Environmental Exposures and Parkinson's Disease.

Parkinson's disease (PD) affects millions around the world. The Braak hypothesis proposes that in PD a pathologic agent may penetrate the nervous system via the olfactory bulb, gut, or both and spreads throughout the nervous system. The agent is unknown, but several environmental exposures have been associated with PD. Here, we summarize and examine the evidence for such environmental exposures. We completed a comprehensive review of human epidemiologic studies of pesticides, selected industrial compounds, and metals and their association with PD in PubMed and Google Scholar until April 2016. Most studies show that rotenone and paraquat are linked to increased PD risk and PD-like neuropathology. Organochlorines have also been linked to PD in human and laboratory studies. Organophosphates and pyrethroids have limited but suggestive human and animal data linked to PD. Iron has been found to be elevated in PD brain tissue but the pathophysiological link is unclear. PD due to manganese has not been demonstrated, though a parkinsonian syndrome associated with manganese is well-documented. Overall, the evidence linking paraquat, rotenone, and organochlorines with PD appears strong; however, organophosphates, pyrethroids, and polychlorinated biphenyls require further study. The studies related to metals do not support an association with PD

Fall Prediction and Prevention Systems: Recent Trends, Challenges, and Future Research Directions.

Fall prediction is a multifaceted problem that involves complex interactions between physiological, behavioral, and environmental factors. Existing fall detection and prediction systems mainly focus on physiological factors such as gait, vision, and cognition, and do not address the multifactorial nature of falls. In addition, these systems lack efficient user interfaces and feedback for preventing future falls. Recent advances in internet of things (IoT) and mobile technologies offer ample opportunities for integrating contextual information about patient behavior and environment along with physiological health data for predicting falls. This article reviews the state-of-the-art in fall detection and prediction systems. It also describes the challenges, limitations, and future directions in the design and implementation of effective fall prediction and prevention systems

Structural MRI Correlates of Episodic Memory Processes in Parkinson's Disease Without Mild Cognitive Impairment.

BackgroundChanges in episodic memory are common early in Parkinson's disease (PD) and may be a risk factor for future cognitive decline. Although medial temporal lobe (MTL) memory and frontostriatal (FS) executive systems are thought to play different roles in distinct components of episodic memory impairment in PD, no study has investigated whether different aspects of memory functioning are differentially associated with MTL and FS volumes in nondemented patients without mild cognitive impairment (PD-woMCI).ObjectivesThe present study investigated MRI markers of different facets of memory functioning in 48 PD-woMCI patients and 42 controls.MethodsRegional volumes were measured in structures comprising the MTL and FS systems and then correlated with key indices of memory from the California Verbal Learning Test.ResultsIn PD-woMCI patients, memory was impaired only for verbal learning, which was not associated with executive, attention/working memory, or visuospatial functioning. Despite an absence of cortical atrophy, smaller right MTL volumes in patients were associated with poorer verbal learning, long delayed free recall, long delayed cued recall, and recognition memory hits and false positives. Smaller right pars triangularis (inferior frontal) volumes were also associated with poorer long delayed cued recall and recognition memory hits. These relationships were not found in controls.ConclusionsThe findings indicate that MTL volumes are sensitive to subtle changes in almost all facets of memory in PD-woMCI, whereas FS volumes are sensitive only to memory performances in cued-testing formats

Neuropathologic basis of frontotemporal dementia in progressive supranuclear palsy.

BackgroundProgressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by neuronal loss in the extrapyramidal system with pathologic accumulation of tau in neurons and glia. The most common clinical presentation of PSP, referred to as Richardson syndrome, is that of atypical parkinsonism with vertical gaze palsy, axial rigidity, and frequent falls. Although cognitive deficits in PSP are often ascribed to subcortical dysfunction, a subset of patients has dementia with behavioral features similar to the behavioral variant of frontotemporal dementia. In this study we aimed to identify the clinical and pathological characteristics of PSP presenting with frontotemporal dementia.MethodsIn this study, we compared clinical and pathologic characteristics of 31 patients with PSP with Richardson syndrome with 15 patients with PSP with frontotemporal dementia. For pathological analysis, we used semiquantitative methods to assess neuronal and glial lesions with tau immunohistochemistry, as well image analysis of tau burden using digital microscopic methods.ResultsWe found greater frontal and temporal neocortical neuronal tau pathology in PSP with frontotemporal dementia compared with PSP with Richardson syndrome. White matter tau pathology was also greater in PSP with frontotemporal dementia than PSP with Richardson syndrome. Genetic and demographic factors were not associated with atypical distribution of tau pathology in PSP with frontotemporal dementia.ConclusionsThe results confirm the subset of cognitive-predominant PSP mimicking frontotemporal dementia in PSP. PSP with frontotemporal dementia has distinct clinical features that differ from PSP with Richardson syndrome, as well as differences in distribution and density of tau pathology. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

Examining the Motor Phenotype of Patients with Both Essential Tremor and Parkinson's Disease

Background: The subset of patients with essential tremor (ET) that develops Parkinson's disease (PD) has not been fully clinically characterized. Methods: Motor features were retrospectively reviewed in 18 ET patients who developed PD (ET→PD), 20 ET and 30 PD patients with similar ages and disease durations. Results: Fewer ET→PD than ET patients had widespread postural and/or action tremor (2/17 [11.8%] vs. 11/17 [64.7%]; p“Š=“Š0.001) and marginally fewer had cerebellar signs (1/15 [6.7%] vs. 6/18 [33.3%], p“Š=“Š0.06). ET→PD patients required fewer ET medications than did their counterparts with ET (p“Š=“Š0.001). ET→PD patients and PD patients did not differ in UPDRS, Hoehn and Yahr, or Schwab and England scores (each p≥0.14). Discussion: ET patients who develop PD may have distinct pre-PD motor features compared to their counterparts with ET who do not develop co-existing PD. Prospective studies are needed to evaluate the predictive value of these clinical features for the emergence of PD

Examining the Motor Phenotype of Patients with Both Essential Tremor and Parkinson's Disease

Background: The subset of patients with essential tremor (ET) that develops Parkinson's disease (PD) has not been fully clinically characterized. Methods: Motor features were retrospectively reviewed in 18 ET patients who developed PD (ET→PD), 20 ET and 30 PD patients with similar ages and disease durations. Results: Fewer ET→PD than ET patients had widespread postural and/or action tremor (2/17 [11.8%] vs. 11/17 [64.7%]; p“Š=“Š0.001) and marginally fewer had cerebellar signs (1/15 [6.7%] vs. 6/18 [33.3%], p“Š=“Š0.06). ET→PD patients required fewer ET medications than did their counterparts with ET (p“Š=“Š0.001). ET→PD patients and PD patients did not differ in UPDRS, Hoehn and Yahr, or Schwab and England scores (each p≥0.14). Discussion: ET patients who develop PD may have distinct pre-PD motor features compared to their counterparts with ET who do not develop co-existing PD. Prospective studies are needed to evaluate the predictive value of these clinical features for the emergence of PD

Rapidly progressive atypical parkinsonism associated with frontotemporal lobar degeneration and motor neuron disease

Objective To report the rare but distinct clinical and neuropathological phenotype of non-familial, rapidly progressive parkinsonism and dementia associated with frontotemporal lobar degeneration with motor neuron disease (FTLD-MND). Methods Subjects included two 70-year-old women presenting with rapidly progressive severe postural instability, axial-predominant parkinsonism, oculomotor dysfunction and frontal-predominant dementia with language impairment and pseudobulbar palsy. One had diffuse weakness without signs of lower motor neuron disease. Post-mortem evaluations included immunohistochemistry with antiphospho-TAR DNA-binding protein 43 (TDP-43) and genetic analysis of the TARDBP and PGRN genes. Results Subjects died within 14 months from symptom onset. TDP-43-positive neuronal intracytoplasmic inclusions were prominent in the primary motor cortex, granule cell layer of the hippocampus, and several cranial and spinal cord nuclei. TDP-43 globular glial inclusions (GGI) were identified in one case. There were no mutations in PGRN or TARDBP genes. Conclusions FTLD-MND due to TDP-43-proteinopathy should be considered in patients with rapidly progressive parkinsonism and dementia phenotype, especially when aphasia and/or weakness are also present