Medicine and Health Sciences Commons^™

Using Imputation To Provide Harmonized Longitudinal Measures Of Cognition Across Aibl And Adni, Rosita Shishegar, Timothy Cox, David Rolls, Pierrick Bourgeat, Vincent Doré, Fiona Lamb, Joanne Robertson, Simon M. Laws, Tenielle Porter, Jurgen Fripp, Duygu Tosun, Paul Maruff, Greg Savage, Christopher C. Rowe, Colin L. Masters, Michael W. Weiner, Victor L. Villemagne, Samantha C. Burnham

Research outputs 2014 to 2021

To improve understanding of Alzheimer’s disease, large observational studies are needed to increase power for more nuanced analyses. Combining data across existing observational studies represents one solution. However, the disparity of such datasets makes this a non-trivial task. Here, a machine learning approach was applied to impute longitudinal neuropsychological test scores across two observational studies, namely the Australian Imaging, Biomarkers and Lifestyle Study (AIBL) and the Alzheimer's Disease Neuroimaging Initiative (ADNI) providing an overall harmonised dataset. MissForest, a machine learning algorithm, capitalises on the underlying structure and relationships of data to impute test scores not measured in one study aligning …

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 …

Potential Of Sorghum Polyphenols To Prevent And Treat Alzheimer's Disease: A Review Article, Nasim Rezaee, Warnakulasuriya Mary Ann Dipika Fernando, Eugene Hone, Hamid R. Sohrabi, Stuart K. Johnson, Stuart Gunzburg, Ralph Martins

Research outputs 2014 to 2021

Alzheimer’s disease (AD) is characterized by the excessive deposition of extracellular amyloid-beta peptide (Aβ) and the build-up of intracellular neurofibrillary tangles containing hyperphosphorylated tau proteins. This leads to neuronal damage, cell death and consequently results in memory and learning impairments leading to dementia. Although the exact cause of AD is not yet clear, numerous studies indicate that oxidative stress, inflammation, and mitochondrial dysfunction significantly contribute to its onset and progression. There is no effective therapeutic approach to stop the progression of AD and its associated symptoms. Thus, early intervention, preferably, pre-clinically when the brain is not significantly affected, is a …

Investigating Auditory Electrophysiological Measures Of Participants With Mild Cognitive Impairment And Alzheimer's Disease: A Systematic Review And Meta-Analysis Of Event-Related Potential Studies, Hadeel Y. Tarawneh, Wilhelmina H. A. M. Mulders, Hamid R. Sohrabi, Ralph N. Martins, Dona M. P. Jayakody

Research outputs 2014 to 2021

Background: Objectively measuring auditory functions has been proposed as an avenue in differentiating normal age-related cognitive dysfunction from Alzheimer's disease (AD) and its prodromal states. Previous research has suggested auditory event-related potentials (AERPs) to be non-invasive, cost-effective, and efficient biomarkers for the diagnosis of AD. Objective: The objective of this paper is to review the published literature on AERPs measures in older adults diagnosed with AD and those at higher risk of developing AD, i.e., mild cognitive impairment (MCI) and subjective cognitive decline. Methods: The search was performed on six major electronic databases (Ovid MEDLINE, OVID EMBASE, PsycINFO, PubMed, Scopus, …

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 …

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 Support Person's Preferences And Perspectives Of Physical Activity Programs For Older Adults With Cognitive Impairment, Terence W. H. Chong, Emily You, Kathryn A. Ellis, Kay L. Cox, Karra D. Harrington, Stephanie R. Rainey-Smith, David Ames, Nicola T. Lautenschlager, Aibl Research Group

Research outputs 2014 to 2021

Objectives: Physical activity (PA) is beneficial for older adults' cognition. There is limited research investigating perspectives of support persons (SPs) of next-of-kins (NOKs) with cognitive impairment. This exploratory study aimed to investigate perspectives of SPs of older adults with Alzheimer's Dementia (AD) or Mild Cognitive Impairment (MCI). Methods: A telephone survey of 213 SPs of NOKs from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL) was undertaken to quantitatively assess SPs' beliefs and knowledge about PA benefits, current PA level of their NOK, and PA program preferences. The contribution of age, gender, diagnosis and mental health symptoms …

Decrease In P3-Alcb37 And P3-Alcb40, Products Of Alcadein B Generated By G-Secretase Cleavages, In Aged Monkeys And Patients With Alzheimer’S Disease, Saori Hata, Chiori Omori, Ayano Kimura, Haruka Saito, Nobuyuki Kimura, Veer Gupta, Steve Pedrini, Eugene Hone, Pratishtha Chatterjee, Kevin Taddei, Kensaku Kasuga, Takeshi Ikeuchi, Masaaki Waragai, Masaki Nishimura, Anqi Hu, Tadashi Nakaya, Laurent Meijer, Masahiro Maeda, Tohru Yamamoto, Colin L. Masters, Chris C. Rowe, David Ames, Kazuo Yamamoto, Ralph N. Martins, Sam Gandy, Toshiharu Suzuki

Research outputs 2014 to 2021

Introduction Neuronal p3-Alcβ peptides are generated from the precursor protein Alcadein β (Alcβ) through cleavage by α- and γ-secretases of the amyloid β (Aβ) protein precursor (APP). To reveal whether p3-Alcβ is involved in Alzheimer's disease (AD) contributes for the development of novel therapy and/or drug targets. Methods We developed new sandwich enzyme-linked immunosorbent assay (sELISA) systems to quantitate levels of p3-Alcβ in the cerebrospinal fluid (CSF). Results In monkeys, CSF p3-Alcβ decreases with age, and the aging is also accompanied by decreased brain expression of Alcβ. In humans, CSF p3-Alcβ levels decrease to a greater extent in those with …

Comparing Biological Markers Of Alzheimer's Disease Across Blood Fraction And Platforms: Comparing Apples To Oranges, Sid E. O'Bryant, Simone Lista, Robert A. Rissman, Melissa Edwards, Fan Zhang, James Hall, Herik Zetterberg, Simon Lovestone, Veer Bular Gupta, Neill Graff-Radford, Ralph N. Martins, Andreas Jeromin, Stephen Waring, Esther Oh, Mitchel Kling, Laura D. Baker, Harald Hampel

Research outputs 2014 to 2021

Introduction:

This study investigated the comparability of potential Alzheimer's disease (AD) biomarkers across blood fractions and assay platforms.

Methods:

Nonfasting serum and plasma samples from 300 participants (150 AD patients and 150 controls) were analyzed. Proteomic markers were obtained via electrochemiluminescence or Luminex technology. Comparisons were conducted via Pearson correlations. The relative importance of proteins within an AD diagnostic profile was examined using random forest importance plots.

Results:

On the Meso Scale Discovery multiplex platform, 10 of the 21 markers shared > 50% of the variance across blood fractions (serum amyloid A R2 = 0.99, interleukin (IL)10 R2 = 0.95, fatty …

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.

Biomarkers Of Alzheimer's Disease Risk In Peripheral Tissues; Focus On Buccal Cells, Maxime François, Wayne Leifert, Ralph Martins, Philip Thomas, Michael Fenech

Research outputs 2014 to 2021

Alzheimer's disease (AD) is a progressive degenerative disorder of the brain and is the most common form of dementia. To-date no simple, inexpensive and minimally invasive procedure is available to confirm with certainty the early diagnosis of AD prior to the manifestations of symptoms characteristic of the disease. Therefore, if population screening of individuals is to be performed, more suitable, easily accessible tissues would need to be used for a diagnostic test that would identify those who exhibit cellular pathology indicative of mild cognitive impairment (MCI) and AD risk so that they can be prioritized for primary prevention. This need …

Altered Cytological Parameters In Buccal Cells From Individuals With Mild Cognitive Impairment And Alzheimer's Disease, Maxime François, Wayne Leifert, Jane Hecker, Jeffrey Faunt, Ralph Martins, Philip Thomas, Michael Fenech

Research outputs 2014 to 2021

Previous studies have shown that mild cognitive impairment (MCI) may be reflective of the early stages of more pronounced neurodegenerative disorders such as Alzheimer's disease (AD). There is a need for a minimally invasive and inexpensive diagnostic to identify those who exhibit cellular pathology indicative of MCI and AD risk so that they can be prioritized for primary preventative measures. The hypothesis was that a minimally invasive approach using cytological markers in isolated buccal mucosa cells can be used to identify individuals of both MCI and AD. An automated buccal cell assay was developed using laser scanning cytometry (LSC) to …