Neuropsychological profile in tuberous sclerosis complex: a study of clinical and cognitive variables in a cohort from Brazil.

BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder with a wide clinical, cognitive, and behavioral expressivity. OBJECTIVE: To assess the neuropsychological profile of individuals clinically diagnosed with TSC and the factors that could significantly impact their cognitive development. METHODS: A total of 62 individuals with ages ranging from 3 to 38 years were followed up in a tertiary attention hospital in Southern Brazil, and they were assessed using a standard battery and the Vineland Adaptive Behavior Scales, when intellectual disability was observed. RESULTS: History of epilepsy was found in 56 participants (90.3%), and 31 (50%) presented an intellectual disability. Among the other half of TSC individuals without intellectual disability, 8 (12.9%) presented borderline classification, 20 (32.2%) presented average scores, and 3 (4.8%) were above average. In total, 17 participants (27.4%) fulfilled the diagnostic criteria for autism spectrum disorder. The results of the multiple linear regression analysis suggested that seizures, age at diagnosis, visual perception, and general attention significantly impact cognitive performance indexes. CONCLUSION: The present study suggests that the occurrence of epileptic seizures and older age at diagnosis contribute to higher impairment in the domains of cognitive development, underlining the importance of early diagnosis and the prevention of epileptic seizures or their rapid control. The development of attentional skills, visual perception, and executive functions must be followed up.

ANTECEDENTES: O complexo da esclerose tuberosa (CET) é uma doença genética autossômica dominante com ampla expressividade clínica, cognitiva e comportamental. OBJETIVO: Avaliar o perfil neuropsicológico de indivíduos com diagnóstico clínico de CET e os fatores que poderiam impactar significativamente o seu desenvolvimento cognitivo. MéTODOS: Ao todo, 62 indivíduos com idades entre 3 e 38 anos foram acompanhados em um hospital terciário do Sul do Brasil e avaliados por meio de uma bateria padrão e das Escalas de Comportamento Adaptativo Vineland, quando observada deficiência intelectual. RESULTADOS: Encontrou-se histórico de epilepsia em 56 participantes (90,3%) e de deficiência intelectual em 31 (50%). Quanto à outra metade dos indivíduos com CET sem deficiência intelectual, 8 (12,9%) apresentaram classificação limítrofe, 20 (32,2%) apresentaram pontuações médias e 3 (4,8%) estavam acima da média. No total, 17 participantes (27,4%) preenchiam os critérios diagnósticos para o transtorno do espectro autista. Os resultados da análise de regressão linear múltipla sugeriram que as crises epilépticas, a idade ao diagnóstico, a percepção visual e a atenção geral impactam significativamente os índices de desempenho cognitivo. CONCLUSãO: Este estudo sugere que a ocorrência de crises epilépticas e a maior idade ao diagnóstico contribuem para um maior comprometimento nos domínios do desenvolvimento cognitivo, e destaca-se a importância do diagnóstico precoce e da prevenção das crises epilépticas ou do seu rápido controle. O desenvolvimento de habilidades de atenção, percepção visual e funções executivas deve ser acompanhado.

Predictive values of pre-treatment brain age models to rTMS effects in neurocognitive disorder with depression: Secondary analysis of a randomised sham-controlled clinical trial.

INTRODUCTION: One major challenge in developing personalised repetitive transcranial magnetic stimulation (rTMS) is that the treatment responses exhibited high inter-individual variations. Brain morphometry might contribute to these variations. This study sought to determine whether individual's brain morphometry could predict the rTMS responders and remitters. METHODS: This was a secondary analysis of data from a randomised clinical trial that included fifty-five patients over the age of 60 with both comorbid depression and neurocognitive disorder. Based on magnetic resonance imaging scans, estimated brain age was calculated with morphometric features using a support vector machine. Brain-predicted age difference (brain-PAD) was computed as the difference between brain age and chronological age. RESULTS: The rTMS responders and remitters had younger brain age. Every additional year of brain-PAD decreased the odds of relieving depressive symptoms by ∼25.7% in responders (Odd ratio [OR] = 0.743, p = .045) and by ∼39.5% in remitters (OR = 0.605, p = .022) in active rTMS group. Using brain-PAD score as a feature, responder-nonresponder classification accuracies of 85% (3rd week) and 84% (12th week), respectively were achieved. CONCLUSION: In elderly patients, younger brain age appears to be associated with better treatment responses to active rTMS. Pre-treatment brain age models informed by morphometry might be used as an indicator to stratify suitable patients for rTMS treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: ChiCTR-IOR-16008191.

Neuropsychological Evaluation in Traumatic Brain Injury.

Neuropsychological evaluations can be helpful in the aftermath of traumatic brain injury. Cognitive functioning is assessed using standardized assessment tools and by comparing an individual's scores on testing to normative data. These evaluations examine objective cognitive functioning as well as other factors that have been shown to influence performance on cognitive tests (eg, psychiatric conditions, sleep) in an attempt to answer a specific question from referring providers. Referral questions may focus on the extent of impairment, the trajectory of recovery, or ability to return to work, sport, or the other previous activity.

Menopause and brain fog: how to counsel and treat midlife women.

Brain fog, referring to menopause-related subjective cognitive difficulties, is common in midlife women. Longitudinal studies find small but reliable declines in objective memory performance as women transition into perimenopause, and these are not explained by advancing age alone. When memory declines occur, performance levels remain within normal limits for all but a very small number of women. Women's experience of brain fog extends beyond memory complaints, reflecting the negative effect on a broad range of cognitive abilities. Clinicians can counsel women about how menopause symptoms, estrogen, hormone therapy, and modifiable risk factors (eg, hypertension, sedentary lifestyle) can influence cognitive health.

[Decreased appetite is associated with a decreased cognitive function in elderly patients with diabetes].

OBJECTIVE: To examine the relationship between decreased appetite and the cognitive function in elderly diabetic patients. METHODS: The study subjects were outpatients with diabetes who were 60 years of age or older, and who were managed at Ise Red Cross Hospital. The cognitive function was assessed using a self-administered Dementia Checklist. The Japanese version of the Simplified Nutritional Appetite Questionnaire (SNAQ) was used to measure decreased appetite. A logistic regression analysis, in which the dependent variable was cognitive decline and the explanatory variables were appetite loss and adjustment variables, was used to calculate the odds ratio for cognitive decline according to the presence of appetite loss. RESULTS: Four hundred eighty patients were included in the analysis. Seventeen percent of the patients had decreased appetite and 21% had a decreased cognitive function. The unadjusted and adjusted odds ratios of cognitive decline for those with decreased appetite were 2.78 (95% confidence interval (CI), 1.66-4.65; P<0.001) and 2.26 (95% CI, 1.16-4.37; P=0.015), respectively, based on the absence of decreased appetite. CONCLUSION: Decreased appetite in elderly patients with diabetes was associated with a decreased cognitive function.

Screening instruments of cognition: The relation of the mini-mental state examination to the Edinburgh cognitive and behavioural ALS screen in amyotrophic lateral sclerosis.

OBJECTIVE: The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) is an established cognitive screening instrument for patients with amyotrophic lateral sclerosis (ALS). Different from tools like the Mini-Mental State Examination (MMSE), it is adjusted for motor impairment, yet, the latter remains one of the most widely used screening instruments, also in ALS studies. Thus, it is of utmost importance to relate outcome scores of both instruments to allow for comparison in ALS patients. This study reports on the performance of ALS patients in both tests with regard to incidence and degree of cognitive impairment, and the correspondence of both, ECAS and MMSE scores. METHODS: We examined N = 84 ALS patients with the German versions of the ECAS and the MMSE. Performance in both tests regarding incidence and degree of cognitive impairment, and correspondence of frequency of cognitive impairment according to both tests was examined. The relationship between ECAS and MMSE scores was modelled with a non-linear regression model. RESULTS: All ALS patients were able to complete the ECAS, 89.3% (N = 75) were capable to complete the MMSE. Prevalence of cognitive impairment was in both tests 22.7%, however agreement was only 52.9%. Despite, regression analyses yielded a strong positive relationship (adjusted R2 = .68) between the ECAS total score and the MMSE total score. Both tests were able to identify all patients with dementia. CONCLUSION: These results suggest that the MMSE is not ideal for cognitive screening in early-stage ALS patients. However, a rough translation of MMSE scores in ECAS scores is possible to estimate the cognitive performance level of patients, with the ECAS being more discriminative in the lower range of cognitive dysfunction (ECAS score: 80-136), for which the MMSE does not define cognitive impairment (corresponding MMSE score: 27-30).

Nimodipine Protects Vascular and Cognitive Function in an Animal Model of Cerebral Small Vessel Disease.

BACKGROUND: Cerebral small vessel disease is a common cause of vascular cognitive impairment and dementia. There is an urgent need for preventative treatments for vascular cognitive impairment and dementia, and reducing vascular dysfunction may provide a therapeutic route. Here, we investigate whether the chronic administration of nimodipine, a central nervous system-selective dihydropyridine calcium channel blocking agent, protects vascular, metabolic, and cognitive function in an animal model of cerebral small vessel disease, the spontaneously hypertensive stroke-prone rat. METHODS: Male spontaneously hypertensive stroke-prone rats were randomly allocated to receive either a placebo (n=24) or nimodipine (n=24) diet between 3 and 6 months of age. Animals were examined daily for any neurological deficits, and vascular function was assessed in terms of neurovascular and neurometabolic coupling at 3 and 6 months of age, and cerebrovascular reactivity at 6 months of age. Cognitive function was evaluated using the novel object recognition test at 6 months of age. RESULTS: Six untreated control animals were terminated prematurely due to strokes, including one due to seizure, but no treated animals experienced strokes and so had a higher survival (P=0.0088). Vascular function was significantly impaired with disease progression, but nimodipine treatment partially preserved neurovascular coupling and neurometabolic coupling, indicated by larger (P<0.001) and more prompt responses (P<0.01), and less habituation upon repeated stimulation (P<0.01). Also, animals treated with nimodipine showed greater cerebrovascular reactivity, indicated by larger dilation of arterioles (P=0.015) and an increase in blood flow velocity (P=0.001). This protection of vascular and metabolic function achieved by nimodipine treatment was associated with better cognitive function (P<0.001) in the treated animals. CONCLUSIONS: Chronic treatment with nimodipine protects from strokes, and vascular and cognitive deficits in spontaneously hypertensive stroke-prone rat. Nimodipine may provide an effective preventive treatment for stroke and cognitive decline in cerebral small vessel disease.

Prevention, Assessment, and Management of Malnutrition in Older Adults with Early Stages of Cognitive Disorders.

Malnutrition is common in older adults, and its risk is greater in those living with dementia. Relative to cognitively healthy peers, the prevalence of malnutrition is also increased in individuals with early stages of cognitive disorders owing to pathophysiological, cognitive, and psychosocial changes related to cognitive impairment. Malnutrition is associated with adverse health outcomes, including faster cognitive and functional decline. Here, we provide an overview of the prevention, assessment, and management of malnutrition in older adults, with a special focus on the aspects that are important to consider in individuals with early stages of cognitive disorders. Strategies to prevent malnutrition include systematic screening for malnourishment using validated tools to detect those at risk. If the screening reveals an increased risk of malnutrition, a detailed assessment including the individual's nutritional, medical, and functional status as well as dietary intake should be performed. The management of malnutrition in the early stages of cognitive disorders should be based on the findings of a comprehensive assessment and be personalized according to the individual's specific characteristics. In the article, we also provide an overview of the evidence on vitamin supplements and specific dietary patterns to prevent cognitive decline or attenuate its progression.

[Uric acid, cognitive disorders, neurodegeneration].

This article examines the role of uric acid (UA) in cognitive changes and neurodegeneration, focusing on its functions as an antioxidant and prooxidant. Research suggests that changes in serum UA levels may be associated with the development or delay of cognitive impairment, especially in the context of neurodegenerative diseases such as Alzheimer's disease. It was revealed that there is a relationship between the level of UA and the dynamics of cognitive functions, indicating the potential neuroprotective properties of UA. Particular attention is paid to the balance between the antioxidant and prooxidant properties of UA, which may play a key role in protecting neurons from damage. However, research results are not clear-cut, highlighting the need for further research to more fully understand the role of UA in cognitive processes. Determining the optimal serum UA level may be an important step in developing strategies for the prevention and treatment of cognitive impairment associated with neurodegeneration. Overall, these studies advance the understanding of the mechanisms underlying the interaction between uric acid metabolism and brain health.

Characterisation of young stroke presentations, pathways of care, and support for 'invisible' difficulties: a retrospective clinical audit study.

Background Young stroke survivors are likely to be discharged home from acute hospital care without rehabilitation more quickly than older survivors, but it is not clear why. File-audit studies capturing real-world clinical practice are lacking for this cohort. We aimed to compare characteristics and care pathways of young and older survivors and describe stroke presentations and predictors of pathways of care in young survivors (≤45years), including a focus on care received for 'invisible' (cognitive, psychological) difficulties. Methods A retrospective audit of 847 medical records (67 young stroke survivors, mean age=36years; 780 older patients, mean age=70years) was completed for stroke survivors admitted to an Australian tertiary hospital. Stroke characteristics and presence of cognitive difficulties (identified through clinician opinion or cognitive screening) were used to predict length of stay and discharge destination in young stroke survivors. Results There were no differences in length of stay between young and older survivors, however, young stroke survivors were more likely to be discharged home without rehabilitation (though this may be due to milder strokes observed in young stroke survivors). For young stroke survivors, stroke severity and age predicted discharge destination, while cognitive difficulties predicted longer length of stay. While almost all young survivors were offered occupational therapy and physiotherapy, none received psychological input (clinical, health or neuropsychology). Conclusions Cognitive and psychological needs of young stroke survivors may remain largely unmet by a service model designed for older people. Findings can inform service development or models of care, such as the new Australian Young Stroke Service designed to better meet the needs of young survivors.

Atypical semantic cognition in schizotypal personality disorder and borderline personality disorder.

Increased schizotypal traits have previously been associated with atypical semantic cognition in community samples. However, no study has yet examined whether adults diagnosed with schizotypal personality disorder (SPD) display atypical semantic fluency and memory. We hypothesized that 24 adults diagnosed with SPD would name more idiosyncratic words on the semantic fluency task and show decreased semantic recall for animal and fruit category words compared with 29 participants with borderline personality disorder (BPD) and a community sample of 96 age-matched controls. We examined whether atypical semantic cognition was specifically associated with disorganized and eccentric speech and thinking, or more broadly with pathological personality traits and personality functioning. Our main hypothesis was confirmed, as the SPD participants named more idiosyncratic words and recalled fewer semantically related words compared with controls. Surprisingly, participants with BPD likewise named more atypical words compared with controls. More idiosyncratic semantic fluency was associated with more eccentric speech and thinking. Increased idiosyncratic semantic fluency and reduced semantic recall were both coupled to increased detachment and lowered personality functioning, while reduced semantic recall further was related to increased interpersonal problems. Our findings suggest that persons with SPD, and to a lesser degree BPD, show atypical semantic cognition, which is associated with eccentric speech and thinking, and more broadly with impaired personality function, social withdrawal, and emotional flatness. The idiosyncratic semantic cognition may worsen difficulties with social reciprocity seen in SPD and BPD.

Oral anticoagulants and cognitive impairment in patients with atrial fibrillation: A systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: This systematic review assesses the likelihood of developing dementia and cognitive impairment in patients with atrial fibrillation (AF) receiving non-vitamin K antagonist oral anticoagulants (NOACs) as opposed to vitamin K antagonists (VKAs). METHODS: We performed a systematic review with meta-analysis and trial sequential analysis (TSA), which encompassed both randomized controlled trials (RCTs) and observational studies. The objective was to assess the impact of NOACs and VKAs on the incidence of dementia in individuals diagnosed with AF. RESULTS: Out of 1914 studies that were screened, 31 studies were included in the final analysis, which consisted of nine RCTs or their subsequent post-hoc analyses, in addition to 22 observational studies. The meta-analysis shows that NOACs were associated with a decreased probability of developing dementia of any cause [Rate Ratio (RR): 0.88; 95 % confidence interval (95 % CI): 0.82-0.94], especially in patients below the age of 75 (RR: 0.78; 95 % CI: 0.73-0.84). Consistent patterns were observed across all forms of dementia and cognitive function decline. The overall evidence indicates notable variability in the outcome with a moderate-to-low degree of certainty. The TSA suggests that the total sample size of the included trials (155,647 patients) was significantly smaller than the required information size of 784,692 patients to discern the true effect of NOAC versus VKA in terms of reducing dementia risk. CONCLUSION: NOACs may reduce the likelihood of developing dementia in patients with AF, particularly in those under the age of 75. This review highlights the urgent necessity for thorough research to determine the efficacy of NOACs in safeguarding cognitive health.

The association of insulin responses and insulin sensitivity with cognition in adults with pre-diabetes: The Diabetes Prevention Program Outcomes Study.

OBJECTIVE: Dysglycemia is a significant risk factor for cognitive impairment. However, which pathophysiologic determinant(s) of dysglycemia, impaired insulin sensitivity (ISens) or the islet ß-cell's response (IResp), contribute to poorer cognitive function, independent of dysglycemia is not established. Among 1052 adults with pre-diabetes from the Diabetes Prevention Program Outcomes Study (DPPOS), we investigated the relationship between IResp, ISens and cognitive function. RESEARCH DESIGN AND METHODS: IResp was estimated by the insulinogenic index (IGI; pmol/mmol) and ISens as 1/fasting insulin from repeated annual oral glucose tolerance tests. The mean IResp and mean ISens were calculated over approximately 12 years of follow-up. Verbal learning (Spanish-English Verbal Learning Test [SEVLT]) and executive function (Digital Symbol Substitution Test [DSST]) were assessed at the end of the follow-up period. Linear regression models were run for each cognitive outcome and were adjusted for dysglycemia and other factors. RESULTS: Higher IResp was associated with poorer performance on the DSST (-0.69 points per 100 unit increase in IGI, 95 % CI: -1.37, -0.01). ISens was not associated with DSST, nor were IResp or ISens associated with performance on the SEVLT. CONCLUSIONS: These results suggest that a greater ß-cell response in people at high risk for type 2 diabetes is associated with poorer executive function, independent of dysglycemia and ISens.

Attenuated adiponectin, omentin, increased interleukin-6 and tumor necrosis factor-alpha levels with altered cognition and depression in non-Hodgkin lymphoma patients: A case-control study.

BACKGROUND AND PURPOSE: Immune dysfunction is one of the risk factors which plays an important role in the development of non-Hodgkin lymphoma (NHL), and inflammation may be involved in its etiology. Minimal data is available on the effect of cytokine levels on neurobehavioral function in lymphoma before the initiation of chemotherapy. Therefore, we aimed to explore the risk of NHL by assessment of cytokine and adipokine levels and their correlation with neurobehavioral changes. METHODS: This case-control study enrolled 62 subjects (age-sex matched: 31 cases and 31 controls). Neurobehavioral assessment was done using Montreal Cognitive Assessment questionnaire (MoCA) and Patient Health Questionnaire (PHQ-9). EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) was used to assess quality of life. Questionnaire assessment and sample collection were done after the patient enrolment and before first cycle of chemotherapy. RESULTS: Mean age of NHL patients and healthy controls was 51.9 ± 11.8 and 50 ± 10.9 years, respectively. NHL patients showed significantly higher levels of IL-6 (0.77 ± 0.11) and TNF- α (1.47 ± 1.31) than controls (0.55 ± 0.4 and 0.66 ± 0.89, respectively) with p-value<0.005. Also, NHL patients showed significantly lower levels of adiponectin (0.31 ± 0.24) and omentin (0.46 ± 0.1) than controls (0.42 ± 0.13 and 0.53 ± 0.11, respectively) with p-value<0.005. Lower MoCA and EORTC QLQ C-30 scores and higher PHQ-9 scores were observed in NHL patients in comparison to healthy control. CONCLUSION: Our results showed that adiponectin, omentin IL-6 and TNF-α may be used as pre-diagnostic markers of NHL risk. Neurobehavioral changes observed in NHL patients may alter the quality of life.

Effectiveness of Psychobiotics in the Treatment of Psychiatric and Cognitive Disorders: A Systematic Review of Randomized Clinical Trials.

In this study, a systematic review of randomized clinical trials conducted from January 2000 to December 2023 was performed to examine the efficacy of psychobiotics-probiotics beneficial to mental health via the gut-brain axis-in adults with psychiatric and cognitive disorders. Out of the 51 studies involving 3353 patients where half received psychobiotics, there was a notably high measurement of effectiveness specifically in the treatment of depression symptoms. Most participants were older and female, with treatments commonly utilizing strains of Lactobacillus and Bifidobacteria over periods ranging from 4 to 24 weeks. Although there was a general agreement on the effectiveness of psychobiotics, the variability in treatment approaches and clinical presentations limits the comparability and generalization of the findings. This underscores the need for more personalized treatment optimization and a deeper investigation into the mechanisms through which psychobiotics act. The research corroborates the therapeutic potential of psychobiotics and represents progress in the management of psychiatric and cognitive disorders.