المؤلفون: Derek B Archer, PhD, Justin T Bricker, MS, Winston T Chu, BS, Roxana G Burciu, PhD, Johanna L McCracken, BS, Song Lai, ProfPhD, Stephen A Coombes, PhD, Ruogu Fang, PhD, Angelos Barmpoutis, PhD, Daniel M Corcos, PhD, Ajay S Kurani, PhD, Trina Mitchell, MS, Mieniecia L Black, MPH, Ellen Herschel, BS, Tanya Simuni, ProfMD, Todd B Parrish, ProfPhD, Cynthia Comella, ProfMD, Tao Xie, MD, Klaus Seppi, ProfMD, Nicolaas I Bohnen, ProfMD, Martijn LTM Müller, PhD, Roger L Albin, ProfMD, Florian Krismer, MD, Guangwei Du, MD, Mechelle M Lewis, PhD, Xuemei Huang, ProfMD, Hong Li, PhD, Ofer Pasternak, PhD, Nikolaus R McFarland, MD, Michael S Okun, ProfMD, David E Vaillancourt, ProfPhD

المصدر: The Lancet: Digital Health, Vol 1, Iss 5, Pp e222-e231 (2019)

مصطلحات موضوعية: Computer applications to medicine. Medical informatics, R858-859.7

الوصف: Summary: Background: Development of valid, non-invasive biomarkers for parkinsonian syndromes is crucially needed. We aimed to assess whether non-invasive diffusion-weighted MRI can distinguish between parkinsonian syndromes using an automated imaging approach. Methods: We did an international study at 17 MRI centres in Austria, Germany, and the USA. We used diffusion-weighted MRI from 1002 patients and the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) to develop and validate disease-specific machine learning comparisons using 60 template regions and tracts of interest in Montreal Neurological Institute space between Parkinson's disease and atypical parkinsonism (multiple system atrophy and progressive supranuclear palsy) and between multiple system atrophy and progressive supranuclear palsy. For each comparison, models were developed on a training and validation cohort and evaluated in an independent test cohort by quantifying the area under the curve (AUC) of receiving operating characteristic curves. The primary outcomes were free water and free-water-corrected fractional anisotropy across 60 different template regions. Findings: In the test cohort for disease-specific comparisons, the diffusion-weighted MRI plus MDS-UPDRS III model (Parkinson's disease vs atypical parkinsonism had an AUC 0·962; multiple system atrophy vs progressive supranuclear palsy AUC 0·897) and diffusion-weighted MRI only model had high AUCs (Parkinson's disease vs atypical parkinsonism AUC 0·955; multiple system atrophy vs progressive supranuclear palsy AUC 0·926), whereas the MDS-UPDRS III only models had significantly lower AUCs (Parkinson's disease vs atypical parkinsonism 0·775; multiple system atrophy vs progressive supranuclear palsy 0·582). These results indicate that a non-invasive imaging approach is capable of differentiating forms of parkinsonism comparable to current gold standard methods. Interpretations: This study provides an objective, validated, and generalisable imaging approach to distinguish different forms of parkinsonian syndromes using multisite diffusion-weighted MRI cohorts. The diffusion-weighted MRI method does not involve radioactive tracers, is completely automated, and can be collected in less than 12 min across 3T scanners worldwide. The use of this test could positively affect the clinical care of patients with Parkinson's disease and parkinsonism and reduce the number of misdiagnosed cases in clinical trials. Funding: National Institutes of Health and Parkinson's Foundation.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2589750019301050Test; https://doaj.org/toc/2589-7500Test

الوصول الحر: https://doaj.org/article/dec94fab248449418d41ab9ce6333e1eTest

المؤلفون: James F Burke, Kenneth M Langa, Rodney A Hayward, Roger L Albin

المصدر: PLoS ONE, Vol 9, Iss 12, p e114339 (2014)

مصطلحات موضوعية: Medicine, Science

الوصف: OBJECTIVES:In this study, we developed a model of presymptomatic treatment of Alzheimer disease (AD) after a screening diagnostic evaluation and explored the circumstances required for an AD prevention treatment to produce aggregate net population benefit. METHODS:Monte Carlo simulation methods were used to estimate outcomes in a simulated population derived from data on AD incidence and mortality. A wide variety of treatment parameters were explored. Net population benefit was estimated in aggregated QALYs. Sensitivity analyses were performed by individually varying the primary parameters. FINDINGS:In the base-case scenario, treatment effects were uniformly positive, and net benefits increased with increasing age at screening. A highly efficacious treatment (i.e. relative risk 0.6) modeled in the base-case is estimated to save 20 QALYs per 1000 patients screened and 221 QALYs per 1000 patients treated. CONCLUSIONS:Highly efficacious presymptomatic screen and treat strategies for AD are likely to produce substantial aggregate population benefits that are likely greater than the benefits of aspirin in primary prevention of moderate risk cardiovascular disease (28 QALYS per 1000 patients treated), even in the context of an imperfect treatment delivery environment.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC4256252?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/5e5ccda846254c7ab799dcfb38a8efa9Test

المؤلفون: Irene M Lelieveld, Martijn L T M Müller, Nicolaas I Bohnen, Robert A Koeppe, Ronald D Chervin, Kirk A Frey, Roger L Albin

المصدر: PLoS ONE, Vol 7, Iss 7, p e40166 (2012)

مصطلحات موضوعية: Medicine, Science

الوصف: Sleep dysfunction and excessive daytime sleepiness are common in Parkinson disease (PD). Several studies suggest that PD patients exhibit high prevalence of sleep-disordered breathing (SDB). PD has a complex profile of neurochemical deficits in which abnormalities of different neurotransmitter systems may play significant and differing roles in the development of non-motor features. In the present study, we investigated whether SDB in PD is related to serotoninergic neuron degeneration. We used a cross-sectional design to assess the correlation between SDB and measures of caudal brainstem serotonin neuron integrity. Fifty one PD participants with mean disease duration of 6.0 (SD 3.7) years and mean age of 63.9 (SD 6.2) years were studied. We measured caudal brainstem serotoninergic innervation with [(11)C]DASB positron emission tomography (PET) imaging and striatal dopaminergic innervation with [(11)C]DTBZ PET imaging. SDB was assessed with polysomnography (PSG) and sleepiness with multiple sleep latency tests. Greater than half of participants exhibited PSG evidence of significant SDB; 12 participants had normal PSGs, 6 had mild SDB, 20 had moderate SDB, and 13 had severe SDB. We found no association between severity of SDB and caudal brainstem serotoninergic innervation in PD participants. Striatal dopaminergic denervation did not correlate with severity of SDB. We did find significant correlations between measures of motor function impairment and sleep quantity and quality in PD. Neither serotoninergic nor dopaminergic neuron degeneration is likely to play a major role in SDB observed in PD patients.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC3390329?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/14b86418ab364ebfb2c1306209d96ea1Test

المؤلفون: Xin Wang, Kelly M. Bakulski, Henry L. Paulson, Roger L. Albin, Sung Kyun Park

المصدر: Scientific Reports, Vol 13, Iss 1, Pp 1-12 (2023)

مصطلحات موضوعية: Medicine, Science

الوصف: Abstract We investigated the complex relations of socioeconomic status (SES) and healthy lifestyles with cognitive functions among older adults in 1313 participants, aged 60 years and older, from the National Health and Nutrition Examination Survey 2011–2014. Cognitive function was measured using an average of the standardized z-scores of the Consortium to Establish a Registry for Alzheimer’s Disease Word Learning and delayed recall tests, the Animal Fluency Test, and the Digit Symbol Substitution Test. Latent class analysis of family income, education, occupation, health insurance, and food security was used to define composite SES (low, medium, high). A healthy lifestyle score was calculated based on smoking, alcohol consumption, physical activity, and the Healthy-Eating-Index-2015. In survey-weighted multivariable linear regressions, participants with 3 or 4 healthy behaviors had 0.07 (95% CI 0.005, 0.14) standard deviation higher composite cognitive z-score, relative to those with one or no healthy behavior. Participants with high SES had 0.37 (95% CI 0.29, 0.46) standard deviation higher composite cognitive z-score than those with low SES. No statistically significant interaction was observed between healthy lifestyle score and SES. Our findings suggested that higher healthy lifestyle scores and higher SES were associated with better cognitive function among older adults in the United States.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-2322Test

الوصول الحر: https://doaj.org/article/351318bf1afc42d19479f7fe3482d3b9Test

المؤلفون: Jeffrey L. B. Bohnen, Roger L. Albin, Nicolaas I. Bohnen

المصدر: Frontiers in Neurology, Vol 14 (2023)

مصطلحات موضوعية: Alzheimer's disease, mild cognitive impairment, Parkinson's disease, ketogenic, effectiveness, Neurology. Diseases of the nervous system, RC346-429

الوصف: BackgroundThere is increasing interest in therapeutic ketosis as a potential therapy for neurodegenerative disorders–in particular, mild cognitive impairment (MCI), Alzheimer's disease (AD), and Parkinson's disease (PD)–following a proof-of-concept study in Parkinson's disease published in 2005.MethodsTo provide an objective assessment of emerging clinical evidence and targeted recommendations for future research, we reviewed clinical trials involving ketogenic interventions in mild cognitive impairment, Alzheimer's disease, and Parkinson's disease reported since 2005. Levels of clinical evidence were systematically reviewed using the American Academy of Neurology criteria for rating therapeutic trials.Results10 AD, 3 MCI, and 5 PD therapeutic ketogenic trials were identified. Respective grades of clinical evidence were objectively assessed using the American Academy of Neurology criteria for rating therapeutic trials. We found class “B” evidence (probably effective) for cognitive improvement in subjects with mild cognitive impairment and subjects with mild-to-moderate Alzheimer's disease negative for the apolipoprotein ε4 allele (APOε4-). We found class “U” evidence (unproven) for cognitive stabilization in individuals with mild-to-moderate Alzheimer's disease positive for the apolipoprotein ε4 allele (APOε4+). We found class “C” evidence (possibly effective) for improvement of non-motor features and class “U” evidence (unproven) for motor features in individuals with Parkinson's disease. The number of trials in Parkinson's disease is very small with best evidence that acute supplementation holds promise for improving exercise endurance.ConclusionsLimitations of the literature to date include the range of ketogenic interventions currently assessed in the literature (i.e., primarily diet or medium-chain triglyceride interventions), with fewer studies using more potent formulations (e.g., exogenous ketone esters). Collectively, the strongest evidence to date exists for cognitive improvement in individuals with mild cognitive impairment and in individuals with mild-to-moderate Alzheimer's disease negative for the apolipoprotein ε4 allele. Larger-scale, pivotal trials are justified in these populations. Further research is required to optimize the utilization of ketogenic interventions in differing clinical contexts and to better characterize the response to therapeutic ketosis in patients who are positive for the apolipoprotein ε4 allele, as modified interventions may be necessary.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fneur.2023.1123290/fullTest; https://doaj.org/toc/1664-2295Test

الوصول الحر: https://doaj.org/article/9ddfb67a08f64b41bc1fb284d3ec5b42Test

المؤلفون: Prabesh Kanel, Robert A. Koeppe, Vikas Kotagal, Stiven Roytman, Martijn L.T.M. Muller, Nicolaas I. Bohnen, Roger L. Albin

المصدر: Aging Brain, Vol 3, Iss , Pp 100071- (2023)

مصطلحات موضوعية: Serotonin, Serotonin transporter, Raphe, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: There are conflicting results regarding regional age-related changes in serotonin terminal density in human brain. Some imaging studies suggest age-related declines in serotoninergic terminals and perikarya. Other human imaging studies and post-mortem biochemical studies suggest stable brain regional serotoninergic terminal densities across the adult lifespan. In this cross-sectional study, we used [11C]3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile positron emission tomography to quantify brain regional serotonin transporter density in 46 normal subjects, ranging from 25 to 84 years of age. Both voxel-based analyses, using sex as a covariate, and volume-of-interest-based analyses were performed. Both analyses revealed age-related declines in [11C]3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile binding in numerous brain regions, including several neocortical regions, striatum, amygdala, thalamus, dorsal raphe, and other subcortical regions. Similar to some other neurotransmitter systems of subcortical origin, we found evidence of age-related declines in regional serotonin terminal density in both cortical and subcortical regions.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2589958923000087Test; https://doaj.org/toc/2589-9589Test

الوصول الحر: https://doaj.org/article/a154505b5a3f4b0f9816e4a812d6a034Test

المؤلفون: Kaiwen Deng, Yueming Li, Hanrui Zhang, Jian Wang, Roger L. Albin, Yuanfang Guan

المصدر: Communications Biology, Vol 5, Iss 1, Pp 1-10 (2022)

مصطلحات موضوعية: Biology (General), QH301-705.5

الوصف: Deng et al. develop deep learning methods that identify Parkinson’s Disease (PD) patients using public accelerometer and position data with higher accuracy than when using gait/rest and voice-based models. Their study demonstrates the complementary predictive power of tapping, gait/rest and voice data and establishes integrative deep learning-based models for identifying PD.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2399-3642Test

الوصول الحر: https://doaj.org/article/09a6e6d4e69a4576858ca1b711572fc2Test

المؤلفون: Steven D. Mitchell, Roger L. Albin, William T. Dauer, John L. Goudreau, Christos Sidiropoulos

المصدر: Case Reports in Neurology, Vol 13, Iss 2, Pp 341-346 (2021)

مصطلحات موضوعية: chorea-acanthocytosis, neuroacanthocytosis, parkinsonism, park2, vacuolar protein sorting 13a, Neurology. Diseases of the nervous system, RC346-429

الوصف: Neuroacanthocytosis (NA) is a diverse group of disorders in which nervous system abnormalities co-occur with irregularly shaped red blood cells called acanthocytes. Chorea-acanthocytosis is the most common of these syndromes and is an autosomal recessive disease caused by mutations in the vacuolar protein sorting 13A (VPS13A) gene. We report a case of early onset parkinsonism and seizures in a 43-year-old male with a family history of NA. Neurologic examinations showed cognitive impairment and marked parkinsonian signs. MRI showed bilateral basal ganglia gliosis. He was found to have a novel heterozygous mutation in the VPS13A gene, in addition a heterozygous mutation in the PARK2 gene. His clinical picture was atypical for typical chorea-acanthocytosis (ChAc). The compound heterozygous mutations of VPS13A and PARK2 provide the most plausible explanation for this patient’s clinical symptoms. This case adds to the phenotypic diversity of ChAc. More research is needed to fully understand the roles of epistatic interactions on phenotypic expression of neurodegenerative diseases.

وصف الملف: electronic resource

العلاقة: https://www.karger.com/Article/FullText/515805Test; https://doaj.org/toc/1662-680XTest

الوصول الحر: https://doaj.org/article/96391b744ee14364a67c070173ca3fddTest

المؤلفون: Tanpreet Kaur, Allen F. Brooks, Katherine M. Liddell, Bradford D. Henderson, Brian G. Hockley, Nicolaas I. Bohnen, Roger L. Albin, Peter J. H. Scott

المصدر: Frontiers in Chemistry, Vol 10 (2022)

مصطلحات موضوعية: MC-1 inhibitors, BCPP-EF, fluorine-18, green chemistry, radiochemistry, positron emission tomography, Chemistry, QD1-999

الوصف: Graphical Abstract

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fchem.2022.878835/fullTest; https://doaj.org/toc/2296-2646Test

الوصول الحر: https://doaj.org/article/2d15678628ff436193ca410810effaf7Test

المؤلفون: Prabesh Kanel, Sygrid van der Zee, Carlos A. Sanchez-Catasus, Robert A. Koeppe, Peter J.H. Scott, Teus van Laar, Roger L. Albin, Nicolaas I. Bohnen

المصدر: Aging Brain, Vol 2, Iss , Pp 100039- (2022)

مصطلحات موضوعية: Acetylcholine transporter, Aging, Normal persons, VAChT PET, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: Acetylcholine plays a major role in brain cognitive and motor functions with regional cholinergic terminal loss common in several neurodegenerative disorders. We describe age-related declines of regional cholinergic neuron terminal density in vivo using the positron emission tomography (PET) ligand [18F](–)5-Fluoroethoxybenzovesamicol ([18F]FEOBV), a vesamicol analogue selectively binding to the vesicular acetylcholine transporter (VAChT). A total of 42 subjects without clinical evidence of neurologic disease (mean 50.55 [range 20–80] years, 24 Male/18 Female) underwent [18F]FEOBV brain PET imaging. We used SPM based voxel-wise statistical analysis to perform whole brain voxel-based parametric analysis (family-wise error corrected, FWE) and to also extract the most significant clusters of regions correlating with aging with gender as nuisance variable. Age-related VAChT binding reductions were found in primary sensorimotor cortex, visual cortex, caudate nucleus, anterior to mid-cingulum, bilateral insula, para-hippocampus, hippocampus, anterior temporal lobes/amygdala, dorsomedial thalamus, metathalamus, and cerebellum (gender and FWE-corrected, P

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2589958922000111Test; https://doaj.org/toc/2589-9589Test

الوصول الحر: https://doaj.org/article/69359eaee2ff496281564e904204a6f1Test