Medicine and Health Sciences Commons^™

Promoting Engagement Of Male Individuals With Alzheimer’S In A Memory Day Care, Tara Brophy

Entry-Level Occupational Therapy Doctorate - Doctoral Capstone Symposium

Alzheimer’s and related dementias impact an individual's cognitive, psychological, social, and physical functions resulting in impairments within the engagement of activities. Activities offer many therapeutic benefits including improvements in mood, alertness, communication, socialization, sleep, cognitive function, and quality of life. The focus of this quality improvement capstone project was to address the decreased level of engagement in male members within a memory day care center setting through engaging them in male-tailored activities. The project included the development of a website that provided tailored male-oriented activities and educational resources that were shared with the staff to revise their day care activity …

Hearing Loss And Cognitive Decline In The Aging Population: Emerging Perspectives In Audiology, Naveen K. Nagaraj

Communicative Disorders and Deaf Education Faculty Publications

In this perspective article, the author explores the connections between hearing loss, central auditory processing, and cognitive decline, offering insights into the complex dynamics at play. Drawing upon a range of studies, the relationship between age-related central auditory processing disorders and Alzheimer’s disease is discussed, with the aim of enhancing our understanding of these interconnected conditions. Highlighting the evolving significance of audiologists in the dual management of cognitive health and hearing impairments, the author focuses on their role in identifying early signs of cognitive impairment and evaluates various cognitive screening tools used in this context. The discussion extends to adaptations …

Suboptimal Self-Reported Sleep Efficiency And Duration Are Associated With Faster Accumulation Of Brain Amyloid Beta In Cognitively Unimpaired Older Adults, Louise N. Pivac, Belinda M. Brown, Kelsey R. Sewell, James D. Doecke, Victor L. Villemagne, Vincent Doré, Michael Weinborn, Hamid R. Sohrabi, Samantha L. Gardener, Romola S. Bucks, Simon M. Laws, Kevin Taddei, Paul Maruff, Colin L. Masters, Christopher Rowe, Ralph N. Martins, Stephanie R. Rainey-Smith

Research outputs 2022 to 2026

INTRODUCTION: This study investigated whether self-reported sleep quality is associated with brain amyloid beta (AB) accumulation. METHODS: Linear mixed effect model analyses were conducted for 189 cognitively unimpaired (CU) older adults (mean ± standard deviation 74.0 ± 6.2; 53.2% female), with baseline self-reported sleep data, and positron emission tomography-determined brain AB measured over a minimum of three time points (range 33.3–72.7 months). Analyses included random slopes and intercepts, interaction for apolipoprotein E (APOE) 4 allele status, and time, adjusting for sex and baseline age. RESULTS: Sleep duration < 6 hours, in APOE 4 carriers, and sleep efficiency < 65%, in the whole sample and APOE 4 non-carriers, is associated with faster accumulation of brain AB. DISCUSSION: These findings suggest a role for self-reported suboptimal sleep efficiency and duration in the accumulation of Alzheimer's disease (AD) neuropathology in CU individuals. Additionally, poor sleep efficiency represents a potential route via which individuals at lower genetic risk may progress to preclinical AD. Highlights: In cognitively unimpaired older adults self-report sleep is associated with brain amyloid beta (AB) accumulation. Across sleep characteristics, this relationship differs by apolipoprotein E (APOE) genotype. Sleep duration < 6 hours is associated with faster brain AB accumulation in APOE 4 carriers. Sleep efficiency < 65% is associated with faster brain AB accumulation in APOE 4 non-carriers. Personalized sleep interventions should be studied for potential to slow AB accumulation.

The Australian Multidomain Approach To Reduce Dementia Risk By Protecting Brain Health With Lifestyle Intervention Study (Au-Arrow): A Study Protocol For A Single-Blind, Multi-Site, Randomized Controlled Trial, Samantha L. Gardener, Stephanie J. Fuller, Sharon L. Naismith, Laura Baker, Miia Kivipelto, Victor L. Villemagne, Stuart M. Grieve, Paul Yates, Stephanie R. Rainey-Smith, Juliana Chen, Belinda Thompson, Nicola J. Armstrong, Malika G. Fernando, Carolina B. Castro, Silochna Meghwar, Rema Raman, Andrew Gleason, Catriona Ireland, Roger Clarnette, Kaarin J. Anstey, Kevin Taddei, Manohar Garg, Hamid R. Sohrabi, Ralph N. Martins

Research outputs 2022 to 2026

INTRODUCTION: The Finnish Geriatric Intervention Study (FINGER) led to the global dementia risk reduction initiative: World-Wide FINGERS (WW-FINGERS). As part of WW-FINGERS, the Australian AU-ARROW study mirrors aspects of FINGER, as well as US-POINTER. METHOD: AU-ARROW is a randomized, single-blind, multisite, 2-year clinical trial (n = 600; aged 55–79). The multimodal lifestyle intervention group will engage in aerobic exercise, resistance training and stretching, dietary advice to encourage MIND diet adherence, BrainHQ cognitive training, and medical monitoring and health education. The Health Education and Coaching group will receive occasional health education sessions. The primary outcome measure is the change in 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 …

Editorial: Neurotoxins In Alzheimer's Disease And Other Dementias, Alexandre Henriques, Philippe L. L. Poindron, Binosha Fernando, Kevin N. Hascup

Research outputs 2022 to 2026

Alzheimer's disease (AD) and other dementias are neurodegenerative disorders characterized by a progressive decline in cognition and independence from activities of daily living. Dementia is multifactorial with numerous risk factors including age, genes, molecules, lifestyle, and environmental contributions to disease onset and progression. In recent years, an emerging focus on neurotoxins has added a new layer of complexity to our understanding of dementia. This editorial aims to discuss recent updates regarding the role of neurotoxins in the pathogenesis of dementia.

Nutrients And Polyphenols-Rich Sorghum Bicolor Genotypes As Complementary Therapy For Alzheimer’S Disease, Rasheed A. Abdulraheem, Ralph N. Martins, Prashant Bharadwaj, Zhaoyu Li, Ranil Coorey, Stuart Johnson, W. M. A. D. Binosha Fernando

Research outputs 2022 to 2026

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and most common cause of dementia among older people. The main pathological hallmarks of AD are formation of insoluble amyloid beta senile plaques and paired helical filaments of neurofibrillary tangles. AD features gradual memory decline, mild to severe cognitive impairment, eventually total dependence of patients on caregivers. Currently available drugs have not been able to modify AD pathology. This has drawn increasing attention to plant food materials with high nutritional and bioactive constituents as potential complementary therapy for AD. Sorghum bicolor is a widely available cost-effective source of proteins, fats, crude fibres, …

The Mediterranean Diet And Alzheimer's Disease, Katilyn Wright, Erin Willis, Joshua Villela, Renee Schroth

NURS 320: Evidence-Based Nursing Student Presentations

Research poster created as part of Nursing 320 class. The poster looks at, "whether implementing the use of the MD amongst those diagnosed with AD contributes to a decrease in the severity of symptoms compared to those not following a diet plan."

Glutamate Receptor Dysregulation And Platelet Glutamate Dynamics In Alzheimer's And Parkinson's Diseases: Insights Into Current Medications, Deepa Gautam, Ulhas Naik, Meghna Naik, Santosh Yadav, Rameshwar Nath Chaurasia, Debabrata Dash

Cardeza Foundation for Hematologic Research

Two of the most prevalent neurodegenerative disorders (NDDs), Alzheimer's disease (AD) and Parkinson's disease (PD), present significant challenges to healthcare systems worldwide. While the etiologies of AD and PD differ, both diseases share commonalities in synaptic dysfunction, thereby focusing attention on the role of neurotransmitters. The possible functions that platelets may play in neurodegenerative illnesses including PD and AD are becoming more acknowledged. In AD, platelets have been investigated for their ability to generate amyloid-ß (Aß) peptides, contributing to the formation of neurotoxic plaques. Moreover, platelets are considered biomarkers for early AD diagnosis. In PD, platelets have been studied for …

Cerebrospinal Fluid Proteomics Define The Natural History Of Autosomal Dominant Alzheimer’S Disease, Erik C. B. Johnson, Shijia Bian, Rafi U. Haque, E. Kathleen Carter, Caroline M. Watson, Brian A. Gordon, Lingyan Ping, Duc M. Duong, Michael P. Epstein, Eric Mcdade, Nicolas R. Barthélemy, Celeste M. Karch, Chengjie Xiong, Carlos Cruchaga, Richard J. Perrin, Aliza P. Wingo, Thomas S. Wingo, Jasmeer P. Chhatwal, Gregory S. Day, James M. Noble, Sarah B. Berman, Ralph Martins, Neill R. Graff-Radford, Peter R. Schofield, Takeshi Ikeuchi, Hiroshi Mori, Johannes Levin, Martin Farlow, James J. Lah, Christian Haass, Mathias Jucker, John C. Morris, Tammie L. S. Benzinger, Blaine R. Roberts, Randall J. Bateman, Anne M. Fagan, Nicholas T. Seyfried, Allan I. Levey, Dominantly Inherited Alzheimer Network

Research outputs 2022 to 2026

Alzheimer’s disease (AD) pathology develops many years before the onset of cognitive symptoms. Two pathological processes—aggregation of the amyloid- (A ) peptide into plaques and the microtubule protein tau into neurofibrillary tangles (NFTs)—are hallmarks of the disease. However, other pathological brain processes are thought to be key disease mediators of A plaque and NFT pathology. How these additional pathologies evolve over the course of the disease is currently unknown. Here we show that proteomic measurements in autosomal dominant AD cerebrospinal fluid (CSF) linked to brain protein coexpression can be used to characterize the evolution of AD pathology over a timescale …

Mid-Life Leukocyte Telomere Length And Dementia Risk: An Observational And Mendelian Randomization Study Of 435,046 Uk Biobank Participants, Rui Liu, Luke C. Pilling, David Melzer, Lihong Wang, Kevin J. Manning, David C. Steffens, Jack Bowden, Richard H. Fortinsky, George A. Kuchel, Taeho G. Rhee, Breno S. Diniz, Chia-Ling Kuo

Health Science Faculty Publications

Telomere attrition is one of biological aging hallmarks and may be intervened to target multiple aging-related diseases, including Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD). The objective of this study was to assess associations of leukocyte telomere length (TL) with AD/ADRD and early markers of AD/ADRD, including cognitive performance and brain magnetic resonance imaging (MRI) phenotypes. Data from European-ancestry participants in the UK Biobank (n = 435,046) were used to evaluate whether mid-life leukocyte TL is associated with incident AD/ADRD over a mean follow-up of 12.2 years. In a subsample without AD/ADRD and with brain imaging data ( …

Plasma Glial Fibrillary Acidic Protein In Autosomal Dominant Alzheimer's Disease: Associations With Aβ-Pet, Neurodegeneration, And Cognition, Pratishtha Chatterjee, Lisa Vermunt, Brian A. Gordon, Steve Pedrini, Lynn Boonkamp, Nicola J. Armstrong, Chengjie Xiong, Abhay K. Singh, Yan Li, Hamid R. Sohrabi, Kevin Taddei, Mark Molloy, Tammie L. S. Benzinger, John C. Morris, Celeste Karch, Sarah Berman, Jasmeer Chhatwal, Carlos Cruchaga, Neill R. Graff-Radford, Gregory S. Day, Martin Farlow, Nick Fox, Alison Goate, Jason Hassenstab, Jae-Hong Lee, Johannes Levin, Eric Mcdade, Hiroshi Mori, Richard Perrin, Raquel Sanchez-Valle, Peter R. Schofield, Allan Levey, Mathias Jucker, Colin L. Masters, Anne M. Fagan, Randall J. Bateman, Ralph N. Martins, Charlotte Teunissen, Dominantly Inherited Alzheimer Network

Research outputs 2022 to 2026

Background: Glial fibrillary acidic protein (GFAP) is a promising candidate blood-based biomarker for Alzheimer's disease (AD) diagnosis and prognostication. The timing of its disease-associated changes, its clinical correlates, and biofluid-type dependency will influence its clinical utility. Methods: We evaluated plasma, serum, and cerebrospinal fluid (CSF) GFAP in families with autosomal dominant AD (ADAD), leveraging the predictable age at symptom onset to determine changes by stage of disease. Results: Plasma GFAP elevations appear a decade before expected symptom onset, after amyloid beta (A ) accumulation and prior to neurodegeneration and cognitive decline. Plasma GFAP distinguished A -positive from A -negative ADAD …

Establishment Of A Consensus Protocol To Explore The Brain Pathobiome In Patients With Mild Cognitive Impairment And Alzheimer's Disease: Research Outline And Call For Collaboration., Richard Lathe, Nikki M Schultek, Brian J. Balin, Garth D Ehrlich, Lavinia Alberi Auber, George Perry, Edward B Breitschwerdt, David B Corry, Richard L Doty, Robert A Rissman, Peter L Nara, Ruth Itzhaki, William A Eimer, Rudolph E Tanzi

PCOM Scholarly Papers

Microbial infections of the brain can lead to dementia, and for many decades microbial infections have been implicated in Alzheimer's disease (AD) pathology. However, a causal role for infection in AD remains contentious, and the lack of standardized detection methodologies has led to inconsistent detection/identification of microbes in AD brains. There is a need for a consensus methodology; the Alzheimer's Pathobiome Initiative aims to perform comparative molecular analyses of microbes in post mortem brains versus cerebrospinal fluid, blood, olfactory neuroepithelium, oral/nasopharyngeal tissue, bronchoalveolar, urinary, and gut/stool samples. Diverse extraction methodologies, polymerase chain reaction and sequencing techniques, and bioinformatic tools will …

First Presentation With Neuropsychiatric Symptoms In Autosomal Dominant Alzheimer's Disease: The Dominantly Inherited Alzheimer's Network Study, Antoinette O'Connor, Helen Rice, Josephine Barnes, Natalie S. Ryan, Kathy Y. Liu, Ricardo Francisco Allegri, Sarah Berman, John M. Ringman, Carlos Cruchaga, Martin R. Farlow, Jason Hassenstab, Jae-Hong Lee, Richard J. Perrin, Chengjie Xiong, Brian Gordon, Allan I. Levey, Alison Goate, Neil Graff-Radford, Johannes Levin, Mathias Jucker, Tammie Benzinger, Eric Mcdade, Hiroshi Mori, James M. Noble, Peter R. Schofield, Ralph N. Martins, Stephen Salloway, Jasmeer Chhatwal, John C. Morris, Randall Bateman, Rob Howard, Suzanne Reeves, Nick C. Fox

Research outputs 2022 to 2026

Behavioural changes and neuropsychiatric symptoms (NPS) commonly occur in Alzheimer’s disease (AD) but may not be recognised as AD-related when they are the presenting feature. NPS are important as they are associated with greater functional impairment, poorer quality of life, accelerated cognitive decline and worsened caregiver burden.1 Autosomal dominant AD (ADAD), although < 1% of total AD cases, provides a valuable opportunity to study the clinical heterogeneity of AD. The young age at onset reduces the prevalence of age-related comorbid pathologies and the near 100% penetrance of pathogenic mutations reduces the likelihood of misdiagnosis.2 Anxiety and depression commonly occur in ADAD family members, with increased levels of depression having been found among predementia female mutation carriers.3 Subsequent studies, however, have shown that anxiety and/or depression are common regardless of mutation status, occurring in almost one in three at-risk individuals, with one study reporting a higher rate of depression in non-carriers (17%) than asymptomatic carriers (5%).4 5 Despite the high frequency of NPS in ADAD families, relatively little is known about the proportion of ADAD cases who present with predominantly behavioural symptoms. Our aims were to assess the first reported clinical change in symptomatic ADAD, to compare presentations across genotypes, and to compare cognitive performance between behavioural and cognitive-led presentations.

Impacts Of Fda Approval And Medicare Restriction On Antiamyloid Therapies For Alzheimer’S Disease: Patient Outcomes, Healthcare Costs, And Drug Development, Rouen Brockmann, Joanna Nixon, Bryan L. Love Pharm D., Ismaeel Yunusa Ph. D.

Faculty Publications

In 2021, the US Food and Drug Administration (FDA) granted approval to aducanumab, an antiamyloid antibody for early-stage Alzheimer's disease, despite a lack of clear clinical evidence demonstrating the drug's cognitive benefits. The manufacturer initially priced the drug at a staggering $56,000 per year, a price that was later reduced to $28,200. Unfortunately, these costs do not include the additional expenses associated with monitoring the treatment. However, the Centers for Medicare and Medicaid Services (CMS) recently announced that they will only cover individuals enrolled in clinical trials and will limit coverage of future antiamyloid antibodies. This discrepancy between the FDA …

Angiotensin-Ii Stimulating Vs Inhibiting Antihypertensive Drugs And The Risk Of Alzheimer's Disease Or Related Dementia In A Large Cohort Of Older Patients With Colorectal Cancer, Xianglin L Du, Zhuoyun Li, Paul E Schulz

Journal Articles

BACKGROUND: Several previous studies showed that patients who received angiotensin II-stimulating antihypertensive medications had a lower incident dementia rate than those angiotensin II-inhibiting antihypertensive users, but no study has been conducted in long-term cancer survivors.

OBJECTIVES: to determine the risk of Alzheimer's disease (AD) and related dementia (ADRD) associated with the types of antihypertensive medications in a large cohort of survivors with colorectal cancer in 2007-2015 with follow-up from 2007 to 2016.

METHODS: We identified 58,699 men and women with colorectal cancer aged 65 or older from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database in 17 SEER areas …

Discovery Of A Missense Mutation (Q222k) Of The Apoe Gene From The Australian Imaging, Biomarker And Lifestyle Study, Blaine R. Roberts, Scott B. Laffoon, Anne M. Roberts, Tenielle Porter, Chris Fowler, Colin L. Masters, Edward A. Dratz, Simon M. Laws

Research outputs 2022 to 2026

After age, polymorphisms of the Apolipoprotein E (APOE) gene are the biggest risk factor for the development of Alzheimer's disease (AD). During our investigation to discovery biomarkers in plasma, using 2D gel electrophoresis, we found an individual with and unusual apoE isoelectric point compared to APOE ϵ2, ϵ3, and ϵ4 carriers. Whole exome sequencing of APOE from the donor confirmed a single nucleotide polymorphism (SNP) in exon 4, translating to a rare Q222K missense mutation. The apoE ϵ4 (Q222K) mutation did not form dimers or complexes observed for apoE ϵ2 ϵ3 proteins.

Plasma Aβ42/40 Ratio, P-Tau181, Gfap, And Nfl Across The Alzheimer's Disease Continuum: A Cross-Sectional And Longitudinal Study In The Aibl Cohort, Pratishtha Chatterjee, Steve Pedrini, James D. Doecke, Rohith Thota, Victor L. Villemagne, Vincent Doré, Abhay K. Singh, Penghao Wang, Stephanie Rainey-Smith, Christopher Fowler, Kevin Taddei, Hamid R. Sohrabi, Mark P. Molloy, David Ames, Paul Maruff, Christopher C. Rowe, Colin L. Masters, Ralph N. Martins, Aibl Research Group

Research outputs 2022 to 2026

Introduction:

Plasma amyloid beta (Aβ)1-42/Aβ1-40 ratio, phosphorylated-tau181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) are putative blood biomarkers for Alzheimer's disease (AD). However, head-to-head cross-sectional and longitudinal comparisons of the aforementioned biomarkers across the AD continuum are lacking.

Methods:

Plasma Aβ1-42, Aβ1-40, p-tau181, GFAP, and NfL were measured utilizing the Single Molecule Array (Simoa) platform and compared cross-sectionally across the AD continuum, wherein Aβ-PET (positron emission tomography)–negative cognitively unimpaired (CU Aβ−, n = 81) and mild cognitive impairment (MCI Aβ−, n = 26) participants were compared with Aβ-PET–positive participants across the AD continuum (CU Aβ+, n = …

Impaired Muscle Function, Including Its Decline, Is Related To Greater Long-Term Late-Life Dementia Risk In Older Women, Simone Radavelli-Bagatini, Helen Macpherson, David Scott, Robin M. Daly, Jonathan M. Hodgson, Simon M. Laws, Kun Zhu, Richard L. Prince, Joshua R. Lewis, Marc Sim

Research outputs 2022 to 2026

Background: Impaired muscle function has been identified as a risk factor for declining cognitive function and cardiovascular health, both of which are risk factors for late-life dementia (after 80 years of age). We examined whether hand grip strength and timed-up-and-go (TUG) performance, including their change over 5 years, were associated with late-life dementia events in older women and whether any associations provided independent information to Apolipoprotein E ℇ4 (APOE ℇ4) genotype. Methods: Grip strength and TUG were assessed in community-dwelling older women (mean ± SD; age 75.0 ± 2.6 years) at baseline (n = 1225) and 5 years (n = …

Longitudinal Trajectories Of Basal Forebrain Volume In Normal Aging And Alzheimer's Disease, Ying Xia, Paul Maruff, Vincent Doré, Pierrick Bourgeat, Simon M. Laws, Christopher Fowler, Stephanie R. Rainey-Smith, Ralph N. Martins, Victor L. Villemagne, Christopher C. Rowe, Colin L. Masters, Elizabeth J. Coulson, Jurgen Fripp

Research outputs 2022 to 2026

Dysfunction of the cholinergic basal forebrain (BF) system and amyloid- (A ) deposition are early pathological features in Alzheimer's disease (AD). However, their association in early AD is not well-established. This study investigated the nature and magnitude of volume loss in the BF, over an extended period, in 516 older adults who completed A -PET and serial magnetic resonance imaging scans. Individuals were grouped at baseline according to the presence of cognitive impairment (CU, CI) and A status (A −, A +). Longitudinal volumetric changes in the BF and hippocampus were assessed across groups. The results indicated that high A …

Physical Activity And Brain Amyloid Beta: A Longitudinal Analysis Of Cognitively Unimpaired Older Adults, Michael G. Slee, Stephanie R. Rainey-Smith, Victor L. Villemagne, James D. Doecke, Hamid R. Sohrabi, Kevin Taddei, David Ames, Vincent Dore, Paul Maruff, Simon M. Laws, Colin L. Masters, Christopher C. Rowe, Ralph N. Martins, Kirk I. Erickson, Belinda M. Brown

Research outputs 2022 to 2026

Introduction: The current study evaluated the relationship between habitual physical activity (PA) levels and brain amyloid beta (A ) over 15 years in a cohort of cognitively unimpaired older adults. Methods: PA and A measures were collected over multiple timepoints from 731 cognitively unimpaired older adults participating in the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Aging. Regression modeling examined cross-sectional and longitudinal relationships between PA and brain A . Moderation analyses examined apolipoprotein E (APOE) 4 carriage impact on the PA-A relationship. Results: PA was not associated with brain A at baseline ( = –0.001, p = 0.72) …

Leukocyte Surface Biomarkers Implicate Deficits Of Innate Immunity In Sporadic Alzheimer's Disease, Xin Huang, Yihan Li, Christopher Fowler, James D. Doecke, Yen Ying Lim, Candace Drysdale, Vicky Zhang, Keunha Park, Brett Trounson, Kelly Pertile, Rebecca Rumble, John W. Pickering, Robert A. Rissman, Floyd Sarsoza, Sara Abdel-Latif, Yong Lin, Vincent Doré, Victor Villemagne, Christopher C. Rowe, Jurgen Fripp, Ralph Martins, James S. Wiley, Paul Maruff, Jacobo E. Mintzer, Colin L. Masters, Ben J. Gu

Research outputs 2022 to 2026

Introduction:

Blood-based diagnostics and prognostics in sporadic Alzheimer's disease (AD) are important for identifying at-risk individuals for therapeutic interventions.

Methods:

In three stages, a total of 34 leukocyte antigens were examined by flow cytometry immunophenotyping. Data were analyzed by logistic regression and receiver operating characteristic (ROC) analyses.

Results:

We identified leukocyte markers differentially expressed in the patients with AD. Pathway analysis revealed a complex network involving upregulation of complement inhibition and downregulation of cargo receptor activity and Aβ clearance. A proposed panel including four leukocyte markers – CD11c, CD59, CD91, and CD163 – predicts patients’ PET Aβ status with an …

A Potential Role For Sirtuin-1 In Alzheimer's Disease: Reviewing The Biological And Environmental Evidence, Mehrane Mehramiz, Tenielle Porter, Eleanor K. O'Brien, Stephanie R. Rainey-Smith, Simon M. Laws

Research outputs 2022 to 2026

Sirtuin-1 (Sirt1), encoded by the SIRT1 gene, is a conserved Nicotinamide adenine dinucleotide (NAD+) dependent deacetylase enzyme, considered as the master regulator of metabolism in humans. Sirt1 contributes to a wide range of biological pathways via several mechanisms influenced by lifestyle, such as diet and exercise. The importance of a healthy lifestyle is of relevance to highly prevalent modern chronic diseases, such as Alzheimer's disease (AD). There is growing evidence at multiple levels for a role of Sirt1/SIRT1 in AD pathological mechanisms. As such, this review will explore the relevance of Sirt1 to AD pathological mechanisms, by describing the involvement …

Rna Editing Of Microtubule-Associated Protein Tau Circular Rnas Promotes Their Translation And Tau Tangle Formation, Justin Ralph Welden, Giorgi Margvelani, Karol Andrea Arizaca Maquera, Bhavani Gudlavalleti, Sandra C. Miranda Sardón, Alexandre Rosa Campos, Noémie Robil, Daniel C. Lee, Alvaro G. Hernandez, Wang-Xia Wang, Jing Di, Pierre De La Grange, Peter T. Nelson, Stefan Stamm

Sanders-Brown Center on Aging Faculty Publications

Aggregation of the microtubule-associated protein tau characterizes tauopathies, including Alzheimer’s disease and frontotemporal lobar degeneration (FTLD-Tau). Gene expression regulation of tau is complex and incompletely understood. Here we report that the human tau gene (MAPT) generates two circular RNAs (circRNAs) through backsplicing of exon 12 to either exon 7 (12→7 circRNA) or exon 10 (12→10 circRNA). Both circRNAs lack stop codons. The 12→7 circRNA contains one start codon and is translated in a rolling circle, generating a protein consisting of multimers of the microtubule-binding repeats R1–R4. For the 12→10 circRNA, a start codon can be introduced by two …

Apoe Ε2 Resilience For Alzheimer’S Disease Is Mediated By Plasma Lipid Species: Analysis Of Three Independent Cohort Studies, Tingting Wang, Kevin Huynh, Corey Giles, Natalie A. Mellett, Thy Duong, Anh Nguyen, Wei L. F. Lim, Alex A. T. Smith, Gavriel Olshansky, Gemma Cadby, Joseph Hung, Jennie Hui, John Beilby, Gerald F. Watts, Pratishtha Chatterjee, Ian Martins, Simon Laws, Ashley I. Bush, Christopher C. Rowe, Victor L. Villemagne, David Ames, Colin L. Masters, Kevin Taddei, Vincent Doré, Jürgen Fripp, Matthias Arnold, Gabi Kastenmüller, Kwangsik Nho, Andrew J. Saykin, Rebecca Baillie, Xianlin Han, Ralph N. Martins, Eric K. Moses, Rima Kaddurah-Daouk, Peter J. Meikle

Research outputs 2022 to 2026

Introduction:

The apolipoprotein E (APOE) genotype is the strongest genetic risk factor for late-onset Alzheimer's disease. However, its effect on lipid metabolic pathways, and their mediating effect on disease risk, is poorly understood.

Methods:

We performed lipidomic analysis on three independent cohorts (the Australian Imaging, Biomarkers and Lifestyle [AIBL] flagship study, n = 1087; the Alzheimer's Disease Neuroimaging Initiative [ADNI] 1 study, n = 819; and the Busselton Health Study [BHS], n = 4384), and we defined associations between APOE ε2 and ε4 and 569 plasma/serum lipid species. Mediation analysis defined the proportion of the treatment effect of the APOE …

Transcriptional Profiles In Olfactory Pathway-Associated Brain Regions Of African Green Monkeys: Associations With Age And Alzheimer’S Disease Neuropathology, Jacob D Negrey, Dorothy L Dobbins, Timothy D Howard, Karin E Borgmann-Winter, C G Hahn, Sergey Kalinin, Douglas L Feinstein, Suzanne Craft, Carol A Shively, Thomas C Register

Department of Neuroscience Faculty Papers

Introduction: Olfactory impairment in older individuals is associated with an increased risk of Alzheimer's disease (AD). Characterization of age versus neuropathology-associated changes in the brain olfactory pathway may elucidate processes underlying early AD pathogenesis. Here, we report age versus AD neuropathology-associated differential transcription in four brain regions in the olfactory pathway of 10 female African green monkeys (vervet, Chlorocebus aethiops sabaeus), a well-described model of early AD-like neuropathology.

Methods: Transcriptional profiles were determined by microarray in the olfactory bulb (OB), piriform cortex (PC), temporal lobe white matter (WM), and inferior temporal cortex (ITC). Amyloid beta (Aβ) plaque load in …

Plasma High-Density Lipoprotein Cargo Is Altered In Alzheimer's Disease And Is Associated With Regional Brain Volume, Steve Pedrini, James D. Doecke, Eugene Hone, Penghao Wang, Rohith Thota, Ashley I. Bush, Christopher C. Rowe, Vincent Dore, Victor L. Villemagne, David Ames, Stephanie Rainey-Smith, Giuseppe Verdile, Hamid R. Sohrabi, Manfred R. Raida, Kevin Taddei, Sam Gandy, Colin L. Masters, Pratishtha Chatterjee, Ralph N. Martins, Aibl Research Group

Research outputs 2022 to 2026

Cholesterol levels have been repeatedly linked to Alzheimer's Disease (AD), suggesting that high levels could be detrimental, but this effect is likely attributed to Low-Density Lipoprotein (LDL) cholesterol. On the other hand, High-Density Lipoproteins (HDL) cholesterol levels have been associated with reduced brain amyloidosis and improved cognitive function. However, recent findings have suggested that HDL-functionality, which depends upon the HDL-cargo proteins associated with HDL, rather than HDL levels, appears to be the key factor, suggesting a quality over quantity status. In this report, we have assessed the HDL-cargo (Cholesterol, ApoA-I, ApoA-II, ApoC-I, ApoC-III, ApoD, ApoE, ApoH, ApoJ, CRP, and SAA) …

Understanding The Relationship Between Age-Related Hearing Loss And Alzheimer's Disease: A Narrative Review, Hadeel Y. Tarawneh, Dona M. P. Jayakody, Hamid R. Sohrabi, Ralph N. Martins, Wilhelmina H.A.M. Mulders

Research outputs 2022 to 2026

Evidence suggests that hearing loss (HL), even at mild levels, increases the long-term risk of cognitive decline and incident dementia. Hearing loss is one of the modifiable risk factors for dementia, with approximately 4 million of the 50 million cases of dementia worldwide possibly attributed to untreated HL. This paper describes four possible mechanisms that have been suggested for the relationship between age-related hearing loss (ARHL) and Alzheimer's disease (AD), which is the most common form of dementia. The first mechanism suggests mitochondrial dysfunction and altered signal pathways due to aging as a possible link between ARHL and AD. The …

The Trend Of Disruption In The Functional Brain Network Topology Of Alzheimer’S Disease, Alireza Fathian, Yousef Jamali, Mohammad Reza Raoufy, The Alzheimer's Disease Neuroimaging Initiative, Michael W. Weiner, Norbert Schuf, Howard J. Rosen, Bruce L. Miller, Thomas Neylan, Jacqueline Hayess, Shannon Finley, Paul Aisen, Zaven Khachaturian, Ronald G. Thomas, Charles D. Smith, Gregory A. Jicha, Peter A. Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad

Sanders-Brown Center on Aging Faculty Publications

Alzheimer’s disease (AD) is a progressive disorder associated with cognitive dysfunction that alters the brain’s functional connectivity. Assessing these alterations has become a topic of increasing interest. However, a few studies have examined different stages of AD from a complex network perspective that cover different topological scales. This study used resting state fMRI data to analyze the trend of functional connectivity alterations from a cognitively normal (CN) state through early and late mild cognitive impairment (EMCI and LMCI) and to Alzheimer’s disease. The analyses had been done at the local (hubs and activated links and areas), meso (clustering, assortativity, and …

Adult Day Services In Maine: Benefits, Challenges, And Opportunities, Elizabeth Gattine Jd, Eileen Griffin Jd, Kimberly I. Snow Mhsa, Ba

Disability & Aging

In Maine and nationally, adult day services tend to be underfunded and underutilized compared to other types of long term services and supports (LTSS). In part, investment in adult day services is hampered by a lack of standardized data collection and limited research on issues of accessibility, cost-effectiveness, and the impact of adult day services on the broader health system. Lack of uniformity in state regulatory frameworks for licensing, program design, service delivery, and other administrative requirements further complicates cross-state comparisons. Considering these limitations, a key goal of this report is to provide a more detailed and comprehensive understanding of …