Abstract
Parkinson's disease (PD) is a complex neurodegenerative disorder that manifests through hallmark motor symptoms, often accompanied by a range of non-motor symptoms. There is a putative delay between the onset of the neurodegenerative process, marked by the death of dopamine-producing cells, and the onset of motor symptoms, creating an urgent need to develop biomarkers that may yield early PD detection. Neuroimaging offers a non-invasive approach to examining the potential utility of a vast number of functional and structural brain characteristics as biomarkers. We present a statistical framework for analyzing neuroimaging data from multiple modalities to determine features that reliably distinguish PD patients from healthy control (HC) subjects. Our approach builds on elastic net, performing regularization and variable selection, while introducing additional criteria centering on parsimony and reproducibility. We apply our method to data from 42 subjects (28 PD patients and 14 HC). Our approach demonstrates extremely high accuracy, assessed via cross-validation, and isolates brain regions that are implicated in the neurodegenerative PD process.
Highlights
Parkinson’s disease (PD) is a devastating, progressive movement disorder affecting 7–10 million individuals worldwide (Parkinson’s Disease Foundation, 2015)
The hallmark pathology of PD is the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), but the disease manifests with a diversity of symptoms referable to multi-system neuropathology
Our analysis provides a broad multimodal view of prevailing alterations in PD, which serve as accurate and reliable predictors
Summary
Parkinson’s disease (PD) is a devastating, progressive movement disorder affecting 7–10 million individuals worldwide (Parkinson’s Disease Foundation, 2015). PD usually affects people over 50 years of age, but a subset of patients experience early onset. The hallmark pathology of PD is the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), but the disease manifests with a diversity of symptoms referable to multi-system neuropathology. Braak et al (2003) posit a process of phased pathology of PD, which suggests that early neurodegeneration occurs in lower brainstem structures and progresses in ascending fashion, in particular affecting the locus coeruleus in Stage II and SNpc in Stage III. The putative delay in the onset of motor symptoms leading to PD diagnosis is portrayed, and the corresponding neurodegeneration occurring throughout this pre-motor period represents a missed opportunity for early therapeutic intervention that may significantly slow or halt the progression of PD related decline The putative delay in the onset of motor symptoms leading to PD diagnosis is portrayed in Figure 1, and the corresponding neurodegeneration occurring throughout this pre-motor period represents a missed opportunity for early therapeutic intervention that may significantly slow or halt the progression of PD related decline
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