1,721,046 research outputs found
Nonmotor Symptoms and Natural History of Parkinson's Disease: Evidence From Cognitive Dysfunction and Role of Noninvasive Interventions
No full textParkinson'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
Characteristics and progression of cognitive deficits in progressive supranuclear palsy vs. multiple system atrophy and Parkinson's disease
No full textCognitive impairment is frequent in progressive supranuclear palsy (PSP) and less common in multiple system atrophy (MSA), but characteristics and progression compared with Parkinson's disease (PD) need to be properly defined. We evaluated 35 PSP with Richardson's syndrome (PSP-RS), 30 MSA as well as 65 age-, sex-, and education-matched PD with an extensive clinical and neuropsychological assessment, allowing Level II cognitive diagnosis. Eighteen PSP, 12 MSA and 30 PD had a second evaluation between 12 and 18 months (mean 15 months) after the first assessment. PSP performance at Montreal Cognitive Assessment (MoCA), verbal fluencies (phonemic and semantic tasks), Stroop test (Error and Time), Digit Span Sequencing (DSS), incomplete letters of Visual Object and Space Perception (VOSP) and Benton's Judgment of Line Orientation (JLO) performance were significantly poorer at baseline compared to PD and MSA. Executive, language and visuospatial abilities declined longitudinally in PSP, but not in PD and MSA. After 1.5 year, 16% of PSP converted to dementia. Our study provides evidence that cognitive progression is more severe and rapid in PSP-RS than PD and MSA. Further, we observed that MoCA, verbal fluency (particularly semantic), DSS and Benton's JLO are valuable tests to detect cognitive progression in PSP-RS and may be proposed as possible biomarker to assess efficacy of disease modification strategies
Dynamic functional connectivity changes associated with dementia in Parkinson's disease
Full text linkDynamic functional connectivity captures temporal variations of functional connectivity during MRI acquisition and it may be a suitable method to detect cognitive changes in Parkinson's disease. In this study, we evaluated 118 patients with Parkinson's disease matched for age, sex and education with 35 healthy control subjects. Patients with Parkinson's disease were classified with normal cognition (n = 52), mild cognitive impairment (n = 46), and dementia (n = 20) based on an extensive neuropsychological evaluation. Resting state functional MRI and a sliding-window approach were used to study the dynamic functional connectivity. Dynamic analysis suggested two distinct connectivity 'States' across the entire group: a more frequent, segregated brain state characterized by the predominance of within-network connections, State I, and a less frequent, integrated state with strongly connected functional internetwork components, State II. In Parkinson's disease, State I occurred 13.89% more often than in healthy control subjects, paralleled by a proportional reduction of State II. Parkinson's disease subgroups analyses showed the segregated state occurred more frequently in Parkinson's disease dementia than in mild cognitive impairment and normal cognition groups. Further, patients with Parkinson's disease dementia dwelled significantly longer in the segregated State I, and showed a significant lower number of transitions to the strongly interconnected State II compared to the other subgroups. Our study indicates that dementia in Parkinson's disease is characterized by altered temporal properties in dynamic connectivity. In addition, our results show that increased dwell time in the segregated state and reduced number of transitions between states are associated with presence of dementia in Parkinson's disease. Further studies on dynamic functional connectivity changes could help to better understand the progressive dysfunction of networks between Parkinson's disease cognitive states
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The contribution of beta-amyloid to dementia in Lewy body diseases: a 1-year follow-up study
Full text linkDementia in Lewy Body Diseases (Parkinson's disease and dementia with Lewy Bodies) affects progression of disabilities, quality of life and well-being. Understanding its pathogenetic mechanisms is critical to properly implement disease-modifying strategies. It has been hypothesized that synuclein- and amyloid-pathology act synergistically aggravating cognitive decline in elderly patients but their precise contribution to dementia is debated. In this study, we aimed at exploring if presence of amyloid deposits influences clinical, cognitive and neuroanatomical correlates of mental decline in a cohort of 40 Parkinson's disease patients with normal cognition (n = 5), mild cognitive impairment (n = 22), and dementia (n = 13) as well as in Dementia with Lewy Bodies (n = 10). Patients underwent simultaneous 3 T PET/MRI with [18F]-flutemetamol and were assessed with an extensive baseline motor and neuropsychological examination, which allowed level II diagnosis of mild cognitive impairment and dementia. The role of amyloid positivity on each cognitive domain, and on the rate of conversion to dementia at 1-year follow-up was explored. A Kaplan Meier and the Log Rank (Mantel-Cox) test were used to assess the pairwise differences in time-to-develop dementia in Parkinson's disease patients with and without significant amyloidosis. Furthermore, the presence of an Alzheimer's dementia-like morphological pattern was evaluated using visual and automated assessment of T1-weighted and T2-weighted MRI images. We observed similar percentage of amyloid deposits in Parkinson's disease dementia and dementia with Lewy Bodies cohorts (50% in each group) with an overall prevalence of 34% of significant amyloid depositions in Lewy Body Diseases. PET amyloid positivity was associated with worse global cognition (Montreal Cognitive Assessment and Mini Mental State Examination), executive and language difficulties. At 12-month follow-up, amyloid positive Parkinson's disease patients were more likely to have become demented than those without amyloidosis. Moreover, there was no difference in the presence of an Alzheimer's disease-like atrophy pattern and in vascular load (at Fazekas scale) between Lewy Body Diseases with and without significant amyloid deposits. Our findings suggest that in Lewy Body Diseases, amyloid deposition enhances cognitive deficits, particularly attention-executive and language dysfunctions. However, the large number of patients without significant amyloid deposits among our cognitively impaired patients indicates that synuclein pathology itself plays a critical role in the development of dementia in Lewy Body Diseases
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