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HIV-1-related neurocognitive impairment affects a significant proportion of people living with HIV, and accelerated brain aging has been implicated in its pathogenesis. This forum explores the application of cellular rejuvenation strategies to target molecular mechanisms of brain aging, promote neuronal health, and combat cognitive decline.
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Infecciones por VIH , VIH-1 , Humanos , Infecciones por VIH/complicaciones , Infecciones por VIH/terapia , Rejuvenecimiento , Envejecimiento/patología , Envejecimiento/psicología , EncéfaloRESUMEN
INTRODUCTION: Neurocognitive decline (NCD) is a common complication after cardiac surgery with implications for outcomes and quality of life. Identifying risk factors can help surgeons implement preventative measures, optimize modifiable risk factors, and counsel patients about risk and prognosis. METHODS: Prospective cohort study at a single academic center. 104 patients planned to undergo cardiac surgery were enrolled. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to measure neurocognitive function preoperatively, on postoperative day four, and postoperative day 30. NCD is defined as a change in RBANS scaled score of < -8 from baseline to postoperative day 4. Patient charts were reviewed for medication history: beta-blockers, angiotensin-converting enzyme and angiotensin receptor blockers, calcium channel blockers, statins, oral hypoglycemic agents, and psychoactive medications. Charts were also reviewed to calculate postoperative opioid usage. RESULTS: NCD was detected in 42.9% of patients. Incidence of NCD was significantly higher in patients taking a psychoactive medication (56.8%) than patients not (31.9%), P < 0.03. There was no relationship between historical use of beta-blocker, calcium-channel blocker, statin, or oral hypoglycemic medications and incidence of NCD. Simple linear regression showed no relationship between change in RBANS total scaled score and opioid usage. There was no difference in incidence of NCD at 1 mo. CONCLUSIONS: Patients with a history of taking psychoactive medications prior to cardiac surgery have an increased risk of acute postoperative NCD.
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Procedimientos Quirúrgicos Cardíacos , Enfermedades no Transmisibles , Humanos , Estudios Prospectivos , Analgésicos Opioides , Enfermedades no Transmisibles/tratamiento farmacológico , Calidad de Vida , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Bloqueadores de los Canales de Calcio/uso terapéutico , Antagonistas Adrenérgicos beta/efectos adversos , Factores de RiesgoRESUMEN
The objective of this paper is 1) to expand the scope of the domains previously published in a natural history study of Mucopolysaccharidosis IIIA (Sanfilippo syndrome type A) (MPS IIIA) and 2) to present evidence regarding the capacity of a new metric, Growth Scale Values (GSVs), in comparison with traditional metrics, to show changes in skills as assessed by the Bayley Scales of Infant Development -III (BSID-III) and the Vineland Adaptive Behavior Scales, Second Edition (VABS-II). We re-analyzed a cohort of 25 children, 20 with rapid progressing disease and 5 with slow progression, who had been followed over two years using the BSID-III, and the VABS-II. Previously findings were reported using age equivalent scores; now we are also presenting findings with GSVs. For the re-analysis, Language and Motor scores were added to the Cognitive scale on the BSID-III, and Domain- and Subdomain-level scores added to the Total VABS-II score (i.e., ABC Composite). We evaluated raw scores, age equivalent scores, and GSVs (and standard scores for the VABS-II only). Individual patient data can be found in the appendices to this publication. Results indicate that 1) Cognition as measured by GSVs was the most sensitive to decline; 2) GSVs showed significant decline in the range of 4 to 6 years of age; 3) For children under 4 years of age, positive growth occurs on most scales and most metrics, with the exception of language which slows somewhat earlier; 4) Other than the Cognitive scale, Receptive Language on the BSID-III and Receptive Communication on the VABS-II showed the most sensitivity to change; 5) Gross Motor skills showed the least decline over time and appeared to lack sensitivity to MPS IIIA motor concerns; and 6) No evidence for sensitivity to change for any metric was found in time intervals less than one year. We conclude that GSVs are a precise measurement of change to detect decline in function, and they are a valuable method for future clinical trials in MPS IIIA. Evidence continues to support cognition as a primary endpoint. Additional work is needed to identify sensitive measures of meaningful endpoints to families.
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Mucopolisacaridosis III , Niño , Lactante , Humanos , Preescolar , CogniciónRESUMEN
Introduction: Lung cancer is a major contributor of burden of disease globally. Early diagnosis plays a crucial role in determining the patient's prognosis. However, diagnostic constraints and healthcare-seeking behavior in rural areas contribute to the increased mortality and morbidity associated with this disease. Case presentation: The authors present a case that came in with mood and personality changes who was diagnosed with lung cancer with metastasis in the brain and did not seek health care services despite a prolonged duration of her neurocognitive symptoms. Clinical discussion: Rural communities face multiple barriers to early diagnosis and treatment, including healthcare-seeking behavior. It is crucial to develop policies aimed at addressing these barriers in order to enhance the health status of rural Nepal. Conclusion: The presentation of lung cancer with atypical symptoms can contribute to delays in diagnosis and treatment, ultimately impacting the overall prognosis of the patient. Late presentation to healthcare centers further exacerbates the burden of the disease, emphasizing the critical importance of proper healthcare-seeking behavior.
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Background and Objectives: The present study explored the utilization of verbal fluency (VF) cognitive strategies, including clustering, switching, intrusions, and perseverations, within both semantic (SVF) and phonemic (PVF) conditions, across a continuum of neurocognitive decline, spanning from normal cognitive ageing (NC) to mild cognitive impairment (MCI) and its subtypes, amnestic (aMCI) and non-amnestic (naMCI), as well as AD. Materials and Methods: The study sample was derived from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) cohort. The sample included 1607 NC individuals, 146 with aMCI (46 single-domain and 100 multi-domain), 92 with naMCI (41 single-domain and 51 multi-domain), and 79 with AD. Statistical analyses, adjusting for sex, age, and education, employed multivariate general linear models to probe differences among these groups. Results: Results showed that AD patients exhibited poorer performance in switching in both VF tasks and SVF clustering compared to NC. Similarly, the aMCI group performed worse than the NC in switching and clustering in both tasks, with aMCI performing similarly to AD, except for SVF switching. In contrast, the naMCI subgroup performed similarly to those with NC across most strategies, surpassing AD patients. Notably, the aMCI subgroup's poor performance in SVF switching was mainly due to the subpar performance of the multi-domain aMCI subgroup. This subgroup was outperformed in switching in both VF tasks by the single-domain naMCI, who also performed better than the multi-domain naMCI in SVF switching. No significant differences emerged in terms of perseverations and intrusions. Conclusions: Overall, these findings suggest a continuum of declining switching ability in the SVF task, with NC surpassing both aMCI and AD, and aMCI outperforming those with AD. The challenges in SVF switching suggest executive function impairment associated with multi-domain MCI, particularly driven by the multi-domain aMCI.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Enfermedad de Alzheimer/complicaciones , Cognición , Función Ejecutiva , Pruebas NeuropsicológicasRESUMEN
Background: Confusion and hallucinations in geriatric patients are frequent symptoms and typically associated with delirium, late-life psychosis or dementia syndromes. A far rarer but well-established differential in patients with rapid cognitive deterioration, acute psychosis, abnormal movements and seizures is autoimmune encephalitis. Exemplified by our case we highlight clinical and economic problems arising in management of geriatric patients with cognitive decline and psychotic symptoms. Case Presentation: A 77-year-old female caucasian patient with an unremarkable medical history was hospitalized after a fall in association with diarrhea and hyponatremia. Upon adequate therapy, disorientation and troubled short-term memory persisted. Within a week the patient developed visual hallucinations. Basic blood and urine samples and imaging (cranial computed tomography and magnetic resonance imaging) were unremarkable. With progressive cognitive decline, amnestic impairment, word finding difficulty and general apathy, psychiatric and neurologic expertise was introduced. Advanced diagnostics did not resolve a final diagnosis; an electroencephalogram showed unspecific generalized slowing. Extended clinical observation revealed visual hallucinations and faciobrachial dystonic seizures. A treatment with anticonvulsants was initiated. Cerebrospinal fluid ultimately tested positive for voltage-gated potassium channel LGl1 (leucine-rich-inactivated-1) antibodies confirming diagnosis of autoimmune anti-LGI1 encephalitis. Immediate immunotherapy (high-dose glucocorticoids and administration of intravenous immunoglobulin G) led to a rapid improvement of the patient's condition. After immunotherapy was tapered, the patient had one relapse and completely recovered with reintroduction of glucocorticoids and initiation of therapy with rituximab. Conclusion: Rapidly progressive dementia in geriatric patients demands a structured and multidisciplinary diagnostic approach. Accurate management and financially supportable care is a major issue in rare diseases such as anti-LGI1-encephalitis. Education and awareness about autoimmune encephalitis of all physicians treating a geriatric population is important in order to involve expertise and establish treatment within reasonable time.
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Demencia , Encefalitis , Encefalitis Límbica , Canales de Potasio con Entrada de Voltaje , Anciano , Anticonvulsivantes/uso terapéutico , Confusión/complicaciones , Confusión/tratamiento farmacológico , Demencia/complicaciones , Encefalitis/diagnóstico , Encefalitis/tratamiento farmacológico , Femenino , Alucinaciones/complicaciones , Alucinaciones/tratamiento farmacológico , Enfermedad de Hashimoto , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Péptidos y Proteínas de Señalización Intracelular/uso terapéutico , Leucina/uso terapéutico , Encefalitis Límbica/diagnóstico , Encefalitis Límbica/tratamiento farmacológico , Canales de Potasio con Entrada de Voltaje/uso terapéutico , Rituximab/uso terapéutico , Convulsiones/tratamiento farmacológico , Convulsiones/etiologíaRESUMEN
Achieving technical excellence in surgery can happen at any point of a surgical career. The accumulation of wisdom brought by the aging surgeon's decades of experience, however, can only come with time and practice. With the accumulated life and professional experience obtained, aging surgeons can still contribute a valuable perspective/point of view to young trainees and colleagues. This article reviews the current literature of the aging surgeon and suggests strategies for how aging surgeons can use their expertise in an innovative fashion to train and develop the future legacy of the specialty.
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Cirujanos , Humanos , EnvejecimientoRESUMEN
Due to the surge in new brain-directed treatments, metrics to detect the alteration in developmental trajectories in cognition and adaptive behavior have become increasingly important. We propose Growth Scale Values (GSVs) as a solution to monitoring children with severe neurologic/neurodegenerative conditions. This report stems from a panel of experts presenting at the Gorlin symposium (WORLD Symposium) and a subsequent open Webinar sponsored by the National MPS Society. Because norm-referenced scores (Standard Scores or Intelligence Quotient, i.e., IQ) do not yield information about gain, stability, or loss of skills, they are not suitable for natural history studies or clinical trials. Age-equivalent (AE) scores have been the standard metric used in natural history studies. While AEs are familiar and interpretable to clinicians and parents, they are imprecise due to lack of standard deviations, standard errors of measurement, and equal intervals between scores. Raw scores also have unequal intervals and are not comparable between ages or ability levels. The GSV, a nonlinear transformation of raw scores using item calibration to make an interval scale score, can be used for accurate measures of within-person change. GSVs have been identified as a useful metric for longitudinal measurement of other conditions involving neurodiversity. These growth scores circumvent inaccurate AEs in infants, are not limited by age and can be used for impaired patients who are chronologically above the normative age range. GSVs have interval properties (a given difference between GSV values represents the same difference in ability at all score levels) and each GSV value has a known standard error of measurement (SEM). GSVs are recommended to measure change in cognitive and adaptive behavior in natural history studies and in clinical trials for children with neurologic disease.
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Enfermedades Neurodegenerativas , Niño , Lactante , Humanos , Enfermedades Neurodegenerativas/diagnóstico , Pruebas de Inteligencia , CogniciónRESUMEN
Tumors of the central nervous system are the most common solid malignancies diagnosed in children. While common, they are also found to have some of the lowest survival rates of all malignancies. Treatment of childhood brain tumors often consists of operative gross total resection with adjuvant chemotherapy or radiotherapy. The current body of literature is largely inconclusive regarding the overall benefit of adjuvant chemo- or radiotherapy. However, it is known that both are associated with conditions that lower the quality of life in children who undergo those treatments. Chemotherapy is often associated with nausea, emesis, significant fatigue, immunosuppression, and alopecia. While radiotherapy can be effective for achieving local control, it is associated with late effects such as endocrine dysfunction, secondary malignancy, and neurocognitive decline. Advancements in radiotherapy grant both an increase in lifetime survival and an increased lifetime for survivors to contend with these late effects. In this review, the authors examined all the published literature, analyzing the results of clinical trials, case series, and technical notes on patients undergoing radiotherapy for the treatment of tumors of the central nervous system with a focus on neurocognitive decline and survival outcomes.
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Background: The survival of people living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome largely depends on good adherence to antiretroviral medications. Neuropsychiatric conditions such as major depressive disorders (MDDs) and neurocognitive disorders, in particular, are common in the HIV population and attributed to suboptimal adherence to antiretroviral treatment and overall poor clinical outcomes. This study aimed to determine the association between neurocognitive disorders and nonadherence to antiretroviral therapy (ART) in the Dodoma region's adult population living with HIV. Methods: The study was conducted in Dodoma Regional Referral Hospital using a cross-sectional design to assess 397 participants through a systematic sampling approach. Montreal Cognitive Assessment was used to determine neurocognitive function, while the Simplified Medical Adherence Questionnaire was used to assess nonadherence to ART. Logistic regression analysis was computed to determine the association between cognitive decline and nonadherence to ART while controlling for sociodemographic and clinical confounders. Results: Out of the 397 recruited participants, 266 (67.00%) and 41 (10.33%) met the criteria for neurocognitive decline and nonadherence to ART. Participants with cognitive impairment had a significantly poorer adherence rate than those without, even after controlling for confounders adjusted odds ratio (aOR): 2.183 (95% confidence interval [CI]: 1.031, 4.630, p = 0.0413). MDD was the only additional factor that remained significantly associated with ART nonadherence (aOR: 4.332, 95% CI: 1.634, 11.485, p = 0.0032). Conclusion: Neurocognitive disorders are strong predictor of suboptimal adherence to ART; a comorbid neuropsychiatric condition such as MDD may further compromise the ART adherence rate leading to poor HIV care and poor clinical outcome. Further research with systematic and more robust studies in the field will provide a baseline to design and integrate appropriate care models to maximize ART adherence in HIV care. Integration of psychiatric services in HIV care can benefit the overall patient outcome.
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Background: Older patients with cancer are more vulnerable to the effects of cognitive impairment affecting their functional status, quality of life, compliance to treatment and ultimately survival. Cancer-related cognitive impairment may be due to the cancer itself or due to the treatment of cancer. There are no data regarding the prevalence of cognitive impairment in older persons with cancer and brain metastasis. Methods: This retrospective analysis was conducted on a prospectively collected data set of patients who attended the geriatric oncology clinic at a tertiary care comprehensive cancer centre in India from June 2018 to July 2021. Patients aged 60 years and above with malignancy were included. Cognition was assessed with the mini-mental status examination (MMSE); the Hindi MMSE was used for illiterate patients. A score of ≤23 on the MMSE was considered abnormal. Correlation between the presence of cognitive impairment and brain metastasis was tested using the chi-square test. Results: A total of 597 patients were included, of which 462 (77.4%) were male. The median age was 69 years (range: 60-100 years). All patients had solid tumours; 244 (40.9%) had lung, 189 (31.7%) had gastrointestinal and 75 (12.6%) had head and neck malignancies. Forty-one (6.9%) patients had brain metastases, of which 10 (24.4%) had solitary, 30 (73.2%) had multiple lesions and 1 (2.4%) had leptomeningeal metastases. Cognitive impairment was noted in 11 (26.8%) of the 41 patients with brain metastases and 91 (16.4%) of the 556 patients without brain metastases. There was no significant correlation between the presence of brain metastases and cognitive impairment, p = 0.086. Conclusion: Older persons with cancer and brain metastases were not found to have a higher occurrence of cognitive impairment than those without brain metastases in this study. The next step is to understand whether older persons with brain metastases are at a higher risk for cognitive decline as a result of therapeutic interventions such as cranial radiotherapy and chemotherapy.
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DESCRIPTION: In June 2021, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved a joint clinical practice guideline for the management and rehabilitation care for those who have symptoms in the post-acute period following mild traumatic brain injury (mTBI). This synopsis describes some of the clinically important recommendations. METHODS: In January 2020, VA and DoD leaders assembled a joint VA/DoD guideline development team of multidisciplinary clinical stakeholders that developed key questions, systematically searched and evaluated the literature, created two 1-page algorithms, and refined 19 recommendations using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The process closely conformed to the National Academy of Medicine's tenets for trustworthy clinical practice guidelines. RECOMMENDATIONS: This synopsis describes clinically important recommendations for the management and rehabilitation of mTBI. Outpatient primary care providers are the target audience for this synopsis and guideline. The current recommendations are an update from the 2016 VA/DoD Clinical Practice Guidelines for the Management of Concussion-Mild Traumatic Brain Injury.
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Conmoción Encefálica , HumanosRESUMEN
Life expectancy in sub-Saharan African women is increasing, and by the late 2020s an estimated 76% of postmenopausal women globally will be living in developing countries. Menopause transition has been associated with cognitive decline in a wide range of studies, but data on cognition and reproductive aging are lacking in sub-Saharan African women. Approximately 72 million people in the region are expected to suffer from dementias and neurocognitive decline by 2050. Studies show that compromised cognitive health in low-income countries has significant implications for adult quality of life and socioeconomic development. There is now an urgent need to further examine risk factors for cognitive decline in these aging women and to understand the ability of public health programs to diagnose and treat cognitive dysfunction. This review examines studies assessing cognition and aging in sub-Saharan African adults, while addressing the significant research gaps. It examines data on the association of the menopause transition with cognitive function and describes how validated tools should be available to assess both menopausal stage and symptoms. Culturally appropriate and validated neurocognitive measures are required to better understand the relationship of reproductive aging with cognition. Longitudinal population-based studies are needed to assess the effect of lifestyle interventions, such as diet and exercise, on cognitive health in sub-Saharan African populations, with an emphasis on women as they transition into menopause.
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Envejecimiento , Trastornos del Conocimiento , Cognición , Calidad de Vida , África del Sur del Sahara/epidemiología , Trastornos del Conocimiento/epidemiología , Femenino , Humanos , MenopausiaRESUMEN
People with HIV (PWH) use cannabis at a higher rate than the general population, but the influence on neural activity is not well characterized. Cannabis use among PWH may have a beneficial effect, as neuroinflammation is known to be a critical problem in PWH and cannabis use has been associated with a reduction in proinflammatory markers. Thus, it is important to understand the net impact of cannabis use on brain and cognitive function in PWH. In this study, we collected magnetoencephalographic (MEG) brain imaging data on 81 participants split across four demographically matched groups (i.e., PWH using cannabis, controls using cannabis, non-using PWH, and non-using controls). Participants completed a visuospatial processing task during MEG. Time-frequency resolved voxel time series were extracted to identify the dynamics of oscillatory and pre-stimulus baseline neural activity. Our results indicated strong theta (4-8 Hz), alpha (10-16 Hz), and gamma (62-72 Hz) visual oscillations in parietal-occipital brain regions across all participants. PWH exhibited significant behavioral deficits in visuospatial processing, as well as reduced theta oscillations and elevated pre-stimulus gamma activity in visual cortices, all of which replicate prior work. Strikingly, chronic cannabis use was associated with a significant reduction in pre-stimulus gamma activity in the visual cortices, such that PWH no longer statistically differed from controls. These results provide initial evidence that cannabis use may normalize some neural aberrations in PWH. This study fills an important gap in understanding the impact of cannabis use on brain and cognitive function in PWH.
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Ondas Encefálicas , Moduladores de Receptores de Cannabinoides/farmacología , Disfunción Cognitiva , Infecciones por VIH/complicaciones , Marihuana Medicinal/farmacología , Corteza Visual , Percepción Visual , Adulto , Ondas Encefálicas/efectos de los fármacos , Ondas Encefálicas/fisiología , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/fisiopatología , Femenino , Humanos , Magnetoencefalografía , Masculino , Persona de Mediana Edad , Corteza Visual/efectos de los fármacos , Corteza Visual/fisiología , Percepción Visual/efectos de los fármacos , Percepción Visual/fisiologíaRESUMEN
INTRODUCTION: We aimed to determine whether obesity or metabolic syndrome (MetS) modify associations between sleep-disordered breathing (SDB), self-reported sleep duration (SD), and phenotypes of combined SDB/SD with 7-year neurocognitive decline (ND) in a community based-cohort of U.S. Hispanic/Latinos (N = 5500) in different age and sex groups. METHODS: The exposures were baseline SDB (respiratory event index ≥ 15), sleepiness (Epworth Sleepiness Scale ≥ 10), SD (< 6 hours, 6-9 hours, ≥ 9 hours). The outcome was 7-year ND. RESULTS: Mean age was 56.0 years, 54.8% were females. Obesity modified the association between SDB/SD and ND in memory (F = 21.49, P < 0.001) and global cognition (F = 9.14, P < 0.001) in the oldest age group. Women without MetS with combined long sleep/SDB exhibited most pronounced decline in global cognition (F = 3.07, P = 0.010). DISCUSSION: The association between combined SDB/long sleep and declines in memory and global cognition was most pronounced in obese older adults. Among women, MetS status modified the association between long sleep/SDB and decline in global cognition.
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Disfunción Cognitiva , Hispánicos o Latinos/estadística & datos numéricos , Obesidad , Autoinforme , Síndromes de la Apnea del Sueño/epidemiología , Trastornos del Sueño-Vigilia/epidemiología , Factores de Edad , Estudios de Cohortes , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Factores Sexuales , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
Self-insertion of foreign bodies into the male urethra is a rare presentation. We report a unique case of urethral insertion involving three AAA batteries and the resulting battery acid leakage and urinary obstruction. This report discusses the approach to management, extraction techniques and effects of battery acid within the male urethra.