99mTc-HMPAO SPECT perfusion signatures associated with clinical progression in patients with isolated REM sleep behavior disorder
Neurology, Volume 102, Issue 4, February 2024
In this study, we sought to find a brain blood flow pattern that could predict the onset of dementia with Lewy bodies. By analyzing brain scans with single-photon computed emission tomography and clinical features of individuals with isolated REM sleep behavior disorder compared to healthy controls and Parkinson's disease people, we identified two key patterns related to cognitive decline and the risk of developing neurodegenerative diseases. One pattern predicted a general risk for such diseases, while the other specifically indicated a transition to dementia with Lewy bodies. This suggests the potential of developing a new biomarker from individual scans to predict dementia in people at risk, offering a significant step forward in early diagnosis and treatment strategies for dementia with Lewy bodies.
Predicting longitudinal brain atrophy in Parkinson's disease using a Susceptible-Infected-Removed agent-based model
Network Neuroscience, Volume 7, Issue 3, October 2023, Pages 906–925
Parkinson's disease unfolds as brain cells deteriorate over time, a process linked to the buildup and spread of a misshapen protein known as alpha-synuclein. This protein is thought to behave similarly to prions, corrupting other normal proteins, spreading through the brain, and causing cell damage. This concept, while still under debate, was explored using a computer model called the Susceptible-Infected-Removed to simulate how alpha-synuclein propagates and inflicts damage within the brain. Through the analysis of over a thousand MRI scans from the Parkinson's Progression Markers Initiative, including scans from both Parkinson's people and healthy controls, we observed patterns of brain damage developing across specific regions over four years. The model accurately mirrored the observed patterns of brain shrinkage seen in Parkinson's disease, underscoring the significant roles of brain network connections and the activity of genes associated with alpha-synuclein. These findings lend support to the prion-like spread theory of Parkinson's and highlight the Susceptible-Infected-Removed model as a potential key tool for delving into the complex nature of neurodegenerative diseases and their progression over time.
Mitochondrial function-associated genes underlie cortical atrophy in prodromal synucleinopathies
Brain, Volume 146, Issue 8, August 2023, Pages 3301-3318
In this study, we investigated brain changes in patients predisposed to developing synucleinopathies like dementia with Lewy bodies and Parkinson’s disease. Using advanced MRI techniques on people with isolated REM sleep behavior disorder and healthy controls, the study identified specific gene expression patterns associated with cortical thinning in isolated REM sleep behavior disorder, highlighting the roles of mitochondrial function and macroautophagy. Furthermore, the research demonstrated that these brain changes are influenced by the brain's structural and functional networks, particularly affecting areas involved in motor and planning functions. Unlike Alzheimer's disease, the genetic and connectivity patterns in isolated REM sleep behavior disorder suggest unique pathways of disease progression, emphasizing the importance of specific genes and brain networks in the development of synucleinopathy-related brain atrophy.
Isolated REM sleep behavior disorder is a condition where people act out their dreams due to a brain disorder related to the same protein involved in Parkinson's disease and dementia with Lewy bodies. Researchers noticed that patients with isolated REM sleep behavior disorder have brain shrinkage similar to those with Parkinson's disease or dementia, but it's unclear how this shrinkage is connected to the protein causing the disorder. In this study, we used brain scans from people with isolated REM sleep behavior disorder and compared them to healthy people to look at brain shrinkage and how it relates to movement and thinking problems. We also used a computer model to simulate how the problematic protein spreads in the brain, considering brain structure and certain gene activity. Our findings showed that the brain shrinkage in isolated REM sleep behavior disorder patients was linked to how well they could move and think. The computer model, which considered how the brain is connected and the activity of specific genes, accurately mirrored the brain shrinkage seen in patients. This suggests that the way the problematic protein spreads and affects certain brain areas can explain the brain shrinkage seen in early stages of Parkinson's disease and dementia. This research supports the idea that the spread of this protein and vulnerability of certain brain regions are key to understanding these diseases, offering new ways to explore treatments to stop the disease from progressing.
Brain atrophy in prodromal synucleinopathy is shaped by structural connectivity and gene expression
Brain, Volume 145, Issue 9, September 2022, Pages 3162–3178
Differentially targeted seeding reveals unique pathological alpha-synuclein propagation patterns
Brain, Volume 145, Issue 5, June 2022, Pages 1743-1756
Parkinson's disease, a condition marked by the buildup of alpha-synuclein protein in the brain, progresses as this harmful protein spreads between cells, a process that's still not fully understood. In our study, we injected mice with a disease-causing form of alpha-synuclein and tracked how the disease spread across their brains over two years, using a detailed brain map and measurements at several time points. Additionally, we used a computer model to simulate this spread, considering both how brain regions are connected and the levels of alpha-synuclein produced by genes. Our findings revealed that the progression of the disease varied based on the injection site, yet most brain areas were susceptible to the disease, and our computer model accurately mirrored these patterns. This suggests that the brain's connectivity and alpha-synuclein levels play a crucial role in making regions more vulnerable to Parkinson's, hinting at a prion-like spread of the disease. This comprehensive dataset and model offer a new avenue for testing theories on halting the spread of Parkinson's disease within the brain.
We focused on studying isolated REM sleep behavior disorder, which is linked to the development of dementia with Lewy bodies and Parkinson's disease. Our goal was to find markers that could help us predict which individuals with isolated REM sleep behavior disorder would eventually develop these conditions, particularly dementia. By analyzing brain scans and clinical data from patients with confirmed isolated REM sleep behavior disorder, we discovered a specific brain-clinical pattern that indicated a higher likelihood of progressing to dementia with Lewy bodies. This pattern was then applied to a longer study involving more people with isolated REM sleep behavior disorder to see if it could predict their progression to diseases related to synucleinopathy, like dementia with Lewy bodies. Our findings showed that this pattern was effective in predicting the onset of dementia with Lewy bodies, but not Parkinson's disease, suggesting it could be a valuable tool for identifying people withisolated REM sleep behavior disorderat risk of developing dementia.
A prodromal brain-clinical pattern of cognition in synucleinopathies
Annals of Neurology, Volume 89, Issue 2, February 2021, Pages 341–357
Brain atrophy in Parkinson's disease with polysomnography-confirmed REM sleep behavior disorder
Sleep, Volume 42, Issue 6, June 2019
We studied brain changes in people with Parkinson's disease who also have REM sleep behavior disorder, confirmed by polysomnography. We compared people with Parkinson’s disease, half of whom had REM sleep behavior disorder, to healthy people, using advanced brain imaging to look at the thickness, shape, and volume of different brain regions. We found that those with REM sleep behavior disorder had thinner areas in certain parts of the brain and changes in the shape and size of brain structures related to movement control, compared to those without REM sleep behavior disorder and to healthy people. These changes were more pronounced in people with both Parkinson’s disease and REM sleep behavior disorder, indicating more severe brain damage. The study suggests that Parkinson’s patients with REM sleep behavior disorder experience more significant brain deterioration, which could explain why their symptoms are often more severe.
This study investigated brain changes in patients with REM sleep behavior disorder, some of whom also had mild cognitive impairment. Using advanced brain scans and cognitive tests, researchers found that patients with mild cognitive impairment showed significant brain thinning and changes in deep brain structures, while those without mild cognitive impairment mainly had thinning in the frontal part of the brain. These brain alterations were linked to declines in thinking abilities and other functions like smell and color vision. The findings suggest that brain changes in REM sleep behavior disorder patients are closely associated with their cognitive health, highlighting the importance of monitoring cognitive status in understanding neurodegenerative processes.
Cortical and subcortical gray matter bases of cognitive deficits in REM sleep behavior disorder
Neurology, Volume 90, Issue 20, May 2018, Pages e1759–1770
Abnormal Gray Matter Shape, Thickness, and Volume in the Motor Cortico-Subcortical Loop in Idiopathic Rapid Eye Movement Sleep Behavior Disorder: Association with Clinical and Motor Features
Cerebral Cortex, Volume 28, Issue 2, February 2018, Pages 658–671
In this study, we studied people with idiopathic rapid eye movement sleep behavior disorder, which is known to increase the risk of Parkinson’s disease and dementia. We used advanced brain scans and motor skill tests on patients with this disorder and compared them to healthy people. Their findings showed that patients with isolated REM sleep behavior disorder had thinner brain areas and less brain volume in parts of the brain important for controlling movements and emotions. They also found changes in the shape of deep brain structures. These brain changes were linked to problems with movement and other symptoms of isolated REM sleep behavior disorder, indicating that the disorder affects certain brain areas involved in movement control.
In this article, we studied people with a sleep disorder called isolated REM sleep behavior disorder, which can make someone more likely to develop dementia with Lewy bodies or Parkinson's disease. This disorder is linked to problems in how certain parts of the brain work, especially in the front and back areas, but it's unclear exactly why these problems happen. The study involved people with this sleep disorder and healthy people, all of whom had brain scans using advanced MRI techniques to look at the brain's structure and connections. They found that people with the disorder had thinner areas in some parts of the brain and less brain volume in one specific area, but there wasn't a significant difference in the brain's wiring between the two groups. These brain changes in people with the disorder were similar to those seen in dementia with Lewy bodies and Parkinson's disease, providing some clues about the physical changes in the brain associated with this disorder.
Patterns of cortical thinning in idiopathic rapid eye movement sleep behavior disorder
Movement Disorders, Volume 30, Issue 5, April 2015, Pages 680–687
