Neurosciences Commons^™

Core Alzheimer’S Disease Cerebrospinal Fluid Biomarker Assays Are Not Affected By Aspiration Or Gravity Drip Extraction Methods, James D. Doecke, Cindy Francois, Christopher J. Fowler, Erik Stoops, Pierrick Bourgeat, Stephanie R. Rainey-Smith, Qiao-Xin Li, Colin L. Masters, Ralph N. Martins, Victor L. Villemagne, Steven J. Collins, Hugo Marcel Vanderstichele

Research outputs 2014 to 2021

Background: CSF biomarkers are well-established for routine clinical use, yet a paucity of comparative assessment exists regarding CSF extraction methods during lumbar puncture. Here, we compare in detail biomarker profiles in CSF extracted using either gravity drip or aspiration. Methods: Biomarkers for β-amyloidopathy (Aβ1–42, Aβ1–40), tauopathy (total tau), or synapse pathology (BACE1, Neurogranin Trunc-p75, α-synuclein) were assessed between gravity or aspiration extraction methods in a sub-population of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study (cognitively normal, N = 36; mild cognitive impairment, N = 8; Alzheimer’s disease, N = 6). Results: High biomarker concordance between extraction methods was seen …

Predictors Of Poststroke Aphasia Recovery: A Systematic Review-Informed Individual Participant Data Meta-Analysis, The Rehabilitation And Recovery Of People With Aphasia After Stroke (Release) Collaborators

Research outputs 2014 to 2021

Background and Purpose: The factors associated with recovery of language domains after stroke remain uncertain. We described recovery of overall-language-ability, auditory comprehension, naming, and functional-communication across participants’ age, sex, and aphasia chronicity in a large, multilingual, international aphasia dataset. Methods: Individual participant data meta-analysis of systematically sourced aphasia datasets described overall-language ability using the Western Aphasia Battery Aphasia-Quotient; auditory comprehension by Aachen Aphasia Test (AAT) Token Test; naming by Boston Naming Test and functional-communication by AAT Spontaneous-Speech Communication subscale. Multivariable analyses regressed absolute score-changes from baseline across language domains onto covariates identified a priori in randomized controlled trials and all …

Play In Children With Neurodevelopmental Disorders: Psychometric Properties Of A Parent Report Measure ‘My Child’S Play’, Dulce Romero-Ayuso, María Ruiz-Salcedo, Sabina Barrios-Fernández, José Matías Triviño-Juárez, Donald Maciver, Janet Richmond, Miguel A. Muñoz

Research outputs 2014 to 2021

Play is essential in childhood, allowing for a positive trend in development and learning. Health professionals need useful tools to assess it, especially in the case of children with neurodevelopmental disorders. The aim of this study was to validate and cross-culturally adapt the My Child’s Play questionnaire and to find out if this instrument allows us to differentiate the play of children with neurodevelopmental disorders from the play of children with neurotypical development. A total of 594 parents completed the questionnaire. A confirmatory factor analysis was conducted, which showed a similar structure to the English version: (1) executive functions; (2) …

Polygenic Score Modifies Risk For Alzheimer's Disease In Ε4 Homozygotes At Phenotypic Extremes, Aamira J. Huq, Brian Fulton-Howard, Moeen Riaz, Simon Laws, Robert Sebra, Joanne Ryan, Alzheimer’S Disease Genetics Consortium, Alan E. Renton, Alison M. Goate, Colin L. Masters, Elsdon Storey, Raj C. Shah, Anne Murray, John Mcneil, Ingrid Winship, Paul A. Jones

Research outputs 2014 to 2021

Introduction: Diversity in cognition among apolipoprotein E () ε4 homozygotes can range from early-onset Alzheimer's disease (AD) to a lifetime with no symptoms. Methods: We evaluated a phenotypic extreme polygenic risk score (PRS) for AD between cognitively healthy ε4 homozygotes aged ≥75 years (n = 213) and early-onset ε4 homozygote AD cases aged ≤65 years (n = 223) as an explanation for this diversity. Results: The PRS for AD was significantly higher in ε4 homozygote AD cases compared to older cognitively healthy ε4/ε4 controls (odds ratio [OR] 8.39; confidence interval [CI] 2.0-35.2; = .003). The difference in the same PRS …

Intake Of Products Containing Anthocyanins, Flavanols, And Flavanones, And Cognitive Function: A Narrative Review, Samantha L. Gardener, Stephanie R. Rainey-Smith, Michael Weinborn, Catherine P. Bondonno, Ralph N. Martins

Research outputs 2014 to 2021

The purpose of this review is to examine human research studies published within the past 6 years which evaluate the role of anthocyanin, flavanol, and flavanone consumption in cognitive function, and to discuss potential mechanisms of action underlying any observed benefits. Evidence to date suggests the consumption of flavonoid-rich foods, such as berries and cocoa, may have the potential to limit, or even reverse, age-related declines in cognition. Over the last 6 years, the flavonoid subgroups of anthocyanins, flavanols, and flavanones have been shown to be beneficial in terms of conferring neuroprotection. The mechanisms by which flavonoids positively modulate cognitive …

Longitudinal Trajectories In Cortical Thickness And Volume Atrophy: Superior Cognitive Performance Does Not Protect Against Brain Atrophy In Older Adults, Samantha Gardener, Michael Weinborn, Hamid R. Sohrabi, James Doecke, Pierrick Bourgeat, Stephanie R. Rainey-Smith, Kai-Kai Shen, Jurgen Fripp, Kevin Taddei, Paul Maruff, Olivier Salvado, Greg Savage, David Ames, Colin L. Masters, Christopher C. Rowe, Ralph Martins, Aibl Research Group

Research outputs 2014 to 2021

Background:

Previous research has identified a small subgroup of older adults that maintain a high level of cognitive functioning well into advanced age. Investigation of those with superior cognitive performance (SCP) for their age is important, as age-related decline has previously been thought to be inevitable.

Objective:

Preservation of cortical thickness and volume was evaluated in 76 older adults with SCP and 100 typical older adults (TOAs) assessed up to five times over six years.

Methods:

Regions of interest (ROIs) found to have been associated with super-aging status (a construct similar to SCP status) in previous literature were investigated, followed …

Spon1 Is Associated With Amyloid-Β And Apoe Ε4-Related Cognitive Decline In Cognitively Normal Adults, Shane Fernandez, Samantha C. Burnham, Lidija Milicic, Greg Savage, Paul Maruff, Madeline Peretti, Hamid R. Sohrabi, Yen Ying Lim, Michael Weinborn, David Ames, Colin L. Masters, Ralph N. Martins, Stephanie Rainey-Smith, Christopher C. Rowe, Olivier Salvado, David Groth, Giuseppe Verdile, Victor L. Villemagne, Tenielle Porter, Simon M. Laws

Research outputs 2014 to 2021

Background: Genetic variation in Spondin-1, specifically rs11023139, has been associated with reduced rates of cognitive decline in individuals with Alzheimer's disease. Objective: The aim of this study was to assess whether the association was present in cognitively normal older adults. Methods: Longitudinal cognitive decline was investigated using linear mixed modelling in a cohort of 590 cognitively normal older adults enrolled in the Australian Imaging, Biomarkers and Lifestyle Study. Results: No independent effect of Spondin-1 rs11023139 on cognitive decline was observed. However, significant associations were observed for the interaction between Apolipoprotein E (APOE) ϵ4 and rs11023139 in individuals with high amyloid-β …

Prevention Of Dementia Using Mobile Phone Applications (Prodemos): Protocol For An International Randomised Controlled Trial, Esmé Eggink, Melanie Hafdi, Marieke P. Hoevenaar-Blom, Manshu Song, Sandrine Andrieu, Linda E. Barnes, Cindy Birck, Rachael L. Brooks, Nicola Coley, Elizabeth Ford, Jean Georges, Abraham Van Der Groep, Willem A. Van Gool, Ron Handels, Haifeng Hou, Dong Li, Hongmei Liu, Jihui Lyu, Harm Van Marwijk, Mark Van Der Meijden, Yixuan Niu, Shanu Sadhwani, Wenzhi Wang, Youxin Wang, Anders Wimo, Xiaoyan Ye, Yueyi Yu, Qiang Zeng, Wei Wang, Carol Brayne, Eric P. Moll Van Charante, Edo Richard

Research outputs 2014 to 2021

Introduction Profiles of high risk for future dementia are well understood and are likely to concern mostly those in low-income and middle-income countries and people at greater disadvantage in high-income countries. Approximately 30%-40% of dementia cases have been estimated to be attributed to modifiable risk factors, including hypertension, smoking and sedentary lifestyle. Tailored interventions targeting these risk factors can potentially prevent or delay the onset of dementia. Mobile health (mHealth) improves accessibility of such prevention strategies in hard-to-reach populations while at the same time tailoring such approaches. In the current study, we will investigate the effectiveness and implementation of a …

Fifteen Years Of The Australian Imaging, Biomarkers And Lifestyle (Aibl) Study: Progress And Observations From 2,359 Older Adults Spanning The Spectrum From Cognitive Normality To Alzheimer's Disease, Christopher Fowler, Stephanie R. Rainey-Smith, Sabine Bird, Julia Bomke, Pierrick Bourgeat, Belinda M. Brown, Samantha C. Burnham, Ashley I. Bush, Carolyn Chadunow, Steven Collins, James Doecke, Vincent Doré, Kathryn A. Ellis, Lis Evered, Amir Fazlollahi, Jurgen Fripp, Samantha L. Gardener, Simon Gibson, Robert Grenfell, Elise Harrison, Richard Head, Liang Jin, Adrian Kamer, Fiona Lamb, Nicola T. Lautenschlager, Simon M. Laws, Qiao-Xin Li, Lucy Lim, Yen Ying Lim, Andrea Louey, S. Lance Macaulay, Lucy Mackintosh, Ralph N. Martins, Paul Maruff, Colin L. Masters, Simon Mcbride, Lidija Milicica, Madeline Peretti, Kelly Pertile, Tenielle Porter, Morgan Radler, Alan Rembach, Joanne Robertson, Mark Rodrigues, Christopher C. Rowe, Rebecca Rumble, Olivier Salvado, Greg Savage, Brendan Silbert, Magdalene Soh, Hamid R. Sohrabi, Kevin Taddei, Tania Taddei, Christine Thai, Brett Trounson, Regan Tyrrell, Michael Vacher, Shiji Varghese, Victor L. Villemagne, Michael Weinborn, Michael Woodward, Ying Xia, David Ames, Aibl Investigators

Research outputs 2014 to 2021

Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Study commenced in 2006 as a prospective study of 1,112 individuals (768 cognitively normal (CN), 133 with mild cognitive impairment (MCI), and 211 with Alzheimer's disease dementia (AD)) as an 'Inception cohort' who underwent detailed ssessments every 18 months. Over the past decade, an additional 1247 subjects have been added as an 'Enrichment cohort' (as of 10 April 2019). Objective: Here we provide an overview of these Inception and Enrichment cohorts of more than 8,500 person-years of investigation. Methods: Participants underwent reassessment every 18 months including comprehensive cognitive testing, neuroimaging (magnetic resonance …

The Sleep Of Shift Workers In A Remote Mining Operation: Methodology For A Randomized Control Trial To Determine Evidence-Based Interventions, Gemma Maisey, Marcus Cattani, Amanda Devine, Johnny Lo, Ian C. Dunican

Research outputs 2014 to 2021

© Copyright © 2021 Maisey, Cattani, Devine, Lo and Dunican. Shiftwork may adversely impact an individual’s sleep-wake patterns and result in sleep loss ( < 6 h. following night shift), due to the circadian misalignment and the design of rosters and shifts. Within a mining operation, this sleep loss may have significant consequences due to fatigue, including an increased risk of accidents and chronic health conditions. This study aims to (i) determine the efficacy of an intervention that comprises a sleep education program and biofeedback through a smartphone app on sleep quality, quantity, and alertness (ii) determine the prevalence of risk for a potential sleep disorder, and (iii) quantify and describe the sleep habits and behaviors of shift workers in a remote mining operation. This study consists of a randomized controlled trial whereby eighty-eight shift workers within a remote mining operation are randomized to a control group or one of three different treatment groups that are: (i) a sleep education program, (ii) biofeedback on sleep through a smartphone app, or (iii) a sleep education program and biofeedback on sleep through a smartphone app. This study utilizes wrist-activity monitors, biomathematical modeling, and a survey instrument to obtain data on sleep quantity, quality, and alertness. A variety of statistical methods will determine the prevalence of risk for a potential sleep disorder and associations with body mass index, alcohol, and caffeine consumption. A generalized linear mixed model will examine the dependent sleep variables assessed at baseline and post-intervention for the control group and intervention groups, as well as within and between groups to determine changes. The findings from this study will contribute to the current understanding of sleep and alertness behaviors, and sleep problems and disorders amongst shift workers. Importantly, the results may inform fatigue policy and practice on interventions to manage fatigue risk within the mining industry. This study protocol may have a broader application in other shiftwork industries, including oil and gas, aviation, rail, and healthcare.

Therapeutic Potential Of Mitophagy-Inducing Microflora Metabolite, Urolithin A For Alzheimer’S Disease, Dona Pamoda W. Jayatunga, Eugene Hone, Harjot Khaira, Taciana Lunelli, Harjinder Singh, Gilles J. Guillemin, Binosha Fernando, Manohar L. Garg, Giuseppe Verdile, Ralph N. Martins

Research outputs 2014 to 2021

Mitochondrial dysfunction including deficits of mitophagy is seen in aging and neuro-degenerative disorders including Alzheimer’s disease (AD). Apart from traditionally targeting amyloid beta (Aβ), the main culprit in AD brains, other approaches include investigating impaired mitochondrial pathways for potential therapeutic benefits against AD. Thus, a future therapy for AD may focus on novel candidates that enhance optimal mitochondrial integrity and turnover. Bi-oactive food components, known as nutraceuticals, may serve as such agents to combat AD. Uro-lithin A is an intestinal microbe-derived metabolite of a class of polyphenols, ellagitannins (ETs). Urolithin A is known to exert many health benefits. Its antioxidant, …

Transcranial Random Noise Stimulation Modulates Neural Processing Of Sensory And Motor Circuits – From Potential Cellular Mechanisms To Behaviour: A Scoping Review, Weronika Potok, Onno Van Der Groen, Marc Bächinger, Dylan Edwards, Nicole Wenderoth

Research outputs 2014 to 2021

Noise introduced in the human nervous system from cellular to systems levels can have a major impact on signal processing. Using transcranial stimulation, electrical noise can be added to cortical circuits to modulate neuronal activity and enhance function in the healthy brain and in neurological patients. Transcranial random noise stimulation (tRNS) is a promising technique that is less well understood than other non-invasive neuromodulatory methods. The aim of the present scoping review is to collate published evidence on the effects of electrical noise at the cellular, systems, and behavioural levels, and discuss how this emerging method might be harnessed to …

Recovery Of Hippocampal-Dependent Learning Despite Blunting Reactive Adult Neurogenesis After Alcohol Dependence, Chelsea G. Nickell, K. Ryan Thompson, James R. Pauly, Kimberly Nixon

Pharmaceutical Sciences Faculty Publications

Background:

The excessive alcohol drinking that occurs in alcohol use disorder (AUD) causes neurodegeneration in regions such as the hippocampus, though recovery may occur after a period of abstinence. Mechanisms of recovery are not clear, though reactive neurogenesis has been observed in the hippocampal dentate gyrus following alcohol dependence and correlates to recovery of granule cell number.

Objective:

We investigated the role of neurons born during reactive neurogenesis in the recovery of hippocampal learning behavior after 4-day binge alcohol exposure, a model of an AUD. We hypothesized that reducing reactive neurogenesis would impair functional recovery.

Methods:

Adult male rats were …

A Transgenic Pig Model Expressing A Cmv-Zsgreen1 Reporter Across An Extensive Array Of Tissues., Amy T Desaulniers, Rebecca A Cederberg, Elizabeth P Carreiro, Channabasavaiah B Gurumurthy, Brett R White

Journal Articles: Pharmacology & Experimental Neuroscience

Since genetic engineering of pigs can benefit both biomedicine and agriculture, selecting a suitable gene promoter is critically important. The cytomegalovirus (CMV) promoter, which can robustly drive ubiquitous transgene expression, is commonly used at present, yet recent reports suggest tissue-specific activity in the pig. The objective of this study was to quantify ZsGreen1 protein (in lieu of CMV promoter activity) in tissues from pigs harboring a CMV-ZsGreen1 transgene with a single integration site. Tissue samples (

Upper And Lower Limb Movement Kinematics In Aging, Zheng Wang, Callie Lane, Matthew Terza, Pravin Khemani, Su Lui, Walker S Mckinney, Matthew W Mosconi

Articles, Abstracts, and Reports

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder associated with a premutation cytosine-guanine-guanine (CGG) trinucleotide repeat expansion of the FMR1 gene. FXTAS is estimated to be the most common single-gene form of ataxia in the aging population. Gait ataxia and intention tremor are the primary behavioral symptoms of FXTAS, though clinical evaluation of these symptoms often is subjective, contributing to difficulties in reliably differentiating individuals with FXTAS and asymptomatic premutation carriers. This study aimed to clarify the extent to which quantitative measures of gait and upper limb kinematics may serve as biobehavioral markers of FXTAS degeneration. Nineteen premutation carriers …

The Role Of Haptic Expectations In Reaching To Grasp: From Pantomime To Natural Grasps And Back Again, Robert L. Whitwell, Nathan J. Katz, Melvyn A. Goodale, James T. Enns

Brain and Mind Institute Researchers' Publications

© Copyright © 2020 Whitwell, Katz, Goodale and Enns. When we reach to pick up an object, our actions are effortlessly informed by the object’s spatial information, the position of our limbs, stored knowledge of the object’s material properties, and what we want to do with the object. A substantial body of evidence suggests that grasps are under the control of “automatic, unconscious” sensorimotor modules housed in the “dorsal stream” of the posterior parietal cortex. Visual online feedback has a strong effect on the hand’s in-flight grasp aperture. Previous work of ours exploited this effect to show that grasps are …

Adult Hippocampal Neurogenesis As A Potential Therapeutic Target In Fetal Alcohol Spectrum Disorders, Kymberly Cheyanne Gustus

Biomedical Sciences ETDs

This dissertation aims to determine if adult hippocampal neurogenesis is a potential therapeutic target in Fetal Alcohol Spectrum Disorders (FASDs). Adult hippocampal neurogenesis plays important and unique roles in certain aspects of learning, memory, and mood (Anacker & Hen, 2017). Individuals with FASDs often demonstrate dysregulation in these arenas (Lewis et al., 2015; Temple, Cook, Unsworth, Rajani, & Mela, 2019). Previous work in our lab using a mouse model of prenatal alcohol exposure demonstrated impairment in enrichment-mediated adult hippocampal neurogenesis (Irene Y. Choi, Andrea M. Allan, & Lee Anna Cunningham, 2005; K. Kajimoto, A. Allan, & L. A. Cunningham, 2013). …

The Role Of Anti-Inflammatory Cytokine Interleukin-10 (Il-10) In Tauopathies, Lea L. Weston

Biomedical Sciences ETDs

Tauopathies are neurodegenerative diseases, including Alzheimer’s disease, that are associated with pathological accumulation of the microtubule associated protein tau (MAPT, or tau) (Lee et al., 2001). Abnormal hyperphosphorylated tau (pTau) strongly correlate with cognitive impairment (Nelson et al., 2012). Neuroinflammation is also associated with tauopathies (Gerhard et al., 2006b; Edison et al., 2008) and is implicated in driving tau pathology (Yoshiyama et al., 2007, Maphis et al., 2015b). Therefore, it is compelling to understand the role of anti-inflammatory cytokines in limiting neuroinflammation and tau pathology. Interleukin-10 (IL-10) is a well-established anti-inflammatory cytokine with roles in limiting inflammation in the central …

The Poststroke Peripheral Immune Response Is Differentially Regulated By Leukemia Inhibitory Factor In Aged Male And Female Rodents, Stephanie M. Davis, Lisa A. Collier, Sarah J. Messmer, Keith R. Pennypacker

Neurology Faculty Publications

Background. The goal of this study was to determine whether leukemia inhibitory factor (LIF) promotes anti-inflammatory activity after stroke in a sex-dependent manner. Methods. Aged (18-month-old) Sprague-Dawley rats of both sexes underwent sham surgery or permanent middle cerebral artery occlusion (MCAO). Animals received three doses of intravenous LIF (125 μg/kg) or PBS at 6, 24, and 48 h before euthanization at 72 h. Spleen weights were measured immediately following euthanization. Western blot was used to measure protein levels of CCL8, CD11b, CXCL9, CXCL10, IL-12 p40, IL-3, and the LIF receptor (LIFR) in spleen tissue. ELISA was used …

Electrophysiological And Imaging Calcium Biomarkers Of Aging In Male And Female 5×Fad Mice, Adam O. Ghoweri, Lara Ouillette, Hilaree N. Frazier, Katie L. Anderson, Ruei-Lung Lin, John C. Gant, Rachel Parent, Shannon Moore, Geoffrey G. Murphy, Olivier Thibault

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: In animal models and tissue preparations, calcium dyshomeostasis is a biomarker of aging and Alzheimer's disease that is associated with synaptic dysfunction, neuritic pruning, and dysregulated cellular processes. It is unclear, however, whether the onset of calcium dysregulation precedes, is concurrent with, or is the product of pathological cellular events (e.g., oxidation, amyloid-β production, and neuroinflammation). Further, neuronal calcium dysregulation is not always present in animal models of amyloidogenesis, questioning its reliability as a disease biomarker.

OBJECTIVE: Here, we directly tested for the presence of calcium dysregulation in dorsal hippocampal neurons in male and female 5×FAD mice on …