Neurology Commons^™

Different Cohort, Disparate Results: Selection Bias Is A Key Factor In Autopsy Cohorts, Kathryn Gauthreaux, Walter A. Kukull, Karin B. Nelson, Charles Mock, Yen-Chi Chen, Kwun C. G. Chan, David W. Fardo, Yuriko Katsumata, Erin L. Abner, Peter T. Nelson

Neurology Faculty Publications

INTRODUCTION: Research-oriented autopsy cohorts provide critical insights into dementia pathobiology. However, different studies sometimes report disparate findings, partially because each study has its own recruitment biases. We hypothesized that a straightforward metric, related to the percentage of research volunteers cognitively normal at recruitment, would predict other inter-cohort differences.

METHODS: The National Alzheimer’s Coordinating Center (NACC) provided data on N = 7178 autopsied participants from 28 individual research centers. Research cohorts were grouped based on the proportion of participants with normal cognition at initial clinical visit.

RESULTS: Cohorts with more participants who were cognitively normal at recruitment contained more individuals who …

Cognitive Decline, Aβ Pathology, And Blood–Brain Barrier Function In Aged 5xfad Mice, Geetika Nehra, Sasivimon Promsan, Ruedeemars Yubolphan, Wijitra Chumboatong, Pornpun Vivithanaporn, Bryan J. Maloney, Anusorn Lungkaphin, Bjoern Bauer, Anika M. S. Hartz

Markey Cancer Center Faculty Publications

Background

Patients with Alzheimer’s disease (AD) develop blood–brain barrier dysfunction to varying degrees. How aging impacts Aβ pathology, blood–brain barrier function, and cognitive decline in AD remains largely unknown. In this study, we used 5xFAD mice to investigate changes in Aβ levels, barrier function, and cognitive decline over time.

Methods

5xFAD and wild-type (WT) mice were aged between 9.5 and 15.5 months and tested for spatial learning and reference memory with the Morris Water Maze (MWM). After behavior testing, mice were implanted with acute cranial windows and intravenously injected with fluorescent-labeled dextrans to assess their in vivo distribution in the …

Oxidative Stress Alters Mitochondrial Homeostasis In Isolated Brain Capillaries, Gopal V. Velmurugan, Hemendra J. Vekaria, Anika M. S. Hartz, Björn Bauer, William Brad Hubbard

Markey Cancer Center Faculty Publications

Background

Neurovascular deficits and blood-brain barrier (BBB) dysfunction are major hallmarks of brain trauma and neurodegenerative diseases. Oxidative stress is a prominent contributor to neurovascular unit (NVU) dysfunction and can propagate BBB disruption. Oxidative damage results in an imbalance of mitochondrial homeostasis, which can further drive functional impairment of brain capillaries. To this end, we developed a method to track mitochondrial-related changes after oxidative stress in the context of neurovascular pathophysiology as a critical endophenotype of neurodegenerative diseases.

Methods

To study brain capillary-specific mitochondrial function and dynamics in response to oxidative stress, we developed an ex vivo model in which …

Nonalcoholic Fatty Liver Disease, Liver Fibrosis, And Structural Brain Imaging: The Cross-Cohort Collaboration, Galit Weinstein, Adrienne O'Donnell, Stefan Frenzel, Tian Xiao, Amber Yaqub, Pinar Yilmaz, Robert J. De Knegt, Gladys E. Maestre, Debora Melo Van Lent, Michelle Long

School of Medicine Publications

Background and purpose

Prior studies reported conflicting findings regarding the association of nonalcoholic fatty liver disease (NAFLD) and liver fibrosis with measures of brain health. We examined whether NAFLD and liver fibrosis are associated with structural brain imaging measures in middle- and old-age adults.

Methods

In this cross-sectional study among dementia- and stroke-free individuals, data were pooled from the Offspring and Third Generation cohorts of the Framingham Heart Study (FHS), the Rotterdam Study (RS), and the Study of Health in Pomerania. NAFLD was assessed through abdominal imaging. Transient hepatic elastography (FibroScan) was used to assess liver fibrosis in FHS and …

Circulating Sphingolipids In Relation To Cognitive Decline And Incident Dementia: The Cardiovascular Health Study, Kristine F Moseholm, Héléne T Cronjé, Manja Koch, Annette L Fitzpatrick, Oscar L Lopez, Marcia C De Oliveira Otto, W T Longstreth, Andrew N Hoofnagle, Kenneth J Mukamal, Rozenn N Lemaitre, Majken K Jensen

Faculty, Staff and Student Publications

INTRODUCTION: Whether circulating levels of sphingolipids are prospectively associated with cognitive decline and dementia risk is uncertain.

METHODS: We measured 14 sphingolipid species in plasma samples from 4488 participants (mean age 76.2 years; 40% male; and 25% apolipoprotein E (

RESULTS: Higher plasma levels of sphingomyelin-d18:1/16:0 (SM-16) were associated with a faster cognitive decline measured with 3MSE, in contrast, higher levels of sphingomyelin-d18:1/22:0 (SM-22) were associated with slower decline in cognition measured with DSST. In Cox regression, higher levels of SM-16 (hazard ration [HR] = 1.24 [95% confidence interval [CI]: 1.08-1.44]) and ceramide-d18:1/16:0 (Cer-16) (HR = 1.26 [95% CI: 1.10-1.45]) …

Higher Baseline Serum Bilirubin Levels Are Associated With Increased Risk Of Early Neurological Deterioration In Women With Acute Ischemic Stroke, Meng Sun, Yingfeng Weng, Jiwei Cheng, Guoyi Li, Qian Xiao

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Early neurological deterioration (END) occurs in up to one-third of patients with acute ischemic stroke (AIS) and associated with poor outcome. The role of serum bilirubin in END remains controversial. This study aims to investigate the association of total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) with END.

METHODS: This study was a cross-sectional retrospective study with 344 AIS patients enrolled. We retrospectively reviewed consecutive AIS patients with END through a medical record retrieval system and enrolled patients as control randomly from the AIS patients without END at the same period. The bilirubin levels were …

Frozen By Worry And Fatigue? A Mixed Methods Approach To Understanding The Lived Experiences Of Freezing Of Gait, Sarah M. Ghose

Theses and Dissertations

This study utilized a mixed methods emergent, phenomenological approach to (1) understanding the lived experience of freezing of gait for individuals diagnosed with Parkinson’s Disease and (2) determining the role of anxiety and sleep in freezing of gait outcomes. Participants included 13 adults diagnosed with Parkinson’s Disease (N=14 for qualitative data, N=13 for quantitative data; 23.1% female-identifying, 76.9% male-identifying) who were predominantly white (92.3%) with an average age of 69 years (SD = 6.73 years). Data collection consisted of semi-structured interviews, self-report measures, actigraphic sleep data, and salivary alpha amylase biomarker collection. Results are organized into …

Dna Methylation In Aging And Alzheimer's Disease, Raymond Cheng, Jingmin Shu, Hai Chen, Ming Li, Xiaodong Cheng, Li Liu

The Brown Foundation: Institute of Molecular Medicine

DNA methylation undergoes significant changes with age. These alterations play a pivotal role in the development of age-related diseases, including Alzheimer's disease (AD). Recent advancements in DNA methylome profiling have revealed global hypomethylation patterns, particularly within repetitive elements, as well as gene-specific changes that are associated with neurodegeneration. Age-related alterations in DNA methylation have been implicated in the disruption of key cellular processes, such as inflammation and proteostasis, both central to AD pathology. However, several challenges persist in this field. One major issue is the inconsistency of findings across different brain regions and tissue types, which complicates result interpretation. Furthermore, …

Utilizing Ai Integrated Neuroimaging Technology To Expand Upon Machine Learning In Positron Emission Tomography Technology With The Aim Of Detecting Amyloid Beta Biomarkers Early In The Onset Of Alzheimer's., Ethan S. Terman

UROP Posters

Early intervention in Alzheimer's is vital for treatment. The earlier a professional can detect symptoms and make a diagnosis the earlier a prognosis can be implemented. With the prevalence of data in our day-to-day world combined with Artificial intelligence (AI), utilizing both for machine learning can pave the way for more accurate and efficient detection of Alzheimer's and other neurodegenerative diseases. AI combined with Machine learning (ML) increases diagnostic efficiency and reduces human errors, making it a valuable resource for physicians and clinicians alike. With the increasing amount of data processing and image interpretation required, the ability to use AI …

An Objective Assessment Of Neuromotor Control Using A Smartphone App After Repeated Subconcussive Blast Exposure, Charlend K. Howard, Masahiro Yamada, Marcia Dovel, Rie Leverett, Alexander Hill, Kenneth A. Manlapaz, David O. Keyser, Rene S. Hernandez, Sheilah S. Rowe, Walter S. Carr, Michael S. Roy, Christopher K. Rhea

Rehabilitation Sciences Faculty Publications

Subconcussive blast exposure has been shown to alter neurological functioning. However, the extent to which neurological dysfunction persists after blast exposure is unknown. This longitudinal study examined the potential short- and long-term effects of repeated subconcussive blast exposure on neuromotor performance from heavy weapons training in military personnel. A total of 214 participants were assessed; 137 were exposed to repeated subconcussive blasts and 77 were not exposed to blasts (controls). Participants completed a short stepping-in-place task while an Android smartphone app placed on their thigh recorded movement kinematics. We showed acute suppression of neuromotor variability 6 h after subconcussive blast …

Prevalence And Patterns Of Cardiovascular Risk Factors In Young Hypertensive Patients, *Raghu V S R Tanuku Dr., Major Venkata Shree Krishna Dr., Sreedhar Tanuku Dr

Digital Journal of Clinical Medicine

Hypertension ranks among the top ten causes of mortality, with around 4% attributed to hypertensive complications. High salt intake, Type 2 diabetes, smoking, elevated serum lipids, a sedentary lifestyle, a diet heavy in saturated fat, genetic predisposition, as well as stress are among the factors that contribute to hypertension. Hypertension affects about 1 billion people worldwide, with considerable differences between populations and ethnic groups [2]. The Framingham Heart Study indicates that a person's lifetime risk of developing hypertension is 90% if they are normotensive at age 55. According to the NHANES IV (4th National Health and Nutrition Examination Survey), the …

Trajectory Clustering Of Immune Cells And Its Association With Clinical Outcomes After Aneurysmal Subarachnoid Hemorrhage, So Young Won, Museong Kim, Han-Gil Jeong, Bosco Seong Kyu Yang, Huimahn Alex Choi, Dong-Wan Kang, Yong Soo Kim, Young Deok Kim, Si Un Lee, Seung Pil Ban, Jae Seung Bang, Moon-Ku Han, O-Ki Kwon, Chang Wan Oh

Faculty, Staff and Student Publications

Background and purpose: The immune response following aneurysmal subarachnoid hemorrhage (aSAH) can exacerbate secondary brain injury and impact clinical outcomes. As the immune response after aSAH is a dynamic process, we aim to track and characterize immune cell trajectories over time to identify patterns associated with various clinical outcomes.

Methods: In this retrospective single-center study of patients with aSAH, we analyzed immune cell count trajectories, including neutrophil, monocyte, and lymphocyte counts, collected from day 1 to day 14. These trajectories were classified into four distinct clusters utilizing the k-means longitudinal clustering method. A comprehensive multivariable analysis was performed to explore …

Personalization Of Sudep Risk: A Survey Of Transient Subclinical Comorbid Changes, Kristina A Simeone, Dawn M Martenz, Shruthi H Iyer, Cameron P Booth, Shelby E Herr, Stephanie A Matthews, Samantha B Draves, Laura L Heinemann, Pierce L Greenberg, Samden D Lhatoo, Elizabeth Donner, Timothy A Simeone

Faculty, Staff and Student Publications

Objective: Preclinical data report within subject modifiable ailments emerge weeks prior to SUDEP, including sleep disorders and cardiorespiratory changes; findings which support anecdotal clinical data. Here, we bridge preclinical findings with future clinical/preclinical studies, and survey whether caretakers or family members of victims noticed transient changes prior to SUDEP. The aim of this pilot study is to identify potential modifiable changes that may synergistically increase SUDEP risk for future research.

Methods: A mobile electronic survey was posted on SUDEP community websites. The survey queried whether changes in seizures, sleep, physical well-being, emotional well-being, cognition, breathing, or heart rate were noticed …

The Contribution Of Amyloid Deposition In The Aortic Valve To Calcification And Aortic Stenosis, Romeesa Khan, Claudia M Di Gesù, Juneyoung Lee, Louise D Mccullough

Faculty, Staff and Student Publications

Trillions of microbes live symbiotically in the host, specifically in mucosal tissues such as the gut. Recent advances in metagenomics and metabolomics have revealed that the gut microbiota plays a critical role in the regulation of host immunity and metabolism, communicating through bidirectional interactions in the microbiota-gut-brain axis (MGBA). The gut microbiota regulates both gut and systemic immunity and contributes to the neurodevelopment and behaviors of the host. With aging, the composition of the microbiota changes, and emerging studies have linked these shifts in microbial populations to age-related neurological diseases (NDs). Preclinical studies have demonstrated that gut microbiota-targeted therapies can …

The Emerging Role Of Notch3 Receptor Signalling In Human Lung Diseases, Grant W Goodman, Patrick Devlin, Bryce E West, Rodney M Ritzel

Faculty, Staff and Student Publications

The recent identification of skull bone marrow as a reactive hematopoietic niche that can contribute to and direct leukocyte trafficking into the meninges and brain has transformed our view of this bone structure from a solid, protective casing to a living, dynamic tissue poised to modulate brain homeostasis and neuroinflammation. This emerging concept may be highly relevant to injuries that directly impact the skull such as in traumatic brain injury (TBI). From mild concussion to severe contusion with skull fracturing, the bone marrow response of this local myeloid cell reservoir has the potential to impact not just the acute inflammatory …

Corrigendum: High-Definition Transcranial Direct Current Stimulation For Upper Extremity Rehabilitation In Moderate-To-Severe Ischemic Stroke: A Pilot Study, Jordan N Williamson, Shirley A James, Dorothy He, Sheng Li, Evgeny V Sidorov, Yuan Yang

Faculty, Staff and Student Publications

No abstract provided.

Responsive Neurostimulation For People With Drug-Resistant Epilepsy And Autism Spectrum Disorder, Madeline C Fields, Christina Marsh, Onome Eka, Emily A Johnson, Lara V Marcuse, Churl-Su Kwon, James J Young, Maite Lavega-Talbott, Mohankumar Kurukumbi, Gretchen Von Allmen, John Zempel, Daniel Friedman, Nathalie Jette, Anuradha Singh, Ji Yeoun Yoo, Leah Blank, Fedor Panov, Saadi Ghatan

Faculty, Staff and Student Publications

PURPOSE: Individuals with autism spectrum disorder (ASD) have comorbid epilepsy at much higher rates than the general population, and about 30% will be refractory to medication. Patients with drug-resistant epilepsy (DRE) should be referred for surgical evaluation, yet many with ASD and DRE are not resective surgical candidates. The aim of this study was to examine the response of this population to the responsive neurostimulator (RNS) System.

METHODS: This multicenter study evaluated patients with ASD and DRE who underwent RNS System placement. Patients were included if they had the RNS System placed for 1 year or more. Seizure reduction and …

Proportional Sway-Based Electrotactile Feedback Improves Lateral Standing Balance, V S Raghav Hari Krishna, Jeonghee Kim, Shuo-Hsiu Chang, Yoonsuck Choe, Hangue Park

Faculty, Staff and Student Publications

INTRODUCTION: Plantar cutaneous augmentation is a promising approach in balance rehabilitation by enhancing motion-dependent sensory feedback. The effect of plantar cutaneous augmentation on balance has been mainly investigated in its passive form (e.g., textured insole) or on lower-limb amputees. In this study, we tested the effect of plantar cutaneous augmentation on balance in its active form (i.e., electrical stimulation) for individuals with intact limbs.

METHODS: Ten healthy subjects participated in the study and were instructed to maintain their balance as long as possible on the balance board, with or without electrotactile feedback evoked on the medial side of the heel, …

Precision Needle-Punch Tumor Enrichment From Paraffin Blocks Improves The Detection Of Clinically Actionable Genomic Alterations And Biomarkers, Douglas I Lin, Richard S P Huang, Ioannis Ladas, Rachel B Keller, Nimesh R Patel, Sotirios Lakis, Brennan Decker, Tyler Janovitz, Douglas A Mata, Jeffrey S Ross, Jo-Anne Vergilio, Julia A Elvin, Roy S Herbst, Philip C Mack, Jonathan K Killian

Faculty, Staff and Student Publications

BACKGROUND: While many molecular assays can detect mutations at low tumor purity and variant allele frequencies, complex biomarkers such as tumor mutational burden (TMB), microsatellite instability (MSI), and genomic loss of heterozygosity (gLOH) require higher tumor purity for accurate measurement. Scalable, quality-controlled, tissue-conserving methods to increase tumor nuclei percentage (TN%) from tumor specimens are needed for complex biomarkers and hence necessary to maximize patient matching to approved therapies or clinical trial enrollment. We evaluated the clinical utility and performance of precision needle-punch enrichment (NPE) compared with traditional razor blade macroenrichment of tumor specimens on molecular testing success.

METHODS: Pathologist-directed NPE …

Assessing Laryngectomy Patient Education On Youtube: Investigating Quality And Reliability, Matthew E Lin, Oluwatobiloba Ayo-Ajibola, Carlos X Castellanos, Jonathan West, Neil Luu, Ian Kim, Niels C Kokot

Faculty, Staff and Student Publications

OBJECTIVE: This study aimed to characterize the quality of laryngectomy-related patient education on YouTube and understand factors impacting video content quality.

STUDY DESIGN: Cross-sectional cohort analysis.

SETTING: Laryngectomy-related videos on YouTube.

METHODS: YouTube was anonymously queried for various laryngectomy procedure search terms. Video quality was evaluated using the validated DISCERN instrument which assesses treatment-related information quality. Descriptive statistics were used to characterize our cohort. Univariate and multivariable linear regression were used to assess factors associated with increased DISCERN score. Significance was set at

RESULTS: Our 78-video cohort exhibited moderate levels of engagement, averaging 13,028.40 views (SD = 24,246.93), 69.79 likes …