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Background: Higuchi's fractal dimension (FD) captures brain dynamics complexity and may be a promising method to analyze resting‐state functional magnetic resonance imaging (fMRI) data and detect the neuronal interaction complexity underlying Parkinson's disease (PD) cognitive decline. Objectives: The aim was to compare FD with a more established index of spontaneous neural activity, the fractional amplitude of low‐frequency fluctuations (fALFF), and identify through machine learning (ML) models which method could best distinguish across PD‐cognitive states, ranging from normal cognition (PD‐NC), mild cognitive impairment (PD‐MCI) to dementia (PDD). Finally, the aim was to explore correlations between fALFF and FD with clinical and cognitive PD features. Methods: Among 118 PD patients age‐, sex‐, and education matched with 35 healthy controls, 52 were classified with PD‐NC, 46 with PD‐MCI, and 20 with PDD based on an extensive cognitive and clinical evaluation. fALFF and FD metrics were computed on rs‐fMRI data and used to train ML models. Results: FD outperformed fALFF metrics in differentiating between PD‐cognitive states, reaching an overall accuracy of 78% (vs. 62%). PD showed increased neuronal dynamics complexity within the sensorimotor network, central executive network (CEN), and default mode network (DMN), paralleled by a reduction in spontaneous neuronal activity within the CEN and DMN, whose increased complexity was strongly linked to the presence of dementia. Further, we found that some DMN critical hubs correlated with worse cognitive performance and disease severity. Conclusions: Our study indicates that PD‐cognitive decline is characterized by an altered spontaneous neuronal activity and increased temporal complexity, involving the CEN and DMN, possibly reflecting an increased segregation of these networks. Therefore, we propose FD as a prognostic biomarker of PD‐cognitive decline. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Enlargement of the third ventricle has been reported in atypical parkinsonism. We investigated whether the measurement of third ventricle width could distinguish Parkinson's disease (PD) from progressive supranuclear palsy (PSP). Methods: We assessed a new MR T1‐weighted measurement (third ventricle width/internal skull diameter) in a training cohort of 268 participants (98 PD, 73 PSP, 98 controls from our center) and in a testing cohort of 291 participants (82 de novo PD patients and 133 controls from the Parkinson's Progression Markers Initiative, 76 early‐stage PSP from an international research group). PD diagnosis was confirmed after a 4‐year follow‐up. Diagnostic performance of the third ventricle/internal skull diameter was assessed using receiver operating characteristic curve with bootstrapping; the area under the curve of the training cohort was compared with the area under the curve of the testing cohort using the De Long test. Results: In both cohorts, third ventricle/internal skull diameter values did not differ between PD and controls but were significantly lower in PD than in PSP patients (P < 0.0001). In PD, third ventricle/internal skull diameter values did not change significantly between baseline and follow‐up evaluation. Receiver operating characteristic analysis accurately differentiated PD from PSP in the training cohort (area under the curve, 0.94; 95% CI, 91.1–97.6; cutoff, 5.72) and in the testing cohort (area under the curve, 0.91; 95% CI, 87.0–97.0; cutoff,: 5.88), validating the generalizability of the results. Conclusion: Our study provides a new reliable and validated MRI measurement for the early differentiation of PD and PSP. The simplicity and generalizability of this biomarker make it suitable for routine clinical practice and for selection of patients in clinical trials worldwide. © 2020 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by motor and nonmotor symptoms (NMS). Several subsequent studies substantiate the great functional burden related to NMS, their progression, and negative effect on quality of life in PD. Additional evidence indicates interesting relationships between striatal dopaminergic function and NMS. The basal ganglia are implicated in the modulation and integration of sensory information and pain, bladder function is under control of both inhibitory (D1) and facilitatory (D2) dopaminergic inputs, finally reduced dopaminergic activity in the mesocortical and mesolimbic pathways is involved in the development of several NMS including mood, motivational, and cognitive alterations. Some NMS fluctuate in response to dopaminergic treatment and are relieved by dopamine replacement therapy, other are insensitive to current therapeutic strategies. The relation among the overall disease complications, perhaps the most important for PD patients and family members' well-being and functionality is dementia that affects most PD patients over the course of disease. Specific pharmacological treatment is lacking, and alternative approaches have been implemented to improve everyday functionality and quality of life. The state of the art suggests that cognitive rehabilitation in PD is possible and may either increase performance or preserve cognitive level over the time. However, it is also evident that cognitive abnormalities in PD are heterogeneous and we still do not have biomarkers to detect early patients at risk for dementia. Cognitive dysfunction is one the most prevalent NMS and is a clinically and functionally important disease milestone. Given the available clinical and imaging evidence it is possible to use cognition to model NMS progression and design nonpharmacological interventions. In this chapter we will address the use of cognitive rehabilitation and noninvasive brain stimulation techniques to modulate cognitive performance and rescue connectivity in affected brain circuitry., (© 2017 Elsevier Inc. All rights reserved.)