensão e DC, seria de esperar que a DC fosse investigada na grande maioria, no entanto apenas 26,7% sempre a avaliam. Não há consenso sobre o método, sendo o MEEM o mais utilizado, com baixa aplicação do teste MoCA e/ou Clock Drawing Test, sendo estes últimos os que avaliam a função executiva, majoritariamente alterada nos DC vinculados à HA. Embora o tratamento das doenças cardiovasculares seja reconhecido como benéfico em relação à DC, o controle da HA em idosos é considerado arriscado. É feito um diagnóstico de uma situação em que é evidente uma disparidade entre o que se reconhece como saber e o que se afirma fazer. Conclusões: O papel da doença vascular no dano cerebral funcional é reconhecido, considerando-se necessário conhecer o estado cognitivo dos pacientes, porém há baixa aplicação de testes de triagem que avaliam a função executiva. Nesse contexto, evidencia-se uma lacuna entre o conhecimento e a prática médica.

Vascular Impairment, Muscle Atrophy, and Cognitive Decline: Critical Age-Related Conditions.

The triad of vascular impairment, muscle atrophy, and cognitive decline represents critical age-related conditions that significantly impact health. Vascular impairment disrupts blood flow, precipitating the muscle mass reduction seen in sarcopenia and the decline in neuronal function characteristic of neurodegeneration. Our limited understanding of the intricate relationships within this triad hinders accurate diagnosis and effective treatment strategies. This review analyzes the interrelated mechanisms that contribute to these conditions, with a specific focus on oxidative stress, chronic inflammation, and impaired nutrient delivery. The aim is to understand the common pathways involved and to suggest comprehensive therapeutic approaches. Vascular dysfunctions hinder the circulation of blood and the transportation of nutrients, resulting in sarcopenia characterized by muscle atrophy and weakness. Vascular dysfunction and sarcopenia have a negative impact on physical function and quality of life. Neurodegenerative diseases exhibit comparable pathophysiological mechanisms that affect cognitive and motor functions. Preventive and therapeutic approaches encompass lifestyle adjustments, addressing oxidative stress, inflammation, and integrated therapies that focus on improving vascular and muscular well-being. Better understanding of these links can refine therapeutic strategies and yield better patient outcomes. This study emphasizes the complex interplay between vascular dysfunction, muscle degeneration, and cognitive decline, highlighting the necessity for multidisciplinary treatment approaches. Advances in this domain promise improved diagnostic accuracy, more effective therapeutic options, and enhanced preventive measures, all contributing to a higher quality of life for the elderly population.

Challenges in evaluating cognitive impairment in diabetics in the Democratic Republic of the Congo.

Dementia is a global public health issue, with 57.5 million people living with at least one type of dementia in 2019 worldwide, and projected to rise to 152 million by 2050. Objective: We assessed the cognitive function in diabetic patients aged 60 or older in Bukavu city, in the eastern Republic of the Congo (DRC). Methods: This case-control study involved 123 patients with established diabetes mellitus (DM) and 123 controls over 60-year-olds also with high rates of illiteracy. Cognitive function was assessed using the Swahili version of the Community Screening Instrument for Dementia (CSI-D). Results: Foremost, our study revealed language-related differences between Swahili spoken in other eastern African countries such as Tanzania and Kenya, where the Swahili CSI-D is readily applied, compared to the Swahili spoken in Bukavu (DRC). Our results also showed that cognitive impairment was present in 18.7% of the total 246 participants. Remarkably, the prevalence rate of cognitive impairment was higher in the non-diabetic group (12.2 versus 25.2%; p=0.009). Participants aged 80 or older were more likely to present with cognitive impairment compared to those aged less than 80 (adjusted odds ratio - aOR=70.27; 95% confidence interval - 95%CI 3.94-125.15; p=0.004). We also found that patients living with DM for more than 20 years were three times more likely to be impaired compared to those who were recently diagnosed with DM (aOR=3.63; 95%CI 1.70-18.81; p=0.026). Conclusion: This study revealed that cognitive impairment was relatively high in Bukavu city. It emphasizes the lack of effective tools to assess cognitive function. This requires, therefore, that research be adapted to the intellect and cultural experiences of the patients.

A demência é uma questão de saúde pública global, afetando 57,5 milhões de pessoas com pelo menos um tipo de demência em 2019 em todo o mundo, com uma previsão de aumento para 152 milhões até 2050. Objetivo: Avaliou-se a função cognitiva em pacientes diabéticos com 60 anos ou mais na cidade de Bukavu, no leste da República Democrática do Congo (RDC). Métodos: Este estudo de caso-controle incluiu 123 pacientes com diabetes mellitus (DM) estabelecido e 123 controles com mais de 60 anos, com altas taxas de analfabetismo. A função cognitiva foi avaliada utilizando a versão swahili do Instrumento de Triagem Comunitária para Demência (Community Screening Instrument for Dementia ­ CSI-D). Resultados: O presente estudo revelou diferenças relacionadas à linguagem entre o swahili falado em outros países do leste da África, como Tanzânia e Quênia, onde o CSI-D swahili é prontamente aplicado, em comparação com o swahili falado em Bukavu (RDC). Observou-se também deficiência cognitiva em 18,7% dos 246 participantes. Notadamente, a taxa de prevalência de deficiência cognitiva foi maior no grupo não diabético (12,2 versus 25,2%; p=0,009). Participantes com 80 anos ou mais tiveram maior probabilidade de apresentar deficiência cognitiva em comparação com aqueles com menos de 80 anos (odds ratios ajustados ­ aOR=70,27; intervalo de confiança de 95% ­ IC95% 3,94­125,15; p=0,004). Também observou-se que pacientes vivendo com DM por mais de 20 anos tinham três vezes mais chances de serem afetados em comparação com aqueles que foram recentemente diagnosticados com DM (aOR=3,63; IC95% 1,70­18,81; p=0,026). Conclusão: Este estudo revelou que a deficiência cognitiva era relativamente alta na cidade de Bukavu. Enfatizou-se a falta de ferramentas eficazes para avaliar a função cognitiva, o que requer, portanto, que a pesquisa seja adaptada ao intelecto e às experiências culturais dos pacientes.

Risk factors of atrial fibrillation complicated with cognitive impairment and the relationship between cardiac function parameters and the degree of cognitive impairment.

OBJECTIVE: To explore the risk factors of Atrial Fibrillation (AF) with Cognitive Impairment (CI) and to analyze the relationship between cardiac function parameters and the degree of CI in patients. METHODS: 120 AF patients were selected, and Montreal Cognitive Assessment (MoCA) was used to distinguish between AF patients with and without CI. Univariate analysis and multivariate Logistic regression analysis were used to evaluate the impact of sociodemographic data, disease-related data, and clinical data on risk factors for AF with CI. Pearson's method was used to analyze the correlation between cardiac function parameters and cognitive function scores in AF patients. RESULTS: There were 89 patients with CI and 31 patients without CI, and the MoCA scores of patients with CI were lower than those in patients without CI. Age, occupational status, educational level, combined smoking history, drinking history, and heart failure, as well as systolic blood pressure, diastolic blood pressure, total cholesterol, triglyceride, C-reactive protein, free thyroxine, free triiodothyronine, and D-dimer were risk factors for the patient with CI. Left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and left atrial maximum volume in patients with CI were higher than those in patients without CI, and left ventricular ejection fraction and peak early diastolic velocity/peak late-diastolic mitral velocity ratio were lower. CONCLUSION: The cardiac function parameters of patients are closely related to attention, orientation, memory, visuospatial, and executive ability. Cardiac function parameters were closely related to cognitive functions.

The association between sleep and Alzheimer's disease: a systematic review.

It is estimated that 45% of individuals with cognitive impairment experience sleep disturbances prior to the onset of cognitive symptoms. Assessing sleeping problems and enhancing sleep quality are critical first steps to reduce the risk of cognitive impairment. Objective: To review existing literature based on predefined eligibility criteria to understand the connection between sleep disturbance and Alzheimer's disease. Methods: A thorough and systematic evaluation of numerous studies was carried out to assess one or more of the following epidemiological factors: (1) sleep disorders, (2) cognitive impairment, and (3) risk estimates for cognitive impairment due to sleep. Results: Studies suggest that individuals who experience memory loss may encounter sleep disturbances before noticing other symptoms. Numerous sleep disorders, such as excessive and inadequate sleep duration, poor sleep quality, circadian rhythm abnormalities, insomnia, and obstructive sleep apnea were found to increase the risk of cognitive dysfunction and dementia. Additionally, lower sleep quality and shorter sleep duration have been linked to higher cerebral-ß-amyloid levels. Objective evidence for the development of cognitive impairment is provided by the architecture of sleep stages. Patients experiencing sleep problems may benefit from specific types of sleep medicine as a preventative measure against cognitive decline. Conclusion: Sleep disorders can have adverse effects on cognitive health. The duration and quality of sleep are fundamental factors for maintaining a healthy brain as we age. Proper sleep can aid prevent cognitive impairment, particularly Alzheimer's disease and dementia.

Acredita-se que 45% dos indivíduos com comprometimento cognitivo experimentem distúrbios do sono antes do início dos sintomas cognitivos. Avaliar problemas de sono e melhorar a qualidade do sono são passos críticos iniciais para reduzir o risco de comprometimento cognitivo. Objetivo: Revisar a literatura existente com base em critérios de elegibilidade predefinidos para entender a conexão entre distúrbios do sono e a Doença de Alzheimer. Métodos: Uma avaliação completa e sistemática de vários estudos foi realizada para avaliar um ou mais dos seguintes fatores epidemiológicos: (1) distúrbios do sono, (2) comprometimento cognitivo e (3) estimativas de risco de comprometimento cognitivo decorrente do sono. Resultados: Os estudos sugerem que indivíduos que experimentam perda de memória podem enfrentar distúrbios do sono antes de notarem outros sintomas. Foi constatado que vários distúrbios do sono, como duração excessiva e inadequada do sono, má qualidade do sono, anormalidades no ritmo circadiano, insônia e apneia obstrutiva do sono, podem aumentar o risco de disfunção cognitiva e demência. Além disso, menor qualidade do sono e duração mais curta do sono têm sido associadas a níveis mais altos de ß-amiloide cerebral. Evidências objetivas para o desenvolvimento de comprometimento cognitivo são fornecidas pela arquitetura dos estágios do sono. Pacientes que experimentam problemas de sono podem se beneficiar de tipos específicos de medicamentos para o sono como medida preventiva contra o declínio cognitivo. Conclusão: Os distúrbios do sono podem ter efeitos adversos na saúde cognitiva. A duração e a qualidade do sono são fatores fundamentais para manter um cérebro saudável à medida que envelhecemos. Um sono adequado pode ajudar a prevenir o comprometimento cognitivo, especialmente a Doença de Alzheimer e a demência.

Quality of life in persons with mild cognitive impairment: a systematic review and meta-analysis.

The global increase in the aging population has raised concerns over various age-related conditions like dementia and mild cognitive impairment (MCI) and their consequences on the affected persons. People with MCI exhibit cognitive deficits more significantly than expected for their age and literacy level. Though the nature of this condition is considered "mild", studies have reported that even more subtle deficits can influence the quality of life (QOL). Objective: The present work aimed at exploring and comparing QOL in older adults with and without MCI through a systematic review and meta-analysis. Methods: After a detailed search of articles till May 2021 in the relevant electronic databases (PubMed Central, PubMed, Scopus, CINAHL Plus, Web of Science, ProQuest, and Cochrane) using the keywords "mild cognitive impairment", "quality of life", "old", "old aged", "aged", "older adult", "geriatrics", "healthy controls", "healthy participants", and "normal controls", we included 23 articles in the systematic review and 12 in the meta-analysis. Results: The quality of all the included articles were assessed using the Modified Downs and Black tool. Most of the studies in the systematic review demonstrated differences in QOL scores in older adults with MCI compared to healthy older adults. However, meta-analysis findings suggest that older adults with MCI had statistically non-significant yet lower differences in QOL compared to their healthy counterparts. Conclusion: Future research should focus on developing QOL assessment tools specifically for older adults with MCI and follow-up studies that could provide better knowledge of their changing cognitive profile and life quality.

O aumento global da população idosa tem suscitado preocupações quanto a condições relacionadas à idade, como demência e comprometimento cognitivo leve (CCL), e seus impactos nas pessoas afetadas. Indivíduos com CCL apresentam déficits cognitivos superiores ao esperado para sua idade e nível de alfabetização, e embora a condição seja considerada leve estudos demonstram que até déficits mais sutis podem afetar a qualidade de vida (QdV). Objetivo: Este trabalho explora e compara a QdV em idosos com e sem CCL, por meio de revisão sistemática e metanálise. Métodos: Após uma busca detalhada de artigos até maio de 2021 em relevantes bases eletrônicas (PubMed Central, PubMed, Scopus, CINAHL Plus, Web of Science, ProQuest e Cochrane) usando as palavras-chave "mild cognitive impairment", "quality of life", "old", "old aged", "aged", "older adult", "geriatrics", "healthy controls", "healthy participants", e "normal controls", incluímos 23 artigos na revisão e 12 na metanálise. Resultados: A qualidade dos artigos foi avaliada com a ferramenta Modified Downs and Black. A revisão revelou diferenças nas pontuações de QdV entre idosos com CCL e saudáveis, mas a metanálise revelou diferenças estatisticamente não significativas, sugerindo uma QdV ligeiramente inferior nos primeiros. Conclusão: Futuras pesquisas devem enfocar ferramentas de avaliação de QdV específicas para idosos com CCL e em estudos de acompanhamento para melhor compreensão do perfil cognitivo em evolução e da qualidade de vida desses indivíduos.

What is the most appropriate handgrip strength testing protocol for sarcopenia screening in older adults with cognitive impairment?

BACKGROUND: Handgrip strength (HGS) testing is a highly recommended method for screening for sarcopenia in older adults. However, there is no consensus on the optimal protocol and number of trials for screening sarcopenia in older adults with cognitive impairment. OBJECTIVE: To investigate the use of the first trial (FT), the mean of three trials (MT), and the highest value (HT) from three trials of the HGS test to screen for sarcopenia in older adults with cognitive impairment. Additionally, to analyze the consistency, agreement, and measurement error in the diagnosis of muscle weakness. METHODS: 176 older adults with cognitive impairment were evaluated. The HGS test was repeated three times. Analyses were performed using the Friedman repeated measures test with Wilcoxon post-hoc, intraclass correlation coefficient (ICC), Standard Error of Measurement (SEM), Minimal Detectable Change (MDC95), and Kappa index tests. RESULTS: There was no significant difference between the first trial (FT) and the mean of three trials (MT) (d = 0.17 [95 % CI: -0.08, 0.42]), but both differed significantly from the highest value (HT) (p < 0.001). The ICC indicated a reliability of 0.97 (95 % CI: 0.95, 0.98) across all participants, while the kappa index demonstrated over 80 % agreement. The SEM for the first measure of HGS ranged from 0.59 to 2.12 kgf. The MDC95 ranged from 1.64 to 5.87 kgf. CONCLUSION: For HGS testing, there was excellent consistency between the FM and MT. All three testing methods demonstrated excellent agreement in diagnosing muscle weakness. The measurement errors confirm that FT can be reliably used to monitor changes during rehabilitation.

Neurologic manifestations of Long COVID in Colombia: a comparative analysis of post-hospitalization vs. non-hospitalized patients.

Objective: To analyze patient-reported outcomes, cognitive function, and persistent symptoms in patients with neurologic post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC) in Colombia. Methods: We recruited patients with laboratory-confirmed COVID-19 and PASC symptoms lasting more than 6 weeks at the CES University and CES Clinic (Medellín, Colombia). We included 50 post-hospitalization Neuro-PASC (PNP) and 50 non-hospitalized Neuro-PASC (NNP) patients. Long-COVID symptoms, cognitive (NIH Toolbox v2.1-Spanish for 18+), patient-reported (PROMIS) outcomes, and relevant medical history were evaluated. Statistical analyses were performed via generalized linear models. Results: Overall, brain fog (60%), myalgia (42%), and numbness or tingling (41%) were the most common neurological symptoms, while fatigue (74%), sleep problems (46%), and anxiety (44%) were the most common non-neurological symptoms. Compared to NNP, PNP patients showed a higher frequency of abnormal neurological exam findings (64% vs. 42%, p = 0.028). Both groups had impaired quality of life (QoL) in domains of cognition, fatigue, anxiety depression and sleep disturbance, and performed worse on processing speed and attention than a normative population. In addition, NNP patients performed worse on executive function than PNP patients (T-score 42.6 vs. 48.5, p = 0.012). PASC symptoms of anxiety and depression were associated with worse QoL and cognitive outcomes. Brain fog and fatigue remained persistent symptoms across all durations of Long COVID. Conclusion: Our findings highlight the high incidence and heterogeneity of the neurologic symptoms and impacts of Long COVID even more than 2 years from disease onset. Early detection, emotional support and targeted management of Neuro-PASC patients are warranted.

Neuropsychological aspects of reversible cerebral vasoconstriction syndrome.

Despite the increasing knowledge in the past years, only minimal attention has been directed to the neuropsychological aspects and the prevalence of cognitive impairment associated with reversible cerebral vasoconstriction syndrome (RCVS). Objective: To describe the frequency and expand the understanding of cognitive dysfunction in RCVS. Methods: The neuropsychological evaluation was performed using a battery consisting of specific neuropsychological instruments that were administered to patients diagnosed with RCVS. A triage was conducted to exclude other potential causes of cognitive impairment. Performance on the tests was treated as a categorical variable, and a cutoff of -1.5 Z-score was adopted to indicate impaired performance. Results: Seven patients diagnosed with RCVS were evaluated, all of whom had a bachelor's degree and normal score in the Mini-Mental State Examination. The average time between diagnosis and neuropsychological evaluation was 1.8 years. Among the patients, 85.6% (n=6) exhibited performance below that of the normal population in at least two of the administered tests. Specifically, 71.4% (n=5) showed alterations in tests from the Psychological Battery for Attention Assessment, with impairment observed in concentrated (n=1), divided (n=3), or alternating (n=4) attention. Furthermore, 28.6% (n=2) demonstrated impairments in the Phonological Verbal Fluency Task, another 28.6% (n=2) exhibited difficulties copying elements of the Rey Complex Figure, and 14.3% (n=1) displayed lower performance in the Five-Digit test, all indicating executive dysfunction. Conclusion: This study provides evidence that cognitive impairment associated with RCVS is more prevalent than previously believed and has not received sufficient attention. Specifically, attention and executive functions are the cognitive domains most significantly impacted by RCVS.

Apesar do crescente conhecimento nos últimos anos, pouca atenção tem sido direcionada aos aspectos neuropsicológicos e à prevalência de declínio cognitivo associado à Síndrome de Vasoconstrição Cerebral Reversível (SVCR). Objetivo: Descrever a frequência e expandir o entendimento da disfunção cognitiva associada à SVCR. Métodos: A avaliação neuropsicológica foi realizada por meio de uma bateria composta de instrumentos neuropsicológicos específicos, que foram aplicados aos pacientes com SVCR. Uma triagem foi realizada para excluir outras potenciais causas de declínio cognitivo. O desempenho nos testes foi considerado como variável categórica, e o corte de −1,5 escore z foi adotado para indicar desempenho comprometido. Resultados: Sete pacientes com diagnóstico de SVCR foram avaliados, os quais tinham todos nível de ensino superior e pontuação normal no Miniexame do Estado Mental. A média de tempo entre o diagnóstico e a avaliação neuropsicológica foi de 1,8 ano. Dentre os pacientes, 85,6%(n=6) apresentaram desempenho comprometido em pelo menos dois dos testes aplicados. Especificamente, 71,4% (n=5) apresentaram alterações nos testes da Bateria Psicológica para Avaliação da Atenção, com comprometimento observado nas atenções concentrada (n=1), dividida (n=3), ou alternada (n=4). Além disso, 28,6% (n=2) demonstraram comprometimento na Fluência Verbal Fonológica, 28,6% (n=2) exibiram dificuldades na cópia da Figura Complexa de Rey e um paciente obteve desempenho alterado no Teste dos Cinco Dígitos, todos indicando disfunção executiva. Conclusão: Este estudo fornece evidência de que o declínio cognitivo associado à SVCR é mais prevalente do que se acreditava anteriormente. Especialmente, os domínios mais significativamente comprometidos foram a atenção e as funções executivas.

Neuroprotective effect of hormone replacement therapy: a review of the literature.

OBJECTIVE: Menopause is a physiological period characterized by the cessation of ovarian activity. Sequential changes during this transition affect multiple systems, including the brain. Sixty percent of women experience cognitive impairment. The objective of this review is to show the neuroprotective effect of hormone replacement therapy (HRT) through the different scales and whether there is a benefit of this in women. METHOD: A search was conducted in six databases. Eligibility criteria included women within 10 years of menopause, receiving HRT controlled with placebo, studies lasting more than 6 months and women without a history of chronic underlying pathology. RESULTS: A total of nine randomized controlled trials met the inclusion criteria. Regarding memory, two studies reported better performance of HRT with a significant odds ratio (OR) of 0.67; regarding attention, one study reported potential improvement in women receiving HRT with a significant OR of 0.87; and neuroimaging assessment found an increase in ventricular volume compared to placebo over a 3-year period. CONCLUSIONS: The early initiation of menopausal HRT in healthy women appears to yield a positive effect on certain cognitive aspects, such as attention and cortical volume in the central nervous system. These findings should be confirmed through future prospective studies.

Allostatic load measures in older adults with subjective cognitive decline and mild cognitive impairment: A cross-sectional analysis from the Brazilian Memory and Aging Study.

INTRODUCTION: An increasing body of research suggests that stress and allostatic load are related to cognitive dysfunction and neurodegeneration. OBJECTIVES: to determine the relationship between allostatic load (AL) and cognitive status in older adults classified with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). METHODOLOGY: Using the Brazilian Memory and Aging Study (BRAMS) database, we analyzed data from 57 older adults with SCD and MCI. Blood neuroendocrine (cortisol, DHEA-s), inflammatory (C-reactive protein, fibrinogen), metabolic (HbA1c, HDL-cholesterol, total cholesterol, creatinine), and cardiovascular (blood pressure, waist/hip ratio) were transformed into an AL index. RESULTS: Despite a significant difference in the univariate analysis between waist/hip ratio (0.94 in the MCI group vs. 0, 88 in the SCD group, p = 0.03), total cholesterol levels (194 vs. 160, p = 0.02), and AL index (36.9 % in the MCI group vs. 27.2 % in the SCD group, p = 0.04), AL was not associated with SCD or MCI in the multivariate analysis. CONCLUSION: Our data suggest that different profiles of AL in MCI compared to individuals with SCD could be due to cofounding factors. These findings need to be confirmed in longitudinal studies investigating profiles of AL changes at preclinical and prodromal stages of Alzheimer's disease.

Diagnostic accuracy of interleukin-6, interleukin-10 and tumor necrosis factor alpha cytokine levels in patients with mild cognitive impairment: systematic review and meta-analysis.

There is growing evidence suggesting an association between neurodegeneration and inflammation playing a role in the pathogenesis of age-associated diseases, including Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI). Objective: A systematic review and meta-analysis were performed to verify evidence on the diagnostic accuracy parameters of the inflammatory cytokines interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor alpha (TNF-α). Methods: A search of Medical Literature Analysis and Retrieval System Online (Medline), Scientific Electronic Library Online (SciELO), Web of Science and Science Direct databases was performed and nine observational studies associated with peripheral inflammatory biomarkers in MCI were identified. Mean (±standard deviation - SD) concentrations of these biomarkers and values of true positives, true negatives, false positives and false negatives for MCI and healthy controls (HC) were extracted from these studies. Results: Significantly higher levels of IL-10 were observed in subjects in the MCI group and Mini-Mental State Examination (MMSE) scores were lower compared to HC. For the other investigations, no differences were found between the groups. Our meta-analysis for the TNF-α biomarker revealed high heterogeneity between studies in terms of sensitivity and specificity. Conclusion: These findings do not support the involvement of inflammatory biomarkers for detection of MCI, although significant heterogeneity was observed. More studies are needed to evaluate the role of these cytokines in MCI, as well as in other stages of cognitive decline and all-cause dementias.

Há evidências crescentes que sugerem uma associação entre a neurodegeneração e a inflamação, desempenhando um papel na patogênese de doenças associadas à idade, incluindo a doença de Alzheimer (DA) e o comprometimento cognitivo leve (CCL). Objetivo: Uma revisão sistemática e metanálise foram realizadas para verificar evidências relativas aos parâmetros de acurácia diagnóstica das citocinas inflamatórias interleucina-6 (IL-6), interleucina-10 (IL-10) e fator de necrose tumoral (TNF-α). Métodos: Foi realizada uma busca nas bases de dados Medical Literature Analysis and Retrieval System Online (Medline), Scientific Electronic Library Online (SciELO), Web of Science e Science Direct, e foram identificados nove estudos observacionais associados a biomarcadores inflamatórios periféricos no CCL. As concentrações médias (desvio padrão ­ ±DP) desses biomarcadores e valores de verdadeiros positivos, verdadeiros negativos, falsos positivos e falsos negativos para CCL e controles saudáveis (CS) foram extraídos desses estudos. Resultados: Níveis significativamente mais elevados de IL-10 foram observados em indivíduos do grupo CCL e os escores do Miniexame do Estado Mental foram mais baixos em comparação com o CS. Para as demais investigações não foram encontradas diferenças entre os grupos. Nossa metanálise para o biomarcador TNF-α revelou alta heterogeneidade entre os estudos em termos de sensibilidade e especificidade. Conclusão: Esses achados não apoiam o envolvimento de biomarcadores inflamatórios na detecção do CCL, embora tenha sido observada heterogeneidade significativa. Mais estudos são necessários para avaliar o papel dessas citocinas no CCL, bem como em outros estágios de declínio cognitivo e demências de todas as causas.

Ginkgo biloba: A Leaf of Hope in the Fight against Alzheimer's Dementia: Clinical Trial Systematic Review.

Alzheimer's disease (AD) is a stealthy and progressive neurological disorder that is a leading cause of dementia in the global elderly population, imposing a significant burden on both the elderly and society. Currently, the condition is treated with medications that alleviate symptoms. Nonetheless, these drugs may not consistently produce the desired results and can cause serious side effects. Hence, there is a vigorous pursuit of alternative options to enhance the quality of life for patients. Ginkgo biloba (GB), an herb with historical use in traditional medicine, contains bioactive compounds such as terpenoids (Ginkgolides A, B, and C), polyphenols, organic acids, and flavonoids (quercetin, kaempferol, and isorhamnetin). These compounds are associated with anti-inflammatory, antioxidant, and neuroprotective properties, making them valuable for cognitive health. A systematic search across three databases using specific keywords-GB in AD and dementia-yielded 1702 documents, leading to the selection of 15 clinical trials for synthesis. In eleven studies, GB extract/EGb 761® was shown to improve cognitive function, neuropsychiatric symptoms, and functional abilities in both dementia types. In four studies, however, there were no significant differences between the GB-treated and placebo groups. Significant improvements were observed in scores obtained from the Mini-Mental State Examination (MMSE), Short Cognitive Performance Test (SKT), and Neuropsychiatric Inventory (NPI). While the majority of synthesized clinical trials show that Ginkgo biloba has promising potential for the treatment of these conditions, more research is needed to determine optimal dosages, effective delivery methods, and appropriate pharmaceutical formulations. Furthermore, a thorough assessment of adverse effects, exploration of long-term use implications, and investigation into potential drug interactions are critical aspects that must be carefully evaluated in future studies.

Proposed protocol for post COVID-19 cognitive rehabilitation for attention and memory.

Since the beginning of the COVID-19 pandemic, many people suffered from Long Covid Syndrome, in which affected individuals do not recover immediately after the end of the infectious and inflammatory process caused by the virus. The most common neuropsychological symptoms of this syndrome are: memory decline, lack of attention, anxiety and depression. Objective: The purpose of this study was to develop a proposed cognitive rehabilitation protocol for post-COVID individuals with cognitive symptoms. Methods: A rehabilitation proposed protocol focusing on attention and memory was developed, based on the tests used in the neuropsychological evaluation of affected patients. Researchers held weekly sessions for six months, each lasting 60 minutes. Homework activities were also assigned and corrected in the following session. The attention and memory sessions were conducted with activities based on the applied tests. Results: Despite the methodological separation of attention and memory, the activities indirectly affect other cognitive functions and abilities, such as executive function, language, reasoning, execution strategies, and cognitive flexibility. A computer, a sheet of paper, and a pen were used to present the slides for the activities. Attention training included all types of attention: sustained, alternating, selective and divided. Memory training sessions included activities that stimulated both short-term and long-term memory. With each session, the difficulty of the activities was gradually increased. Conclusion: Cognitive rehabilitation already has more consolidated evidence about its effectiveness for the treatment of other pathologies, so it can be thought that it will also be a promising strategy for COVID-19 too.

Desde o início da pandemia de COVID-19, muitas pessoas sofreram com a síndrome da COVID longa, em que os indivíduos afetados não se recuperam após o término do processo infeccioso e inflamatório causado pelo vírus. Os sintomas neuropsicológicos mais comuns dessa síndrome são: declínio da memória, falta de atenção, ansiedade e depressão. Objetivo: Desenvolver uma proposta de protocolo de reabilitação cognitiva para indivíduos pós-COVID com sintomas cognitivos. Métodos: Foi desenvolvida uma proposta de protocolo de reabilitação com foco na atenção e na memória, baseada nos testes utilizados na avaliação neuropsicológica dos pacientes afetados. Os pesquisadores realizaram sessões semanais durante seis meses, cada uma com duração de 60 minutos. As atividades de lição de casa também foram atribuídas e corrigidas na sessão seguinte. As sessões de atenção e memória foram realizadas com atividades baseadas nos testes aplicados. Resultados: Apesar da separação metodológica entre atenção e memória, as atividades afetam indiretamente outras funções e habilidades cognitivas, como função executiva, linguagem, raciocínio, estratégias de execução e flexibilidade cognitiva. Foram utilizados computador, folha de papel e caneta para a apresentação dos slides das atividades. O treinamento da atenção incluiu todos os tipos de atenção: sustentada, alternada, seletiva e dividida. As sessões de treinamento de memória incluíram atividades que estimularam memória de curto e longo prazo. A cada sessão, a dificuldade das atividades foi aumentando gradativamente. Conclusão: A reabilitação cognitiva já possui evidências mais consolidadas sobre a sua eficácia para o tratamento de outras patologias, pelo que se pode pensar que na COVID-19 será também uma estratégia promissora.

Post-COVID-19 cognitive symptoms in patients assisted by a teleassistance service: a retrospective cohort study.

Introduction: Four years after the onset of the COVID-19 pandemic, the frequency of long-term post-COVID-19 cognitive symptoms is a matter of concern given the impact it may have on the work and quality of life of affected people. Objective: To evaluate the incidence of post-acute COVID-19 cognitive symptoms, as well as the associated risk factors. Methods: Retrospective cohort, including outpatients with laboratory-confirmed COVID-19 and who were assisted by a public telehealth service provided by the Telehealth Network of Minas Gerais (TNMG), during the acute phase of the disease, between December/2020 and March/2022. Data were collected through a structured questionnaire, applied via phone calls, regarding the persistence of COVID-19 symptoms after 12 weeks of the disease. Cognitive symptoms were defined as any of the following: memory loss, problems concentrating, word finding difficulties, and difficulty thinking clearly. Results: From 630 patients who responded to the questionnaire, 23.7% presented cognitive symptoms at 12 weeks after infection. These patients had a higher median age (33 [IQR 25-46] vs. 30 [IQR 24-42] years-old, p = 0.042) with a higher prevalence in the female sex (80.5% vs. 62.2%, p < 0.001) when compared to those who did not present cognitive symptoms, as well as a lower prevalence of smoking (8.7% vs. 16.2%, p = 0.024). Furthermore, patients with persistent cognitive symptoms were more likely to have been infected during the second wave of COVID-19 rather than the third (31.0% vs. 21.3%, p = 0.014). Patients who needed to seek in-person care during the acute phase of the disease were more likely to report post-acute cognitive symptoms (21.5% vs. 9.3%, p < 0,001). In multivariate logistic regression analysis, cognitive symptoms were associated with female sex (OR 2.24, CI 95% 1.41-3.57), fatigue (OR 2.33, CI 95% 1.19-4.56), depression (OR 5.37, CI 95% 2.19-13.15) and the need for seek in-person care during acute COVID-19 (OR 2.23, CI 95% 1.30-3.81). Conclusion: In this retrospective cohort of patients with mostly mild COVID-19, cognitive symptoms were present in 23.7% of patients with COVID-19 at 12 weeks after infection. Female sex, fatigue, depression and the need to seek in-person care during acute COVID-19 were the risk factors independently associated with this condition.

Long COVID: neurological manifestations - an updated narrative review.

Infection with the SARS-CoV-2 virus can lead to neurological symptoms in the acute phase and in the Long COVID phase. These symptoms usually involve cognition, sleep, smell disorders, psychiatric manifestations, headache and others. This condition is more commonly described in young adults and women. This symptomatology can follow severe or mild cases of the disease. The importance of this issue resides in the high prevalence of neurological symptoms in the Long COVID phase, which entails significant morbidity in this population. In addition, such a condition is associated with high health care costs, with some estimates hovering around 3.7 trillion US dollars. In this review, we will sequentially describe the current knowledge about the most prevalent neurological symptoms in Long COVID, as well as their pathophysiology and possible biomarkers.

A infecção pelo vírus SARS-CoV-2 pode levar a sintomas neurológicos na fase aguda e na fase de COVID longa. Esses sintomas geralmente envolvem cognição, sono, distúrbios do olfato, manifestações psiquiátricas, dor de cabeça e outros. Esta condição é mais comumente descrita em adultos jovens e mulheres. A sintomatologia pode acompanhar casos graves ou leves da doença. A importância desta questão reside na elevada prevalência de sintomas neurológicos na fase de COVID longa, o que acarreta morbilidade significativa nesta população. Além disso, tal condição está associada a elevados custos de cuidados de saúde, com algumas estimativas em torno de 3,7 trilhões de dólares americanos. Nesta revisão, descrevemos sequencialmente o conhecimento atual sobre os sintomas neurológicos mais prevalentes na COVID longa, bem como sua fisiopatologia e possíveis biomarcadores.

Cognitive impairment and neuropsychiatric symptoms among individuals with history of symptomatic SARS-CoV-2 infection: a retrospective longitudinal study.

COVID-19 is a multisystem disease caused by the RNA virus (coronavirus 2 or SARS-CoV-2) that can impact cognitive measures. Objective: To identify the main cognitive and neuropsychiatric symptoms in adults who had no cognitive complaints prior to the infection. Specifically, to observe the trajectory of cognitive and neuropsychiatric performance after 6 months. Methods: This is a retrospective longitudinal study. Forty-nine patients (29 reassessed after 6 months), with a positive PCR test, with no prior cognitive complaints that only presented after the infection and without a history of structural, neurodegenerative or psychiatric neurological diseases. A brief cognitive assessment battery (MoCA), the Trail Making Test (TMT-A, B, ∆), and the Verbal Fluency Test were used, as well as the scales (Hospital Anxiety and Depression Scale-HADS, Fatigue Severity Scale-FSS). Correlation tests and group comparison were used for descriptive and inferential statistics. Level of significance of α=5%. Results: Mean age of 50.4 (11.3), 12.7 (2.8) years of education, higher percentage of women (69.8%). No psycho-emotional improvement (depression and anxiety) was observed between the evaluations, and patients maintained the subjective complaint of cognitive changes. The HAD-Anxiety scale showed a significant correlation with TMT-B errors. The subgroup participating in cognitive stimulation and psychoeducation showed improvement in the global cognition measure and the executive attention test. Conclusion: Our results corroborate other studies that found that cognitive dysfunctions in post-COVID-19 patients can persist for months after disease remission, as well as psycho-emotional symptoms, even in individuals with mild infection. Future studies, with an increase in casuistry and control samples, are necessary for greater evidence of these results.

A COVID-19 é uma doença multissistêmica causada pelo vírus RNA (coronavírus 2 ou SARS-CoV-2) que pode ocasionar repercussão em medidas cognitivas. Objetivo: Identificar os principais sintomas cognitivos e neuropsiquiátricos em adultos sem queixas cognitivas anteriores à infecção. Especificamente, verificar a trajetória do desempenho cognitivo e neuropsiquiátrico após 6 meses. Métodos: Trata-se de um estudo retrospectivo e longitudinal. Foram incluídos 49 pacientes (29 reavaliados após 6 meses), com exame de PCR positivo, sem queixas cognitivas prévias que só se apresentaram após a infecção ou histórico de doenças neurológicas estruturais ou neurodegenerativas. Foram utilizados a bateria de avaliação cognitiva breve (MoCA), o Teste de Trilhas (TMT-A, B e ∆) e o Teste de Fluência Verbal; assim como a Escala Hospitalar de Ansiedade e Depressão (HADS), e a escala de Severidade da Fadiga (ESF/BR). Testes de correlação e comparação de grupos foram utilizados para estatística descritiva e inferencial. Esta ocorreu através de. Nível de significância de α=5%. Resultados: idade média de 50,4 anos (11,3), anos de escolaridade 12,7 (2,8), maior proporção de mulheres (69,8%). Não foi observada melhora psicoemocional (depressão e ansiedade) entre as avaliações, assim como os pacientes mantiveram a queixa subjetiva de alteração cognitiva. A escala HAD-Ansiedade apresentou correlação significativa com os erros do TMT-B. O subgrupo que participou da estimulação cognitiva e psicoeducação apresentou melhora na medida de cognição global e no teste de atenção executiva. Conclusão: Nossos resultados corroboram com os demais estudos que constataram que a disfunção cognitiva em pacientes pós-COVID-19 pode persistir por meses após a remissão da doença, assim como sintomas psicoemocionais, mesmo em indivíduos com quadros leves da infecção. Estudos futuros, com aumento de casuística e amostras de controle, são necessários para maior evidência desses resultados.

Frailty and brain changes in older adults without cognitive impairment: A scoping review.

Little is known about changes in the brain associated with frailty, in particular, which brain areas could be related to frailty in older people without cognitive impairment. This scoping review mapped evidence on functional and/or structural brain changes in frail older adults without cognitive impairment. The methodology proposed by the JBI® was used in this study. The search in PubMed, PubMed PMC, BVS/BIREME, EBSCOHOST, Scopus, Web of Science, Embase, and PROQUEST was conducted up to January 2023. Studies included following the population, concepts, context and the screening and data extraction were performed by two independent reviewers. A total of 9,912 records were identified, 5,676 were duplicates and were excluded. The remaining articles were screened; 31 were read in full and 17 articles were included. The results showed that lesions in white matter hyperintensities, reduced volume of the hippocampus, cerebellum, middle frontal gyrus, low gray matter volume, cortical atrophy, decreased connectivity of the supplementary motor area, presence of amyloid-beta peptide (aß) in the anterior and posterior putamen and precuneus regions were more frequently observed in frail older adults, compared with non-frail individuals. Studies have suggested that such findings may be of neurodegenerative or cerebrovascular origin. The identification of these brain alterations in frail older adults through neuroimaging studies contributes to our understanding of the underlying mechanisms of frailty. Such findings may have implications for the early detection of frailty and implementation of intervention strategies.

Long-Term Environmental Methylmercury Exposure Is Associated with Peripheral Neuropathy and Cognitive Impairment among an Amazon Indigenous Population.

Widespread contamination of the Amazon basin with mercury has been reported to occur since at least the mid-80s due to heavy gold mining activity. Although initial studies have indicated that this may lead to deleterious neurological consequences to the indigenous populations living in the region, further research is needed to better characterize the neurological burden of such long-term exposure. With this aim, a cross-sectional exploratory study has been conducted with the Yanomami indigenous population residing in a northern Amazon region. All participants underwent a structured interview; detailed neurological examination, including assessment for cognitive, motor, coordination, and sensory functions; and laboratorial testing for serum hemoglobin, blood glucose, and methylmercury levels in hair samples. This study enrolled 154 individuals of 30.9 ± 16.8 years of age, of which 56.1% were female. Mean methylmercury levels in hair were 3.9 ± 1.7 µg/g. Methylmercury levels in hair > 6.0 µg/g were found in 10.3%. Among participants with hair methylmercury levels ≥ 6.0 µg/g, the prevalences of peripheral neuropathy and reduced cognitive performance were, respectively, 78.8% (95%CI 15-177%, p = 0.010) and 95.9% (95%CI 16-230.8%, p = 0.012) higher than those of individuals with lower levels. These results suggest that chronic mercury exposure may lead to significant and potentially irreversible neurotoxicity to Yanomami population living in the northern Amazon basin.

Inhibidores de la bomba de protones: el impacto en la salud cognitiva de los adultos mayores / Proton pump inhibitors: the impact on cognitive health in older adults

RESUMEN Los inhibidores de la bomba de protones (IBP) son los medicamentos más potentes para inhibir la secreción gástrica ácida, y se utilizan en el tratamiento de la mayor parte de las afecciones inflamatorias de la mucosa gástrica. Forman parte de los fármacos más recetados y sobreprescritos en todo el mundo; por ejemplo, en los Estados Unidos, según la Encuesta nacional de salud y nutrición, casi duplicaron su uso en los adultos de 40 años de un 4,9 % hasta un 8,3 %, entre los años 1999 a 2012. Aunque, en general, se consideran bien tolerados, algunos estudios epidemiológicos ―que extraen información a partir de grandes bases de datos― han reportado una serie de efectos adversos asociados con su uso prolongado, entre los cuales están el deterioro cognitivo, la enfermedad renal crónica, el infarto de miocardio, el accidente cerebrovascular, las fracturas óseas e incluso la muerte, entre otros. El objetivo fue realizar una revisión narrativa de la literatura acerca de los efectos del uso crónico de los IBP sobre el deterioro cognitivo en los adultos mayores. Se revisaron artículos a partir de una búsqueda en las bases de datos Pudmed, Scopus y Scielo con las palabras clave y términos Mesh/DeCS relacionados tanto en inglés como en español. Los efectos secundarios a nivel neurológico inducidos por el uso crónico de los IBP pueden estar relacionados indirectamente con la presencia de alteraciones sistémicas secundarias (deficiencia de magnesio y vitamina B12) o con efectos directos sobre el funcionamiento neuronal después de pasar a través de la barrera hematoencefálica. Si bien se han descrito varios mecanismos neurobiológicos por medio de los cuales los IBP podrían favorecer el desarrollo de la demencia ―que comprenden el funcionamiento de la proteína tau, la acumulación de beta amiloide (βA) y la deficiencia de cobalamina, entre otros―, la mayor parte de la evidencia clínica disponible no ha encontrado una asociación significativa entre el uso de los IBP y el riesgo de demencia o el deterioro cognitivo. Para establecer de una manera más clara los efectos clínicos adversos del uso crónico de los IBP, en especial, en el funcionamiento cerebral, se necesitan estudios de cohorte bien diseñados, con tamaños de muestra grandes y periodos de seguimiento prolongados, con un método confiable para ajustar los factores de confusión estandarizados y, además, realizar análisis por subgrupos.

ABSTRACT Proton pump inhibitors (PPIs) are the most potent drugs to inhibit gastric acid secretion, being used in the treatment of most inflammatory conditions of the gastric mucosa. They are among the most prescribed and overprescribed medications worldwide; for example, in the United States, according to the National Health and Nutrition Examination Survey, they almost doubled their use in adults aged 40 years and older from 4.9 % to 8.3 % between 1999 and 2012. Although they are generally considered well tolerated, some epidemiological studies extracting information from large databases have reported a number of adverse effects associated with their prolonged use, including cognitive impairment, chronic kidney disease, myocardial infarction, stroke, bone fractures and even death, among others. The objective was to conduct a narrative review of the literature on the effects of chronic use of PPIs on cognitive impairment in older adults. Articles were reviewed based on a search in the PubMed, Scopus and SciELO databases using both English and Spanish keywords and related MeSH/DeCS terms. Neurological side effects induced by chronic PPI use may be indirectly related to secondary systemic disorders (magnesium and vitamin B12 deficiency) or to direct effects on neuronal functioning after passing through the blood-brain barrier. Although several neurobiological mechanisms by which PPIs could favor the development of dementia-which involve Tau protein function, beta-amyloid [βA] accumulation and cobalamin deficiency, among others-have been described, most of the available clinical evidence has not shown a significant association between PPI use and the risk of dementia or cognitive impairment. To establish the adverse clinical effects of chronic PPI use more clearly, especially on brain functioning, well-designed cohort studies with large sample sizes and long follow-up periods, with a reliable method to adjust for standardized confounders, as well as subgroup analyses are needed.