Life Sciences Commons^™

Relationship Between Gut Microbiota And Dementia, Saad Ahmed, Zackary Harris, Russell David Levi

Rowan-Virtua Research Day

This paper explores the complex relationship between gut microbiota, dietary habits, and dementia, focusing particularly on Alzheimer's disease (AD). Growing evidence suggests a significant link between the composition of gut bacteria, dietary choices, and susceptibility to dementia. Notably, individuals with dementia demonstrate a noticeable reduction in gut bacteria diversity, highlighting the crucial role of a balanced microbiome in maintaining cognitive health. Conversely, dietary preferences characterized by excessive consumption of processed foods and sugars are associated with an increased risk of dementia, emphasizing the critical influence of diet on shaping gut microbiota and subsequent neurocognitive outcomes. Importantly, dietary interventions featuring a …

Alzheimer's Disease, Dylan L. Weber

Student Publications

An overview of the background, etiology, pathophysiology, clinical features, diagnosis, treatment and prevention of Alzheimer's disease.

Alzheimer's And Patient Caregiver Burnout: A Review Of The Literature, Madeline Hekeler

James Madison Undergraduate Research Journal (JMURJ)

The term “silent epidemic” is fitting for Alzheimer’s disease (AD), as its negative impact is widely felt but rarely discussed. Burnout among AD caregivers has become an epidemic of its own as caregivers experience an increase in health risks, stress, and financial burden. This literature review focuses on caregiver burnout and how imperative it is that caregivers are better supported in their role. Researchers have developed instruments to assess and intervene in caregiver burnout that have shown effectiveness among caregivers and their families.Nevertheless, further longitudinal research is warranted regarding more effective interventions, including stress management and social support mechanisms.

Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast

Senior Honors Theses

This paper reviews functions of Amyloid-β (Aβ) in healthy individuals compared to the consequences of aberrant Aβ in Alzheimer’s disease (AD). As extraneuronal Aβ accumulation and plaque formation are characteristics of AD, it is reasonable to infer a pivotal role for Aβ in AD pathogenesis. Establishing progress of the disease as well as the mechanism of neurodegeneration from AD have proven difficult (Selkoe, 1994). This thesis provides evidence suggesting the pathogenesis of AD is due to dysfunctional neuronal processes involving Aβ’s synaptic malfunction, abnormal interaction with tau, and disruption of neuronal homeostasis. Significant evidence demonstrates that AD symptoms are partially …

An Animal-Assisted Intervention Study In The Nursing Home: Lessons Learned, Lonneke G. J. A. Schuurmans, Inge Noback, Jos M. G. A. Schols, Marie-Jose Enders-Slegers

People and Animals: The International Journal of Research and Practice

AAI studies in the nursing home pose a specific set of challenges. In this article the practical and ethical issues encountered during a Dutch psychogeriatric nursing home AAI study are addressed with the aim of sharing our experiences for future researchers as well as AAI practitioners in general.

In our study we compared three groups of clients with dementia who participated in group sessions of either visiting dog teams, visiting FurReal Friend robot animals, or visiting students (control group) and monitored the effect on social interaction and neuropsychiatric symptoms through video analysis and questionnaires. We encountered the following four categories …

Hyperhomocysteinemia As A Risk Factor For Vascular Contributions To Cognitive Impairment And Dementia, Brittani R. Price, Donna M. Wilcock, Erica M. Weekman

Physiology Faculty Publications

Behind only Alzheimer’s disease, vascular contributions to cognitive impairment and dementia (VCID) is the second most common cause of dementia, affecting roughly 10–40% of dementia patients. While there is no cure for VCID, several risk factors for VCID, such as diabetes, hypertension, and stroke, have been identified. Elevated plasma levels of homocysteine, termed hyperhomocysteinemia (HHcy), are a major, yet underrecognized, risk factor for VCID. B vitamin deficiency, which is the most common cause of HHcy, is common in the elderly. With B vitamin supplementation being a relatively safe and inexpensive therapeutic, the treatment of HHcy-induced VCID would seem straightforward; however, …

Ca2+, Astrocyte Activation And Calcineurin/Nfat Signaling In Age-Related Neurodegenerative Diseases, Pradoldej Sompol, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Mounting evidence supports a fundamental role for Ca²⁺ dysregulation in astrocyte activation. Though the activated astrocyte phenotype is complex, cell-type targeting approaches have revealed a number of detrimental roles of activated astrocytes involving neuroinflammation, release of synaptotoxic factors and loss of glutamate regulation. Work from our lab and others has suggested that the Ca²⁺/calmodulin dependent protein phosphatase, calcineurin (CN), provides a critical link between Ca²⁺ dysregulation and the activated astrocyte phenotype. A proteolyzed, hyperactivated form of CN appears at high levels in activated astrocytes in both human tissue and rodent tissue around regions of amyloid and …

Metabolic And Vascular Imaging Biomarkers In Down Syndrome Provide Unique Insights Into Brain Aging And Alzheimer Disease Pathogenesis, Elizabeth Head, David K. Powell, Frederick A. Schmitt

Pharmacology and Nutritional Sciences Faculty Publications

People with Down syndrome (DS) are at high risk for developing Alzheimer disease (AD). Neuropathology consistent with AD is present by 40 years of age and dementia may develop up to a decade later. In this review, we describe metabolic and vascular neuroimaging studies in DS that suggest these functional changes are a key feature of aging, linked to cognitive decline and AD in this vulnerable cohort. FDG-PET imaging in DS suggests systematic reductions in glucose metabolism in posterior cingulate and parietotemporal cortex. Magentic resonance spectroscopy studies show consistent decreases in neuronal health and increased myoinositol, suggesting inflammation. There are …

Bilateral Carotid Artery Stenosis Causes Unexpected Early Changes In Brain Extracellular Matrix And Blood-Brain Barrier Integrity In Mice, Jill M. Roberts, Michael E. Maniskas, Gregory J. Bix

Neuroscience Faculty Publications

Bilateral carotid artery stenosis (BCAS) is one experimental model of vascular dementia thought to preferentially impact brain white matter. Indeed, few studies report hippocampal and cortical pathology prior to 30 days post-stenosis; though it is unclear whether those studies examined regions outside the white matter. Since changes in the blood-brain barrier (BBB) permeability precede more overt brain pathology in various diseases, we hypothesized that changes within the BBB and/or BBB-associated extracellular matrix (ECM) could occur earlier after BCAS in the hippocampus, cortex and striatum and be a precursor of longer term pathology. Here, C57Bl/6 mice underwent BCAS or sham surgeries …

Calcineurin/Nfat Signaling In Activated Astrocytes Drives Network Hyperexcitability In AΒ-Bearing Mice, Pradoldej Sompol, Jennifer L. Furman, Melanie M. Pleiss, Susan D. Kraner, Irina A. Artiushin, Seth R. Batten, Jorge E. Quintero, Linda A. Simmerman, Tina L. Beckett, Mark A. Lovell, M. Paul Murphy, Greg A. Gerhardt, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Hyperexcitable neuronal networks are mechanistically linked to the pathologic and clinical features of Alzheimer's disease (AD). Astrocytes are a primary defense against hyperexcitability, but their functional phenotype during AD is poorly understood. Here, we found that activated astrocytes in the 5xFAD mouse model were strongly associated with proteolysis of the protein phosphatase calcineurin (CN) and the elevated expression of the CN-dependent transcription factor nuclear factor of activated T cells 4 (NFAT4). Intrahippocampal injections of adeno-associated virus vectors containing the astrocyte-specific promoter Gfa2 and the NFAT inhibitory peptide VIVIT reduced signs of glutamate-mediated hyperexcitability in 5xFAD mice, measured in vivo with …

Csf Protein Changes Associated With Hippocampal Sclerosis Risk Gene Variants Highlight Impact Of Grn/Pgrn, David W. Fardo, Yuriko Katsumata, John S. K. Kauwe, Yuetiva Deming, Oscar Harari, Carlos Cruchaga, Alzheimer’S Disease Neuroimaging Initiative, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Objective—Hippocampal sclerosis of aging (HS-Aging) is a common cause of dementia in older adults. We tested the variability in cerebrospinal fluid (CSF) proteins associated with previously identified HS-Aging risk single nucleotide polymorphisms (SNPs).

Methods—Alzheimer’s Disease Neuroimaging Initiative cohort (ADNI; n=237) data, combining both multiplexed proteomics CSF and genotype data, were used to assess the association between CSF analytes and risk SNPs in four genes (SNPs): GRN (rs5848), TMEM106B (rs1990622), ABCC9 (rs704180), and KCNMB2 (rs9637454). For controls, non-HS-Aging SNPs in APOE (rs429358/rs7412) and MAPT (rs8070723) were also analyzed against Aβ1-42 and total tau CSF analytes.

Results—The GRN risk …

Neuropathological And Genetic Correlates Of Survival And Dementia Onset In Synucleinopathies: A Retrospective Analysis, David J. Irwin, Murray Grossman, Daniel Weintraub, Howard I. Hurtig, John E. Duda, Sharon X. Xie, Edward B. Lee, Vivianna M. Van Deerlin, Oscar L. Lopez, Julia K. Kofler, Peter T. Nelson, Gregory A. Jicha, Randy Woltjer, Joseph F. Quinn, Jeffery Kaye, James B. Leverenz, Debby Tsuang, Katelan Longfellow, Dora Yearout, Walter Kukull, C. Dirk Keene, Thomas J. Montine, Cyrus P. Zabetian, John Q. Trojanowski

Sanders-Brown Center on Aging Faculty Publications

Background

Great heterogeneity exists in survival and the interval between onset of motor symptoms and dementia symptoms across synucleinopathies. We aimed to identify genetic and pathological markers that have the strongest association with these features of clinical heterogeneity in synucleinopathies.

Methods

In this retrospective study, we examined symptom onset, and genetic and neuropathological data from a cohort of patients with Lewy body disorders with autopsy-confirmed α synucleinopathy (as of Oct 1, 2015) who were previously included in other studies from five academic institutions in five cities in the USA. We used histopathology techniques and markers to assess the burden of …

The Role Of Capillaries In The Lesser Ailments Of Old Age And In Alzheimer's Disease And Vascular Dementia: The Potential Of Pro-Therapeutic Angiogenesis, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Apart from chronic diseases (arthritis, diabetes, etc.), old age is generally characterized by three lesser ailments: muscle weakness, minor memory lapses, and cold intolerance. This trio of complaints may have a common, underlying cause, namely, the age-associated reduced microcirculation in muscles, brain, skin, and elsewhere in the body. The Angiogenesis Hypothesis proposes that old age is in part a deficiency disease due to the decline in angiogenic (AG) factors, resulting in a reduced capillary density (CD) throughout the body. Over fifty published papers document waning levels of AG factors and/or decreased CD in various organ systems of aged animals and …

The Effect Of A Multiple Modality Mind-Motor Exercise Intervention On Single And Dual-Task Gait, Balance, And Executive Function, In Community Dwelling Older Adults With A Subjective Cognitive Complaint: A Randomized Controlled Trial., John P. Bocti

Electronic Thesis and Dissertation Repository

Cognitive decline disorders are becoming increasingly prevalent, with older adults at increased risk. Combined exercise has been recently explored as an intervention to help to prevent the decline, however cognitive activation in combination with physical activity has yet to be explored. Therefore, the purpose of the study is to determine the effects of multiple modality exercise programs in combination with a mind-motor task and their effects on mobility and cognitive variables. A total of (n=89) older adults (55+ yrs), with subjective cognitive complaints participated in a multiple modality exercise class, three days a week over six months, with the intervention …

A Therapeutic Approach For Senile Dementias: Neuroangiogenesis, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Alzheimer's disease (AD) and related senile dementias (SDs) represent a growing medical and economic crisis in this country. Apart from cautioning persons about risk factors, no practical, effective therapy is currently available. Much of the recent research in AD has been based on the amyloid cascade theory. Another approach assumes a vascular basis for SDs. This paper presents evidence from a score of studies that cerebral capillary density (CCD) declines during old age in animals and people as well as in AD. Neuroangiogenic (NAG) factors initiate and maintain capillaries in the brain. Thus a waning level of these factors and …

Self-Reported Head Injury And Risk Of Late-Life Impairment And Ad Pathology In An Ad Center Cohort, Erin L. Abner, Peter T. Nelson, Frederick A. Schmitt, Steven R. Browning, David W. Fardo, Lijie Wan, Gregory A. Jicha, Gregory E. Cooper, Charles D. Smith, Allison M. Caban-Holt, Linda J. Van Eldik, Richard J. Kryscio

Sanders-Brown Center on Aging Faculty Publications

Aims: To evaluate the relationship between self-reported head injury and cognitive impairment, dementia, mortality, and Alzheimer's disease (AD)-type pathological changes. Methods: Clinical and neuropathological data from participants enrolled in a longitudinal study of aging and cognition (n = 649) were analyzed to assess the chronic effects of self-reported head injury. Results: The effect of self-reported head injury on the clinical state depended on the age at assessment: for a 1-year increase in age, the OR for the transition to clinical mild cognitive impairment (MCI) at the next visit for participants with a history of head injury was 1.21 and 1.34 …

Neuropsychological And Neurophysiological Effects Of Low-Intensity Strengthening Exercise On Cognition, Vadim V. Yerokhin

Honors Theses

With the growing aging population, it’s becoming increasingly important to find ways to either deter or prevent dementia. To date, most research has concentrated on the effects of aerobic exercise on cognition. Unfortunately, a large portion of older adults are often contraindicated to perform aerobic exercise due to different risk factors, which increase with age. Alas, alternate ways of exercise are necessary. Low-intensity strengthening exercise is a type of exercise aimed at improving balance and strengthening muscles without requiring one to overstrain. The current 11-week long exercise study test neuropsychological effects of exercise with a neuropsychological battery and neurophysiological effects …

Human Cerebral Neuropathology Of Type 2 Diabetes Mellitus, Peter T. Nelson, Charles D. Smith, Erin L. Abner, Frederick A. Schmitt, Stephen W. Scheff, Gregory J. Davis, Jeffrey N. Keller, Gregory A. Jicha, Daron Davis, Wang-Xia Wang, Adria Hartman, Douglas G. Katz, William R. Markesbery

Pathology and Laboratory Medicine Faculty Publications

The cerebral neuropathology of Type 2 diabetes (CNDM2) has not been positively defined. This review includes a description of CNDM2 research from before the ‘Pubmed Era’. Recent neuroimaging studies have focused on cerebrovascular and white matter pathology. These and prior studies about cerebrovascular histopathology in diabetes are reviewed. Evidence is also described for and against the link between CNDM2 and Alzheimer's disease pathogenesis. To study this matter directly, we evaluated data from University of Kentucky Alzheimer's Disease Center (UK ADC) patients recruited while non-demented and followed longitudinally. Of patients who had come to autopsy (N = 234), 139 met …