Neurosciences Commons^™

Alzheimer's Disease Genetic Risk And Changes In Brain Atrophy And White Matter Hyperintensities In Cognitively Unimpaired Adults, Anja Soldan, Jiangxia Wang, Corinne Pettigrew, Christos Davatzikos, Guray Erus, Timothy J. Hohman, Logan Dumitrescu, Murat Bilgel, Susan M. Resnick, Leonardo A. Rivera-Rivera, Rebecca Langhough, Sterling C. Johnson, Tammie Benzinger, John C. Morris, Simon M. Laws, Jurgen Fripp, Colin L. Masters, Marilyn S. Albert

Research outputs 2022 to 2026

Reduced brain volumes and more prominent white matter hyperintensities on MRI scans are commonly observed among older adults without cognitive impairment. However, it remains unclear whether rates of change in these measures among cognitively normal adults differ as a function of genetic risk for late-onset Alzheimer's disease, including APOE- ε4, APOE-ε2 and Alzheimer's disease polygenic risk scores (AD-PRS), and whether these relationships are influenced by other variables. This longitudinal study examined the trajectories of regional brain volumes and white matter hyperintensities in relationship to APOE genotypes (N = 1541) and AD-PRS (N = 1093) in a harmonized dataset of middle-aged …

Midline Brain Structures In Adult Niemann-Pick Type C Disease: A Cross-Sectional Study, Mark Walterfang, Tsutomu Takahashi, Maria A. Di Biase, Vanessa L. Cropley, Daiki Sasabayashi, Michio Suzuki, Dennis Velakoulis, Christos Pantelis

Research outputs 2022 to 2026

Objective: A range of neuropathological changes occur in the brains of individuals with adult Niemann-Pick type C disease (NPC), a recessive disorder of cholesterol trafficking that results in accumulation of cholesterol and gangliosides in lysosomes, particularly in neurons. One of the most significant regions of grey matter loss occurs in the thalami, which abut the midline. What is not known is whether these are neurodevelopmental in origin well prior to symptomatic onset. We aimed to examine other markers of midline developmental anomalies in adults with NPC. Method: We examined the size of adhesio interthalamica (AI) and cavum septum pellucidum (CSP) …

Changes In Sleep Effort Mediate Insomnia Severity In Older Adults Following Online Cognitive Behavioural Therapy, Yvonne Kutzer, Lisa Whitehead, Eimear Quigley, Mandy Stanley

Research outputs 2022 to 2026

Background

To examine treatment mechanisms of digitally delivered cognitive behavioural therapy for insomnia (CBT-I), this study assessed the mediating effects of dysfunctional beliefs, hyperarousal, locus of control, self-efficacy, sleep effort, and safety behaviours on self-reported insomnia severity in older adults before and following the completion of a self-guided, online CBT-I program.

Methods

The baseline and follow-up measurements were completed by 62 older adults (55 female, 89%). This was a two-condition within-participant design. Mediation analysis using a parallel mediation model was conducted using the MEMORE macro for repeated measure designs.

Results

Out of all the included mediator variables, only a reduction …

Excitatory Drive To Spinal Motoneurones Is Necessary For Serotonin To Modulate Motoneurone Excitability Via 5-Ht2 Receptors In Humans, Tyler T. Henderson, Janet L. Taylor, Jacob R. Thorstensen, Justin J. Kavanagh

Research outputs 2022 to 2026

Serotonin modulates corticospinal excitability, motoneurone firing rates and contractile strength via 5-HT2 receptors. However, the effects of these receptors on cortical and motoneurone excitability during voluntary contractions have not been explored in humans. Therefore, the purpose of this study was to investigate how 5-HT2 antagonism affects corticospinal and motoneuronal excitability with and without descending drive to motoneurones. Twelve individuals (aged 24 ± 4 years) participated in a double-blind, placebo-controlled, crossover study, whereby the 5-HT2 antagonist cyproheptadine was administered. Transcranial magnetic stimulation (TMS) was delivered to the motor cortex to produce motor evoked potentials (MEPs), and electrical stimulation at the cervicomedullary …

Predicting Neurodegeneration From Sleep Related Biofluid Changes, Yue Yang, Woojin S. Kim, Johannes C. Michaelian, Simon J. G. Lewis, Craig L. Phillips, Angela L. D'Rozario, Pratishtha Chatterjee, Ralph N. Martins, Ron Grunstein, Glenda M. Halliday, Sharon L. Naismith

Research outputs 2022 to 2026

Sleep-wake disturbances are common in neurodegenerative diseases and may occur years before the clinical diagnosis, potentially either representing an early stage of the disease itself or acting as a pathophysiological driver. Therefore, discovering biomarkers that identify individuals with sleep-wake disturbances who are at risk of developing neurodegenerative diseases will allow early diagnosis and intervention. Given the association between sleep and neurodegeneration, the most frequently analyzed fluid biomarkers in people with sleep-wake disturbances to date include those directly associated with neurodegeneration itself, such as neurofilament light chain, phosphorylated tau, amyloid-beta and alpha-synuclein. Abnormalities in these biomarkers in patients with sleep-wake disturbances …

Unveiling The Link Between Systemic Inflammation Markers And Cognitive Performance Among Older Adults In The Us: A Population-Based Study Using Nhanes 2011–2014 Data, Zheng Guo, Yulu Zheng, Jian Geng, Zhiyuan Wu, Tao Wei, Guangle Shan, Yahong Zhu, Yuanyuan Zheng, Xingang Li

Research outputs 2022 to 2026

Purpose: This study aimed to evaluate the association between systemic inflammation markers and cognitive performance among older US adults. Methods: This cross-sectional study assessed 3,632 older participants from the 2011–2014 National Health and Nutrition Examination Survey (NHANES). The main analysis included participants aged over 60 years. Systemic inflammation markers were quantified by calculating the composite inflammation indicators from the blood routine count, and cognitive performance was assessed using Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test, Animal Fluency test (AFT), and Digit Symbol Substitution test (DSST). Results: There were 2,743 individuals enrolled in the current analysis. The overall …

Exploration Of Alzheimer's Disease-Related Gene Expression Following High-Intensity And Moderate-Intensity Exercise Interventions, Kieran J. Marston, Jaisalmer De Frutos-Lucas, Tenielle Porter, Lidija Milicic, Michael Vacher, Kelsey R. Sewell, Jeremiah J. Peiffer, Simon M. Laws, Belinda M. Brown

Research outputs 2022 to 2026

Objectives: There are currently 29 genome regions that demonstrate associations with Alzheimer's disease (AD) risk. Regular physical exercise can promote systemic change in gene expression and may modify the risk of cognitive decline and AD. This study is a secondary analysis of a randomised controlled trial and examines the effect of a six-month exercise intervention versus control on AD-related gene expression. Design: Single-site parallel pilot randomised controlled trial. Methods: 91 cognitively unimpaired older adults were enrolled in the Intense Physical Activity and Cognition (IPAC) study. Participants were randomised into one of three groups: high-intensity exercise, moderate-intensity exercise, or inactive control …

Neuropsychiatric Symptoms Of Dementia In Those With And Without A Recorded History Of Psychological Trauma: A Comparative Study From An Australian Dementia Support Service, Monica Cations, Mustafa Atee, Thomas Morris, Daniel Whiting

Research outputs 2022 to 2026

Objective: To compare the number and severity of neuropsychiatric symptoms (NPS) and associated caregiver distress between those with and without a noted history of psychological trauma among those referred to a specialised national dementia NPS support service. Methods: This was a 5-year retrospective observational study of records from the Dementia Support Australia NPS support service. NPS were reported by formal or informal caregivers at service entry using the Neuropsychiatric Inventory Nursing Home version or Questionnaire version. A history of psychological trauma was recorded in the person's social or medical history and/or endorsed as a contributor to NPS by a trained …

Longitudinal Associations Between Exercise And Biomarkers In Autosomal Dominant Alzheimer's Disease, Kelsey R. Sewell, James D. Doecke, Chengjie Xiong, Tammie Benzinger, Colin L. Masters, Christoph Laske, Mathias Jucker, Francisco Lopera, Brian A. Gordon, Jorge Llibre-Guerra, Johannes Levin, Edward D. Huey, Jason Hassenstab, Peter R. Schofield, Gregory S. Day, Nick C. Fox, Jasmeer Chhatwal, Laura Ibanez, Jee Hoon Roh, Richard Perrin, Jae Hong Lee, Ralph N. Martins, Stephanie Rainey-Smith, Samantha L. Gardener, Hamid R. Sohrabi, Belinda Brown

Research outputs 2022 to 2026

INTRODUCTION: We investigated longitudinal associations between self-reported exercise and Alzheimer's disease (AD)-related biomarkers in individuals with autosomal dominant AD (ADAD) mutations. METHODS: Participants were 308 ADAD mutation carriers aged 39.7 ± 10.8 years from the Dominantly Inherited Alzheimer's Network. Weekly exercise volume was measured via questionnaire and associations with brain volume (magnetic resonance imaging), cerebrospinal fluid biomarkers, and brain amyloid beta (Aβ) measured by positron emission tomography were investigated. RESULTS: Greater volume of weekly exercise at baseline was associated with slower accumulation of brain Aβ at preclinical disease stages β = –0.16 [–0.23 to –0.08], and a slower decline in …

Sleep Discrepancy And Brain Glucose Metabolism In Community-Dwelling Older Adults, Nadia Soh, Michael Weinborn, James D. Doecke, Rodrigo Canovas, Vincent Doré, Ying Xia, Jurgen Fripp, Kevin Taddei, Romola S. Bucks, Hamid R. Sohrabi, Ralph N. Martins, Melissa Ree, Stephanie R. Rainey-Smith

Research outputs 2022 to 2026

Sleep discrepancy (negative discrepancy reflects worse self-reported sleep than objective measures, such as actigraphy, and positive discrepancy the opposite) has been linked to adverse health outcomes. This study is first to investigate the relationship between sleep discrepancy and brain glucose metabolism (assessed globally and regionally via positron emission tomography), and to evaluate the contribution of insomnia severity and depressive symptoms to any associations. Using data from cognitively unimpaired community-dwelling older adults (N = 68), cluster analysis was used to characterise sleep discrepancy (for total sleep time (TST), wake after sleep onset (WASO), and sleep efficiency (SE)), and logistic regression was …

The Association Between Plasma Igg N-Glycosylation And Neonatal Hypoxic–Ischemic Encephalopathy: A Case-Control Study, Liangao Wang, Xinxia Lu, Meng Wang, Xuezhen Zhao, Peirui Li, Haitao Zhang, Qingtang Meng, Yujing Zhang, Yingjie Wang, Wei Wang, Long Ji, Haifeng Hou, Dong Li

Research outputs 2022 to 2026

Introduction: Hypoxic-ischemic encephalopathy (HIE) is one of severe neonatal brain injuries, resulting from inflammation and the immune response after perinatal hypoxia and ischemia. IgG N-glycosylation plays a crucial role in various inflammatory diseases through mediating the balance between anti-inflammatory and pro-inflammatory responses. This study aimed to explore the effect of IgG N-glycosylation on the development of HIE. Methods: This case-control study included 53 HIE patients and 57 control neonates. An ultrahigh-performance liquid chromatography (UPLC) method was used to determine the features of the plasma IgG N-glycans, by which 24 initial glycan peaks (GPs) were quantified. Multivariate logistic regression was used …

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.

A Systematic Review Of Dementia Research Priorities, Manonita Ghosh, Pelden Chejor, Melanie Baker, Davina Porock

Research outputs 2022 to 2026

Introduction: Patient involvement is a critical component of dementia research priority-setting exercises to ensure that research benefits are relevant and acceptable to those who need the most. This systematic review synthesises research priorities and preferences identified by people living with dementia and their caregivers. Methods: Guided by Joanna Briggs Institute methodology, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework, we conducted a systematic search in five electronic databases: CINAHL, Medline, PsycINFO, Web of Science and Scopus. The reference lists of the included studies were also manually searched. We combined quantitative and qualitative data for synthesis and descriptive thematic …

Fluid Biomarkers In Cerebral Amyloid Angiopathy, Seyed M. Savar, Bin Ma, Eugene Hone, Farzana Jahan, Shaun Markovic, Steve Pedrini, Soudabeh Shemehsavar, Vandhana Easwaran, Kevin Taddei, Samantha Gardener, Jasmeer P. Chhatwal, Ellis S. Van Etten, Matthias J. P. Van Osch, Daniel Clarke, Anastazija Gnjec, Mark A. Van Buchem, Marieke J. H. Wermer, Graeme J. Hankey, Steven M. Greenberg, Ralph N. Martins, Hamid R. Sohrabi

Research outputs 2022 to 2026

Cerebral amyloid angiopathy (CAA) is a type of cerebrovascular disorder characterised by the accumulation of amyloid within the leptomeninges and small/medium-sized cerebral blood vessels. Typically, cerebral haemorrhages are one of the first clinical manifestations of CAA, posing a considerable challenge to the timely diagnosis of CAA as the bleedings only occur during the later disease stages. Fluid biomarkers may change prior to imaging biomarkers, and therefore, they could be the future of CAA diagnosis. Additionally, they can be used as primary outcome markers in prospective clinical trials. Among fluid biomarkers, blood-based biomarkers offer a distinct advantage over cerebrospinal fluid biomarkers …