Medicine and Health Sciences Commons^™

Cerebrospinal Fluid Neurofilament Light Concentration Predicts Brain Atrophy And Cognition In Alzheimer's Disease, Kunal Dhiman, Veer Bala Gupta, Victor L. Villemagne, Dhamidhu Eratne, Petra L. Graham, Christopher Fowler, Pierrick Bourgeat, Qiao-Xin Li, Steven Collins, Ashley I. Bush, Christopher C. Rowe, Colin L. Masters, David Ames, Eugene Hone, Kaj Blennow, Henrik Zetterberg, Ralph N. Martins

Research outputs 2014 to 2021

Introduction
This study assessed the utility of cerebrospinal fluid (CSF) neurofilament light (NfL) in Alzheimer's disease (AD) diagnosis, its association with amyloid and tau pathology, as well as its potential to predict brain atrophy, cognition, and amyloid accumulation.
Methods
CSF NfL concentration was measured in 221 participants from the Australian Imaging, Biomarkers & Lifestyle Flagship Study of Ageing (AIBL).
Results
CSF NfL levels as well as NfL/amyloid β (Aβ42) were significantly elevated in AD compared to healthy controls (HC; P < .001), and in mild cognitive impairment (MCI) compared to HC (P = .008 NfL; P< .001 NfL/Aβ42). CSF NfL and NfL/Aβ42 differentiated AD from HC with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.84 and 0.90, respectively. CSF NfL and NfL/Aβ42 predicted cortical amyloid load, brain atrophy, and cognition.
Discussion
CSF NfL is a biomarker of neurodegeneration, correlating with cognitive impairment and brain neuropathology.

Brainwave Nets: Are Sparse Dynamic Models Susceptible To Brain Manipulation Experimentation?, Diego C. Nascimento, Marco A. Pinto-Orellana, Joao P. Leite, Dylan J. Edwards, Francisco Louzada, Taiza E.G. Santos

Research outputs 2014 to 2021

© Copyright © 2020 Nascimento, Pinto-Orellana, Leite, Edwards, Louzada and Santos. Sparse time series models have shown promise in estimating contemporaneous and ongoing brain connectivity. This paper was motivated by a neuroscience experiment using EEG signals as the outcome of our established interventional protocol, a new method in neurorehabilitation toward developing a treatment for visual verticality disorder in post-stroke patients. To analyze the [complex outcome measure (EEG)] that reflects neural-network functioning and processing in more specific ways regarding traditional analyses, we make a comparison among sparse time series models (classic VAR, GLASSO, TSCGM, and TSCGM-modified with non-linear and iterative optimizations) …

Altering Brain Dynamics With Transcranial Random Noise Stimulation, Onno Van Der Groen, Jason B. Mattingley, Nicole Wenderoth

Research outputs 2014 to 2021

Random noise can enhance the detectability of weak signals in nonlinear systems, a phenomenon known as stochastic resonance (SR). This concept is not only applicable to single threshold systems but can also be applied to dynamical systems with multiple attractor states, such as observed during the phenomenon of binocular rivalry. Binocular rivalry can be characterized by marginally stable attractor states between which the brain switches in a spontaneous, stochastic manner. Here we used a computational model to predict the effect of noise on perceptual dominance durations. Subsequently we compared the model prediction to a series of experiments where we measured …

Mediterranean Diet Adherence And Rate Of Cerebral Aβ-Amyloid Accumulation: Data From The Australian Imaging, Biomarkers And Lifestyle Study Of Ageing, Stephanie Rainey-Smith, Yian Gu, Samantha Gardener, James D Doecke, Victor L Villemagne, Belinda M Brown, Kevin Taddei, Simon M Laws, Hamid R. Sohrabi, Michael Weinborn, David Ames, Christopher Fowler, S Lance Macaulay, Paul Maruff, Colin L Masters, Olivier Salvado, Christopher C Rowe, Nikolaos Scarmeas, Ralph N. Martins

Research outputs 2014 to 2021

Accumulating research has linked Mediterranean diet (MeDi) adherence with slower cognitive decline and reduced Alzheimer's disease (AD) risk. However, no study to-date has examined the relationship between MeDi adherence and accumulation of cerebral Aβ-amyloid (Aβ; a pathological hallmark of AD) in older adults. Cognitively normal healthy control participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Ageing completed the Cancer Council of Victoria Food Frequency Questionnaire at baseline, which was used to construct a MeDi score for each participant (score range 0-9; higher score indicating higher adherence). Cerebral Aβ load was quantified by Pittsburgh Compound B positron emission …

Statistical Analysis Plan (Sap) For The Very Early Rehabilitation In Speech (Verse) After Stroke Trial: An International 3-Arm Clinical Trial To Determine The Effectiveness Of Early, Intensive, Prescribed, Direct Aphasia Therapy, Erin Godecke, Tapan Rai, Dominique A Cadilhac, Elizabeth Armstrong, Sandy Middleton, Natalie Ciccone, Anne Whitworth, Miranda L Rose, Audrey Holland, Fiona Ellery, Graeme J Hankey, Julie Bernhardt

Research outputs 2014 to 2021

Background Limited evidence exists to support very early intensive aphasia rehabilitation after stroke. VERSE is a PROBE trial designed to determine whether two types of intensive aphasia therapy, beginning within 14 days of acute stroke, provide greater therapeutic and cost-effectiveness than usual care. Objective To publish the detailed statistical analysis plan for the VERSE trial prior to unblinding. This statistical analysis plan was based on the published and registered VERSE trial protocol and was developed by the blinded steering committee and management team, led by the trial statistician. This plan was developed using outcome measures and trial data collection forms. …

Genetic Variation In Aquaporin-4 Moderates The Relationship Between Sleep And Brain Aβ-Amyloid Burden, Stephanie Rainey-Smith, Gavin N. Mazzucchelli, Victor L. Villemagne, Belinda M. Brown, Tenielle Porter, Michael Weinborn, Romola Bucks, Lidija Milicic, Hamid R. Sohrabi, Kevin Taddei, David J. Ames, Paul T. Maruff, Colin L. Masters, Christopher C. Rowe, Olivier Salvado, Ralph N. Martins, Simon M. Laws

Research outputs 2014 to 2021

The glymphatic system is postulated to be a mechanism of brain Aβ-Amyloid clearance and to be most effective during sleep. Ablation of the astrocytic end-feet expressed water-channel protein, Aquaporin-4, in mice, results in impairment of this clearance mechanism and increased brain Aβ-Amyloid deposition, suggesting that Aquaporin-4 plays a pivotal role in glymphatic function. Currently there is a paucity of literature regarding the impact of AQP4 genetic variation on sleep, brain Aβ-Amyloid burden and their relationship to each other in humans. To address this a cross-sectional observational study was undertaken in cognitively normal older adults from the Australian Imaging, Biomarkers and …

Manipulation Of Human Verticality Using High-Definition Transcranial Direct Current Stimulation, Taiza E.G. Santos, Diandra B. Favoretto, Iman Ghodratti Toostani, Diego C. Nascimento, Brunna P. Rimoli, Eduardo Bergonzoni, Tenysson Will Lemos, Dennis Q. Truong, Alexandre C.B. Delbem, Bahador Makkiabadi, Renato Moraes, Francisco Louzada, Marom Bikson, Joao P. Leite, Dylan J. Edwards

Research outputs 2014 to 2021

Background: Using conventional tDCS over the temporo-parietal junction (TPJ) we previously reported that it is possible to manipulate subjective visual vertical (SVV) and postural control. We also demonstrated that high-definition tDCS (HD-tDCS) can achieve substantially greater cortical stimulation focality than conventional tDCS. However, it is critical to establish dose-response effects using well-defined protocols with relevance to clinically meaningful applications.

Objective: To conduct three pilot studies investigating polarity and intensity-dependent effects of HD-tDCS over the right TPJ on behavioral and physiological outcome measures in healthy subjects. We additionally aimed to establish the feasibility, safety, and tolerability of this stimulation protocol.

Methods: …

Decreased Body Mass Index In The Preclinical Stage Of Autosomal Dominant Alzheimer's Disease, Stephan A. Müller, Oliver Preische, Hamid R. Sohrabi, Susanne Gräber, Mathias Jucker, Janko Dietzsch, John M. Ringman, Ralph Martins, Eric M. Mcdade, Peter R. Schofield, Bernardino F. Ghetti, Martin N. Rossor, Neill R. Graff-Radford, Johannes Levin, Douglas R. Galasko, Kimberly A. Quaid, Stephen P. Salloway, Chengjie Xiong, Tammie L. Benzinger, Virginia D. Buckles, C. L. Masters, Reisa A. Sperling, Randall J. Bateman, John C. Morria, Christoph Laske

Research outputs 2014 to 2021

The relationship between body-mass index (BMI) and Alzheimeŕs disease (AD) has been extensively investigated. However, BMI alterations in preclinical individuals with autosomal dominant AD (ADAD) have not yet been investigated. We analyzed cross-sectional data from 230 asymptomatic members of families with ADAD participating in the Dominantly Inherited Alzheimer Network (DIAN) study including 120 preclinical mutation carriers (MCs) and 110 asymptomatic non-carriers (NCs). Differences in BMI and their relation with cerebral amyloid load and episodic memory as a function of estimated years to symptom onset (EYO) were analyzed. Preclinical MCs showed significantly lower BMIs compared to NCs, starting 11.2 years before …

Amyloid Β–Associated Cognitive Decline In The Absence Of Clinical Disease Progression And Systemic Illness, Karra Harrington, Yen Lim, David Ames, Jason Hassenstab, Simon Laws, Ralph Martins, Stephanie Rainey-Smith, Joanne Robertson, Christopher Rowe, Olivier Salvado, Vincent Dore, Victor Villemagne, Peter Snyder, Colin Masters, Paul Maruff, Aibl Research Group

Research outputs 2014 to 2021

Introduction

High levels of amyloid β (Aβ) are associated with cognitive decline in cognitively normal (CN) older adults. This study investigated the nature of cognitive decline in healthy individuals who did not progress to mild cognitive impairment or dementia.

Method

Cognition was measured over 72 months and compared between low (Aβ−) and high (Aβ+) CN older adults (n = 335) who did not progress to mild cognitive impairment or dementia and who remained free of severe or uncontrolled systemic illness.

Results

Compared to the Aβ− group, the Aβ+ group showed no cognitive impairment at baseline but showed substantial decline …

Altered Levels Of Blood Proteins In Alzheimer's Disease Longitudinal Study: Results From Australian Imaging Biomarkers Lifestyle Study Of Ageing Cohort, Veer B. Gupta, Eugene Hone, Steve Pedrini, James D. Doecke, Sid E. O'Bryant, Ian James, Ashley I. Bush, Christopher C. Rowe, Victor L. Villemagne, David Ames, Colin L. Masters, Ralph N. Martins

Research outputs 2014 to 2021

Introduction

A blood-based biomarker panel to identify individuals with preclinical Alzheimer's disease (AD) would be an inexpensive and accessible first step for routine testing.

Methods

We analyzed 14 biomarkers that have previously been linked to AD in the Australian Imaging Biomarkers lifestyle longitudinal study of aging cohort.

Results

Levels of apolipoprotein J (apoJ) were higher in AD individuals compared with healthy controls at baseline and 18 months (P =.0003) and chemokine-309 (I-309) were increased in AD patients compared to mild cognitive impaired individuals over 36 months (P =.0008).

Discussion

These data suggest that apoJ may have potential in the context …

Insulin Resistance Is Associated With Reductions In Specific Cognitive Domains And Increases In Csf Tau In Cognitively Normal Adults, Simon M. Laws, Scott Gaskin, Amy Woodfield, Velandai K. Srikanth, David G. Bruce, Paul E. Fraser, Tenielle Porter, Philip N. Newsholme, Nadeeja Wijesekara, Samantha C. Burnham, Vincent Doré, Qiaoxin Li, Paul T. Maruff, Colin L. Masters, Stephanie R. Rainey-Smith, Christopher C. Rowe, Olivier Salvado, Victor L. Villemagne, Ralph N. Martins, Giuseppe Verdile

Research outputs 2014 to 2021

Growing evidence supports the hypothesis that type 2 diabetes (T2D) increases the risk of developing dementia. Experimental evidence from mouse models demonstrates that the induction of T2D/insulin resistance (IR) can promote the accumulation of Alzheimer's disease (AD) pathological features. However, the association of T2D with pathological and clinical phenotypes in humans is unclear. Here we investigate the relationship of indices of IR (HOMA-IR) and pancreatic β-cell function (HOMA-B) with cognitive performance across several domains (Verbal/Visual Episodic Memory, Executive Function, Language and a measure of Global cognition) and AD biomarkers (CSF Aβ42, T-tau/P-tau, hippocampal volume and neocortical Aβ-amyloid burden). We reveal …

Finding Chemopreventatives To Reduce Amyloid Beta In Yeast, Ian Macreadie, Costa Arvanitis, Prashant Bharadwaj

Research outputs 2014 to 2021

Alzheimer's disease (AD) is the most common form of age-related dementia with the latest report (WorldAlzheimerReport, 2015) showing 46.8 million people are currently affected by dementia. That number is expected to double every 20 years unless there is effective therapeutic intervention.

Developmental Transcription Factors In Age-Related Cns Disease: A Phoenix Rising From The Ashes?, Robert White, Meghan Thomas

Research outputs 2014 to 2021

Few would doubt that understanding the developmental landscape from which a mature neuron is derived is essential to understand its biology. The temporal and spatial position of a cell from the very earliest stages of development predicts the unique combinations of growth factors it will subsequently be exposed to. This combination of factors determines the transcriptional platform set within the cell by its specific combination of transcription factors, who direct the show. This, in turn, determines what cell type it will differentiate into, and what connections it will make. How this developmental platform translates to maintenance of a differentiated neuron …

Aβ-Related Memory Decline In Apoe Ε4 Noncarriers: Implications For Alzheimer Disease, Yen Ying Lim, Simon Laws, Victor Villemagne, Robert Pietrzak, Tenielle Porter, David Ames, Christoher Fowler, Stephanie Rainey-Smith, Peter Snyder, Ralph Martins, Olivier Salvado, Pierrick Bourgeat, Christopher Rowe, Colin Masters, Paul Maruff

Research outputs 2014 to 2021

Objective:

As the absence of Aβ-related memory decline in APOE ϵ4 noncarriers may be due to the relative brevity of previous studies, we aimed to characterize Aβ-related cognitive decline over 72 months in APOE ϵ4 carriers and noncarriers who were cognitively normal (CN).

Methods:

CN older adults (n 423) underwent Aβ imaging and APOE genotyping. Participants completed comprehensive neuropsychological testing at baseline 18-, 36-, 54-, and 72-month assessments.

Results:

Relative to Aβ- CN ϵ4 noncarriers, both Aβ+ CN ϵ4 carriers and noncarriers showed significantly increased decline in measures of memory, language, and executive function as well as higher rates of …

Changes In The Plasma Proteome At Asymptomatic And Symptomatic Stages Of Autosomal Dominant Alzheimer's Disease, Julia Muenchhoff, Anne Poljak, Anbupalam Thalamuthu, Veer Gupta, Pratishtha Chatterjee, Mark Raftery, Colin Masters, John Morris, Randall Bateman, Anne Fagan, Ralph Martins, Perminder Sachdev

Research outputs 2014 to 2021

The autosomal dominant form of Alzheimer's disease (ADAD) is far less prevalent than late onset Alzheimer's disease (LOAD), but enables well-informed prospective studies, since symptom onset is near certain and age of onset is predictable. Our aim was to discover plasma proteins associated with early AD pathology by investigating plasma protein changes at the asymptomatic and symptomatic stages of ADAD. Eighty-one proteins were compared across asymptomatic mutation carriers (aMC, n = 15), symptomatic mutation carriers (sMC, n = 8) and related noncarriers (NC, n = 12). Proteins were also tested for associations with cognitive measures, brain amyloid deposition and glucose …

Amyloid-Related Memory Decline In Preclinical Alzheimer's Disease In Dependent On Apoe Ε4 And Is Detectable Over 18-Months, Christine Thai, Yen Ying Lim, Victor L. Villemagne, Simon Laws, David Ames, Kathryn A. Ellis, Stephanie Rainey-Smith, Ralph Martins, Colin L. Masters, Christopher C. Rowe, Paul Maruff, Australian Imaging, Biomarkers And Lifestyle (Aibl) Research Group

Research outputs 2014 to 2021

High levels of β-amyloid (Aβ) in the brain and carriage of the APOE ε4 allele have each been linked to cognitive impairment in cognitively normal (CN) older adults. The aim of this study was to investigate the relationship between cerebral Aβ level, APOE ε4 carrier status, and cognitive decline over 18 monthes, in 317 cognitively healthy (CN) older adults (47% males, 52.4% females) aged between 60 and 89 years (Mean = 69.9, SC = 6.8). Cognition was assessed using the Cogstate Brief Battery (CBB) and the California Verbal Learning Test, Second Edition (CVLT-II). Planned comparisons indicated that CN older adults …

Alzheimer's Disease Cerebrospinal Fluid Biomarkers Are Not Influenced By Gravity Drip Or Aspiration Extraction Methodology, Alan Rembach, Lisbeth A. Evered, Qiao-Xin Li, Tabitha Nash, Lesley Vidaurre, Christopher J. Fowler, Kelly K. Pertile, Rebecca L. Rumble, Brett O. Trounson, Sarah Maher, Francis Mooney, Maree Farrow, Kevin Taddei, Stephanie Rainey-Smith, Simon Laws, S. Lance Macaulay, William Wilson, David G. Darby, Ralph N. Martins, David Ames, Steven Collins, Brendon Silbert, Colin L. Masters, James D. Doecke

Research outputs 2014 to 2021

Introduction Cerebrospinal fluid (CSF) biomarkers, although of established utility in the diagnostic evaluation of Alzheimer’s disease (AD), are known to be sensitive to variation based on pre-analytical sample processing. We assessed whether gravity droplet collection versus syringe aspiration was another factor influencing CSF biomarker analyte concentrations and reproducibility. Methods Standardized lumbar puncture using small calibre atraumatic spinal needles and CSF collection using gravity fed collection followed by syringe aspirated extraction was performed in a sample of elderly individuals participating in a large long-term observational research trial. Analyte assay concentrations were compared. Results For the 44 total paired samples of gravity …

Inflamation And Oxidative Stress : The Molecular Connectivity Between Insulin Resistance, Obesity And Alzheimer's Disease, Guiseppe Verdile, Kevin N. Keane, Vinicius F. Cruzat, Sandra Medic, Miheer Sabale, Joanne Rowles, Nadeeja Wijesekara, Ralph Martins, Paul E. Fraser, Philip Newsholme

Research outputs 2014 to 2021

Type 2 diabetes (T 2 DM), Alzheimer’s disease (AD), and insulin resistance are age-related conditions and increased prevalence is of public concern. Recent research has provided evidence that insulin resistance and impaired insulin signalling may be a contributory factor to the progression of diabetes, dementia, and other neurological disorders. Alzheimer’s disease (AD) is the most common subtype of dementia. Reduced release (for T 2 DM) and decreased action of insulin are central to the development and progression of both T 2 DM and AD. A literature search was conducted to identify molecular commonalities between obesity, diabetes, and AD. Insulin resistance …

The Clinical Utility Of Multidisciplinary Rehabilitation In Individuals With Huntington’S Disease, Travis Miles Cruickshank

Theses: Doctorates and Masters

Background

Huntington’s disease (HD) is a chronic neurodegenerative disorder characterised by a progressive loss of cognitive function, motor control and psychiatric features. Individuals also display a variety of systemic features. Progressive neuronal dysfunction and neuronal cell death are thought to underlie the onset and progression of many clinical features of HD.

Despite scientific progress, there is still no cure or disease modifying therapy for HD, and available pharmaceutical agents only provide partial relief of motor and psychiatric features. An emerging body of evidence indicates that lifestyle enrichment may delay the onset and progression of clinical features, and exert favourable effects …

Pulmonary Function In Patients With Huntington's Disease, Alvaro Reyes, Travis Cruickshank, Mel Ziman, Ken Nosaka

Research outputs 2014 to 2021

Background: Huntington's disease (HD) is a neurodegenerative disorder characterized by progressive motor, cognitive and psychiatric disturbances. Chest muscle rigidity, respiratory muscle weakness, difficulty in clearing airway secretions and swallowing abnormalities have been described in patients with neurodegenerative disorders including HD. However limited information is available regarding respiratory function in HD patients. The purpose of this study was to investigate pulmonary function of patients with HD in comparison to healthy volunteers, and its association with motor severity.Methods: Pulmonary function measures were taken from 18 (11 male, 7 female) manifest HD patients (53 ± 10 years), and 18 (10 male, 8 female) …

Parkinson's Diagnosis From The Caregiver's Perspective, Helen Maree Bradley

Theses : Honours

Parkinson’s disease (Parkinson’s) is a progressive neurodegenerative disorder. The irreversible and accumulating disability experienced means that people with Parkinson’s progressively lose their autonomy, eventually requiring complete care. Consequently, Parkinson’s significantly impacts sufferers and the people who care for them. Informal care, predominantly provided by female spouses becomes exceptionally demanding over time, and caregivers experience significant morbidity. Stress manifests across all stages of the caregiving trajectory, with diagnosis reported as a particularly stressful period for caregivers; however, few attempts have been made to understand what makes it stressful. The current study explored female spousal caregivers’ subjective experience of the Parkinson’s diagnosis, …

Investigating The Impact Of Cd147 And Its Expression On Neurodegenaration And Alzheimer's Disease (Ad), Limbikani J. Kanyenda

Theses: Doctorates and Masters

CD147, also known as basigin, extracellular matrix metalloproteinase inducer, neurothelin, tumour cell-derived collagenase stimulatory factor, M6, HT7, OX47 or gp42, is a transmembrane glycoprotein of the immunoglobulin super-family. It is expressed in many neuronal and non-neuronal tissues with high expression in the hippocampus, pre-frontal cortex, thyroid, heart, early erythroid, amygdala and placenta. This protein is involved in various cellular and biological functions such as lymphocyte migration and maturation, tissue repair, cancer progression, T and B lymphocyte activation and induction of extracellular matrix metalloproteinase. The CD147 protein interacts with with cyclophilin A, cyclophilin B, sterol carrier protein, caveolin-1 and integrins, and …

Associatioin Of Plasma Aβ Peptides With Blood Pressure In The Elderly, Jean-Charles Lambert, Jean Dallongeville, Kathryn A. Ellis, Susanna Schraen-Maschke, James Lui, Simon Laws, Julie Dumont, Florence Richard, Dominque Cottel, Claudine Berr, David Ames, Colin L. Masters, Christopher C. Rowe, Cassandra Szoeke, Christophe Tzourio, Jean-Francois Dartigues, Luc Buee, Ralph Martins, Philippe Amouyel

Research outputs 2011

Background Aß peptides are often considered as catabolic by-products of the amyloid ß protein precursor (APP), with unknown physiological functions. However, several biological properties have been tentatively attributed to these peptides, including a role in vasomotion. We assess whether plasma Aß peptide levels might be associated with systolic and diastolic blood pressure values (SBP and DBP, respectively). Methodology/Principal Findings Plasma Aß1-40 and Aß1-42 levels were measured using an xMAP-based assay in 1,972 individuals (none of whom were taking antihypertensive drugs) from 3 independent studies: the French population-based 3C and MONA-LISA (Lille) studies (n = 627 and n = 769, respectively) …

Localisation Of The Gene For A Novel Form Of Charcot-Marie-Tooth Disease In An Isolated Population, Kaite Honeyman

Theses : Honours

Localising the gene for a previously undescribed autosomal recessive form of CMT involved the use of a relatively new approach to rapid genome screening based on the identification of segments which are inherited identical by descent (IBD) from common founding ancestors. It is most feasible for populations which have been founded relatively recently (say less than 25 generations) and which have remained relatively isolated either geographically or culturally. The method is not suitable for highly inbred populations, that is with first and second cousin matings, as many segments will be inherited by chance. It appears to be a suitable screening …