Amy Brodtmann

Amy Brodtmann
Monash University (Australia) · Van Cleef/Roet Centre for Nervous Diseases, and Department of Neuroscience

MBBS PhD

About

232
Publications
26,735
Reads
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4,081
Citations
Citations since 2017
162 Research Items
3438 Citations
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Introduction
I examine vascular contributions to late-life cognition via cohort and imaging studies. I am interested in modifiable risk and identifying interventions to prevent post-stroke dementia and pathological cognitive aging. I am interested in improving the diagnostic pathway for people with dementia and their carers by developing novel biomarkers.
Additional affiliations
February 2018 - present
The Royal Melbourne Hospital
Position
  • Neurologist Cognitive Neurology Lead
January 2009 - October 2020
The Florey Institute of Neuroscience and Mental Health
Position
  • Co-Theme Head
January 2006 - present
University of Melbourne
Position
  • Co-Division Head, Behavioural Neuroscience

Publications

Publications (232)
Preprint
Full-text available
Investigators in the cognitive neurosciences have turned to Big Data to address persistent replication and reliability issues by increasing sample sizes, statistical power, and representativeness of data. While there is tremendous potential to advance science through open data sharing, these efforts unveil a host of new questions about how to integ...
Article
Background: Insomnia is one of the most common sleep disorders yet its relationship to the biology of Alzheimer's disease remains equivocal. Objective: We investigated the cross-sectional relationship between insomnia symptom severity and cerebrospinal fluid (CSF) concentrations of Alzheimer's disease biomarkers in a cognitively unimpaired middl...
Article
Left ventricular hypertrophy (LVH) is common in people with type 2 diabetes mellitus (T2DM), and both are independently associated with increased dementia risk. Neurofilament light chain protein (NfL) is exclusively expressed in neurons and is an emerging plasma marker of neurodegeneration. We investigated the relationship between LVH, plasma NfL l...
Article
Amyloid production increases during wakefulness before being cleared during sleep. Insomnia is one of the commonest sleep disorders, yet its relationship to core markers of preclinical Alzheimer’s disease remains unknown. We investigated the cross‐sectional relationship between insomnia symptom severity, APOE e4 carriage, and cerebrospinal spinal f...
Article
Dual decline in gait speed and cognition is associated with an increased risk of dementia. However, it is unclear if risks are conferred by decline in domain‐specific cognition and gait. We aimed to examine associations between dual decline in gait speed and cognition (global cognition, memory, processing speed and verbal fluency) with risk of deme...
Article
Objective: To examine the utility of neuroimaging characteristics as biomarkers of prognosis in seropositive autoimmune encephalitis (AE). Methods: In this multi-center study, we retrospectively analyzed 66 cases of seropositive AE. The MRI and PET imaging was assessed by independent visual inspection. Whole brain and regional volumes were imput...
Article
Background: The BetterBrains Randomized Controlled Trial (RCT) will evaluate the effectiveness of an online, person-centered, risk factor management, coaching intervention in community-dwelling, healthy adults at risk of cognitive decline. Multi-component interventions are challenging to evaluate due to program complexity and personalization to in...
Article
Full-text available
Poor performance on verbal fluency tasks is associated with an increased risk of post-stroke cognitive impairment. Grey matter regions supporting verbal fluency have been identified via lesion–symptom mapping, but the links between verbal fluency and white matter structure remain less well described. We examined white matter correlates of semantic...
Article
Objective To use a systems paradigm to examine upper limb (UL) motor intervention elements driving biomarker and clinical measure improvement after stroke. Methods Databases were searched up to March 2022. Eligibility screening was completed by 2 authors. Studies using biomarkers and clinical measures pre- and post-upper limb intervention were inc...
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Cortical thinning has been described in many neurodegenerative diseases and used for both diagnosis and disease monitoring. The imaging signatures of post-stroke vascular cognitive impairment have not been well described. We investigated the trajectory of cortical thickness over 3 years following ischaemic stroke compared to healthy stroke-free age...
Article
Full-text available
Background: Frontotemporal dementia (FTD) syndromes, mimics, phenocopy (phFTD), and slowly progressive behavioral variant FTD (bvFTD) can be difficult to distinguish clinically. Biomarkers such as neurofilament light chain (NfL) may be helpful. Objective: To study plasma NfL levels in people with FTD syndromes and determine if plasma NfL can dis...
Article
Background: In the clinical setting, identification of the genetic cause in patients with early-onset dementia (EOD) is challenging due to multiple types of genetic tests required to arrive at a diagnosis. Whole-genome sequencing (WGS) has the potential to serve as a single diagnostic platform, due to its superior ability to detect common, rare an...
Article
Full-text available
Preclinical studies of remote degeneration have largely focused on brain changes over the first few days or weeks after stroke. Accumulating evidence suggests that neurodegeneration occurs in other brain regions remote to the site of infarction for months and even years following ischemic stroke. Brain atrophy appears to be driven by both axonal de...
Article
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Accurate lesion segmentation is critical in stroke rehabilitation research for the quantification of lesion burden and accurate image processing. Current automated lesion segmentation methods for T1-weighted (T1w) MRIs, commonly used in stroke research, lack accuracy and reliability. Manual segmentation remains the gold standard, but it is time-con...
Article
Importance: Dual decline in gait speed and cognition has been found to be associated with increased dementia risk in previous studies. However, it is unclear if risks are conferred by a decline in domain-specific cognition and gait. Objective: To examine associations between dual decline in gait speed and cognition (ie, global, memory, processin...
Article
Full-text available
Background Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is vulnerable to poststroke secondary degeneration and is involved in sensorimotor behavior but has not been widely studied within the context of poststroke upper‐limb sensorimotor impairment. We investigated associations between non‐l...
Article
Full-text available
Introduction: Sodium selenate increases tau dephosphorylation through protein phosphatase 2 activation. Here we report an open-label Phase 1b study of sodium selenate as a disease-modifying treatment for behavioral variant frontotemporal dementia (bvFTD). Methods: Twelve participants with bvFTD received sodium selenate (15 mg, three times a day)...
Preprint
Full-text available
Sensorimotor performance after stroke is strongly related to focal injury measures such as corticospinal tract lesion load. However, the role of global brain health is less clear. Here, we examined the impact of brain age, a measure of neurobiological aging derived from whole brain structural neuroimaging, on sensorimotor outcomes. We hypothesized...
Article
Purpose: White matter hyperintensities (WMHs) are associated with post-stroke cognitive decline and mortality. Physical activity (PA) may decrease WMH risk by reducing vascular risk factors and promoting cerebral perfusion. However, the association between post-stroke PA and WMH progression remains unclear. We examined the association between PA a...
Article
Poststroke cognitive impairment and dementia (PSCID) is a major source of morbidity and mortality after stroke worldwide. PSCID occurs as a consequence of ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage. Cognitive impairment and dementia manifesting after a clinical stroke is categorized as vascular even in people with comorbi...
Preprint
Diffusion-weighted imaging has produced useful biomarkers of verbal fluency post-stroke but acquiring diffusion data is not always clinically feasible. Further, it has been demonstrated that subcortical regions may contribute to verbal fluency, though the predominant focus in the literature has been on cortical contributions to verbal fluency. Fina...
Article
Objectives Cognitive and mood dysfunction are major contributors to post-stroke disability. The longer-term trajectories of mood and cognition post-stroke remain unclear, as do which cognitive domains decline, improve, or remain stable after stroke, and in which patients. We aimed to characterize the cognitive trajectories of mild ischemic stroke s...
Article
Background: Despite the rapid increase in research examining outcomes in Autoimmune Encephalitis (AE) patients, there are few cohort studies examining cognitive outcomes in this population. Methods: This retrospective observational study collected psychometric data from 59 patients across six secondary and tertiary referral centres in metropolit...
Article
High blood pressure (BP) is detrimental to brain health. High BP contributes to cognitive impairment and dementia through pathways independent of clinical stroke. Emerging evidence shows that the deleterious effect of high BP on cognition occurs across the life span, increasing the risk for early-onset and late-life dementia. The term vascular cogn...
Article
Full-text available
Dynamic whole-brain changes occur following stroke, and not just in association with recovery. We tested the hypothesis that the presence of a specific behavioural deficit after stroke would be associated with structural decline (atrophy) in the brain regions supporting the affected function, by examining language deficits post-stroke. We quantifie...
Article
Full-text available
Favorable cerebral collateral circulation contributes to hindering penumbral tissue from progressing to infarction and is associated with positive clinical outcomes after stroke. Given its clinical importance, improving cerebral collateral circulation is considered a therapeutic target to reduce burden after stroke. We provide a hypothesis-generati...
Article
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Background and Purpose The evolution of total brain volume early after stroke is not well understood. We investigated the associations between age and imaging features and brain volume change in the first month after stroke. Methods We retrospectively studied patients with acute ischemic stroke enrolled in the AXIS-2 trial. Total brain volume chan...
Article
Full-text available
Movement-based mindfulness interventions (MBI) are complex, multi-component interventions for which the design process is rarely reported. For people with stroke, emerging evidence suggests benefits, but mainstream programs are generally unsuitable. We aimed to describe the processes involved and to conduct a formative evaluation of the development...
Article
Full-text available
Introduction Sodium selenate is a potential disease-modifying treatment for Alzheimer’s disease (AD) which reduces hyperphosphorylated tau through activation of the protein phosphatase 2A enzyme. We have shown sodium selenate to be safe and well tolerated in a 24-week, phase 2a double-blind placebo-controlled randomised controlled trial (RCT), also...
Preprint
Full-text available
Accurate lesion segmentation is critical in stroke rehabilitation research for the quantification of lesion burden and accurate image processing. Current automated lesion segmentation methods for T1-weighted (T1w) MRIs, commonly used in rehabilitation research, lack accuracy and reliability. Manual segmentation remains the gold standard, but it is...
Article
Full-text available
Damage to specific brain circuits can cause specific neuropsychiatric symptoms. Therapeutic stimulation to these same circuits may modulate these symptoms. To determine whether these circuits converge, we studied depression severity after brain lesions (n = 461, five datasets), transcranial magnetic stimulation (n = 151, four datasets) and deep bra...
Article
Type 2 diabetes Mellitus (T2DM) is recognised as a major contributor to cognitive decline. People with T2DM demonstrate increased white matter hyperintensity (WMH) abnormalities on MRI compared to control individuals. We investigated associations between a validated vascular risk score: The Framingham Risk Score (FRS), WMH volumes and cognitive fun...
Article
We aimed to chart white matter integrity over 3 years after stroke, to examine if post‐stroke loss of white matter continues to be accelerated compared to control participants. We applied a longitudinal “fixel”‐based analysis, sensitive to fibre tract‐specific differences within a voxel, to assess axonal loss in stroke (N=71, 22 women) compared to...
Article
Background: Neuropsychiatric symptoms (NPS) are behavioural and psychological disturbances frequent in people with dementia that have been linked with lower quality of life, lower cognitive functioning and greater caregiver distress, especially for caregivers of people with younger-onset dementia (YOD) (1). Several drug and non-drug treatments tar...
Article
Background The structural integrity of hippocampal subfields has been investigated in many neurological disorders and was shown to be better associated with cognitive performance than whole hippocampus. In stroke, hippocampal atrophy is linked to cognitive impairment, but it is unknown whether the hippocampal subfields atrophy differently. Purpose...
Preprint
Full-text available
Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is involved in sensorimotor behavior but has not been widely studied within the context of post-stroke upper limb sensorimotor impairment. The hippocampus is vulnerable to secondary degeneration after stroke, and damage to this region could furth...
Article
Full-text available
Up to two-thirds of stroke survivors experience persistent sensorimotor impairments. Recovery relies on the integrity of spared brain areas to compensate for damaged tissue. Deep grey matter structures play a critical role in the control and regulation of sensorimotor circuits. The goal of this work is to identify associations between volumes of sp...
Article
This systematic review aimed to investigate timing, dose, and efficacy of upper limb intervention during the first 6 months poststroke. Three online databases were searched up to July 2020. Titles/abstracts/full-text were reviewed independently by 2 authors. Randomized and nonrandomized studies that enrolled people within the first 6 months poststr...
Article
Objective(s) To investigate the relationship between the elements of upper limb motor therapy, neuroimaging biomarkers and clinical outcomes. Data Sources A systematic search of Cochrane Register of Controlled Trials (CENTRAL), EMBASE and Medline was conducted. Study Selection Studies with adult stroke survivors who underwent motor interventions...
Article
Animal modeling has played an important role in our understanding of the pathobiology of stroke. The vast majority of this research has focused on the acute phase following severe forms of stroke that result in clear behavioral deficits. Human stroke, however, can vary widely in severity and clinical outcome. There is a rapidly building body of wor...
Article
Full-text available
Background: Stroke survivors are at high risk of dementia, associated with increasing age and vascular burden and with pre-existing cognitive impairment, older age. Brain atrophy patterns are recognised as signatures of neurodegenerative conditions, but the natural history of brain atrophy after stroke remains poorly described. We sought to determi...
Article
Full-text available
Brain health is essential for physical and mental health, social well‐being, productivity, and creativity. Current neurological research focuses mainly on treating a diseased brain and preventing further deterioration rather than on developing and maintaining brain health. The pandemic has forced a shift toward virtual working environments that acc...
Article
Background: Several modifiable risk factors for dementia have been identified, although the extent to which their modification leads to improved cognitive outcomes remains unclear. Objective: The primary aim is to test the hypothesis that a behavior modification intervention program targeting personalized risk factors prevents cognitive decline...
Preprint
Full-text available
Background: Stroke survivors are at high risk of dementia, associated with increasing age and vascular burden and with pre-existing cognitive impairment, older age. Brain atrophy patterns are recognised as signatures of neurodegenerative conditions, but the natural history of brain atrophy after stroke remains poorly described. We sought to determi...
Article
Background and Objective Significant health care resources are allocated to monitoring high risk pregnancies to minimize growth compromise, reduce morbidity and prevent stillbirth. Fetal movement has been recognized as an important indicator of fetal health. Studies have shown that 25% of pregnancies with decreased fetal movement in the third trime...
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Full-text available
Background Blood pressure variability (BPV) in midlife increases risk of late‐life dementia, but the impact of BPV on the cognition of adults who have already reached older ages free of major cognitive deficits is unknown. We examined the risk of incident dementia and cognitive decline associated with long‐term, visit‐to‐visit BPV in a post hoc ana...
Article
Full-text available
Introduction: Hippocampal subfield volumes are more closely associated with cognitive impairment than whole hippocampal volume in many diseases. Both memory and whole hippocampal volume decline after stroke. Understanding the subfields' temporal evolution could reveal valuable information about post-stroke memory. Methods: We sampled 120 partici...
Article
Background and Purpose Polygenic risk scores (PRSs) can be used to predict ischemic stroke (IS). However, further validation of PRS performance is required in independent populations, particularly older adults in whom the majority of strokes occur. Methods We predicted risk of incident IS events in a population of 12 792 healthy older individuals...
Article
Full-text available
Few studies have measured the effect of genetic factors on dementia and cognitive decline in healthy older individuals followed prospectively. We studied cumulative incidence of dementia and cognitive decline, stratified by APOE genotypes and polygenic risk score (PRS) tertiles, in 12,978 participants of the ASPirin in Reducing Events in the Elderl...
Article
Full-text available
Hippocampal atrophy is increasingly described in many neurodegenerative syndromes in humans, including stroke and vascular cognitive impairment. However, the progression of brain volume changes after stroke in rodent models is poorly characterized. We aimed to monitor hippocampal atrophy occurring in mice up to 48-weeks post-stroke. Male C57BL/6J m...
Article
Objective/Background Sleep-wake dysfunction is bidirectionally associated with the incidence and evolution of acute stroke. It remains unclear whether sleep disturbances are transient post-stroke or are potentially enduring sequelae in chronic stroke. Here, we characterize sleep architectural dysfunction, sleep-respiratory parameters, and hemispher...
Preprint
Full-text available
Background and Purpose. Fatigue is associated with poor functional outcomes and increased mortality following stroke. Survivors identify fatigue as one of their key unmet needs. Despite the growing body of research into post-stroke fatigue, the specific neural mechanisms remain largely unknown. Methods. This observational study included 63 stroke s...
Article
Background and purpose: Functional outcome after stroke may be related to preexisting brain health. Several imaging markers of brain frailty have been described including brain atrophy and markers of small vessel disease. We investigated the association of these imaging markers with functional outcome after acute ischemic stroke. Methods: We retros...
Article
Objective: The timing of brain atrophy after stroke is not well understood. We investigated the associations between age and imaging features and brain volume change in the first month after stroke. Methods: We retrospectively studied patients with acute ischemic stroke enrolled in the AXIS-2 trial. Total brain volume change from hyperacute MRI dat...
Article
Hippocampal atrophy is seen in many neurodegenerative disorders and may be a cardinal feature of vascular neurodegeneration. We examined hippocampal volume (HV) in a group of ischemic stroke survivors with amyloid 18F-NAV4694 PET imaging three years after stroke. We compared HV between the amyloid-positive (n = 4) and amyloid-negative (n = 29) grou...
Article
Background Admission stroke severity is an important clinical predictor of stroke outcomes. Pre-stroke physical activity (PA) contributes to stroke prevention and may also be associated with reduced stroke severity. Summarising the evidence to-date will inform strategies to reduce burden after stroke. Aims To summarise the published evidence for th...
Article
Full-text available
Using advanced diffusion MRI, we aimed to assess the microstructural properties of normal-appearing white matter (NAWM) preceding conversion to white matter hyperintensities (WMHs) using 3-tissue diffusion signal compositions in ischemic stroke. Data were obtained from the Cognition and Neocortical Volume After Stroke (CANVAS) study. Diffusion-weig...
Article
Objective To examine the prognostic value of CSF abnormalities in seropositive autoimmune encephalitis (AE). Methods We retrospectively studied 57 cases of seropositive AE. Primary outcomes were mortality and modified Rankin Scale, while secondary outcomes were first line treatment failure, ICU admission and relapse. Regression analysis was perfor...
Article
Background and Purpose Functional outcome after stroke may be related to preexisting brain health. Several imaging markers of brain frailty have been described including brain atrophy and markers of small vessel disease. We investigated the association of these imaging markers with functional outcome after acute ischemic stroke. Methods We retrosp...
Article
Full-text available
Purpose: Quantitative susceptibility mapping (QSM) is a novel MR technique that allows mapping of tissue susceptibility values from MR phase images. QSM is an ill-conditioned inverse problem, and although several methods have been proposed in the field, in the presence of a wide range of susceptibility sources, streaking artifacts appear around hi...
Article
Full-text available
Objective To examine the utility of the peripheral blood neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) as biomarkers of prognosis in seropositive autoimmune encephalitis (AE). Methods In this multicenter study, we retrospectively analyzed 57 cases of seropositive AE with hospital admissions between January 2008 and Ju...
Article
Dose articulation is a universal issue of intervention development and testing. In stroke recovery, dose of a nonpharmaceutical intervention appears to influence outcome but is often poorly reported. The challenges of articulating dose in nonpharmacological stroke recovery research include: (1) the absence of specific internationally agreed dose re...
Article
Up to two thirds of ischaemic stroke survivors develop cognitive impairment, predominantly impacting executive and attentional processing. Animal models are essential for effective translation and development of therapies. However, accurately modelling cognitive dysfunction in animal models of stroke has been limited. To address this, we aimed to l...
Article
Neuropsychiatric symptoms (NPS), including depression, anxiety, apathy, aggression and agitation, among others, are highly prevalent in people with dementia (PWD), and are associated with lower quality of life and greater caregiver distress1. Over recent years there has been a proliferation of research aimed at exploring the cause of NPS and the re...
Article
Hippocampal atrophy, long thought to be an imaging signature of Alzheimer’s disease, is seen in a range of neurodegenerative disorders, and in association with vascular risk factors in people without dementia. We examined hippocampal volume (HV) in a group of ischemic stroke patients who participated in an amyloid PET imaging study 3 years after th...
Article
Cardiovascular risk factors and stroke are associated with increased risk of all‐cause dementia. More than one third of stroke patients will develop dementia, but mechanisms are unclear. Vascular brain burden from accumulated risk factors may contribute to cognitive impairment at the time of stroke, with the stroke being yet another manifestation o...
Article
Older adults with type 2 diabetes mellitus (T2DM) are at an increased risk of cognitive decline and dementia. Left ventricular hypertrophy (LVH) is prevalent in T2DM and is independently associated with cognitive decline. We conducted a study to establish whether T2DM patients with LVH have increased rates of brain atrophy and cognitive impairment....
Article
Cortical atrophy is associated with cognitive decline and dementia, but few studies have examined cerebral atrophy after ischemic stroke. In this exploratory study, we examined changes in cortical volumes over 3 years in ischemic stroke patients and healthy age‐ and sex‐matched controls. Participants with first‐ever stroke were sampled from the Cog...
Article
Growing evidence suggests that increased cardiovascular risk might accelerate brain atrophy and cognitive decline. The aim of this analysis was to investigate associations between the Framingham Risk Score (FRS), brain volume and cognitive function in individuals with type 2 diabetes (T2DM) participating in the Diabetes‐and‐Dementia (D2) study. Nin...