Project description:Detecting early signs of cognitive decline is crucial for early detection and treatment of Alzheimer's Disease. Most of the current screening tools for Alzheimer's Disease represent a significant burden, requiring invasive procedures, or intensive and costly clinical testing. Recent findings have highlighted changes to speech and language patterns that occur in Alzheimer's Disease, and may be detectable prior to diagnosis. Automated tools to assess speech have been developed that can be used on a smartphone or tablet, from one's home, in under 10 min. In this study, we present the results of a study of older adults who completed a digital speech assessment task over a 6-month period. Participants were grouped according to those who scored above (N = 18) or below (N = 18) the recommended threshold for detecting cognitive impairment on the Montreal Cognitive Assessment (MoCA) and those with diagnoses of mild cognitive impairment (MCI) or early Alzheimer's Disease (AD) (N = 14). Older adults who scored above the MoCA threshold had better performance on speech composites reflecting language coherence, information richness, syntactic complexity, and word finding abilities. Those with MCI and AD showed more rapid decline in the coherence of language from baseline to 6-month follow-up, suggesting that this score may be useful both for detecting cognitive decline and monitoring change over time. This study demonstrates that automated speech assessments have potential as sensitive tools to detect early signs of cognitive impairment and monitor progression over time.
Project description:The dementia population is increasing as the world's population is growing older. The current systematic review aims to identify digital cognitive biomarkers from computerized tests for detecting dementia and its risk state of mild cognitive impairment (MCI), and to evaluate the diagnostic performance of digital cognitive biomarkers. A literature search was performed in three databases, and supplemented by a Google search for names of previously identified computerized tests. Computerized tests were categorized into five types, including memory tests, test batteries, other single/multiple cognitive tests, handwriting/drawing tests, and daily living tasks and serious games. Results showed that 78 studies were eligible. Around 90% of the included studies were rated as high quality based on the Newcastle-Ottawa Scale (NOS). Most of the digital cognitive biomarkers achieved comparable or even better diagnostic performance than traditional paper-and-pencil tests. Moderate to large group differences were consistently observed in cognitive outcomes related to memory and executive functions, as well as some novel outcomes measured by handwriting/drawing tests, daily living tasks, and serious games. These outcomes have the potential to be sensitive digital cognitive biomarkers for MCI and dementia. Therefore, digital cognitive biomarkers can be a sensitive and promising clinical tool for detecting MCI and dementia.
Project description:IntroductionRemote unsupervised cognitive assessments have the potential to complement and facilitate cognitive assessment in clinical and research settings.MethodsHere, we evaluate the usability, validity, and reliability of unsupervised remote memory assessments via mobile devices in individuals without dementia from the Swedish BioFINDER-2 study and explore their prognostic utility regarding future cognitive decline.ResultsUsability was rated positively; remote memory assessments showed good construct validity with traditional neuropsychological assessments and were significantly associated with tau-positron emission tomography and downstream magnetic resonance imaging measures. Memory performance at baseline was associated with future cognitive decline and prediction of future cognitive decline was further improved by combining remote digital memory assessments with plasma p-tau217. Finally, retest reliability was moderate for a single assessment and good for an aggregate of two sessions.DiscussionOur results demonstrate that unsupervised digital memory assessments might be used for diagnosis and prognosis in Alzheimer's disease, potentially in combination with plasma biomarkers.HighlightsRemote and unsupervised digital memory assessments are feasible in older adults and individuals in early stages of Alzheimer's disease. Digital memory assessments are associated with neuropsychological in-clinic assessments, tau-positron emission tomography and magnetic resonance imaging measures. Combination of digital memory assessments with plasma p-tau217 holds promise for prognosis of future cognitive decline. Future validation in further independent, larger, and more diverse cohorts is needed to inform clinical implementation.
Project description:ImportanceTelemedicine is increasingly used to provide outpatient pediatric neurology consultations in underserved communities. Although telemedicine clinics have been shown to improve access, little is known about how they alter patients' utilization of hospital services.ObjectiveTo evaluate the association between access to telemedicine clinics and hospital utilization among underserved children with neurologic conditions.Design, setting, and participantsThis retrospective cross-sectional study included 4169 patients who received outpatient care from pediatric neurologists affiliated with an academic children's hospital in California between January 1, 2009, and July 31, 2017, either in person or using telemedicine.ExposuresConsultation modality (telemedicine or in person) in the outpatient neurology clinics.Main outcomes and measuresDemographic and clinical variables were abstracted from the hospital's electronic medical records. The association between the modality of outpatient neurology care and patients' utilization of the emergency department and hospitalizations was evaluated. Both all-cause and neurologic condition-related hospital utilization were analyzed using multivariable negative binomial regression in overall and matched samples.ResultsThe telemedicine cohort comprised 378 patients (211 [55.8%] male), and the in-person cohort comprised 3791 patients (2090 [55.1%] male). The mean (SD) age at the first encounter was 7.4 (5.4) years for the telemedicine cohort and 7.8 (5.1) years for the in-person cohort. The telemedicine cohort was more likely than the in-person cohort to have nonprivate insurance (public insurance, self-pay, or uninsured), lower education, and lower household income. The rates of all-cause and neurologic hospital encounters were lower among children who received pediatric neurology consultations over telemedicine compared with children who received care in the in-person clinics (5.7 [95% CI, 3.5-8.0] vs 20.1 [95% CI, 18.1-22.1] per 100 patient-years and 3.7 [95% CI, 2.0-5.3] vs 8.9 [95% CI, 7.8-10.0] per 100 patient-years, respectively; P?<?.001). Even after adjusting for demographic and clinical factors, the telemedicine cohort had a lower risk of hospital encounters (emergency department visits and admissions) with an adjusted incidence rate ratio of 0.57 (95% CI, 0.38-0.88) for all-cause encounters and an adjusted incidence rate ratio of 0.60 (95% CI, 0.36-0.99) for neurologic encounters. After matching on travel time to the neurology clinic, the adjusted incidence rate ratio was 0.19 (95% CI, 0.04-0.83) for all-cause admissions and 0.14 (95% CI, 0.02-0.82) for neurologic admissions.Conclusions and relevancePediatric neurology care through real-time, audiovisual telemedicine consultations was associated with lower hospital utilization compared with in-person consultations, suggesting that high-cost hospital encounters can be prevented by improving subspecialty access.
Project description:ObjectivesThe burden of neurological diseases in developing countries is rising although little is known about the epidemiology and clinical pattern of neurological disorders. The objective of this study was to understand the burden of disease faced by neurologists a in tertiary care setting.ResultsA prospective observational study was conducted of all presentations to neurology clinics at Aga Khan University Hospital Karachi over a period of 2 years. A total of 16,371 out-patients with neurological diseases were seen during the study period. The mean age of the study participants were 46.2 ± 18.3 years and 8508 (52%) were male. Headache disorders were present in 3058 (18.6%) of patients followed by vascular diseases 2842 (17.4%), nerve and root lesions 2311 (14.1%) and epilepsies 2055 (12.5%). Parkinson's disease was more prevalent in male participants 564 (70.8%) as compared to female 257 (62.1%) (p = 0.002). Migraines and vertigo disease were more diagnosed in females as compared to males. Epilepsies were seen more in younger age groups. Parkinson's disease was seen in 50.9% of participants between the ages of 45 and 65 years, and the frequency increased with age.
Project description:The integrity of structural connectivity in a functional brain network supports the efficiency of neural processing within relevant brain regions. This study aimed to quantitatively investigate the short- and long-range fibers, and their differential roles in the lower cognitive efficiency in aging and dementia. Three groups of healthy young, healthy older adults and patients with Alzheimer's disease (AD) participated in this combined functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) study on prospective memory (PM). Short- and long-range fiber tracts within the PM task engaged brain networks were generated. The correlation between the fMRI signal change, PM performance and the DTI characters were calculated. FMRI results showed that the PM-specific frontal activations in three groups were distributed hierarchically along the rostrocaudal axis in the frontal lobe. In an overall PM condition generally activated brain network among the three groups, tractography was used to generate the short-range fibers, and they were found impaired in both healthy older adults and AD patients. However, the long-range fiber tracts were only impaired in AD. Additionally, the mean diffusivity (MD) of short-range but not long-range fibers was positively correlated with fMRI signal change and negatively correlated with the efficiency of PM performance. This study suggests that the disintegrity of short-range fibers may contribute more to the lower cognitive efficiency and higher compensatory brain activation in healthy older adults and more in AD patients.
Project description:Background and purposeDementia is one of the most common disorders and is associated with increased morbidity, mortality and decreased quality of life. The present guideline addresses important medical management issues including systematic medical follow-up, vascular risk factors in dementia, pain in dementia, use of antipsychotics in dementia and epilepsy in dementia.MethodsA systematic review of the literature was carried out. Based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework, we developed a guideline. Where recommendations based on GRADE were not possible, a good practice statement was formulated.ResultsSystematic management of vascular risk factors should be performed in patients with mild to moderate dementia as prevention of cerebrovascular pathology may impact on the progression of dementia (Good Practice statement). Individuals with dementia (without previous stroke) and atrial fibrillation should be treated with anticoagulants (weak recommendation). Discontinuation of opioids should be considered in certain individuals with dementia (e.g. for whom there are no signs or symptoms of pain or no clear indication, or suspicion of side effects; Good Practice statement). Behavioral symptoms in persons with dementia should not be treated with mild analgesics (weak recommendation). In all patients with dementia treated with opioids, assessment of the individual risk-benefit ratio should be performed at regular intervals. Regular, preplanned medical follow-up should be offered to all patients with dementia. The setting will depend on the organization of local health services and should, as a minimum, include general practitioners with easy access to dementia specialists (Good Practice statement). Individuals with dementia and agitation and/or aggression should be treated with atypical antipsychotics only after all non-pharmacological measures have been proven to be without benefit or in the case of severe self-harm or harm to others (weak recommendation). Antipsychotics should be discontinued after cessation of behavioral disturbances and in patients in whom there are side effects (Good Practice statement). For treatment of epilepsy in individuals with dementia, newer anticonvulsants should be considered as first-line therapy (Good Practice statement).ConclusionThis GRADE-based guideline offers recommendations on several important medical issues in patients with dementia, and thus adds important guidance for clinicians. For some issues, very little or no evidence was identified, highlighting the importance of further studies within these areas.
Project description:Digital Health Technologies (DHTs) such as connected sensors offer particular promise for improving data collection and patient empowerment in neurology research and care. This study analyzed the recent evolution of the use of DHTs in trials registered on ClinicalTrials.gov for four chronic neurological disorders: epilepsy, multiple sclerosis, Alzheimer's, and Parkinson's disease. We document growth in the collection of both more established digital measures (e.g., motor function) and more novel digital measures (e.g., speech) over recent years, highlighting contexts of use and key trends.
Project description:Low response rates to certain tumor types remain a major challenge for immune checkpoint blockade therapy. In this study, we first conducted an integrated biomarker evaluation of bladder cancer patients from confirmatory cohorts (IMvigor210) and found that no significant differences exist between sexes before acceptance of anti-PD-L1 treatment, whereas male patients showed a better response. Thus, we then focused on sex-related changes post anti-PD-L1 treatment and found no obvious impact on the gut microbiota in male mice but a significant decrease in the sex hormone levels. Further, castration dramatically enhanced the antitumor efficacy against murine colon adenocarcinoma in male mice. Moreover, a narrow-spectrum antibiotic, colistin was innovatively used for deregulation of testosterone levels to enhance the immunotherapy efficiency in male mice. These findings indicate that the impact on the sex hormone levels in males may contribute to the sexual dimorphism in response and provide a promising way to enhance immunotherapy efficiency.