Medicine and Health Sciences Commons^™

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 …

In Sickness And In Health-Type I Interferon And The Brain, Wei Cao

Journal Articles

Type I interferons (IFN-I) represent a group of pleiotropic cytokines renowned for their antiviral activity and immune regulatory functions. A multitude of studies have unveiled a critical role of IFN-I in the brain, influencing various neurological processes and diseases. In this mini-review, I highlight recent findings on IFN-I's effects on brain aging, Alzheimer's disease (AD) progression, and central nervous system (CNS) homeostasis. The multifaceted influence of IFN-I on brain health and disease sheds light on the complex interplay between immune responses and neurological processes. Of particular interest is the cGAS-STING-IFN-I axis, which extensively participates in brain aging and various forms …

Accuracy Of True-Net In Comparison To Established White Matter Hyperintensity Segmentation Methods: An Independent Validation Study, Jeremy F Strain, Maryam Rahmani, Donna Dierker, Christopher Owen, Hussain Jafri, Andrei G Vlassenko, Kyle Womack, Jurgen Fripp, Duygu Tosun, Tammie L S Benzinger, Michael Weiner, Colin Masters, Jin-Moo Lee, John C Morris, Manu S Goyal, Adopic And Adni Investigators

2020-Current year OA Pubs

White matter hyperintensities (WMH) are nearly ubiquitous in the aging brain, and their topography and overall burden are associated with cognitive decline. Given their numerosity, accurate methods to automatically segment WMH are needed. Recent developments, including the availability of challenge data sets and improved deep learning algorithms, have led to a new promising deep-learning based automated segmentation model called TrUE-Net, which has yet to undergo rigorous independent validation. Here, we compare TrUE-Net to six established automated WMH segmentation tools, including a semi-manual method. We evaluated the techniques at both global and regional level to compare their ability to detect the …

Advanced Structural Brain Aging In Preclinical Autosomal Dominant Alzheimer Disease, Peter R Millar, Brian A Gordon, Julie K Wisch, Tammie L.S. Benzinger, Carlos Cruchaga, Jason J Hassenstab, Laura Ibanez, Celeste Karch, Jorge J Llibre-Guerra, John C Morris, Richard J Perrin, Charlene Supnet-Bell, Chengjie Xiong, Randall J Bateman, Beau M Ances, Eric M Mcdade, Et Al.

2020-Current year OA Pubs

BACKGROUND: "Brain-predicted age" estimates biological age from complex, nonlinear features in neuroimaging scans. The brain age gap (BAG) between predicted and chronological age is elevated in sporadic Alzheimer disease (AD), but is underexplored in autosomal dominant AD (ADAD), in which AD progression is highly predictable with minimal confounding age-related co-pathology.

METHODS: We modeled BAG in 257 deeply-phenotyped ADAD mutation-carriers and 179 non-carriers from the Dominantly Inherited Alzheimer Network using minimally-processed structural MRI scans. We then tested whether BAG differed as a function of mutation and cognitive status, or estimated years until symptom onset, and whether it was associated with established …

Single-Cell Atlas Of Healthy Human Blood Unveils Age-Related Loss Of Nkg2c+Gzmb−Cd8+ Memory T Cells And Accumulation Of Type 2 Memory T Cells, Marina Terekhova, Amanda Swain, Pavla Bohacova, Ekaterina Aladyeva, Laura Arthur, Anwesha Laha, Denis A Mogilenko, Samantha Burdess, Vladimir Sukhov, Denis Kleverov, Barbora Echalar, Petr Tsurinov, Roman Chernyatchik, Kamila Husarcikova, Maxim N Artyomov

2020-Current year OA Pubs

Extensive, large-scale single-cell profiling of healthy human blood at different ages is one of the critical pending tasks required to establish a framework for the systematic understanding of human aging. Here, using single-cell RNA/T cell receptor (TCR)/BCR-seq with protein feature barcoding, we profiled 317 samples from 166 healthy individuals aged 25-85 years old. From this, we generated a dataset from ∼2 million cells that described 55 subpopulations of blood immune cells. Twelve subpopulations changed with age, including the accumulation of GZMK

Reimagining A Caregiver-Friendly Society, Jodi L. Southerland

Journal of Appalachian Health

Demographic aging is accelerating in the Appalachian Region, resulting in a growing proportion of caregivers living in areas that lack services to support their needs. Strategies are urgently needed in Appalachia to address deficiencies in the region’s long-term supports and services for older adults and their caregivers. Strengthening equitable access to care and community supports for family caregivers is a policy priority for state and community leaders in Appalachia.

Sirtuin 6 Activation Rescues The Age-Related Decline In Dna Damage Repair In Primary Human Chondrocytes, Michaela E. Copp, Jacqueline Shine, Hannon L. Brown, Kirti R. Nimmala, Oliver B. Hansen, Susan Chubinskaya, John A. Collins, Richard F. Loeser, Brian O. Diekman

Department of Orthopaedic Surgery Faculty Papers

While advanced age is widely recognized as the greatest risk factor for osteoarthritis (OA), the biological mechanisms behind this connection remain unclear. Previous work has demonstrated that chondrocytes from older cadaveric donors have elevated levels of DNA damage as compared to chondrocytes from younger donors. The purpose of this study was to determine whether a decline in DNA repair efficiency is one explanation for the accumulation of DNA damage with age, and to quantify the improvement in repair with activation of Sirtuin 6 (SIRT6). After acute damage with irradiation, DNA repair was shown to be more efficient in chondrocytes from …

Accessiblehomepro As An Educational Intervention: Preparing Occupational Therapy Students To Perform Home Safety Assessments, Laryn O'Donnell

Theses and Dissertations

The growing aging population of the United States urges occupational therapy practitioners to address the population's home safety needs. However, current occupational therapists need more resources and education to conduct comprehensive home safety evaluations. This study employed a pretest-posttest mixed methods design using occupational therapy students (n=17) to investigate the potential of AccessibleHomePRO as an educational intervention to enhance OT student knowledge of home safety assessments, perceived knowledge, which is known as the belief in your level of knowledge, and self-efficacy, which refers to the confidence in completing a task. AccessibleHomePRO (AHP) is a novel multifaceted assessment that leverages artificial …

Art Of Aging – A Portraiture Study, Alaina Mann

Theses/Capstones/Creative Projects

The process of aging can be viewed through different lenses within our society. In the past, scientists and medical professionals performed various studies to better understand and analyze different facets of aging, medicine, and health in general. Historically the arts have reflected multiple aspects of medicine and treatments while more recently, the arts have been used in a research capacity to provide different ways to represent illness, suffering, and care. This study used art-based research methods and portraiture to gather qualitative observations on the older populations within our community. Data collected included drawings, a field journal, and interviews. This study …

Effects Of Exercise Training On Muscle Quality In Older Individuals: A Systematic Scoping Review With Meta-Analyses, Tibor Hortobágyi, Tomas Vetrovsky, Jennifer S. Brach, Martijn Van Haren, Krystof Volesky, Regis Radaelli, Pedro Lopez, Urs Granacher

Research outputs 2022 to 2026

Background: The quantity and quality of skeletal muscle are important determinants of daily function and metabolic health. Various forms of physical exercise can improve muscle function, but this effect can be inconsistent and has not been systematically examined across the health-neurological disease continuum. The purpose of this systematic scoping review with meta-analyses was to determine the effects and potential moderators of exercise training on morphological and neuromuscular muscle quality (MMQ, NMQ) in healthy older individuals. In addition and in the form of a scoping review, we examined the effects of exercise training on NMQ and MMQ in individuals with neurological …

Supra-Additive Effect Of Chronic Inflammation And Atherogenic Dyslipidemia On Developing Type 2 Diabetes Among Young Adults: A Prospective Cohort Study, Yulong Lan, Dan Wu, Zhiwei Cai, Yuancheng Xu, Xiong Ding, Weiqiang Wu, Shaocong Lan, Lan Chen, Zheng Guo, Lois Balmer, Xingang Li, Manshu Song, Shouling Wu, Jingli Gao, Wei Wang, Youren Chen

Research outputs 2022 to 2026

Background: Both elevated inflammation and atherogenic dyslipidemia are prominent in young-onset diabetes and are increasingly identified as biologically intertwined processes that contribute to diabetogenesis. We aimed to investigate the age-specific risks of type 2 diabetes (T2D) upon concomitant chronic inflammation and atherogenic dyslipidemia. Methods: Age-stratified Cox regression analysis of the risk of incident diabetes upon co-exposure to time-averaged cumulative high-sensitivity C-reactive protein (CumCRP) and atherogenic index of plasma (CumAIP) among 42,925 nondiabetic participants from a real-world, prospective cohort (Kailuan Study). Results: During a median 6.41 years of follow-up, 3987 T2D developed. Isolated CumAIP and CumCRP were significantly associated with incident …

Environmental Exposures And Aging., Daniel Chris Gomes

Electronic Theses and Dissertations

In recent years, research into air pollution has shown that exposure to certain components in air pollution, primarily PM2.5 can accelerate biological aging and thereby lead to increased susceptibility to multiple diseases. We hypothesize that prolonged exposure to air pollutants can result in premature aging leading to extensive tissue dysfunction and susceptibility to diseases. To examine this, we exposed mice to PM2.5 for 9, 15, and 21 days, then measured the telomere lengths, cellular senescence, and histone methylation patterns of multiple cell types. We found consistently increased telomere attrition, cellular senescence and advanced age-consistent histone methylation patterns in groups exposed …

Organ Aging Signatures In The Plasma Proteome Track Health And Disease, Hamilton Se-Hwee Oh, Yun Ju Sung, Lihua Wang, Jigyasha Timsina, Dan Western, Menghan Liu, Pat Kohlfeld, John Budde, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Animal studies show aging varies between individuals as well as between organs within an individual

Social Capital Associates With Better Cognitive Health, Oral Health And Epigenetic Age Deceleration: Findings From The Canadian Longitudinal Study On Aging., Aileen Liang, Noha Gomaa

Department of Medicine Publications

Background: Social exposures are linked to an array of health outcomes, especially around aging. In this study, we examined the association of social capital, defined as social relationships and networks, with clinical and biological outcomes including cognitive health, oral inflammation, and epigenetic aging. Methods: We used data from the Canadian Longitudinal Study on Aging (CLSA) (n =1,479; aged 45–85 years), categorizing social capital as structural and cognitive capital. Oral inflammation was determined as the presence of gum bleeding. Epigenetic aging was computed as the difference between chronological age and DNA methylation age. We constructed multivariable regression models adjusted for covariates …

T Cell Control Of Inflammaging, Irina Shchukina, Pavla Bohacova, Maxim N Artyomov

2020-Current year OA Pubs

T cells are a critical component of the immune system, found in abundance in blood, secondary lymphoid organs, and peripheral tissues. As individuals age, T cells are particularly susceptible to changes, making them one of the most affected immune subsets. These changes can have significant implications for age-related dysregulations, including the development of low-grade inflammation - a hallmark of aging known as inflammaging. In this review, we first present age-related changes in the functionality of the T cell compartment, including dysregulation of cytokine and chemokine production and cytotoxicity. Next, we discuss how these changes can contribute to the development and …

Identifying And Reverting The Adverse Effects Of White Matter Hyperintensities On Cortical Surface Analyses, Yuki Oi, Masakazu Hirose, Hiroki Togo, Kenji Yoshinaga, Thai Akasaka, Tomohisa Okada, Toshihiko Aso, Ryosuke Takahashi, Matthew F Glasser, Takuya Hayashi, Takashi Hanakawa

2020-Current year OA Pubs

The Human Connectome Project (HCP)-style surface-based brain MRI analysis is a powerful technique that allows precise mapping of the cerebral cortex. However, the strength of its surface-based analysis has not yet been tested in the older population that often presents with white matter hyperintensities (WMHs) on T2-weighted (T2w) MRI (hypointensities on T1w MRI). We investigated T1-weighted (T1w) and T2w structural MRI in 43 healthy middle-aged to old participants. Juxtacortical WMHs were often misclassified by the default HCP pipeline as parts of the gray matter in T1w MRI, leading to incorrect estimation of the cortical surfaces and cortical metrics. To revert …

Depression By Gender And Associated Factors Among Older Adults In India: Implications For Age-Friendly Policies, Ronak Paul, T. Muhammad, Rashmi Rashmi, Palak Sharma, Shobhit Srivastava, Preeti Zanwar

College of Population Health Faculty Papers

Inspite of implementing policies to control mental health problems, depression remains a severe health concern among older adults in India. We examined self-reported differences in the depression among older men and women in India and examined associated factors for gender differences in depression at the population level. We utilized nationally representative data from the Longitudinal Aging Study in India (LASI) wave I, for years 2017-2019. Our analytical sample comprised of 30,637 older adults ages 60 years and above (14,682 men and 15,655 women). We conducted descriptive statistics and Chi-Square tests followed by binary logistic regression and multivariate decomposition analyses to …

Longitudinal Associations Between Cognitive Functioning And Depressive Symptoms Among Couples In The Mexican Health And Aging Study, Joan K Monin, Gail Mcavay, Katie Newkirk, Rafael Samper-Ternent

Journal Articles

OBJECTIVE: To examine the bidirectional associations between older adult spouses' cognitive functioning and depressive symptoms over time and replicate previous findings from the United States (US) in Mexico.

DESIGN: Longitudinal, dyadic path analysis with the actor-partner interdependence model.

SETTING: Data were from the three most recent interview waves (2012, 2015, and 2018) of the Mexican Health and Aging Study (MHAS), a longitudinal national study of adults aged 50+ years in Mexico.

PARTICIPANTS: Husbands and wives from 905 community-dwelling married couples (N = 1,810).

MEASUREMENTS: The MHAS cognitive battery measured cognitive function. Depressive symptoms were assessed using a modified nine-item Center …

Fornix Volumetric Increase During Aging Associates To Microglia Activation Leading To Defective Cognitive Performance, Marcela Cárdenas Tueme, Luis Ángel Trujillo-Villarreal, Victor Ramírez-Amaya, Eduardo Garza-Villarreal, Alberto Camacho-Morales, Diana Reséndez-Pérez

Research Symposium

Background: Ageing displays a low-grade pro-inflammatory profile in blood and brain. It has been documented proinflammatory cytokines accumulation leading to neuroinflammation during aging. Aged brains integrate pro inflammatory cytokines accumulation, active microglia and volumetric changes which correlates with defective cognitive performance and neurodegeneration.

Methods: Mice from 2-,12- and 20-months-old of age were submitted to different memory tests: Y-maze, Barnes maze, object location test and object location test. Afterwards, we performed structural MRI to evaluate macrostructural changes related to memory and learning regions. Following this, we also evaluated in peripheral blood and in brain tissue the presence of pro-inflammatory cytokines …

Apoe Polymorphism And Its Association With Dementia, Neuropsychiatric Disorders, And Demographic Factors In U.S Hispanic Population, Victoria I. Padilla

Research Symposium

In 2019, the United States Census revealed that Hispanics are the greatest minority group in the U.S, 18% of the population; in 2060, it is expected to increase by 28%. Hispanics ages 65 have one of the highest rates of Alzheimer’s disease (AD) in the U.S. Studies have linked AD and other cognitive impairments, MCI, with apolipoprotein or APOE gene. APOE has also shown to increase the risk of neuropsychiatric disorders in individuals. However, there are limited studies in U.S Hispanics. This study examines the APOE gene and its associations with dementiarelated phenotypes, neuropsychiatric disorders, and demographic factors in U.S …

The Impact Of Access To Oral Health Care On Inadequate Oral Health And Multimorbidity, Luis Limo

Electronic Thesis and Dissertation Repository

The connection between oral health and other non-communicable chronic conditions—commonly referred in the dental literature as the oral-systemic health connection—emphasizes the role of oral health care on both oral diseases and chronic conditions, particularly in vulnerable populations like the elderly. This thesis comprises 2 studies: the first is a systematic review on the impact of oral health care interventions, as an indicator of access to oral health care, on chronic conditions of which their co-existence would result in multimorbidity; the second study is a cross-sectional investigation of the associations between oral health, access to oral health care, and multimorbidity among …

Comparison Of Aging Techniques In Wild Bottlenose Dolphins (Tursiops Truncatus) Of Unknown Age From The Mississippi Sound., Christa Elizabeth Barrett

Theses and Dissertations

Age determination of bottlenose dolphins (Tursiops truncatus) is a critical tool in understanding their health. There are many methods of aging dolphins including morphometrics, counting growth layer groups (GLGs) of teeth, comparing dentin to pulp cavity ratio on dental radiographs, analysis of the pectoral flipper radiographs, and epigenetic testing. The most common method for aging toothed cetaceans is the counting of GLGs in the teeth. Since there are many challenges associated with aging dolphins based on the counting of GLGs, a processing technique that results in better resolution of GLGs is needed. This is a two-part study that …

The Importance Of Addressing Sleep As An Occupation Within Assisted Living Communities, Brittany Kiattitananan, Kendra Orcutt, Lisa Griggs-Stapleton

Summer 2023 Virtual OTD Capstone Symposium

Around 40-70% of older adults have difficulty sleeping (Sheth & Thomas, 2019). This poster presents an occupation-based sleep intervention program developed for residents of an assisted living community and serves to inform OT practitioners on addressing sleep in their own practice.

Older Women’S Stories Of Covid-19 Loss: Communicated Narrative Sense-Making Through Photography, Anne Walker

Electronic Theses and Dissertations

The diverse array of challenges associated with the COVID-19 pandemic make it difficult to assess the full impact of this global health crisis. More than 300,000 older Americans died, leaving a nation of grieving survivors in their absence. This profound loss of life will undoubtedly inform the field’s understanding of grief and grieving for many years to come. Pre-pandemic, older women in the United States understood grief to be part of their life stage; COVID-19 amplified the grief experience through both cumulative losses and the isolation particular to the novel coronavirus response. However, few qualitative studies explore older women’s grief, …

Cardiovascular And Metabolic Health Is Associated With Functional Brain Connectivity In Middle-Aged And Older Adults: Results From The Human Connectome Project-Aging Study, Barnaly Rashid, Matthew F Glasser, Thomas Nichols, David Van Essen, Meher R Juttukonda, Nadine A Schwab, Douglas N Greve, Essa Yacoub, Allison Lovely, Melissa Terpstra, Michael P Harms, Susan Y Bookheimer, Beau M Ances, David H Salat, Steven E Arnold

2020-Current year OA Pubs

Several cardiovascular and metabolic indicators, such as cholesterol and blood pressure have been associated with altered neural and cognitive health as well as increased risk of dementia and Alzheimer's disease in later life. In this cross-sectional study, we examined how an aggregate index of cardiovascular and metabolic risk factor measures was associated with correlation-based estimates of resting-state functional connectivity (FC) across a broad adult age-span (36-90+ years) from 930 volunteers in the Human Connectome Project Aging (HCP-A). Increased (i.e., worse) aggregate cardiometabolic scores were associated with reduced FC globally, with especially strong effects in insular, medial frontal, medial parietal, and …

Urolithin A As A Potential Agent For Prevention Of Age-Related Disease: A Scoping Review., Breanne Kothe, Sarah Klein, Stephanie N. Petrosky

HPD Articles

The aging of an organism is hallmarked by systemic loss of functional tissue, resulting in increased fragility and eventual development of age-related neurodegenerative, musculoskeletal, cardiovascular, and neoplastic diseases. Growing scientific evidence points to mitochondrial dysfunction as a key contributor in the aging process and subsequent development of age-related pathologies. Under normal physiologic conditions, the body removes dysfunctional mitochondria via an autophagic process known as mitophagy. Urolithin A (UA), a metabolite produced when gut microflora digests the polyphenol compounds ellagitannin and ellagic acid, is a known inducer of mitophagy via several identified mechanisms of action. The primary objective of this scoping …

Abstracts From The 2023 Health Care Systems Research Network (Hcsrn) Annual Conference, Denver, Colorado

Journal of Patient-Centered Research and Reviews

The Health Care Systems Research Network (HCSRN) is comprised of 20 learning health systems with embedded population-based research units. The network’s annual conference serves as a forum for research teams from member institutions to disseminate project findings, explore scientific collaborations, and share insights about conducting research in real-world care delivery settings. Abstracts presented at HCSRN 2023 are published in this issue supplement of Journal of Patient-Centered Research and Reviews, the journal of record for HCSRN’s annual conference proceedings.

Associations Between Age, Sex, Apoe Genotype, And Regional Vascular Physiology In Typically Aging Adults, Nikou L Damestani, John Jacoby, Shrikanth M Yadav, Allison E Lovely, Aurea Michael, Melissa Terpstra, Marziye Eshghi, Barnaly Rashid, Carlos Cruchaga, David H Salat, Meher R Juttukonda

2020-Current year OA Pubs

Altered blood flow in the human brain is characteristic of typical aging. However, numerous factors contribute to inter-individual variation in patterns of blood flow throughout the lifespan. To better understand the mechanisms behind such variation, we studied how sex and APOE genotype, a primary genetic risk factor for Alzheimer's disease (AD), influence associations between age and brain perfusion measures. We conducted a cross-sectional study of 562 participants from the Human Connectome Project - Aging (36 to >90 years of age). We found widespread associations between age and vascular parameters, where increasing age was associated with regional decreases in cerebral blood …

Apoe Gene Associated With Dementia-Related Traits, Depression, And Anxiety In The Hispanic Population, Chun Xu, Victoria Padilla, Stephanie Lozano, Daniela Gamez, Brenda Bin Su, Xuan Wang, Gladys Maestre, Kesheng Wang

Health & Biomedical Sciences Faculty Publications and Presentations

Alzheimer's disease (AD), a main cause of dementia, is commonly seen in aging populations with a strong genetic component. AD is one of the most common neurodegenerative disorders; it is a genetically and clinically heterogeneous disease. Specific demographic factors and genetic variants have been identified in non-Hispanic populations; however, limited studies have observed the Hispanic population. Therefore, we focused on investigating a known gene, APOE, associated with AD-related phenotypes and two psychiatric diseases (depression and anxiety) within the U.S. Hispanic population in our current study. A total of 1382 subjects were studied based on data collected from the Texas Alzheimer's …

Aerobic Exercise Reverses Aging-Induced Depth-Dependent Decline In Cerebral Microcirculation, Paul Shin, Ikbal Şencan-Eğilmez, Et Al.

2020-Current year OA Pubs

Aging is a major risk factor for cognitive impairment. Aerobic exercise benefits brain function and may promote cognitive health in older adults. However, underlying biological mechanisms across cerebral gray and white matter are poorly understood. Selective vulnerability of the white matter to small vessel disease and a link between white matter health and cognitive function suggests a potential role for responses in deep cerebral microcirculation. Here, we tested whether aerobic exercise modulates cerebral microcirculatory changes induced by aging. To this end, we carried out a comprehensive quantitative examination of changes in cerebral microvascular physiology in cortical gray and subcortical white …