Simulating the progression of brain structural alterations in Parkinson’s disease

Abstract

Considering brain structural alterations as neurodegenerative consequences of Parkinson's disease (PD), we sought to infer the progression of PD via the ordering of brain structural alterations from cross-sectional MRI observations. Having measured cortical thinning in gray matter (GM) regions and disintegrity in white matter (WM) regions as MRI markers of structural alterations for 130 patients with PD (69 ± 10 years, 72 men), stochastic simulation based on the probabilistic relationship between the brain regions was conducted to infer the ordering of structural alterations across all brain regions and the staging of structural alterations according to changes in clinical status. The ordering of structural alterations represented WM disintegrity tending to occur earlier than cortical thinning. The staging of structural alterations indicated structural alterations happening mostly before major disease complications such as postural instability and dementia. Later disease states predicted by the sequence of structural alterations were significantly related to more severe clinical symptoms. The relevance of the ordering of brain structural alterations to the severity of clinical symptoms suggests the clinical feasibility of predicting PD progression states.

Plantamajoside Alleviates Substantia Nigra Damage in Parkinson’s Disease Mice by Inhibiting HDAC2/MAPK Signaling and Reducing Microglia Polarization

“…Parkinson’s disease (PD) is known as a common neurodegenerative disease with major clinical manifestations of motor dysfunction, such as cognitive impairment. , PD usually occurs in people with the age of over 65 and is caused by the progressive degeneration of dopaminergic neurons in the substantia nigra (SN). − The cause of PD is still elusive. Previous studies have demonstrated that the pathogenesis of PD is related to aging factors, environmental factors, genetic factors, oxidative stress, free radical formation, and associated nerve inflammation, but recent evidence suggests that chronic nerve inflammation caused by microglia activation may be important in the degenerative process. , Activated microglia are a major factor in neuroinflammation and dopaminergic neurodegeneration. , Overactivation of microglia results in the release of several neurotoxic factors, which contributes to the process of dopaminergic neurodegeneration. , Therefore, inhibition of microglial activation may contribute to the treatment and prevention of PD. In addition, finding more drugs is needed to combat this disease.…”

“…6,7 Activated microglia are a major factor in neuroinflammation and dopaminergic neurodegeneration. 8,9 Overactivation of microglia results in the release of several neurotoxic factors, which contributes to the process of dopaminergic neurodegeneration. 10,11 Therefore, inhibition of microglial activation may contribute to the treatment and prevention of PD.…”