Environmental Exposures and Parkinson's Disease Nandipati, Sirisha; Litvan, Irene
International journal of environmental research and public health,
09/2016, Volume:
13, Issue:
9
Journal Article
Peer reviewed
Open access
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.
A diagnosis of motor Parkinson's disease (PD) is preceded by a prolonged premotor phase with accumulating neuronal damage. Here we examined the temporal relation between α-synuclein (α-syn) T cell ...reactivity and PD. A longitudinal case study revealed that elevated α-syn-specific T cell responses were detected prior to the diagnosis of motor PD, and declined after. The relationship between T cell reactivity and early PD in two independent cohorts showed that α-syn-specific T cell responses were highest shortly after diagnosis of motor PD and then decreased. Additional analysis revealed significant association of α-syn-specific T cell responses with age and lower levodopa equivalent dose. These results confirm the presence of α-syn-reactive T cells in PD and show that they are most abundant immediately after diagnosis of motor PD. These cells may be present years before the diagnosis of motor PD, suggesting avenues of investigation into PD pathogenesis and potential early diagnosis.
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.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Summary Progressive supranuclear palsy (PSP), previously believed to be a common cause of atypical parkinsonism, is now recognised as a range of motor and behavioural syndromes that are associated ...with a characteristic 4-repeat tau neuropathology. New research criteria that recognise early presentations of PSP and operationalise diagnosis of the full spectrum of clinical phenotypes have been reported. The Movement Disorders Society PSP diagnostic criteria include syndromes with few or mild symptoms that are suggestive of underlying PSP pathology and could provide an opportunity for earlier therapeutic interventions in the future. These criteria also include definitions for variant PSP syndromes with different patterns of movement, language, or behavioural features than have been conclusively associated with PSP pathology. Data from new diagnostic biomarkers can be combined with the clinical features of disease to increase the specificity of the new criteria for underlying PSP pathology. Because PSP is associated with tau protein abnormalities, there is growing interest in clinical trials of new tau-directed therapies. These therapies are hypothesised to have disease-modifying effects by reducing the concentration of toxic forms of tau in the brain or by compensating for loss of tau function. Since tau pathology is also central to Alzheimer's disease and chronic traumatic encephalopathy, a successful tau therapeutic for PSP might inform treatment of other neurodegenerative diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Summary A dopaminergic deficiency in patients with Parkinson's disease (PD) causes abnormalities of movement, behaviour, learning, and emotions. The main motor features (ie, tremor, rigidity, and ...akinesia) are associated with a deficiency of dopamine in the posterior putamen and the motor circuit. Hypokinesia and bradykinesia might have a dual anatomo-functional basis: hypokinesia mediated by brainstem mechanisms and bradykinesia by cortical mechanisms. The classic pathophysiological model for PD (ie, hyperactivity in the globus pallidus pars interna and substantia nigra pars reticulata) does not explain rigidity and tremor, which might be caused by changes in primary motor cortex activity. Executive functions (ie, planning and problem solving) are also impaired in early PD, but are usually not clinically noticed. These impairments are associated with dopamine deficiency in the caudate nucleus and with dysfunction of the associative and other non-motor circuits. Apathy, anxiety, and depression are the main psychiatric manifestations in untreated PD, which might be caused by ventral striatum dopaminergic deficit and depletion of serotonin and norepinephrine. In this Review we discuss the motor, cognitive, and psychiatric manifestations associated with the dopaminergic deficiency in the early phase of the parkinsonian state and the different circuits implicated, and we propose distinct mechanisms to explain the wide clinical range of PD symptoms at the time of diagnosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
With the potential development of new disease-modifying Alzheimer's disease (AD) therapies, simple, widely available screening tests are needed to identify which individuals, who are experiencing ...symptoms of cognitive or behavioral decline, should be further evaluated for initiation of treatment. A blood-based test for AD would be a less invasive and less expensive screening tool than the currently approved cerebrospinal fluid or amyloid β positron emission tomography (PET) diagnostic tests. We examined whether plasma tau phosphorylated at residue 181 (pTau181) could differentiate between clinically diagnosed or autopsy-confirmed AD and frontotemporal lobar degeneration. Plasma pTau181 concentrations were increased by 3.5-fold in AD compared to controls and differentiated AD from both clinically diagnosed (receiver operating characteristic area under the curve of 0.894) and autopsy-confirmed frontotemporal lobar degeneration (area under the curve of 0.878). Plasma pTau181 identified individuals who were amyloid β-PET-positive regardless of clinical diagnosis and correlated with cortical tau protein deposition measured by
F-flortaucipir PET. Plasma pTau181 may be useful to screen for tau pathology associated with AD.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary To date, there have been few systematic attempts to provide a standard operating procedure for the neuropathological diagnosis of Parkinson's disease (PD). Pathological examination cannot ...classify the clinical syndrome with certainty; therefore, the neuropathological diagnosis is, at best, a probability statement. The neuropathological diagnosis of parkinsonism has become increasingly based on fundamental molecular underpinnings, with recognition that the genetics of parkinsonism is heterogeneous and includes disorders that are associated with and without Lewy bodies. The advent of α-synuclein immunohistochemistry has substantially improved the ability to identify Lewy pathology, particularly cortical Lewy bodies and smaller aggregates within processes and the neuropil. In this Review we discuss the diagnostic criteria for the neuropathological assessment of PD. These criteria are provisional and need to be validated through an iterative process that could help with their refinement. Additionally, we suggest future directions for neuropathology research on PD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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