Neurology Commons^™

Blood Biomarkers In Down Syndrome: Facilitating Alzheimer’S Disease Detection And Monitoring, Melissa E. Petersen, Lisi Flores-Aguilar, Elizabeth Head, Laia Montoliu-Gaya, Andre Strydom, Sarah E. Pape, Juan Fortea, Nicholas J. Ashton, Chinedu Udeh-Momoh, Sid E. O’Bryant, Dwight German, Florin Despa, Mark Mapstone, Henrik Zetterberg

Neurology Faculty Publications

Blood-based biomarkers continue to be explored for disease detection, monitoring of progression, and therapeutic outcomes as the diagnostic determination of Alzheimer’s Disease in Down Syndrome (DS-AD) remains challenging in clinical settings. This perspective highlights the current status of this effort. Overall, amyloid (A), tau (T), and neurodegeneration (AT[N]) blood-based biomarkers have been shown to increase with disease pathology for individuals with DS. Phosphorylated tau biomarkers (p-tau217, p-tau181) have been consistently shown to track disease progression for DS-AD and are likely good candidates for use in clinical settings. Biomarkers of inflammation (glial fibrillary acidic protein) also show promise; however, additional work …

Weighted Family History Density Of Substance Use: Influence On Participant Substance Use Onset, Escalation, And Duration, Carleigh A. Litteral

Theses and Dissertations--Psychology

Substance use disorders impose a staggering toll on the United States (U.S.), straining healthcare systems, destabilizing communities, and profoundly impacting both individuals and families. Approximately one in six Americans aged 12 and older had a past-year substance use disorder in 2022 (Key Substance Use, 2022), and nearly one-third of adults experience a substance use disorder in their lifetime (Wu, 2010), contributing to an economic burden exceeding $400 billion annually (National Drug Threat Assessment, 2011). Family history of substance use disorders is a key predictor of vulnerability, with individuals who have affected relatives being 2–8 times more …

Biological Validation Of Peak-Width Of Skeletonized Mean Diffusivity As A Vcid Biomarker: The Markvcid Consortium, Alison M Luckey, Saptaparni Ghosh, Chen-Pin Wang, Alexa Beiser, Rebecca Bernal, Zhiguang Li, Djass Mbangdadji, Elyas Fadaee, Haykel Snoussi, Angel Gabriel Velarde Dediós, Hector A Trevino, Monica Goss, Laura J Hillmer, Christopher E Bauer, Adam M Staffaroni, Lara Stables, Marilyn Albert, Jayandra J Himali, Thomas H Mosley, Lars Forsberg, Vilmundur Guðnason, Baljeet Singh, Herpreet Singh, Kristin Schwab, Joel H Kramer, Gary A Rosenberg, Karl G Helmer, Steven M Greenberg, Mohamad Habes, Danny J J Wang, Brian T Gold, Hanzhang Lu, Arvind Caprihan, Myriam Fornage, Lenore J Launer, Konstantinos Arfanakis, Sudha Seshadri, Charles Decarli, Pauline Maillard, Claudia L Satizabal

Faculty, Staff and Student Publications

BACKGROUND: Peak-width of skeletonized mean diffusivity (PSMD), a neuroimaging marker of cerebral small vessel disease (SVD), has shown excellent instrumental properties. Here, we extend our work to perform a biological validation of PSMD.

METHODS: We included 396 participants from the Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID-1) Consortium and three replication samples (Cohorts for Heart and Aging Research in Genomic Epidemiology = 6172, Rush University Medical Center = 287, University of California Davis Alzheimer's Disease Research Center = 567). PSMD was derived from diffusion tensor imaging using an automated algorithm. We related PSMD to a composite measure …

Association Of Common And Rare Variants With Alzheimer’S Disease In More Than 13,000 Diverse Individuals With Whole-Genome Sequencing From The Alzheimer’S Disease Sequencing Project, Wan-Ping Lee, Seung Hoan Choi, Margaret G Shea, Po-Liang Cheng, Beth A Dombroski, Achilleas N Pitsillides, Nancy L Heard-Costa, Hui Wang, Katia Bulekova, Amanda B Kuzma, Yuk Yee Leung, John J Farrell, Honghuang Lin, Brian W Kunkle, Adam Naj, Elizabeth E Blue, Frederick Nusetor, Dongyu Wang, Eric Boerwinkle, William S Bush, Xiaoling Zhang, Philip L De Jager, Josée Dupuis, Lindsay A Farrer, Myriam Fornage, Eden Martin, Margaret Pericak-Vance, Sudha Seshadri, Ellen M Wijsman, Li-San Wang, Alzheimer's Disease Sequencing Project;, Gerard D Schellenberg, Anita L Destefano, Jonathan L Haines, Gina M Peloso

Faculty, Staff and Student Publications

INTRODUCTION: Alzheimer's disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous.

METHODS: We investigated the association of AD with both common variants and aggregates of rare coding and non-coding variants in 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data.

RESULTS: Pooled-population analyses of all individuals identified genetic variants at apolipoprotein E (APOE) and BIN1 associated with AD (p < 5 × 10

DISCUSSION: We observed that complementary pooled-population and subgroup-specific analyses offered unique insights into the genetic architecture of AD.

HIGHLIGHTS: We determine the association of genetic variants with Alzheimer's disease (AD) using …

Association Of Common And Rare Variants With Alzheimer’S Disease In More Than 13,000 Diverse Individuals With Whole-Genome Sequencing From The Alzheimer’S Disease Sequencing Project, Wan-Ping Lee, Seung Hoan Choi, Margaret G Shea, Po-Liang Cheng, Beth A Dombroski, Achilleas N Pitsillides, Nancy L Heard-Costa, Hui Wang, Katia Bulekova, Amanda B Kuzma, Yuk Yee Leung, John J Farrell, Honghuang Lin, Brian W Kunkle, Adam Naj, Elizabeth E Blue, Frederick Nusetor, Dongyu Wang, Eric Boerwinkle, William S Bush, Xiaoling Zhang, Philip L De Jager, Josée Dupuis, Lindsay A Farrer, Myriam Fornage, Eden Martin, Margaret Pericak-Vance, Sudha Seshadri, Ellen M Wijsman, Li-San Wang, Alzheimer's Disease Sequencing Project, Gerard D Schellenberg, Anita L Destefano, Jonathan L Haines, Gina M Peloso

Center for Medical Ethics and Health Policy Staff Publications

Introduction: Alzheimer's disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous.

Methods: We investigated the association of AD with both common variants and aggregates of rare coding and non-coding variants in 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data.

Results: Pooled-population analyses of all individuals identified genetic variants at apolipoprotein E (APOE) and BIN1 associated with AD (p < 5 × 10-8). Subgroup-specific analyses identified a haplotype on chromosome 14 including PSEN1 associated with AD in Hispanics, further supported by aggregate testing of rare coding and non-coding variants in the region. Common variants in LINC00320 were observed associated with AD in Black individuals (p = 1.9 × 10-9). Finally, we observed rare non-coding variants in the promoter of TOMM40 distinct of APOE in pooled-population analyses (p = 7.2 × 10-8).

Discussion: We observed that complementary pooled-population and subgroup-specific analyses offered unique insights into the genetic architecture of AD.

Highlights: We determine the association of genetic variants with Alzheimer's disease (AD) using …

Parallel Electrophysiological Abnormalities Due To Covid-19 Infection And To Alzheimer’S Disease And Related Dementia, Yang Jiang, Jennifer Neal, Pradoldej Sompol, Görsev Yener, Xianghong Arakaki, Christopher M. Norris, Francesca R. Farina, Agustin Ibanez, Susanna Lopez, Abdulhakim Al-Ezzi, Voyko Kavcic, Bahar Güntekin, Claudio Babiloni, Mihály Hajós

Neurology Faculty Publications

Many coronavirus disease 2019 (COVID-19) positive individuals exhibit abnormal electroencephalographic (EEG) activity reflecting “brain fog” and mild cognitive impairments even months after the acute phase of infection. Resting-state EEG abnormalities include EEG slowing (reduced alpha rhythm; increased slow waves) and epileptiform activity. An expert panel conducted a systematic review to present compelling evidence that cognitive deficits due to COVID-19 and to Alzheimer’s disease and related dementia (ADRD) are driven by overlapping pathologies and neurophysiological abnormalities. EEG abnormalities seen in COVID-19 patients resemble those observed in early stages of neurodegenerative diseases, particularly ADRD. It is proposed that similar EEG abnormalities in …

Clonal Hematopoiesis Of Indeterminate Potential Is Associated With Reduced Risk Of Cognitive Impairment In Patients With Chronic Kidney Disease, Cissy Xiao, Manjula Kurella Tamura, Yang Pan, Varun Rao, Celestin Missikpode, Caitlyn Vlasschaert, Tetsushi Nakao, Xiao Sun, Changwei Li, Zhijie Huang, Amanda Anderson, Md Mesbah Uddin, Do-Kyun Kim, Jonathan Taliercio, Rajat Deo, Zeenat Bhat, Dawei Xie, Panduranga Rao, Jing Chen, James P Lash, Jiang He, Pradeep Natarajan, James E Hixson, Kristine Yaffe, Tanika N Kelly, Cric Study Investigators

Faculty, Staff and Student Publications

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) and dementia disproportionately burden patients with chronic kidney disease (CKD). The association between CHIP and cognitive impairment in CKD patients is unknown.

Methods: We conducted time-to-event analyses in up to 1452 older adults with CKD from the Chronic Renal Insufficiency Cohort who underwent CHIP gene sequencing. Cognition was assessed using four validated tests in up to 6 years mean follow-up time. Incident cognitive impairment was defined as a test score one standard deviation below the baseline mean.

Results: Compared to non-carriers, CHIP carriers were markedly less likely to experience impairment in attention (adjusted …

The Seattle Amyotrophic Lateral Sclerosis (Als) Patient Project Database: Observational, Longitudinal, Dyadic Characterization Of People With Als And Their Partners, Suzanne C. Segerstrom, Edward J. Kasarskis

Neurology Faculty Publications

Introduction: The median survival time in ALS is approximately 3 years, but survival times range from less than a year to more than 10 years and much variance in disease course remains to be explained. As is true for physical outcomes, there is considerable variance in QOL, which is influenced by psychological health, coping, and social support, among other psychosocial factors. The Seattle ALS Patient Project Database (SALSPPD) provides a unique opportunity for researchers to address established and novel hypotheses about disease progression and QOL in ALS.

Methods: The SALSPPD is a longitudinal dataset of people with ALS (n = …

A Genome-Wide Association Meta-Analysis Of All-Cause And Vascular Dementia, Mega Vascular Cognitive Impairment And Dementia (Megavcid) Consortium

Faculty, Staff and Students Publications

INTRODUCTION: Dementia is a multifactorial disease with Alzheimer's disease (AD) and vascular dementia (VaD) pathologies making the largest contributions. Yet, most genome-wide association studies (GWAS) focus on AD.

METHODS: We conducted a GWAS of all-cause dementia (ACD) and examined the genetic overlap with VaD. Our dataset includes 800,597 individuals, with 46,902 and 8702 cases of ACD and VaD, respectively. Known AD loci for ACD and VaD were replicated. Bioinformatic analyses prioritized genes that are likely functionally relevant and shared with closely related traits and risk factors.

RESULTS: For ACD, novel loci identified were associated with energy transport (SEMA4D), neuronal excitability …

Spinal Cord Stimulator Implantation For Complex Regional Pain Syndrome In Patient With Extensive Vertebral Surgical History: A Case Report, Munfarid A Zaidi, Mily Talati, Krishna Shah

Faculty, Staff and Students Publications

Spinal cord stimulation (SCS) has emerged as a novel therapeutic option for refractory complex regional pain syndrome (CRPS). However, SCS placement is often complicated by a prior history of surgical manipulation and hardware implantation along the spinal column. Through this case exploration, we aim to expand the technical approach to SCS implantation in CRPS and encourage further research into innovative approaches for this treatment modality. Our patient is a 61-year-old female with a past medical history of bilateral C7 cervical pedicle fracture status and extensive surgical manipulation, including cervical laminectomy and hardware placement along the cervical spine. The development of …

Cerebrovascular Reactivity Mri As A Biomarker For Cerebral Small Vessel Disease–Related Cognitive Decline: Multi-Site Validation In The Markvcid Consortium, Peiying Liu, Zixuan Lin, Kaisha Hazel, George Pottanat, Cuimei Xu, Dengrong Jiang, Jay J. Pillai, Emma Lucke, Christopher E. Bauer, Brian T. Gold, Steven M. Greenburg, Karl G. Helmer, Kay Jann, Gregory Jicha, Joel Kramer, Pauline Maillard, Rachel M. Mulavelil, Pavel Rodriguez, Claudia L. Satizabal, Kristin Schwab, Sudha Seshadri, Herpreet Singh, Ángel G. Velarde Dediós, Danny J. J. Wang, Rita R. Kalyani, Abhay Moghekar, Paul B. Rosenberg, Sevil Yasar, Marilyn Albert, Hanzhang Lu

Neurology Faculty Publications

INTRODUCTION: Vascular contributions to cognitive impairment and dementia (VCID) represent a major factor in cognitive decline in older adults. The present study examined the relationship between cerebrovascular reactivity (CVR) measured by magnetic resonance imaging (MRI) and cognitive function in a multi-site study, using a predefined hypothesis.

METHODS: We conducted the study in a total of three analysis sites and 263 subjects. Each site performed an identical CVR MRI procedure using 5% carbon dioxide inhalation. A global cognitive measure of Montreal Cognitive Assessment (MoCA) and an executive function measure of item response theory (IRT) score were used as outcomes.

RESULTS: CVR …

Self-Harm In Female Youth With Undiagnosed Adhd: Implementing American Academy Of Pediatrics Screening Guidelines, Roselie M. Woodard

Dissertations

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity. If undiagnosed or untreated, ADHD can lead to severe psychosocial issues such as academic failure, substance abuse, unplanned pregnancy, and incarceration. The financial burden in the U.S. from diagnostic errors creates an immense, rising fiscal impact. Early diagnosis and management are crucial to prevent these complications.

Females with ADHD, particularly those with the inattentive subtype, often face diagnostic challenges due to symptom masking and over-compensation. This results in poorer cognitive functioning and self-esteem compared to males with ADHD. ADHD is linked to autonomic nervous …

Decentralized Clinical Trials For Medications To Reduce The Risk Of Dementia: Consensus Report And Guidance, Leanne Howard, Carla Abdelnour, Erin Abner, Ricardo F. Allegri, Hiroko H. Dodge, Serge Gauthier, Camilla M. Hoyos, Gregory Jicha, Patrick G. Kehoe, Catherine J. Mummery, Adesola Ogunniyi, Nikolaos Scarmeas, Xiaoying Chen, Jodie R. Titiner, Christopher R. Weber, Ruth Peters

Neurology Faculty Publications

INTRODUCTION: Recent growth in the functionality and use of technology has prompted an increased interest in the potential for remote or decentralized clinical trials in dementia. There are many potential benefits associated with decentralized medication trials, but we currently lack specific recommendations for their delivery in the dementia field.

METHODS: A modified Delphi method engaged an expert panel to develop recommendations for the conduct of decentralized medication trials in dementia prevention. A working group of researchers and clinicians with expertise in dementia trials further refined the recommendations.

RESULTS: Overall, the recommendations support the delivery of decentralized trials in dementia prevention …

Prediction Of Disease-Free Survival For Precision Medicine Using Cooperative Learning On Multi-Omic Data, Georg Hahn, Dmitry Prokopenko, Julian Hecker, Sharon M Lutz, Kristina Mullin, Leinal Sejour, Winston Hide, Ioannis Vlachos, Stacia Desantis, Rudolph E Tanzi, Christoph Lange

Faculty, Staff and Student Publications

In precision medicine, both predicting the disease susceptibility of an individual and forecasting its disease-free survival are areas of key research. Besides the classical epidemiological predictor variables, data from multiple (omic) platforms are increasingly available. To integrate this wealth of information, we propose new methodology to combine both cooperative learning, a recent approach to leverage the predictive power of several datasets, and polygenic hazard score models. Polygenic hazard score models provide a practitioner with a more differentiated view of the predicted disease-free survival than the one given by merely a point estimate, for instance computed with a polygenic risk score. …

Overcoming Disparities In The Treatment Of Alzheimer’S Disease, Christian Gamboa, Tribhuvan Lanka, Elaine Flowers, Nayarith Lopez

Rowan-Virtua Research Day

Background: Deaths due to Alzheimer’s have been increasing at an exponential rate for the last 24 years, with an astounding 145% increase between the years 2000-2024. Early detection is key to slowing down the rate of decline. Unfortunately, Latino and African American individuals delay seeking care, which predisposes them to worse outcomes. To date, socioeconomic limitations are the main factors leading to delayed care in Latino and African American communities. A service project was developed with the aim of addressing limitations that result in delays to seeking care within Latino and African American communities.

Methods: A systematic review of available …

Alterations In Brain Morphometric Networks And Their Relationship With Memory Dysfunction In Patients With Type 2 Diabetes Mellitus, Rye Young Kim, Yoonji Joo, Eunji Ha, Haejin Hong, Chaewon Suh, Youngeun Shim, Hyeonji Lee, Yejin Kim, Jae-Hyoung Cho, Sujung Yoon, In Kyoon Lyoo

Faculty, Staff and Student Publications

Cognitive dysfunction, a significant complication of type 2 diabetes mellitus (T2DM), can potentially manifest even from the early stages of the disease. Despite evidence of global brain atrophy and related cognitive dysfunction in early-stage T2DM patients, specific regions vulnerable to these changes have not yet been identified. The study enrolled patients with T2DM of less than five years’ duration and without chronic complications (T2DM group, n=100) and demographically similar healthy controls (control group, n=50). High-resolution T1-weighted magnetic resonance imaging data were subjected to independent component analysis to identify structurally significant components indicative of morphometric networks. Within these networks, the groups’ …

The Impact Of Neurological Diseases In Kisumu, Kenya: Case Studies At Jootrh And Kcrh, Jack F. Dunham

Independent Study Project (ISP) Collection

Introduction: The burden that neurological diseases put on health systems is high, and growing across the globe, especially in Low- and Middle-Income Countries (LMICs) like Kenya. For this reason, our study sought out to study the burden and impact of neurological diseases at Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH) and Kisumu County Referral Hospital (KCRH), which are in Western Kenya.

Methods: Utilizing data from handwritten patient records spanning 23 months, our study collected said data and analyzed the prevalence, incidence, distribution, and outcomes of different neurological diseases as they impact the Kisumu community.

Results/Discussion: Comparing …

Unveiling Gene Interactions In Alzheimer's Disease By Integrating Genetic And Epigenetic Data With A Network-Based Approach, Keith L Sanders, Astrid M Manuel, Andi Liu, Boyan Leng, Xiangning Chen, Zhongming Zhao

Faculty, Staff and Student Publications

Alzheimer’s Disease (AD) is a complex disease and the leading cause of dementia in older people. We aimed to uncover aspects of AD’s pathogenesis that may contribute to drug repurposing efforts by integrating DNA methylation and genetic data. Implementing the network-based tool, a dense module search of genome-wide association studies (dmGWAS), we integrated a large-scale GWAS dataset with DNA methylation data to identify gene network modules associated with AD. Our analysis yielded 286 significant gene network modules. Notably, the foremost module included the BIN1 gene, showing the largest GWAS signal, and the GNAS gene, the most significantly hypermethylated. We conducted …

Racial Disparities In The Utilization Of Invasive Neuromodulation Devices For The Treatment Of Drug-Resistant Focal Epilepsy, Juan Luis Alcala-Zermeno, Brandy Fureman, Caitlin L. Grzeskowiak, Ojas Potnis, Maria Taveras, Margaret W. Logan, Delanie Rybacki, Daniel Friedman, Daniel Lowenstein, Ruben Kuzniecky, Jacqueline French, Hep2 Investigators

Student Papers, Posters & Projects

Racial disparities affect multiple dimensions of epilepsy care including epilepsy surgery. This study aims to further explore these disparities by determining the utilization of invasive neuromodulation devices according to race and ethnicity in a multicenter study of patients living with focal drug-resistant epilepsy (DRE). We performed a post hoc analysis of the Human Epilepsy Project 2 (HEP2) data. HEP2 is a prospective study of patients living with focal DRE involving 10 sites distributed across the United States. There were no statistical differences in the racial distribution of the study population compared to the US population using census data except for …

A Novel Spatiotemporal Graph Convolutional Network Framework For Functional Connectivity Biomarkers Identification Of Alzheimer’S Disease, Ying Zhang, Le Xue, Shuoyan Zhang, Jiacheng Yang, Qi Zhang, Min Wang, Luyao Wang, Mingkai Zhang, Jiehui Jiang, Yunxia Li

Faculty, Staff and Student Publications

BACKGROUND: Functional connectivity (FC) biomarkers play a crucial role in the early diagnosis and mechanistic study of Alzheimer's disease (AD). However, the identification of effective FC biomarkers remains challenging. In this study, we introduce a novel approach, the spatiotemporal graph convolutional network (ST-GCN) combined with the gradient-based class activation mapping (Grad-CAM) model (STGC-GCAM), to effectively identify FC biomarkers for AD.

METHODS: This multi-center cross-racial retrospective study involved 2,272 participants, including 1,105 cognitively normal (CN) subjects, 790 mild cognitive impairment (MCI) individuals, and 377 AD patients. All participants underwent functional magnetic resonance imaging (fMRI) and T1-weighted MRI scans. In this study, …

Techniques In Medicine: Ipsilateral Transforaminal Epidural Steroid Injection In Bertolotti’S Syndrome, Peter D Vu, Christopher L Robinson, Omar Viswanath, Ivan Urits, Jamal Hasoon

Faculty, Staff and Student Publications

Bertolotti's syndrome, also known as lumbosacral transitional vertebrae, is a relatively rare spinal condition characterized by an anatomical variation in the lower spine. Conservative approaches such as physical therapy, anti-inflammatory medications and lifestyle modifications may be recommended for mild cases. In more severe cases or when conservative measures fail to provide relief, injections such as may be considered to alleviate pain. This case is unique in that we document a challenging technique of ipsilateral transforaminal epidural steroid injection in a patient with Bertolotti's syndrome.

Risk Of Alzheimer's Disease And Related Dementias In Persons With Glaucoma: A National Cohort Study, Casey Crump, Jan Sundquist, Weiva Sieh, Kristina Sundquist

Faculty, Staff and Student Publications

PURPOSE: Glaucoma is a heterogeneous group of optic neuropathies that potentially may be associated with other cerebral neurodegenerative processes leading to dementia. However, prior studies have been inconsistent. We examined dementia risks after glaucoma diagnosis in a large population-based cohort.

DESIGN: National matched cohort study.

PARTICIPANTS: A total of 324 730 persons diagnosed with glaucoma during 1995-2017 in Sweden and 3 247 300 age- and sex-matched population-based controls without prior dementia.

METHODS: Cox regression was used to compute hazard ratios (HRs) for Alzheimer's disease (AD), vascular dementia (VaD), and all-cause dementia in persons with glaucoma compared with controls, adjusting for …

Association Of Plasma Ykl-40 With Mri, Csf, And Cognitive Markers Of Brain Health And Dementia, Matthew P Pase, Jayandra J Himali, Raquel Puerta, Alexa S Beiser, Mitzi M Gonzales, Claudia L Satizabal, Qiong Yang, Hugo J Aparicio, Daniel J Kojis, Charles S Decarli, Oscar L Lopez, Will Longstreth, Vilmundur Gudnason, Thomas H Mosley, Joshua C Bis, Alison Fohner, Bruce M Psaty, Mercè Boada, Pablo García-González, Sergi Valero, Marta Marquié, Russell Tracy, Lenore J Launer, Agustín Ruiz, Myriam Fornage, Sudha Seshadri

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Higher YKL-40 levels in the CSF are a known biomarker of brain inflammation. We explored the utility of plasma YKL-40 as a biomarker for accelerated brain aging and dementia risk.

METHODS: We performed cross-sectional and prospective analyses of 4 community-based cohorts in the United States or Europe: the Age, Gene/Environment Susceptibility-Reykjavik Study, Atherosclerosis Risk in the Communities study, Coronary Artery Risk Development in Young Adults study, and Framingham Heart Study (FHS). YKL-40 was measured from stored plasma by a single laboratory using Mesoscale Discovery with levels log transformed and standardized within each cohort. Outcomes included MRI total …

Alzheimer’S Disease And Inflammatory Biomarkers Positively Correlate In Plasma In The Uk-Adrc Cohort, Kate E. Foley, Zachary Winder, Tiffany L. Sudduth, Barbara J. Martin, Peter T. Nelson, Gregory Jicha, Jordan P. Harp, Erica M. Weekman, Donna M. Wilcock

Neurology Faculty Publications

INTRODUCTION: Protein-based plasma assays provide hope for improving accessibility and specificity of molecular diagnostics to diagnose dementia. METHODS: Plasma was obtained from participants (N = 837) in our community-based University of Kentucky Alzheimer’s Disease Research Center cohort. We evaluated six Alzheimer’s disease (AD)- and neurodegeneration-related (Aβ40, Aβ42, Aβ42/40, p- tau181, total tau, and NfLight) and five inflammatory biomarkers (TNF𝛼, IL6, IL8, IL10, and GFAP) using the SIMOA-based protein assay platform. Statistics were performed to assess correlations. RESULTS: Our large cohort reflects previous plasma biomarker findings. Relationships between biomarkers to understand AD–inflammatory biomarker correlations showed significant associations between AD and inflammatory …

Study Design And Methods: Us Study To Protect Brain Health Through Lifestyle Intervention To Reduce Risk (Us Pointer), Laura D Baker, Heather M Snyder, Mark A Espeland, Rachel A Whitmer, Miia Kivipelto, Nancy Woolard, Jeffrey Katula, Kathryn V Papp, Jennifer Ventrelle, Sarah Graef, Marcus A Hill, Scott Rushing, Julia Spell, Laura Lovato, Deborah Felton, Benjamin J Williams, Mina Ghadimi Nouran, Rema Raman, Tiia Ngandu, Alina Solomon, Sharon Wilmoth, Maryjo L Cleveland, Jeff D Williamson, Katherine L Lambert, Sarah Tomaszewski Farias, Claire E Day, Christy C Tangney, Darren R Gitelman, Olivia Matongo, Terrianne Reynolds, Valory N Pavlik, Melissa M Yu, Ashley S Alexander, Richard Elbein, Ann Marie Mcdonald, Stephen Salloway, Rena R Wing, Susan Antkowiak, Martha Clare Morris, Maria C Carrillo

Faculty, Staff and Students Publications

INTRODUCTION: The U.S. study to protect brain health through lifestyle intervention to reduce risk (U.S. POINTER) is conducted to confirm and expand the results of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) in Americans.

METHODS: U.S. POINTER was planned as a 2-year randomized controlled trial of two lifestyle interventions in 2000 older adults at risk for dementia due to well-established factors. The primary outcome is a global cognition composite that permits harmonization with FINGER.

RESULTS: U.S. POINTER is centrally coordinated and conducted at five clinical sites (ClinicalTrials.gov: NCT03688126). Outcomes assessments are completed at baseline and …

The Ddhd2-Stxbp1 Interaction Mediates Long-Term Memory Via Generation Of Saturated Free Fatty Acids, Isaac O Akefe, Saber H Saber, Benjamin Matthews, Bharat G Venkatesh, Rachel S Gormal, Daniel G Blackmore, Suzy Alexander, Emma Sieriecki, Yann Gambin, Jesus Bertran-Gonzalez, Nicolas Vitale, Yann Humeau, Arnaud Gaudin, Sevannah A Ellis, Alysee A Michaels, Mingshan Xue, Benjamin Cravatt, Merja Joensuu, Tristan P Wallis, Frédéric A Meunier

Faculty, Staff and Students Publications

The phospholipid and free fatty acid (FFA) composition of neuronal membranes plays a crucial role in learning and memory, but the mechanisms through which neuronal activity affects the brain's lipid landscape remain largely unexplored. The levels of saturated FFAs, particularly of myristic acid (C14:0), strongly increase during neuronal stimulation and memory acquisition, suggesting the involvement of phospholipase A1 (PLA1) activity in synaptic plasticity. Here, we show that genetic ablation of the PLA1 isoform DDHD2 in mice dramatically reduces saturated FFA responses to memory acquisition across the brain. Furthermore, DDHD2 loss also decreases memory performance in reward-based learning and spatial memory …

Multi-Site Benchmark Classification Of Major Depressive Disorder Using Machine Learning On Cortical And Subcortical Measures, Vladimir Belov, Tracy Erwin-Grabner, Moji Aghajani, Andre Aleman, Alyssa R Amod, Zeynep Basgoze, Francesco Benedetti, Bianca Besteher, Robin Bülow, Christopher R K Ching, Colm G Connolly, Kathryn Cullen, Christopher G Davey, Danai Dima, Annemiek Dols, Jennifer W Evans, Cynthia H Y Fu, Ali Saffet Gonul, Ian H Gotlib, Hans J Grabe, Nynke Groenewold, J Paul Hamilton, Ben J Harrison, Tiffany C Ho, Benson Mwangi, Natalia Jaworska, Neda Jahanshad, Bonnie Klimes-Dougan, Sheri-Michelle Koopowitz, Thomas Lancaster, Meng Li, David E J Linden, Frank P Macmaster, David M A Mehler, Elisa Melloni, Bryon A Mueller, Amar Ojha, Mardien L Oudega, Brenda W J H Penninx, Sara Poletti, Edith Pomarol-Clotet, Maria J Portella, Elena Pozzi, Liesbeth Reneman, Matthew D Sacchet, Philipp G Sämann, Anouk Schrantee, Kang Sim, Jair C Soares, Dan J Stein, Sophia I Thomopoulos, Aslihan Uyar-Demir, Nic J A Van Der Wee, Steven J A Van Der Werff, Henry Völzke, Sarah Whittle, Katharina Wittfeld, Margaret J Wright, Mon-Ju Wu, Tony T Yang, Carlos Zarate, Dick J Veltman, Lianne Schmaal, Paul M Thompson, Roberto Goya-Maldonado, Enigma Major Depressive Disorder Working Group

Faculty, Staff and Student Publications

Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy …

Outpatient Fall Prevention In Ambulatory Adults 65 Years Old And Over, Dorothy L. Osborne-White

Doctor of Nursing Practice (DNP) Scholarly Projects - Archive

Background: In the United States (U.S.), falls are the leading cause of injury among adults 65 and over, resulting in 36 million falls yearly (Moreland et al., 2020). According to the Centers for Disease Control and Prevention (CDC, 2023), one in four older adults experiences a fall each year. Falls are the world's second most prominent cause of accidental deaths (World Health Organization [WHO], 2021). Falls are the leading cause of both fatal and non-fatal injuries among older adults (Moreland et al., 2020).

Methods: A quality improvement project that included a fall bundle was implemented in a primary clinic. A …

An Ewas Of Dementia Biomarkers And Their Associations With Age, African Ancestry, And Ptsd, Mark W. Miller, Erika J. Wolf, Xiang Zhao, Mark W. Logue, Sage E. Hawn

Psychology Faculty Publications

Background

Large-scale cohort and epidemiological studies suggest that PTSD confers risk for dementia in later life but the biological mechanisms underlying this association remain unknown. This study examined this question by assessing the influences of PTSD, APOE ε4 genotypes, DNA methylation, and other variables on the age- and dementia-associated biomarkers Aβ40, Aβ42, GFAP, NfL, and pTau-181 measured in plasma. Our primary hypothesis was that PTSD would be associated with elevated levels of these markers.

Methods

Analyses were based on data from a PTSD-enriched cohort of 849 individuals. We began by performing factor analyses of the biomarkers, the results of which …

Neuroticism Mediates The Association Between Autistic Traits And Choice Reaction Time Among Young Adults, Kassandra De Jesus Cintron, Xiao Yang

Psychology Faculty Publications

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that influences an individual’s cognitive functions and social interaction. While most studies have focused on children and adolescents diagnosed with ASD, elevated levels of autistic traits in subclinical populations may also influence individuals’ daily functioning. Autistic traits are also linked to the Big Five personality. In particular, neuroticism (emotion instability) has been shown to be positively associated with autistic traits, which may contribute to behavioral symptoms of autistic traits. The present study aimed to investigate the association between autistic symptoms and sensorimotor processing among a subclinical population. One hundred young adults (M …