Michael Donohue
A5030911639- Dementia and Cognitive Impairment Research
- Alzheimer's disease research and treatments
- Functional Brain Connectivity Studies
- Health Systems, Economic Evaluations, Quality of Life
- Health, Environment, Cognitive Aging
- Anesthesia and Pain Management
- Advanced Neuroimaging Techniques and Applications
- Statistical Methods and Inference
- Statistical Methods in Clinical Trials
- Bioinformatics and Genomic Networks
- Neurological Disease Mechanisms and Treatments
- Spine and Intervertebral Disc Pathology
- Genetic Associations and Epidemiology
- Statistical Methods and Bayesian Inference
- Parkinson's Disease Mechanisms and Treatments
- Frailty in Older Adults
- Machine Learning in Healthcare
- Nausea and vomiting management
- Advanced Causal Inference Techniques
- Ethics in Clinical Research
- Shoulder Injury and Treatment
- Diet and metabolism studies
- Meta-analysis and systematic reviews
- Neurological Disorders and Treatments
- Cholinesterase and Neurodegenerative Diseases
University of Southern California
2016-2025
Southern States University
2016-2024
Autism Research Institute
2016-2024
University of Pennsylvania
2015-2024
University of California, San Diego
2015-2024
Alzheimer’s Disease Neuroimaging Initiative
2013-2024
University of California, Irvine
2024
Indiana University – Purdue University Indianapolis
2024
Janssen (United States)
2024
Harvard University
2024
<b>Background:</b> Neuroimaging measures and chemical biomarkers may be important indices of clinical progression in normal aging mild cognitive impairment (MCI) need to evaluated longitudinally. <b>Objective:</b> To characterize cross-sectionally longitudinally controls, subjects with MCI, Alzheimer disease (AD) enable the assessment utility neuroimaging biomarker measures. <b>Methods:</b> A total 819 (229 cognitively normal, 398 192 AD) were enrolled at baseline followed for 12 months...
Abstract Multifactorial mechanisms underlying late-onset Alzheimer’s disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels relation to LOAD progression. We analyse over 7,700 images tens of plasma cerebrospinal fluid biomarkers the Disease Neuroimaging Initiative (ADNI). Through a...
A new secondary prevention trial in older people with amyloid accumulation at high risk for Alzheimer’s disease dementia should provide insights into whether anti-amyloid therapy can delay cognitive decline.
Abstract The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct trajectories. Here we introduce machine-learning technique—Subtype Stage Inference (SuStaIn)—able uncover data-driven with temporal progression patterns, from widely available cross-sectional patient studies. Results imaging studies in two reveal subgroups their trajectories regional...
Tau is a hallmark pathology of Alzheimer's disease, and animal models have suggested that tau spreads from cell to through neuronal connections, facilitated by β-amyloid (Aβ). We test this hypothesis in humans using an epidemic spreading model (ESM) simulate spread, compare these simulations observed patterns measured tau-PET 312 individuals along disease continuum. Up 70% the variance overall spatial pattern can be explained our model. Surprisingly, ESM predicts irrespective whether brain...
<h3>Importance</h3> Among cognitively normal individuals, elevated brain amyloid (defined by cerebrospinal fluid assays or positron emission tomography regional summaries) can be related to risk for later Alzheimer-related cognitive decline. <h3>Objective</h3> To characterize and quantify the decline among individuals with amyloid. <h3>Design, Setting, Participants</h3> Exploratory analyses were conducted longitudinal biomarker data from 445 in United States Canada. Participants observed...
In Brief BACKGROUND: Continuous peripheral nerve blocks (CPNB) may induce muscle weakness, and multiple recently published series emphasize patient falls after postarthroplasty CPNB. However, none have included an adequate control group, therefore the relationship between CPNB remains speculative. METHODS: We pooled data from 3 previously published, randomized, triple-masked, placebo-controlled studies of involving femoral knee hip arthroplasty. RESULTS: No patients receiving perineural...
<h3>Objective:</h3> To compare the diagnostic accuracy of CSF biomarkers and amyloid PET for diagnosing early-stage Alzheimer disease (AD). <h3>Methods:</h3> From prospective, longitudinal BioFINDER study, we included 122 healthy elderly 34 patients with mild cognitive impairment who developed AD dementia within 3 years (MCI-AD). β-Amyloid (Aβ) deposition in 9 brain regions was examined [<sup>18</sup>F]-flutemetamol PET. analyzed INNOTEST EUROIMMUN ELISAs. The results were replicated 146...
Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative condition marked by decline in cognitive functions with no validated modifying treatment. It critical for timely treatment to detect AD its earlier stage before clinical manifestation. Mild impairment (MCI) an intermediate between cognitively normal older adults and AD. To predict conversion from MCI probable AD, we applied deep learning approach, multimodal recurrent neural network. We developed integrative framework that...
To estimate a regional progression pattern of amyloid deposition from cross-sectional amyloid-sensitive PET data and evaluate its potential for in vivo staging an individual's pathology.
Pirfenidone is an oral antifibrotic agent that benefits diabetic nephropathy in animal models, but whether it effective for human unknown. We conducted a randomized, double-blind, placebo-controlled study 77 subjects with who had elevated albuminuria and reduced estimated GFR (eGFR) (20 to 75 ml/min per 1.73 m²). The prespecified primary outcome was change eGFR after 1 year of therapy. randomly assigned 26 placebo, pirfenidone at 1200 mg/d, 25 2400 mg/d. Among the 52 completed study, mean...
There is considerable debate whether Alzheimer's disease (AD) originates in basal forebrain or entorhinal cortex. Here we examined longitudinal decreases and cortex grey matter volume were interdependent sequential. In a large cohort of age-matched older adults ranging from cognitively normal to AD, demonstrate that predicts degeneration. Models parallel degeneration origin received negligible support. We then integrated volumetric measures with an amyloid biomarker sensitive pre-symptomatic...
Abstract Brain iron elevation is implicated in Alzheimer’s disease (AD) pathogenesis, but the impact of on outcomes has not been previously explored a longitudinal study. Ferritin major storage protein body; by using cerebrospinal fluid (CSF) levels ferritin as an index, we whether brain status impacts Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF were negatively associated with cognitive performance over 7 years 91 cognitively normal, 144 mild impairment (MCI) and...
<h3>Importance</h3> Insulin modulates aspects of brain function relevant to Alzheimer disease and can be delivered the using intranasal devices. To date, use insulin treat persons with mild cognitive impairment Alzheimer's dementia remains examined in a multi-site trial. <h3>Objective</h3> examine feasibility, safety, efficacy for treatment phase 2/3 multisite clinical <h3>Design, Setting, Participants</h3> A randomized (1:1) double-blind trial was conducted between 2014 2018. Participants...
Abstract In Alzheimer’s diseases (AD), tau pathology is strongly associated with cognitive decline. Preclinical evidence suggests that spreads across connected neurons in an activity-dependent manner. Supporting this, cross-sectional AD studies show deposition patterns resemble functional brain networks. However, whether higher connectivity rates of accumulation unclear. Here, we combine resting-state fMRI longitudinal tau-PET two independent samples including 53 (ADNI) and 41 (BioFINDER)...
<h3>Importance</h3> The Anti-Amyloid Treatment in Asymptomatic Alzheimer disease (A4) Study is an ongoing prevention trial clinically normal older individuals with evidence of elevated brain amyloid. large number participants screened amyloid positron emission tomography (PET) and standardized assessments provides unprecedented opportunity to evaluate factors associated <h3>Objective</h3> To investigate the association demographic lifestyle factors, apolipoprotein E (APOE),...
Plasma phosphorylated tau at threonine 181 (p-tau181) has been proposed as an easily accessible biomarker for the detection of Alzheimer disease (AD) pathology, but its ability to monitor progression in AD remains unclear.To study potential longitudinal plasma p-tau181 measures assessing neurodegeneration and cognitive decline comparison neurofilament light chain (NfL), a disease-nonspecific marker neuronal injury.This cohort included data from Alzheimer's Disease Neuroimaging Initiative...
Reduced cerebrospinal fluid amyloid-β42 and increased retention of florbetapir positron emission tomography are biomarkers reflecting cortical amyloid load in Alzheimer's disease. However, these measurements do not always agree may represent partly different aspects the underlying disease pathology. The goal this study was therefore to test if amyloid-β independently related other markers, examine individuals who discordantly classified by two biomarker modalities. Cerebrospinal were...
Abstract Introduction Our objective was to investigate the effect of sex on cognitive decline within context amyloid β (Aβ) burden and apolipoprotein E genotype. Methods We analyzed sex‐specific effects Aβ‐positron emission tomography, apolipoprotein, rates change Preclinical Alzheimer Cognitive Composite‐5 across three cohorts, such as Alzheimer's Disease Neuroimaging Initiative, Australian Imaging, Biomarker Lifestyle, Harvard Aging Brain Study (n = 755; clinical dementia rating 0; age...
Patients with Alzheimer's disease have reduced cerebral blood flow measured by arterial spin labelling magnetic resonance imaging, but it is unclear how this related to amyloid-β pathology. Using 182 subjects from the Disease Neuroimaging Initiative we tested associations of regional in healthy controls (n = 51), early 66) and late 41) mild cognitive impairment, dementia 24). Based on theory that starts accumulation progresses symptoms secondary pathologies different trajectories, if...