Impaired exploration induced by type 1 diabetes is related to locomotor activity rather than a reduction in motivation.

Type 1 diabetes mellitus (T1D) is associated with cognitive impairments in humans. A well-established animal model of T1D is induced through the administration of streptozotocin (STZ), a glucose analog that induces pancreatic ß-cell death, resulting in hyperglycemia and cognitive impairment linked to neuroinflammation and oxidative stress. Tumor necrosis factor (TNF)-α, a key inflammatory mediator, is elevated in the central nervous system (CNS) of diabetic animals. In this study, we utilized TNFR1 knockout mice to investigate the role of TNFR1 signaling in short-term T1D-related cognitive impairment. Our findings showed that diabetic animals did not develop cognitive damage within the first 2 weeks of T1D but exhibited reduced exploration in all behavioral tests. Our findings suggest that this reduction in exploration was attributable to motor impairment, as there was no reduction in motivated novelty-seeking behavior. Additionally, deletion of TNFR1 signaling attenuated gait speed impairment in diabetic mice, but did not affect other motor-related or exploratory behaviors.

An alpha 5-GABAA receptor positive allosteric modulator attenuates social and cognitive deficits without changing dopamine system hyperactivity in rats exposed to valproic acid in utero.

Autism spectrum disorders (ASDs) are characterized by core behavioral symptoms in the domains of sociability, language/communication, and repetitive or stereotyped behaviors. Deficits in the prefrontal and hippocampal excitatory/inhibitory balance due to a functional loss of GABAergic interneurons are proposed to underlie these symptoms. Increasing the postsynaptic effects of GABA with compounds that selectively modulate GABAergic receptors could be a potential target for treating ASD symptoms. In addition, deficits in GABAergic interneurons have been linked to dopamine (DA) system dysregulation, and, despite conflicting evidence, abnormalities in the DA system activity may underly some ASD symptoms. Here, we investigated whether the positive allosteric modulator of α5-containing GABAA receptors (α5-GABAARs) SH-053-2'F-R-CH3 (10 mg/kg) attenuates behavioral abnormalities in rats exposed to valproic acid (VPA) in utero, an established risk factor for autism. We also evaluated if animals exposed to VPA in utero present changes in the ventral tegmental area (VTA) DA system activity using in vivo electrophysiology and if SH-053-2'F-R-CH3 could attenuate these changes. SH-053-2'F-R-CH3 was administered intraperitoneally 30 min before each behavioral test and electrophysiology. In utero VPA exposure caused male and female rats to present increased repetitive behavior (self-grooming) in early adolescence and deficits in social interaction in adulthood. Male, but not female VPA rats, also presented deficits in recognition memory as adults. SH-053-2'F-R-CH3 attenuated the impairments in sociability and cognitive function in male VPA-exposed rats without attenuating the decreased social interaction in females. Adult male and female VPA-exposed rats also showed an increased VTA DA neuron population activity, which was not changed by SH-053-2'F-R-CH3. Despite sex differences, our findings indicate that α5-GABAARs positive allosteric modulators may effectively attenuate some core ASD symptoms.

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 relationship between cognitive function and functional capacity, and cognitive reserve and reaction time in patients with multiple sclerosis.

BACKGROUND: Cognitive dysfunction is frequently seen in multiple sclerosis (MS). However, there are conflicting findings regarding the factors it is associated with. OBJECTIVE: To investigate the relationship between aerobic capacity, strength, disability, depression, fatigue, and cognitive reserve and function. METHODS: The mobile applications Trail Making Test (TMT A-B), Digit Span Test (DST), Visuospatial Memory Test (VSMT), and Tap Fast were used in the cognitive function evaluation. Functional performance was assessed with the 6-minute walk test (6MWT), 5-Time Sit-to-Sand (5STS) test, and grip strength. Cognitive Reserve Index (CRI), Beck Depression Inventory, Fatigue Severity Scale (FSS), and Nottingham Health Profile were also used. RESULTS: A significant difference was found between the MS and control groups only in the 6MWT, STS-5, grip strength, TMT, VSMT, and Tap Fast. Good correlation was found between the TMT-A and 6MWT and physical mobility. A fair correlation was shown between grip strength, energy, and pain status. A good correlation was found between TMT-B and 6MWT, and a fair relationship with disability, cognitive reserve, and pain. Good correlation was observed between the DST and 6MWT, left grip strength, pain, and energy status; fair correlations were found between right grip strength, cognitive reserve, and physical mobility. Good correlation was found between the VSMT and energy. A fair relationship between disability, cognitive reserve, and pain was demonstrated. Good correlation was observed between the Tap Fast score and disability, 5STS, FSS, energy, and physical mobility. A fair relationship was found between pain and social isolation. CONCLUSION: It has been shown that cognitive performance in MS is related to disability, functional performance, cognitive reserve, fatigue, and general health. TRIAL REGISTRATION: NCT06084182.

ANTECEDENTES: A disfunção cognitiva é frequentemente observada na esclerose múltipla (EM). No entanto, existem resultados conflitantes sobre os fatores aos quais está associada. OBJETIVO: Investigar a relação entre capacidade aeróbica, força, incapacidade, depressão, fadiga e reserva e função cognitiva. MéTODOS: Os aplicativos móveis Trail Making Test (TMT A-B), Digit Span Test (DST), Visuoespacial Memory Test (VSMT) e Tap Fast foram utilizados na avaliação da função cognitiva. O desempenho funcional foi avaliado por meio do teste de caminhada de 6 minutos (TC6), Teste de Sentar-Levantar Cinco Vezes (TSL5) e força de preensão manual. Também foram utilizados Índice de Reserva Cognitiva (IRC), Inventário de Depressão de Beck, Escala de Gravidade de Fadiga (EGF) e Perfil de Saúde de Nottingham. RESULTADOS: Foi encontrada diferença significativa entre os grupos EM e controle apenas no TC6, TSL5, força de preensão, TMT, VSMT e Tap Fast. Foi encontrada boa correlação entre o TMT-A e o TC6 e a mobilidade física. Foi demonstrada uma correlação razoável entre força de preensão, energia e estado de dor. Foi encontrada uma boa correlação entre o TMT-B e o TC6, e uma relação razoável com incapacidade, reserva cognitiva e dor. Foi observada boa correlação entre o DST e o TC6, força de preensão esquerda, dor e estado energético; correlações justas foram encontradas entre força de preensão direita, reserva cognitiva e mobilidade física. Foi encontrada boa correlação entre o VSMT e a energia. Foi demonstrada uma relação justa entre incapacidade, reserva cognitiva e dor. Foi observada boa correlação entre o escore Tap Fast e incapacidade, TLS5, EGF, energia e mobilidade física. Foi encontrada uma relação justa entre dor e isolamento social. CONCLUSãO: Foi demonstrado que o desempenho cognitivo na EM está relacionado com incapacidade, desempenho funcional, reserva cognitiva, fadiga e saúde geral. REGISTRO DE TESTE: NCT06084182.

Assessment of cognitive function in elderly patients with heart failure.

OBJECTIVE: To compare the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) tests for the identification of cognitive deficit (CD) in elderly patients with heart failure (HF). METHODS: This was a cross-sectional study with an observational design involving 43 elderly patients with HF of both sexes, treated by the Unified Health System, who were able to understand and follow the study instructions. A sociodemographic and clinical questionnaire and the MMSE and MoCA neurocognitive tests were applied. RESULTS: The mean age of the patients was 67 years; 67.44% were male; 53.49% were white; 58.14% had 1-4 years of schooling; 58.14% had an income of half to one minimum wage; 55.81% were married; 53.49% had a family history of HF; 90.7% denied smoking; 83.72% denied alcohol intake; 65.12% did not practice physical activity; 83.72% were hypertensive; 30.23% were diabetic; 57.89% had LVEF ≥ 50%; 39.53% have NYHA II; and 88.37% did not have a pacemaker. In the identification of CD, the MMSE test detected it in 25.58% of the patients, while the MoCA test identified it in 23.26% (p=0.043). CONCLUSION: It was concluded that the MMSE test performed better than the MoCA test in the identification of CD in elderly patients with HF.

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.

Regional-based static and dynamic alterations in Alzheimer disease: a longitudinal study.

BACKGROUND: Alzheimer disease (AD) leads to cognitive decline and alters functional connectivity (FC) in key brain regions. Resting-state functional magnetic resonance imaging (rs-fMRI) assesses these changes using static-FC for overall correlation and dynamic-FC for temporal variability. OBJECTIVE: In AD, there is altered FC compared to normal conditions. The present study investigates possible region-specific functional abnormalities occurring longitudinally over 1 year. Our aim is to evaluate the potential usefulness of the static and dynamic approaches in identifying biomarkers of AD progression. METHODS: The study involved 15 AD and 20 healthy participants from the Alzheimer's Disease Neuroimaging Initiative 2 (ADNI2) database, tracked over 2 visits within 1 year. Using constrained-independent component analysis, we assessed FC changes across 80-regions of interest in AD over the year, examining both static and dynamic conditions. RESULTS: The average regional FC decreased in AD compared to healthy subjects at baseline and after 1 year. The dynamic condition identifies similarities with a few additional changes in the FC compared to the static condition. In both analyses, the baseline assessment revealed reduced connectivity between the following regions: right-middle-occipital and left-superior-occipital, left-hippocampus and right-postcentral, left-lingual and left-fusiform, and precuneus and left-thalamus. Additionally, increased connectivity was found between the left-superior-occipital and precuneus regions. In the 1-year AD assessment, increased connectivity was noted between the right-superior-temporal-pole and right-insular, right-hippocampus and left-caudate, right-middle-occipital and right-superior-temporal-pole, and posterior-cingulate-cortex and middle-temporal-pole regions. CONCLUSION: Significant changes were observed at baseline in the frontal, occipital, and core basal-ganglia regions, progressing towards the temporal lobe and subcortical regions in the following year. After 1 year, we observed the aforementioned region-specific neurological differences in AD, significantly aiding diagnosis and disease tracking.

ANTECEDENTES: A doença de Alzheimer (DA) leva ao declínio cognitivo e altera a conectividade funcional (CF) em regiões-chave do cérebro. A ressonância magnética funcional em estado de repouso (rs-fMRI) avalia essas alterações usando CF estática para correlação geral e CF dinâmica para variabilidade temporal. OBJETIVO: Na DA, há CF alterada em relação às condições normais. O presente estudo investiga possíveis anormalidades funcionais específicas da região que ocorrem longitudinalmente ao longo de um ano. Nosso objetivo é avaliar a utilidade potencial das abordagens estáticas e dinâmicas na identificação de biomarcadores da progressão da DA. MéTODOS: O estudo envolveu 15 participantes com DA e 20 participantes saudáveis do banco de dados da Iniciativa de Neuroimagem da Doença de Alzheimer 2 (ADNI2), rastreados em duas visitas no período de um ano. Usando análise de componentes independentes e restritos, avaliamos as mudanças de CF em 80 regiões de interesse na DA ao longo do ano, examinando condições estáticas e dinâmicas. RESULTADOS: A CF regional média diminuiu na DA em comparação com indivíduos saudáveis no início do estudo e após um ano. A condição dinâmica identifica semelhanças com algumas alterações adicionais na CF em comparação com a condição estática. Em ambas as análises, a avaliação inicial revelou conectividade reduzida entre as seguintes regiões: occipital médio direito e occipital superior esquerdo, hipocampo esquerdo e pós-central direito, lingual esquerdo e fusiforme esquerdo, e precuneus e tálamo esquerdo. Além disso, foi encontrada maior conectividade entre as regiões occipital superior esquerda e precuneus. Na avaliação de DA de um ano, foi observada conectividade aumentada entre o polo temporal superior direito e o insular direito, o hipocampo direito e o caudado esquerdo, occipital médio direito e o polo temporal superior direito, e regiões posteriores do córtex cingulado e do polo temporal médio. CONCLUSãO: Mudanças significativas foram observadas no início do estudo nas regiões frontal, occipital e dos gânglios basais centrais, progredindo em direção ao lobo temporal e regiões subcorticais no ano seguinte. Após um ano, observamos as diferenças neurológicas específicas da região acima mencionadas na DA, auxiliando significativamente no diagnóstico e no rastreamento da doença.

Association Between Subclinical Thyroid Dysfunction and Cognitive Decline: Findings From the ELSA-Brasil Study.

BACKGROUND: Thyroid dysfunction has been associated with cognitive decline and dementia. However, the role of subtle thyroid hormone alterations in cognitive function is still debatable. METHODS: Participants without overt thyroid dysfunction aged 35-74 years at baseline were evaluated in 3 study waves (2008-2010, 2012-2014, and 2017-2019). We assessed baseline thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3). Cognitive performance was evaluated every 4 years in each wave using 10-word immediate and late recall, word recognition, semantic (animals category) and phonemic (letter f) verbal fluency, and the trail-making B-version tests. A global composite z-score was derived from these tests. The associations of TSH, FT4, and FT3 levels with cognitive decline over time were evaluated using linear mixed-effect models adjusted for sociodemographic, clinical, and lifestyle variables. RESULTS: In 9 524 participants (mean age 51.2 ±â€…8.9 years old, 51% women, 52% White), there was no association between baseline TSH, FT4, and FT3 levels and cognitive decline during the follow-up. However, increase in FT4 levels over time was associated with faster memory (ß = -0.004, 95% CI = -0.007; -0.001, p = .014), verbal fluency (ß = -0.003, 95% CI = -0.007; -0.0005, p = .021), executive function (ß = -0.004, 95% CI = -0.011; -0.003, p < .001), and global cognition decline (ß = -0.003, 95% CI = -0.006; -0.001, p = .001). Decrease in FT4 levels over time was associated with faster verbal fluency (ß = -0.003, 95% CI = -0.007; -0.0004, p = .025) and executive function (ß = -0.004, 95% CI = -0.007; -0.0003, p = .031) decline. CONCLUSIONS: An increase or decrease in FT4 levels over time was associated with faster cognitive decline in middle-aged and older adults without overt thyroid dysfunction during 8 years of follow-up.

Glutamatergic Neurotransmission in Aging and Neurodegenerative Diseases: A Potential Target to Improve Cognitive Impairment in Aging.

Aging is characterized by the decline in many of the individual's capabilities. It has been recognized that the brain undergoes structural and functional changes during aging that are occasionally associated with the development of neurodegenerative diseases. In this sense, altered glutamatergic neurotransmission, which involves the release, binding, reuptake, and degradation of glutamate (Glu) in the brain, has been widely studied in physiological and pathophysiological aging. In particular, changes in glutamatergic neurotransmission are exacerbated during neurodegenerative diseases and are associated with cognitive impairment, characterized by difficulties in memory, learning, concentration, and decision-making. Thus, in the present manuscript, we aim to highlight the relevance of glutamatergic neurotransmission during cognitive impairment to develop novel strategies to prevent, ameliorate, or delay cognitive decline. To achieve this goal, we provide a comprehensive review of the changes reported in glutamatergic neurotransmission components, such as Glu transporters and receptors during physiological aging and in the most studied neurodegenerative diseases. Finally, we describe the current therapeutic strategies developed to target glutamatergic neurotransmission.

Elderly people with hearing loss and cognitive decline: speech perception performance in noise. / Idosos com perda auditiva e declínio cognitivo: desempenho da percepção de fala no ruído.

PURPOSE: To verify the influence of verbal intellectual-cognitive skills on speech perception in noise, in elderly with sensorineural hearing loss, considering education, age, and degree of hearing loss. METHODS: 36 elderly between 60 and 89 years old with bilateral sensorineural hearing loss participated in the study. After psychological assessment using the Wechsler Intelligence Scale for Adults (WAIS-III), they were grouped into (GI) 24 elderly without cognitive alteration and (GII) 12 elderly with risk of cognitive alteration. They underwent otorhinolaryngological assessment, audiological interview, pure tone audiometry, and assessment of speech perception in noise using the Hearing in Noise Test (HINT-Brazil). The Mann-Whitney U statistical test compared the results between the groups, and the Spearman correlation verified the variable's age, degree of hearing loss, and level of education. RESULTS: There was no difference between the groups in the ability to perceive speech in noise, except in the noise on the left condition, in which GII showed better performance in HINT-Brazil. The degree of hearing loss and level of education influenced the perception of speech in noise. The level of education was correlated with the WAIS-III results. CONCLUSION: The decline in verbal intellectual-cognitive skills did not affect speech perception of noise in the elderly with hearing loss. The degree of hearing loss and level of education influenced the performance of the elderly in the speech perception test in noise. Performance in verbal cognitive skills varied according to the level of education.

OBJETIVO: Verificar a influência das habilidades intelectuais-cognitivas verbais na percepção de fala no ruído, em idosos com perda auditiva sensorioneural, considerando a escolaridade, a idade e o grau da perda auditiva. MÉTODO: Participaram 36 idosos entre 60 e 89 anos com perda auditiva sensorioneural bilateral, que após avaliação psicológica por meio do Wechsler Intelligence Scale for Adults (WAIS III), foram divididos em (GI) 24 idosos sem alteração cognitiva e (GII) 12 idosos com risco de alteração cognitiva. Foram submetidos à avaliação otorrinolaringológica, entrevista audiológica, audiometria tonal liminar e a avaliação da percepção de fala no ruído por meio do Hearing in Noise Test (HINT-Brasil). O teste estatístico U de Mann-Whitney comparou os resultados entre os grupos, e a correlação de Spearman verificou as variáveis idade, grau da perda auditiva e nível de escolaridade. RESULTADOS: Não houve diferença entre os grupos na habilidade de percepção de fala no ruído, exceto na condição ruído à esquerda, no qual o GII apresentou melhor desempenho no HINT-Brasil. O grau da perda auditiva e o nível de escolaridade influenciaram na percepção de fala no ruído. O nível de escolaridade teve correlação com os resultados do WAIS III. CONCLUSÃO: O declínio das habilidades intelectuais-cognitivas verbais não interferiu na percepção de fala no ruído nos idosos com perda auditiva. O grau da perda auditiva e o nível de escolaridade influenciaram no desempenho dos idosos no teste de percepção de fala no ruído. O desempenho nas habilidades cognitivas verbais variou com o nível de escolaridade.

Differences between Alzheimer's disease and mild cognitive impairment using brain networks from magnetic resonance texture analysis.

Several studies have aimed at identifying biomarkers in the initial phases of Alzheimer's disease (AD). Conversely, texture features, such as those from gray-level co-occurrence matrices (GLCMs), have highlighted important information from several types of medical images. More recently, texture-based brain networks have been shown to provide useful information in characterizing healthy individuals. However, no studies have yet explored the use of this type of network in the context of AD. This work aimed to employ texture brain networks to investigate the distinction between groups of patients with amnestic mild cognitive impairment (aMCI) and mild dementia due to AD, and a group of healthy subjects. Magnetic resonance (MR) images from the three groups acquired at two instances were used. Images were segmented and GLCM texture parameters were calculated for each region. Structural brain networks were generated using regions as nodes and the similarity among texture parameters as links, and graph theory was used to compute five network measures. An ANCOVA was performed for each network measure to assess statistical differences between groups. The thalamus showed significant differences between aMCI and AD patients for four network measures for the right hemisphere and one network measure for the left hemisphere. There were also significant differences between controls and AD patients for the left hippocampus, right superior parietal lobule, and right thalamus-one network measure each. These findings represent changes in the texture of these regions which can be associated with the cortical volume and thickness atrophies reported in the literature for AD. The texture networks showed potential to differentiate between aMCI and AD patients, as well as between controls and AD patients, offering a new tool to help understand these conditions and eventually aid early intervention and personalized treatment, thereby improving patient outcomes and advancing AD research.

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.

Association between gait speed deterioration and EEG abnormalities.

Physical and cognitive decline at an older age is preceded by changes that accumulate over time until they become clinically evident difficulties. These changes, frequently overlooked by patients and health professionals, may respond better than fully established conditions to strategies designed to prevent disabilities and dependence in later life. The objective of this study was twofold; to provide further support for the need to screen for early functional changes in older adults and to look for an early association between decline in mobility and cognition. A cross-sectional cohort study was conducted on 95 active functionally independent community-dwelling older adults in Havana, Cuba. We measured their gait speed at the usual pace and the cognitive status using the MMSE. A value of 0.8 m/s was used as the cut-off point to decide whether they presented a decline in gait speed. A quantitative analysis of their EEG at rest was also performed to look for an associated subclinical decline in brain function. Results show that 70% of the sample had a gait speed deterioration (i.e., lower than 0.8 m/s), of which 80% also had an abnormal EEG frequency composition for their age. While there was no statistically significant difference in the MMSE score between participants with a gait speed above and below the selected cut-off, individuals with MMSE scores below 25 also had a gait speed<0.8 m/s and an abnormal EEG frequency composition. Our results provide further evidence of early decline in older adults-even if still independent and active-and point to the need for clinical pathways that incorporate screening and early intervention targeted at early deterioration to prolong the years of functional life in older age.

Shedding Light on the Effects of Blood Pressure on Cognitive Decline and Dementia Risk by Way of Neurobiological Evidence.

Midlife cerebrovascular risk factors increase risk of late life cognitive impairment and dementia, while their presence in patients with dementia may lead to cognitive improvement or stabilization in late life. Defining the best measure of blood pressure (BP) to be associated with cognitive decline remains debatable, also due to possible bidirectionality. BP variability, pulse pressure, systolic and diastolic BP have been associated with cognitive status, dementia risk and Alzheimer's disease biomarkers. Proper BP control notwithstanding, BP variability increases risk for pathophysiological change in the Alzheimer's disease continuum, implying the need for selection of anti-hypertensive drugs with neurobiological evidence of benefits.

Observational evidence of the association between physical and psychological determinants of aging with cognition in older adults.

Aging involves physical and cognitive deterioration in older adults. Detecting predictors of dementia early is crucial to identify its onset. This study aimed to associate physical and psychological determinants with cognitive performance in older adults. Observational study with 221 older adults, classified according to cognitive impairment. We evaluated cognitive function by Mini-Mental State Examination. Physical determinants encompassed muscle strength, functional mobility, and cardiorespiratory fitness, while psychological consisted of quality of life and activities of daily living. Multiple linear regression was performed to investigate this relationship. Physical and psychological determinants were significantly linked to cognitive impairment, including lower muscle strength, reduced functional mobility and of cardiorespiratory fitness. The influence of environment, autonomy, and engagement in daily activities on cognitive impairment was also observed. The analysis of physical and psychological determinants could help to aid in distinguishing individuals with cognitive impairment.

Cognitive function is associated with performance in time up and go test and with leptin blood levels in community-dwelling older women.

Considering the challenge that cognitive dysfunction and dementia represent to health is imperative to prioritize early diagnosis strategies and explore the pathophysiological mechanisms. There is no consensus on specific markers and physical tests that indicate cognitive decline in older. The objective of this study was to evaluate a panel of inflammatory biomarkers and physical function and investigate their association with cognitive function in community-dwelling older women. Seventy-one participants were included in this study. Cognitive function was assessed by Mini Mental State Examination, muscle strength using dynamometer, body composition using Dual X-ray absorptiometry, respiratory muscle strength using manuvacuometer, and physical function using the Short Physical Performance Battery and Time Up and Go (TUG) tests. Blood samples were collected to analyze a panel of inflammatory biomarkers. The cognitive function was associated with TUG (ß = - 0.48; 95%IC = - 0.54 to - 0.21; p < 0.001), inspiratory muscle strength (ß = 0.30; 95%IC = 0.005-0.03; p = 0.009), and leptin concentrations (ß = 0.32; 95% IC = 0.001-0.006; 0.007). Time spent on TUG test and leptin levels accounted for 27% of variability in cognitive function independent of age. Poorer physical function with leptin plasma levels is associated with decreased cognitive function in older women. These findings contribute to comprehension of pathophysiology underlying cognitive decline and informing the development of new approaches to prevent, diagnose, monitoring and treat cognitive decline in aging.

Cognitive impairment and its association with clinical variables in Mexican persons with neuromyelitis optica spectrum disorder.

INTRODUCTION: Cognitive impairment has a substantial impact on the daily function of people living with demyelinating diseases. However, the study of cognitive failures and their association with clinical variables in people suffering from neuromyelitis optica spectrum disorder (NMOSD) has been scarce, especially in the latin american (Mexican) population at early and middle stages of the disease. METHOD: We applied the Rao's Brief Repeatable Battery of Neuropsychological tests and obtained data of lesion burden through magnetic resonance imaging (MRI), expression of AQPQ4-IgG antibodies, and degree of disability in 30 patients with NMOSD and 30 healthy participants as a control group. RESULTS: About half of the NMOSD patients (47%) showed some degree of cognitive impairment, especially in the executive domain compared to the control group. Executive function scores were positively associated with the degree of physical disability. We found no associations between cognitive dysfunction and disease duration, AQPQ4-IgG antibodies, lesion burden, nor depression. CONCLUSIONS: Executive functioning impairment is present in NMOSD and may predict the degree of functional disability in patients. Cognitive failures were not associated with immunological or radiological data, which emphasizes the relevance of applying systematic neuropsychological assessments in this clinical population.

Neurocognition and brain functional connectivity in a non-clinical population-based sample with psychotic experiences.

We characterized the neurocognitive profile of communed-based individuals and unaffected siblings of patients with psychosis from Brazil reporting psychotic experiences (PEs). We also analyzed associations between PEs and the intra and inter-functional connectivity (FC) in the Default Mode Network (DMN), the Fronto-Parietal Network (FPN) and the Salience Network (SN) measured by functional magnetic resonance imaging. The combined sample of communed-based individuals and unaffected siblings of patients with psychosis comprised 417 (neurocognition) and 85 (FC) volunteers who were divided as having low (<75th percentile) and high (≥75th percentile) PEs (positive, negative, and depressive dimensions) assessed by the Community Assessment of Psychic Experiences. The neurocognitive profile and the estimated current brief intellectual quotient (IQ) were assessed using the digit symbol (processing speed), arithmetic (working memory), block design (visual learning) and information (verbal learning) subtests of Wechsler Adult Intelligence Scale-third edition. Logistic regression models were performed for neurocognitive analysis. For neuroimaging, we used the CONN toolbox to assess FC between the specified regions, and ROI-to-ROI analysis. In the combined sample, high PEs (all dimensions) were related to lower processing speed performance. High negative PEs were related to poor visual learning performance and lower IQ, while high depressive PEs were associated with poor working memory performance. Those with high negative PEs presented FPN hypoconnectivity between the right and left lateral prefrontal cortex. There were no associations between PEs and the DMN and SN FC. Brazilian individuals with high PEs showed neurocognitive impairments like those living in wealthier countries. Hypoconnectivity in the FPN in a community sample with high PEs is coherent with the hypothesis of functional dysconnectivity in schizophrenia.

Perfil cognitivo en el Mareo Perceptual Postural Persistente: Implicancias sobre su fisiopatología como disfunción cognitiva viso-vestibular superior / Cognitive profile in Persistent Postural Perceptual Dizziness: Implications on its pathophysiology as a superior visio-vestibular cognitive dysfunction

Introducción: El mareo perceptual postural persistente (MPPP) es, probablemente, la causa más prevalente de mareo crónico. Sin embargo, su fisiopatología es aún motivo de duda y debate. En el presente artículo, proponemos que el MPPP se caracteriza por disfunciones cognitivas de orden superior, al punto de diferenciarse en estas dimensiones de controles sanos y pacientes con patologías vestibulares no-MPPP. Objetivo: Determinar si pacientes con MPPP presentan alteraciones discriminantes respecto a grupos controles, en ámbitos de atención, memoria de trabajo visoespacial, planificación espacial, funciones ejecutivas y rendimiento cognitivo global. Material y Método: Estudio descriptivo transversal con sujetos de entre 18 y 65 años, reclutados de una unidad de otoneurología ambulatoria. Se aplicaron pruebas Montreal Cognitive Assessment (MoCA), tarea de retención de dígitos, Trail Making Test, Corsi Block-Tapping Task y Torre de Londres. Resultados: 30 pacientes fueron categorizados en tres grupos: grupo MPPP (n = 14), grupo vestibular no-MPPP (n = 11) y grupo control (n = 5). El grupo MPPP exhibió un rendimiento significativamente inferior en pruebas de planificación, velocidad de procesamiento y funciones ejecutivas en ámbitos visoespaciales, mientras que en atención y memoria visoespacial no hubo diferencias entre grupos. Conclusión: El MPPP podría caracterizarse por una disfunción de procesos cognitivos superiores de construcción espacial de mayor complejidad, respetando funciones visoespaciales de menor orden como la memoria de trabajo. Estos hallazgos ofrecen nuevas luces para comprender la fisiopatología del MPPP y sus implicancias clínicas.

Introduction: Persistent postural-perceptual dizziness (PPPD) is probably the most prevalent cause of chronic dizziness. However, its pathophysiology is still a matter of uncertainty and debate. In this article, we propose that PPPD is characterized by higher-order cognitive dysfunctions, to the point of differentiating it from healthy controls and patients with non-PPPD vestibular pathologies. Aim: To determine whether patients with PPPD exhibit discriminant alterations compared to control groups in the areas of attention, visuospatial working memory, spatial planning, executive functions, and global cognitive performance. Materials and Methods: A cross-sectional descriptive study was conducted with subjects between the ages of 18 and 65 years, recruited from an outpatient otoneurology unit. Tests included the Montreal Cognitive Assessment (MoCA), digit retention task, Trail Making Test, Corsi Block-Tapping Task, and the Tower of London. Results: 30 patients were categorized into three groups: PPPD group (n = 14), non-PPPD vestibular group (n = 11), and control group (n = 5). The PPPD group showed significantly lower performance on tests of planning, processing speed, and executive function in visuospatial domains, while there were no differences between groups in attention and visuospatial memory. Conclusion: PPPD may be characterized by dysfunction of higher-order cognitive processes related to spatial construction of greater complexity, while sparing lower-order visuospatial functions such as working memory. These findings offer new insights into the pathophysiology of PPPD and its clinical implications.

Disfunção cognitiva canina: tratamentos disponíveis / Canine cognitive dysfunction: Available treatments

A disfunção cognitiva canina (DCC) é uma enfermidade que causa alterações fisiológicas e comportamentais em cães idosos, e que apresenta uma fisiopatogenia semelhante à doença de Alzheimer (DA), que acomete seres humanos. Os sinais clínicos são representados pela sigla DISHA (desorientação, mudanças na interação com pessoas/animais, alterações no ciclo sono-vigília, falha no aprendizado/memória e nível de atividades alteradas). A principal forma de diagnóstico da doença é baseada em um questionário respondido pelo tutor, relacionado ao comportamento do animal. O tratamento é multimodal, consistindo basicamente em uso de fármacos, mudanças na alimentação, e enriquecimento ambiental e mental. Os fármacos utilizados são de diversas classes farmacológicas e agem diretamente em substâncias relacionadas com a fisiopatogenia da DCC, além de atenuarem alguns sinais clínicos da enfermidade. Essa ação dos fármacos é potencializada com a adição de alimentos específicos, enriquecimento do ambiente que o animal vive e estimulação mental, principalmente por meio de passeios. A união de todas essas modalidades de tratamento auxilia na melhoria do bem-estar do animal acometido. Como a disfunção não tem cura, o tratamento é longo e, muitas vezes, não é possível visualizar melhora evidente no animal. Dessa forma, alguns tutores acabam optando pela eutanásia. Apesar de ser frequente em cães idosos e haver uma ampla base literária acerca da DCC, não há um protocolo terapêutico específico. Sendo assim, há diversos tratamentos disponibilizados de forma isolada na literatura, fazendo com que os clínicos veterinários encontrem dificuldades para achar um compilado de informações em uma única fonte.

Canine cognitive dysfunction (CCD) is a disease that causes physiological and behavioral changes in elderly dogs and presents a physiopathogeny similar to Alzheimer's disease (AD), which affects humans. Clinical signs are represented by the acronym DISHA (disorientation, changes in interaction with people/animals, changes in the sleep-wake cycle, learning/memory failure, and altered activity level). The main form of diagnosis of illness is based on a questionnaire answered by the tutor, related to the animal behavior. The treatment is multimodal, basically consisting of drug use, changes in the diet, and environmental and mental enrichment. The drugs used are of various pharmacological classes and act directly on substances related to the physiopathogeny of CCD, besides attenuating some clinical signs of the disease. This drug action is enhanced with the addition of specific foods, enrichment of the environment where the animal lives and mental stimulation, mainly through tours. The union of all these treatment modalities helps to improve the welfare of the affected animal. As the disease has no cure, the treatment is long and it is often not possible to visualize evident improvement in the animal. In this way, some tutors opt for euthanasia. Despite being frequent in elderly dogs and there is a broad literature on CCD, there is no specific therapeutic protocol. There are several treatments available in isolation in the literature, causing veterinary clinicians find it difficult to locate a compilation of information from a single source.