Publications by authors named "Jason W Adams"

10 Publications

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Pharmacological reversal of synaptic and network pathology in human MECP2-KO neurons and cortical organoids.

EMBO Mol Med 2021 Jan 8;13(1):e12523. Epub 2020 Dec 8.

Department of Pediatrics/Rady Children's Hospital, Department of Cellular & Molecular Medicine, School of Medicine, University of California San Diego, La Jolla, CA, USA.

Duplication or deficiency of the X-linked MECP2 gene reliably produces profound neurodevelopmental impairment. MECP2 mutations are almost universally responsible for Rett syndrome (RTT), and particular mutations and cellular mosaicism of MECP2 may underlie the spectrum of RTT symptomatic severity. No clinically approved treatments for RTT are currently available, but human pluripotent stem cell technology offers a platform to identify neuropathology and test candidate therapeutics. Using a strategic series of increasingly complex human stem cell-derived technologies, including human neurons, MECP2-mosaic neurospheres to model RTT female brain mosaicism, and cortical organoids, we identified synaptic dysregulation downstream from knockout of MECP2 and screened select pharmacological compounds for their ability to treat this dysfunction. Two lead compounds, Nefiracetam and PHA 543613, specifically reversed MECP2-knockout cytologic neuropathology. The capacity of these compounds to reverse neuropathologic phenotypes and networks in human models supports clinical studies for neurodevelopmental disorders in which MeCP2 deficiency is the predominant etiology.
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http://dx.doi.org/10.15252/emmm.202012523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799367PMC
January 2021

Successful treatment of highly recurrent facial baroparesis in a frequent high-altitude traveler: a case report.

J Med Case Rep 2020 Nov 12;14(1):218. Epub 2020 Nov 12.

School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.

Background: Facial baroparesis is a palsy of the seventh cranial nerve resulting from increased pressure compressing the nerve along its course through the middle ear cavity. It is a rare condition, most commonly reported in barotraumatic environments, in particular scuba diving and high-altitude air travel. We report here an unusual case of highly frequent baroparesis, workup, and successful treatment.

Case Presentation: A 57-year-old Caucasian male frequent commercial airline traveler presented with a 4-year history of recurrent episodes of right-sided facial paralysis and otalgia, increasing in both frequency and severity. Incidents occurred almost exclusively during rapid altitude changes in aircraft, mostly ascent, but also during rapid altitude change in an automobile. Self-treatment included nasal and oral decongestants, nasal corticosteroids, and warm packs. Temporal bone computed tomography (CT) scan revealed possible right-sided dehiscence of the tympanic bone segment; audiogram and magnetic resonance imaging of the internal auditory canals were unremarkable. After a diagnosis of facial nerve baroparesis was made, the patient underwent myringotomy with insertion of a pressure equalization tube (PET) into the right tympanic membrane. Despite re-exposure to altitude change multiple times weekly post-treatment, the patient reported being symptom-free for more than 6 months following intervention.

Conclusions: Prompt PET insertion may represent the preferred treatment for individuals who suffer recurrent episodes of facial baroparesis. Education regarding this rare condition may prevent unnecessary testing and treatment of affected patients. Future studies should explore the pathophysiology and risk factors, compare therapeutic options, and provide follow-up data to optimize the management of affected patients.
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http://dx.doi.org/10.1186/s13256-020-02557-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659090PMC
November 2020

Association of probable REM sleep behavior disorder with pathology and years of contact sports play in chronic traumatic encephalopathy.

Acta Neuropathol 2020 12 17;140(6):851-862. Epub 2020 Sep 17.

Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA.

Probable rapid eye movement (REM) sleep behavior disorder (pRBD) is a synucleinopathy-associated parasomnia in which loss of REM sleep muscle atonia results in motor behavior during REM sleep, including dream enactment. Traumatic brain injury is independently associated with increased risk of pRBD and Lewy body disease, and both pRBD and Lewy body disease are often observed in chronic traumatic encephalopathy (CTE). However, the frequency and pathological substrate of pRBD in CTE have not been formally studied and remain unknown. Of the total sample of 247 men, age at death of 63.1 ± 18.8 years (mean ± SD), 80 [32%] were determined by informant report to have symptoms of pRBD. These participants had played more years of contact sports (18.3 ± 11.4) than those without pRBD (15.1 ± 6.5; P = 0.02) and had an increased frequency of Lewy body disease (26/80 [33%] vs 28/167 [17%], P = 0.005). Of the 80 participants with pRBD, 54 [68%] did not have Lewy body disease; these participants were more likely to have neurofibrillary tangles and pretangles in the dorsal and median raphe (41 of 49 [84%] non-LBD participants with pRBD symptoms vs 90 of 136 [66%] non-LBD participants without pRBD symptoms, P = 0.02), brainstem nuclei with sleep regulatory function. Binary logistic regression modeling in the total study sample showed that pRBD in CTE was associated with dorsal and median raphe nuclei neurofibrillary tangles (OR = 3.96, 95% CI [1.43, 10.96], P = 0.008), Lewy body pathology (OR = 2.36, 95% CI [1.18, 4.72], P = 0.02), and years of contact sports participation (OR = 1.04, 95% CI [1.00, 1.08], P = 0.04). Overall, pRBD in CTE is associated with increased years of contact sports participation and may be attributable to Lewy body and brainstem tau pathologies.
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http://dx.doi.org/10.1007/s00401-020-02206-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669574PMC
December 2020

Brain Organoids as Tools for Modeling Human Neurodevelopmental Disorders.

Physiology (Bethesda) 2019 09;34(5):365-375

Department of Pediatrics/Rady Children's Hospital San Diego, School of Medicine, University of California San Diego, San Diego, California.

Brain organoids recapitulate in vitro the specific stages of in vivo human brain development, thus offering an innovative tool by which to model human neurodevelopmental disease. We review here how brain organoids have been used to study neurodevelopmental disease and consider their potential for both technological advancement and therapeutic development.
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http://dx.doi.org/10.1152/physiol.00005.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863377PMC
September 2019

Lewy Body Pathology and Chronic Traumatic Encephalopathy Associated With Contact Sports.

J Neuropathol Exp Neurol 2018 09;77(9):757-768

Department of Neurology.

Traumatic brain injury has been associated with increased risk of Parkinson disease and parkinsonism, and parkinsonism and Lewy body disease (LBD) can occur with chronic traumatic encephalopathy (CTE). To test whether contact sports and CTE are associated with LBD, we compared deceased contact sports athletes (n = 269) to cohorts from the community (n = 164) and the Boston University Alzheimer disease (AD) Center (n = 261). Participants with CTE and LBD were more likely to have β-amyloid deposition, dementia, and parkinsonism than CTE alone (p < 0.05). Traditional and hierarchical clustering showed a similar pattern of LBD distribution in CTE compared to LBD alone that was most frequently neocortical, limbic, or brainstem. In the community-based cohort, years of contact sports play were associated with neocortical LBD (OR = 1.30 per year, p = 0.012), and in a pooled analysis a threshold of >8 years of play best predicted neocortical LBD (ROC analysis, OR = 6.24, 95% CI = 1.5-25, p = 0.011), adjusting for age, sex, and APOE ɛ4 allele status. Clinically, dementia was significantly associated with neocortical LBD, CTE stage, and AD; parkinsonism was associated with LBD pathology but not CTE stage. Contact sports participation may increase risk of developing neocortical LBD, and increased LBD frequency may partially explain extrapyramidal motor symptoms sometimes observed in CTE.
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http://dx.doi.org/10.1093/jnen/nly065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097837PMC
September 2018

Spray droplet size and carrier volume effect on dicamba and glufosinate efficacy.

Pest Manag Sci 2018 Mar 13. Epub 2018 Mar 13.

Department of Agronomy & Horticulture, University of Nebraska-Lincoln, North Platte, NE, USA.

Background: Pesticide applications using a specific droplet size and carrier volume could maximize herbicide efficacy while mitigating particle drift in a precise and efficient manner. The objectives of this study were to investigate the influence of spray droplet size and carrier volume on dicamba and glufosinate efficacy, and to determine the plausibility of droplet-size based site-specific weed management strategies.

Results: Generally, across herbicides and carrier volumes, as droplet size increased, weed control decreased. Increased carrier volume (187 L ha ) buffered this droplet size effect, thus greater droplet sizes could be used to mitigate drift potential while maintaining sufficient levels of weed control. To mitigate drift potential and achieve satisfactory weed control (≥ 90% of maximum observed control), a 900 µm (Ultra Coarse) droplet size paired with 187 L ha carrier volume is recommended for dicamba applications and a 605 µm (Extremely Coarse) droplet size across carrier volumes is recommended for glufosinate applications. Although general droplet size recommendations were created, optimum droplet sizes for weed control varied significantly across site-years.

Conclusion: Convoluted interactions occur between droplet size, carrier volume, and other application parameters. Recommendations for optimizing herbicide applications based on droplet size should be based on a site-specific management approach to better account for these interactions. © 2018 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.4913DOI Listing
March 2018

The effects of age on the learning and forgetting of primacy, middle, and recency components of a multi-trial word list.

J Clin Exp Neuropsychol 2017 Nov 17;39(9):900-912. Epub 2017 Jan 17.

a Department of Psychology , University of Colorado , Colorado Springs , CO , USA.

The serial position effect reveals that recall of a supraspan list of words follows a predictable pattern, whereby words at the beginning (primacy) and end (recency) of a list are recalled more easily than words in the middle. This effect has typically been studied using single list-learning trials, but in neuropsychology, multi-trial list-learning tests are more commonly used. The current study examined trends in learning for primacy, middle, and recency effects across multiple trials in younger and older age cohorts. Participants were 158 volunteers, including 79 adults aged 17-36 ("younger" group) and 79 adults aged 54-89 years ("older" group). Each participant completed four learning trials and one delayed (5-10 min) recall trial from the Memory Assessment Scales. Scores were divided into primacy (first four words), middle (middle four words), and recency (final four words) scores for all trials. For list acquisition, mixed effects modeling examined the main effects of and interactions between learning slope (logarithmic), age group, and serial position. Rate of learning increased logarithmically over four trials and varied by serial position, with growth of middle and recency word acquisition increasing more rapidly than recall of primacy words; this interaction did not differ by age group. Delayed retention differed according to age group and serial position; both older and younger adults demonstrated similar retention for primacy words, but older adults showed reduced retention for middle and recency words. Although older adults acquired less information across learning trials, the reason for this reduced acquisition was related to initial learning, not to rate of learning over time. Older compared to younger adults were less efficient at transferring middle and recency words from short-term to long-term memory.
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http://dx.doi.org/10.1080/13803395.2017.1278746DOI Listing
November 2017

Assessing clinicopathological correlation in chronic traumatic encephalopathy: rationale and methods for the UNITE study.

Alzheimers Res Ther 2015 Oct 12;7(1):62. Epub 2015 Oct 12.

Alzheimer's Disease Center, Boston University School of Medicine, 72 East Concord Street, B-7800, Boston, MA, 02118, USA.

Introduction: Chronic traumatic encephalopathy (CTE) is a progressive neurodegeneration associated with repetitive head impacts. Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) is a U01 project recently funded by the National Institute of Neurological Disorders and Stroke and the National Institute of Biomedical Imaging and Bioengineering. The goal of the UNITE project is to examine the neuropathology and clinical presentation of brain donors designated as "at risk" for the development of CTE based on prior athletic or military exposure. Here, we present the rationale and methodology for UNITE.

Methods: Over the course of 4 years, we will analyze the brains and spinal cords of 300 deceased subjects who had a history of repetitive head impacts sustained during participation in contact sports at the professional or collegiate level or during military service. Clinical data are collected through medical record review and retrospective structured and unstructured family interviews conducted by a behavioral neurologist or neuropsychologist. Blinded to the clinical data, a neuropathologist conducts a comprehensive assessment for neurodegenerative disease, including CTE, using published criteria. At a clinicopathological conference, a panel of physicians and neuropsychologists, blinded to the neuropathological data, reaches a clinical consensus diagnosis using published criteria, including proposed clinical research criteria for CTE.

Results: We will investigate the validity of these clinical criteria and sources of error by using recently validated neuropathological criteria as a gold standard for CTE diagnosis. We also will use statistical modeling to identify diagnostic features that best predict CTE pathology.

Conclusions: The UNITE study is a novel and methodologically rigorous means of assessing clinicopathological correlation in CTE. Our findings will be critical for developing future iterations of CTE clinical diagnostic criteria.
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http://dx.doi.org/10.1186/s13195-015-0148-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601147PMC
October 2015

The δ latent dementia phenotype in the uniform data set: Cross-validation and extension.

Neuropsychology 2015 May 25;29(3):344-52. Epub 2014 Aug 25.

Department of Psychology, University of Colorado, Colorado Springs.

Objective: Royall and colleagues identified a latent dementia phenotype, "δ", reflecting the "cognitive correlates of functional status." We sought to cross-validate and extend these findings in a large clinical case series of adults with and without dementia.

Method: A confirmatory factor analysis (CFA) model for δ was fit to National Alzheimer's Coordinating Center data (n = 26,068). Factor scores derived from δ were compared with the Clinical Dementia Rating Sum of Boxes (CDR-SB) and to clinically diagnosed dementia. A longitudinal parallel-process growth model compared changes in δ with changes in CDR-SB over 6 annual evaluations.

Results: The CFA model fit well; CFI = 0.971, RMSEA = 0.070. Factor scores derived from δ discriminated between demented and nondemented participants with an area under the curve of .96. The growth model also fit well, CFI = 0.969, RMSEA = 0.032.

Conclusions: The δ construct represents a novel approach to measuring dementia-related changes and has potential to improve cognitive assessment of neurodegenerative diseases.
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http://dx.doi.org/10.1037/neu0000128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340822PMC
May 2015

Base rate of performance invalidity among non-clinical undergraduate research participants.

Arch Clin Neuropsychol 2014 Aug;29(5):415-21

Department of Psychology, University at Albany, State University of New York, Albany, NY, USA Albany Neuropsychological Associates, Albany, NY, USA.

Neuropsychological research frequently uses non-clinical undergraduate participants to evaluate neuropsychological tests. However, a recent study by An and colleagues (2012, Archives of Clinical Neuropsychology, 27, 849-857) called into question that the extent to which the interpretation of these participants' performance on neuropsychological tests is valid. This study found that in a sample of 36 participants, 55.6% exhibited performance invalidity at an initial session and 30.8% exhibited performance invalidity at a follow-up session. The current study attempted to replicate these findings in a larger, more representative sample using a more rigorous methodology. Archival data from 133 non-clinical undergraduate research participants were analyzed. Participants were classified as performance invalid if they failed any one PVT. In the current sample, only 2.26% of participants exhibited performance invalidity. Thus, concerns regarding insufficient effort and performance invalidity when using undergraduate research participants appear to be overstated.
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http://dx.doi.org/10.1093/arclin/acu028DOI Listing
August 2014