ArticleLiterature Review

Epidemiology of Parkinson disease

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Abstract

The causes of Parkinson's disease (PD), the second most common neurodegenerative disorder, are still largely unknown. Current thinking is that major gene mutations cause only a small proportion of all cases and that in most cases, non-genetic factors play a part, probably in interaction with susceptibility genes. Numerous epidemiological studies have been done to identify such non-genetic risk factors, but most were small and methodologically limited. Larger, well-designed prospective cohort studies have only recently reached a stage at which they have enough incident patients and person-years of follow-up to investigate possible risk factors and their interactions. In this article, we review what is known about the prevalence, incidence, risk factors, and prognosis of PD from epidemiological studies.

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... and then we used Eq. (2) to calculate values of the Laplacian mask for the entire averaged interval. Finally, all the calculated values in the interval of the segment for given auditory task were averaged to obtain a single value, which we used as a classification feature. ...
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One of the most common diseases that affects human brain is Parkinson’s disease. Detection of Parkinson’s disease (PD) poses a serious challenge. Robust methods for feature extraction allowing separation between the electroencephalograms (EEG) of healthy subjects and PD patients are required. We used the EEG records of healthy subjects and PD patients which were subject to auditory tasks. We used the common spatial patterns (CSP) and Laplacian mask as methods to allow robust selection and extraction of features. We used the derived CSP whitening matrix to determine those channels that are the most promising in the terms of differentiating between EEGs of healthy controls and of PD patients. Using the selection of features calculated using the CSP we managed to obtain the classification accuracy of 85% when classifying EEG records belonging to groups of controls or PD patients. Using the features calculated using the Laplacian operator we obtained the classification accuracy of 90%. Diagnosing the PD in early stages using EEG is possible. The CSP proved to be a promising technique to detect informative channels and to separate between the groups. Use of the combination of features calculated using the Laplacian offers good separability between the two groups.
... First, the thrashing of SNpc neurons gives rise to striatal DA deficiency, which is accountable for the foremost symptoms of PD. Second, the replacement of striatal A. Arshad and U. Bacha DA through the oral administration of the DA precursor levodopa (L-3,4dihydroxyphenylalanine) assuages most of these symptoms (Dauer and Przedborski 2003;de Lau and Breteler 2006;Davie 2008). ...
... Parkinson's disease (PD) is the second most common neurodegenerative disease [1]. The deposition of Lewy bodies formed by the aggregation of α-synuclein in the midbrain substantia nigra is the pathological hallmark of PD [2]. ...
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Full-text available
Patients with Parkinson’s disease (PD) exhibit distinct gut microbiota, which may promote gut-derived inflammation. Rifaximin is a nonabsorbable antibiotic that can modify gut microbiota. The present study investigated the effect of rifaximin on gut microbiota and inflammation status in PD. The study examined the effect of long-term rifaximin treatment on in vivo transgenic PD mice (MitoPark) and short-term rifaximin treatment on patients with PD. Rifaximin treatment caused a significant change in gut microbiota in the transgenic PD mice; in particular, it reduced the relative abundance of Prevotellaceae UCG-001 and increased the relative abundance of Bacteroides, Muribaculum, and Lachnospiraceae UCG-001. Rifaximin treatment attenuated serum interleukin-1β, interleukin-6 and tumor necrosis factor-α, claudin-5 and occludin, which indicated the reduction of systemic inflammation and the protection of the blood–brain barrier integrity. The rifaximin-treated MitoPark mice exhibited better motor and memory performance than did the control mice, with lower microglial activation and increased neuronal survival in the hippocampus. In the patients with PD, 7-day rifaximin treatment caused an increase in the relative abundance of Flavonifractor 6 months after treatment, and the change in plasma proinflammatory cytokine levels was negatively associated with the baseline plasma interleukin-1α level. In conclusion, the present study demonstrated that rifaximin exerted a neuroprotective effect on the transgenic PD mice by modulating gut microbiota. We observed that patients with higher baseline inflammation possibly benefited from rifaximin treatment. With consideration for the tolerability and safety of rifaximin, randomized controlled trials should investigate the disease-modification effect of long-term treatment on select patients with PD.
... Parkinson's disease (PD) is the commonest movement disorder caused by progressive neurodegenerative processes with an incidence of 8-18,6/100,000 person-years (de Lau and Breteler, 2006). It is characterized by motor symptoms as bradykinesia, rigidity, and tremor; often preceded by or associated with severe non-motor symptoms such as sleep disturbances, dysautonomia, sensory changes (affecting sense of smell and colour vision), mood disorders, chronic pain, and cognitive dysfunction (Chaudhuri and Schapira, 2009;Martinez-Martin et al., 2007). ...
Article
Study objectives Sleep disturbances and altered sleep macrostructure are common in Parkinson's disease (PD). Few studies have addressed the changes in sleep spindle (SS) properties in this movement disorder so far. SS seem to be fundamental of both sleep architecture and memory consolidation. The aim of our comparative study was to investigate the changes of SS characteristics in PD, and reveal the relationship between SS properties and cognitive function. Methods We investigated 20 PD patients and 18 age-matched controls. All participants underwent a 24-hour-long polygraphic EEG recording after extensive clinical investigation. We detected slow and fast SS properties automatically using individual adjusting method (IAM). The data were statistically evaluated. Results We found significantly lower fast spindle amplitude in PD comparing with controls. We did not find significant differences in SS densities, duration and oscillatory frequency between the groups. We detected significant positive correlation between fast SS amplitude and memory in PD, and between fast SS density and retrograde memory in controls. The total Addenbrooke's cognitive score correlated negatively with slow SS density and duration in controls. Conclusions By the time clinical diagnosis of PD is established, the pathological process is already spreading. Changes in sleep macrostructure and SS properties might become a useful biomarker of the neurodegenerative process in PD. In addition, decreased fast SS amplitude might predict further cognitive deterioration and indicate early involvement of corresponding cortical area. Our study results strengthen the importance of EEG examination in PD, and the use of IAM method in SS analysis.
... Parkinson's disease PD is the second most common neurodegenerative disease after Alzheimer's disease, and it is expected to place an increasing medical and economic burden on society as the population ages (de Lau and Breteler, 2006). Typical PD symptoms are resting tremor, rigidity, bradykinesia, postural instability (Aarsland et al., 2017), and pathology characterized by degeneration and death of dopaminergic neurons in the substantia nigra (Obeso et al., 2008). ...
Article
Objective: Evidence from observational studies suggests that Sjögren's syndrome (SS) may contribute to an elevated risk of Parkinson's disease (PD) and dementia. However, few studies have been undertaken to summarize and assess the consistency of the data quantitatively. Therefore, we evaluated the risk of dementia and PD in SS patients through a systematic review and meta-analysis approach. Methods: Two reviewers independently conducted a systematic search of PubMed, Embase, and Web of Science databases (updated to February 14, 2022) to identify published literature on the association between SS and dementia or PD. The risk estimates of dementia or PD in patients with SS were pooled using fixed or random-effects models. Results: Of the 631 studies initially searched, 10 were eventually included. Pooled results suggested that the risk of developing dementia significantly increased in patients with SS (HR = 1.24, 95% CI: 1.15-1.33, P < 0.001), and such risk in females with SS was similar to that in males. The risk of PD was 1.36 times higher in SS (HR = 1.36, 95% CI: 1.23-1.50, P < 0.001). The association between SS and PD risk appeared to occur primarily in female patients (female: HR = 1.28, 95% CI: 1.21-1.35; P < 0.001 vs. male: HR = 1.00, 95% CI: 0.87-1.16, P = 0.962, respectively). No significant effect of age was observed on the risk of developing PD and dementia in SS patients. Conclusion: Our study supports that people with SS are at higher risk of PD and dementia than the general population. Further studies are needed to elucidate the underlying mechanisms and to assess whether interventions for SS have the potential to affect dementia and PD development.
... Parkinson disease (PD) is a neurodegenerative disease, the second most common worldwide after Alzheimer's disease [1]. The conjugation of symptoms such as bradykinesia and postural instability generates new gait patterns in these patients characterized by a decrease in walking speed and stride length in addition to a marked trunk flexion [2,3]. ...
Article
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People with Parkinson disease suffer from a loss of dopaminergic neurons, which are involved in walking speed. Currently, virtual reality (VR) has emerged as a useful tool for the rehabilitation of people with neurological diseases, optimizing results in balance and gait. This review aimed to evaluate the effectiveness of VR or video games (through face-to-face sessions and not telerehabilitation) in improving walking speed and other spatio-temporal parameters of gait, balance, and quality of life in patients with Parkinson disease. A bibliographic search was carried out in the MEDLINE, Web of Science, Scopus, and PEDro databases. This systematic review adhered to the PRISMA guideline statement and was registered in PROSPERO (CRD42020180836). From a total of 119 records, 5 studies met the inclusion criteria for qualitative analysis, of which 3 contributed to the meta-analysis; inconclusive findings were found on gait speed, balance, and quality of life after the use of non-immersive VR systems face-to-face. A greater number of studies are necessary, with a greater number of participants, to differentiate between those VR specific systems (specifically designed for rehabilitation) from commercial video games, including immersive systems, and obtain more conclusive evidence. Furthermore, it would be interesting to compare the administration of this treatment in person versus its administration via telerehabilitation, which will help plan treatment programs.
... Parkinson's disease is-after Alzheimer's disease-the second most common neurodegenerative disorder affecting 1-2% of the general population over the age of 60 years with increasing incidences in industrialized populations. 1,2 Currently, there is no curative or preventive therapy available for Parkinson's disease, which is in part attributable to our lack of understanding its aetiology. More than 90% of the disease is genetically complex, i.e. it is determined by a combination and likely interaction of multiple genetic, environmental, lifestyle and other intrinsic risk factors. ...
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Dysregulation of microRNA gene expression has been implicated in many neurodegenerative diseases, including Parkinson’s disease. However, the individual dysregulated microRNAs remain largely unknown. Previous meta-analyses have highlighted several microRNAs being differentially expressed in post-mortem Parkinson’s disease and Alzheimer's disease brains versus controls, but they were based on small sample sizes. In this study, we quantified the expression of the most compelling Parkinson’s and Alzheimer’s disease microRNAs from these meta-analyses (‘candidate miRNAs’) in one of the largest Parkinson’s/Alzheimer’s disease case–control post-mortem brain collections available (n = 451), thereby quadruplicating previously investigated sample sizes. Parkinson’s disease candidate microRNA hsa-miR-132-3p was differentially expressed in our Parkinson’s (P = 4.89E−06) and Alzheimer’s disease samples (P = 3.20E−24) compared with controls. Alzheimer’s disease candidate microRNAs hsa-miR-132-5p (P = 4.52E−06) and hsa-miR-129-5p (P = 0.0379) were differentially expressed in our Parkinson’s disease samples. Combining these novel data with previously published data substantially improved the statistical support (α = 3.85E−03) of the corresponding meta-analyses, clearly implicating these microRNAs in both Parkinson’s and Alzheimer’s disease. Furthermore, hsa-miR-132-3p/-5p (but not hsa-miR-129-5p) showed association with α-synuclein neuropathological Braak staging (P = 3.51E−03/P = 0.0117), suggesting that hsa-miR-132-3p/-5p play a role in α-synuclein aggregation beyond the early disease phase. Our study represents the largest independent assessment of recently highlighted candidate microRNAs in Parkinson’s and Alzheimer’s disease brains, to date. Our results implicate hsa-miR-132-3p/-5p and hsa-miR-129-5p to be differentially expressed in both Parkinson’s and Alzheimer’s disease, pinpointing shared pathogenic mechanisms across these neurodegenerative diseases. Intriguingly, based on publicly available high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation data, hsa-miR-132 may interact with SNCA messenger RNA in the human brain, possibly pinpointing novel therapeutic approaches in fighting Parkinson’s disease.
... Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting about 1% of the population >60 years of age [15]. The pathological hallmark of PD is the progressive degeneration of dopaminergic neurons in the substantia nigra and striatum [16], ultimately leading to motor (e.g., tremor, akinesia, rigidity, gait impairments) and non-motor (e.g., anxiety, depression, cognitive deficits) symptoms. ...
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Non-Invasive Brain Stimulation (NIBS) techniques, such as transcranial Direct Current Stimulation (tDCS) and repetitive Magnetic Transcranial Stimulation (rTMS), are well-known non-pharmacological approaches to improve both motor and non-motor symptoms in patients with neurodegenerative disorders. Their use is of particular interest especially for the treatment of cognitive impairment in Alzheimer’s Disease (AD), as well as axial disturbances in Parkinson’s (PD), where conventional pharmacological therapies show very mild and short-lasting effects. However, their ability to interfere with disease progression over time is not well understood; recent evidence suggests that NIBS may have a neuroprotective effect, thus slowing disease progression and modulating the aggregation state of pathological proteins. In this narrative review, we gather current knowledge about neuroprotection and NIBS in neurodegenerative diseases (i.e., PD and AD), just mentioning the few results related to stroke. As further matter of debate, we discuss similarities and differences with Deep Brain Stimulation (DBS)—induced neuroprotective effects, and highlight possible future directions for ongoing clinical studies.
... The aim of this exploratory study was to investigate the relationship between substantia nigra hyperechogenicity, reduced short-interval intracortical inhibition within the primary motor cortex, and neurochemical markers of activity in the pre-SMA obtained using magnetic resonance spectroscopy. A secondary aim was to determine whether the previously documented relationship between substantia nigra hyperechogenicity and reduced short-interval intracortical inhibition within primary motor cortex of healthy adults aged 72-84 years is also evident in healthy adults spanning (aged 50-70 years) the average diagnostic age for Parkinson's disease (60 years, for review see de Lau & Breteler, 2006). We hypothesized that substantia nigra hyperechogenicity in healthy adults aged 50-70 years is associated with reduced short-interval intracortical inhibition in the primary motor cortex and that the reduced intracortical inhibition is associated with neurochemical markers of activity in the pre-SMA. ...
Article
Substantia nigra (SN) hyperechogenicity, viewed with transcranial ultrasound, is a risk marker for Parkinson's disease. We hypothesized that SN hyperechogenicity in healthy adults aged 50-70 years is associated with reduced short-interval intracorti-cal inhibition in primary motor cortex, and that the reduced intracortical inhibition is associated with neurochemical markers of activity in the pre-supplementary motor area (pre-SMA). Short-interval intracortical inhibition and intracortical facilitation in primary motor cortex was assessed with paired-pulse transcranial magnetic stimulation in 23 healthy adults with normal (n = 14; 61 ± 7 yrs) or abnormally enlarged (hyperechogenic; n = 9; 60 ± 6 yrs) area of SN echogenicity. Thirteen of these participants (7 SN− and 6 SN+) also underwent brain magnetic resonance spectroscopy to investigate pre-SMA neurochemistry. There was no relationship between area of SN echogenicity and short-interval intracortical inhibition in the ipsilateral primary motor cortex. There was a significant positive relationship, however, between area of echogenicity in the right SN and the magnitude of intracortical facilitation in the right (ipsilateral) primary motor cortex (p = .005; multivariate regression), evidenced by the amplitude of the conditioned motor evoked potential (MEP) at the 10–12 ms interstimulus interval. This relationship was not present on the left side. Pre-SMA glutamate did not predict primary motor cortex inhibition or facilitation. The results suggest that SN hyperechogenicity in healthy older adults may be associated with changes in excitability of motor cortical circuitry. The results advance understanding of brain changes in healthy older adults at risk of Parkinson's disease.
... Parkinson's disease (PD), with an ever-increasing prevalence in the elderly, has long been recognized as the second most common neurodegenerative disease and the most frequent movement disorder [1]. PD patients suffer from classical motor dysfunction as well as a variety of non-motor symptoms. ...
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Parkinson’s disease (PD) is characterized by progressive loss of dopaminergic neurons and accumulation of misfolded alpha-synuclein (αSyn) into Lewy bodies. In addition to motor impairment, PD commonly presents with cognitive impairment, a non-motor symptom with poor outcome. Cortical αSyn pathology correlates closely with vascular risk factors and vascular degeneration in cognitive impairment. However, how the brain microvasculature regulates αSyn pathology and neurodegeneration remains unclear. Here, we constructed a rapidly progressive PD model by injecting alpha-synuclein preformed fibrils (αSyn PFFs) into the cerebral cortex and striatum. Brain capillaries in mice with cognitive impairment showed a reduction in diameter and length after 6 months, along with string vessel formation. The intracellular domain of low-density lipoprotein receptor-related protein-1 (LRP1-ICD) was upregulated in brain microvascular endothelium. LRP1-ICD promoted αSyn PFF uptake and exacerbated endothelial damage and neuronal apoptosis. Then, we overexpressed LRP1-ICD in brain capillaries using an adeno-associated virus carrying an endothelial-specific promoter. Endothelial LRP1-ICD worsened αSyn PFF-induced vascular damage, αSyn pathology, or neuron death in the cortex and hippocampus, resulting in severe motor and cognitive impairment. LRP1-ICD increased the synthesis of poly(adenosine 5′-diphosphate-ribose) (PAR) in the presence of αSyn PFFs. Inhibition of PAR polymerase 1 (PARP1) prevented vascular-derived injury, as did loss of PARP1 in the endothelium, which was further implicated in endothelial cell proliferation and inflammation. Together, we demonstrate a novel vascular mechanism of cognitive impairment in PD. These findings support a role for endothelial LRP1-ICD/PARP1 in αSyn pathology and neurodegeneration, and provide evidence for vascular protection strategies in PD therapy.
... According to the Global Burden of Disease Study, neurological diseases are the leading cause of disability-adjusted life years and the second leading cause of death [1]. Parkinson's disease (PD), one of the most common neurological diseases, affects 1.5-22 persons per 100,000 in all age groups and 529 persons per 100,000 older adults [2,3]. Furthermore, a recent meta-analysis showed that the number of patients with PD is expected to double from 6.9 million in 2015 to 14.2 million in 2040 [4]. ...
Article
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The maintenance and improvement of balance and walking function in patients with Parkinson’s disease (PD) is essential. Toe dysfunction in patients with PD is related to balance and walking. Recently, insoles have been developed to improve toe function, but their effects on the physical functions of patients with PD remain unclear. In this randomized controlled study, we investigated the effects of insoles with a toe-grip bar on balance and walking function in such patients. Twenty-nine patients with PD in Hoehn and Yahr stages II–IV were randomly assigned to an intervention or control group. Patients in the intervention and control groups wore shoes having insoles with and without a toe-grip bar for 4 weeks, respectively. The center of gravity sway of standing posture (total trajectory length, envelope area, and maximum anterior–posterior center of pressure [AP-COP] distance) and walking parameters at normal and fast speeds were measured pre- and post-intervention in the rehabilitation room. All measurements were performed with the participants being barefoot. The maximum AP-COP distance and step length of the fast-walking condition were significantly improved in the intervention compared to the control group (p < 0.05). Thus, insoles with a toe-grip bar may improve balance and walking function in patients with PD.
... First, the thrashing of SNpc neurons gives rise to striatal DA deficiency, which is accountable for the foremost symptoms of PD. Second, the replacement of striatal A. Arshad and U. Bacha DA through the oral administration of the DA precursor levodopa (L-3,4dihydroxyphenylalanine) assuages most of these symptoms (Dauer and Przedborski 2003;de Lau and Breteler 2006;Davie 2008). ...
Chapter
Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) are medically unexplained disorders that occur with somatic or psychiatric symptoms presenting during the luteal phase of the menstrual cycle, ending within a few days after the onset of menstruation. Worldwide, the prevalence of PMS is remarkably high, and its causes are still unclear and are multifactorial. This chapter aims to understand better the etiopathogenesis, clinical features, diagnosis, contemporary, and integrative holistic approaches of PMS management. A thorough literature survey from various scientific databases such as Web of Science, ScienceDirect, PubMed, Google Scholar, Scopus, and other databases was retrieved for the evidence connected to premenstrual syndrome, and PMDD was undertaken. The biochemical changes of PMS involve sex steroids, neurotransmitters such as cholecystokinin GABA, serotonin, and regulation of the renin-angiotensin-aldosterone system, genetic vulnerabilities, diet, and lifestyle. The most common symptoms of PMS are affective symptoms (anger outburst, anxiety, depression, confusion, irritability, social withdrawal) or somatic symptoms (headache, breast tenderness, abdominal bloating, and swelling of extremities) that affect the quality of life negatively. Its diagnosis is based on the time of appearance and the type of symptoms in the menstrual cycle. The initial step embraces lifestyle changes and diet regulation, teaching women self-screening, creating awareness about PMS, and methods of coping with stress. Complementary alternative therapies and cognitive behavioral therapy are implemented in the second step. The third step is initiated with pharmacological treatment if the problem continues, and in the fourth step, surgical treatment is applied.
... Additionally, it has been shown that men are twice as likely to develop PD than women, but that women tend to have a higher mortality rate [3]. The incidence of PD increases with age [2], and the mean onset age for PD diagnosis is in the 60s for most individuals [4][5][6]. ...
... Parkinson's disease (PD) is a kind of neurodegenerative disease (NDD) affecting over 6 million people worldwide, which is going to rise to 9.3 million by 2030 [1,2]. Clinically, PD is manifested as progressive locomotive disorder and cognitive impairment, which is thought to be associated with Lewy bodies (LBs) and dopaminergic (DAergic) neuronal death in the substantia nigra (SN) [3,4]. ...
Article
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Parkinson’s disease (PD) is a neurodegenerative disease (NDD) with high and ongoing morbidity, bringing heavy burdens to PD patients seriously. Finding neurotrophic drugs still remains vital due to the limited drug spectrum available currently. Substantial evidence suggests that glucagon-like peptide 1 (GLP-1) exerts neuroprotection on PD, yet the short-lived biological activity markedly hindered its application. Herein, we investigated the neurotrophic role of the next-generation probiotic strain L. lactis MG1363-pMG36e-GLP-1 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice and elucidated the mechanisms. Our data suggested that L. lactis MG1363-pMG36e-GLP-1 markedly enhanced motor deficits induced by MPTP via rescuing dopaminergic (DAergic) neurodegeneration in substantia nigra (SN). We found that L. lactis MG1363-pMG36e-GLP-1 exerts neurotrophic effects via activating the Keap1/Nrf2/GPX4 signalling pathway to down-regulate ACSL4 and up-regulate FSP1 to suppress ferroptosis. Additionally, the decreased oxidative stress levels via suppressing generations of ROS and MDA supported our findings. Lastly, we identified that the L. lactis MG1363-pMG36e-GLP-1 administration reversed dysbiosis in PD mice by increasing Akkermansia, Oscillospira, and Sutterella at the genus level. These results indicated that the neurotrophic effects of the next-generation probiotics L. lactis MG1363-pMG36e-GLP-1 against MPTP-induced Parkinsonism are mediated by modulating oxidative stress, inhibiting ferroptosis, and redressing dysbiosis.
... Parkinson's disease (PD) is the second most common neurodegenerative disorder in the United States. The prevalence of PD is about 1% in individuals over the age of 60 [1]. It is projected that by 2040, the number of people living with PD in the United States will be around 770,000 individuals at minimum [2]. ...
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Introduction Previous observational studies assessing β2-agonist/-antagonist use on PD risk have yielded conflicting results. We evaluated the relationship between β2-agonist use and the incidence of Parkinson’s disease in patients with chronic lung disease. Methods We performed a retrospective cohort analysis on a 20% random sample abstracted from a traditional (fee-for-service) Medicare program in the United States. Inclusion criteria were individuals over 65 years old diagnosed with asthma, COPD, and/or bronchiectasis who were enrolled in a prescription drug (standalone Part D) plan over 2007–2010 and alive through 2014. The main outcome measure was a diagnosis of Parkinson’s disease over the period 2011–2014, in relation to the number of 30-day-equivalent drug claims over 2007–2010. Logistic regression analysis was performed on a sample including 236,201 Medicare beneficiaries. Results The sample was 68% female, 80% white, and on average 77 years old as of 2010. Compared to non-users, β2-agonist users were more likely to be younger (76.3y versus 78.0y), smokers (40.4% versus 31.1%) and asthmatic (62.4% versus 28.3%). The odds ratio for a β2-agonist claim on PD development was 0.986 (95% CI 0.977–0.995) after adjusting for demographics, smoking history, respiratory exacerbations, comorbidities, and other drug use. Risk reductions were larger for males than females (0.974 versus 0.994, P = 0.032), and for individuals with COPD compared to those with asthma (0.968 versus 0.998, P = 0.049). Reverse causality was addressed with a Cox analysis that allowed β2-agonist use to vary from medication initiation to disease onset. By the end of the follow-up period, β2-agonist use was shown to be associated with a true protective effect against PD onset. Discussion β2-agonist use is associated with decreased risk of PD incidence. Further investigation, possibly including clinical trials, is warranted to strengthen the evidence base supporting clinical decision-makers looking to repurpose pharmaceuticals to prevent neurodegenerative disease onset.
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An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Chapter
An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Chapter
An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Chapter
An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Chapter
An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Chapter
An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Chapter
An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Chapter
An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Chapter
An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Chapter
An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Chapter
An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
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An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Chapter
An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Chapter
An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Chapter
An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Chapter
An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Article
Aims Parkinsonism is characterized by degeneration of dopaminergic neurons and impairment in neuroplasticity. Empagliflozin (EMPA) is an anti-diabetic drug that has been shown to improve cognitive dysfunctions and exerted antioxidant and anti-inflammatory effects in different models. This study aimed to determine the neuroprotective effects of EMPA against rotenone (ROT)-induced parkinsonism. Main methods ROT (1.5 mg/kg) was injected subcutaneously three times per week for two successive weeks. Mice were treated with EMPA (3 and 10 mg/kg, orally) for one week prior ROT administration and for another two weeks along with ROT. After that, motor functions and histopathological changes were assessed, and brains were isolated for biochemical analyses and immunohistochemical investigation. Key findings Results indicated that, in a dose dependent manner, EMPA improved motor functions and histopathological changes induced by ROT, increased brain content of reduced glutathione (GSH), dopamine (DA), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), nuclear factor erythroid 2–related factor 2 (Nrf2), inositol trisphosphate (IP3), calcium (Ca²⁺), calcium/calmodulin-dependent protein kinase type IV (CaMKIV) and phospho-Protein kinase B (p-Akt) levels compared to ROT group. Additionally, EMPA decreased the levels of malondialdehyde (MDA), and tumor necrosis factor-α (TNF-α), and inactivated glycogen synthase kinase-3 beta (GSK-3β). Improvement in neuroplasticity was also observed indicated by elevation in brain derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and neuronal PAS domain Protein 4 (Npas4). Significance EMPA improved motor functions possibly through improving neuroplasticity markers and antioxidant, anti-inflammatory, and neuroprotective effects in a dose dependent manner.
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An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Article
Numerous factors are implicated in the onset and progression of ageing and neurodegenerative disorders, with defects in cell energy supply and free radicals regulation designated as being the main functions of mitochondria and highly accentuated in plentiful studies. Hence, analysing the role of mitochondria as one of the main factors implicated in these disorders could undoubtedly come in handy with respect to disease prevention and treatment. In this review, first, we will explore how mitochondria account for neurodegenerative disorders and ageing and later will draw the various pathways contributing to mitochondrial dysfunction in their distinct way. Also, we will discuss the deviation-countering mechanisms, particularly mitophagy, a subset of autophagy known as a much larger cellular defence mechanism and regulatory system, along with its potential therapeutic effects. Last but not least, we will be highlighting the mitochondrial transfer experiments with animal models of neurodegenerative disorders.
Article
Résumé Contexte/objectifs Le vieillissement accéléré en Afrique s’accompagne d’une augmentation de la prévalence de la maladie de Parkinson. L’objectif de cette étude était de décrire les caractéristiques des patients âgés atteints de la maladie de Parkinson au Sénégal. Matériels et méthodes Il s’agissait d’une étude rétrospective, descriptive allant du 1er août 2018 au 31 juillet 2021, sur une population, de personnes âgées de 60 ans ou plus présentant une maladie de Parkinson, reçue en consultation externe de gériatrie. Les caractéristiques épidémiologiques, cliniques et évolutives étaient recueillies et analysées à l’aide du logiciel epi.info.7. Résultats Sur 1858 patients reçus durant cette période, 28 présentaient une maladie de Parkinson, soit une fréquence de 1,51 %. La moyenne d’âge était de 74 ± 7 ans sans prédominance de sexe. L’âge moyen de survenue était de 65,5 ± 7 ans avec une durée moyenne d’évolution 9 ± 5 ans. La polypathologie concernait 24,4 % des patients. Les comorbidités les plus fréquentes étaient l’hypertension artérielle (60,7 %), les pathologies ostéoarticulaires (35,7 %) et le diabète de type 2 (17,8 %). Les manifestations motrices étaient dominées par la forme akinéto-hypertonique (100 % akinésie et 82,1 % hypertonie) et l’instabilité posturale (60,7 %). Les symptômes non moteurs retrouvaient essentiellement la constipation (71,4 %) et les troubles du sommeil (64,3 %). Les syndromes gériatriques les plus fréquents étaient la perte d’autonomie fonctionnelle (71,4 %) et la dénutrition (32,14 %). Un épuisement de l’aidant principal était retrouvé chez 85,7 % des patients. La consommation d’eau de puits était le principal facteur de risque retrouvé (42,9 %). La dopathérapie isolée était le traitement médicamenteux le plus utilisé (60,7 %). Les principales complications étaient à type de chute (67,8 %) et de fluctuations d’efficacité du traitement (42,9 %). Conclusion La prévalence de la maladie de Parkinson reste importante et probablement sous-diagnostiquée chez les personnes âgées au Sénégal. L’akinésie et l’hypertonie dominaient la symptomatologie classique de la maladie. Les syndromes gériatriques, souvent sous-estimés, étaient fréquents et potentiellement graves. La prise en charge est complexe et doit être précoce et multidisciplinaire.
Article
Parkinson's disease (PD) is the world's second primary neurodegenerative disease, and the diagnosis and treatment of PD have become mainstream research. Over the past decades, several studies have identified potential biomarkers for diagnosing PD. Among them, extracellular vesicles (EVs) can carry specific biomarkers reflecting the physiological and pathological state of the body. Due to the blood-brain barrier (BBB) limitation, peripheral blood is limited in diagnosing neurodegenerative diseases. With the increasing research on EVs, their ability to pass through BBB indicated that peripheral blood could depict disease status like cerebrospinal fluid (CSF). Peripheral blood is a clinically available sample and has recently been widely used by researchers in various studies. In this review, we summarized previous studies on PD diagnosis biomarkers in peripheral blood EVs and evaluated their diagnostic value. Some EV surface markers were also described, which can extract EVs from specific cell origins. In addition, the combination of several biomarkers demonstrated good diagnostic performance in PD diagnosis compared with a single biomarker, suggesting the focus of future research.
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Parkinson’s Disease (PD) is a neurodegenerative disease that primarily manifests through cognitive, motor and speech disorders. But it has been proven that voice changes in Parkinson’s patients are among the symptoms that appear early. In this research paper, we propose a speech processing based approach for early Parkinson disease detection. Our approach evaluate the use of a deep convolutional autoencoder to extract the deep features from raw speech of PD patients and healthy subjects. Then, a classification step with MultiLayer Perceptron (MLP) which uses these deep features to build up a PD discriminant model. For an evaluation step we use a UCI dataset, our proposed approach achieve an accuracy of 95.52%, which is better than the related works accuracies using the same dataset. This prove that our system can be strongly recommended to monitor the progression of PD.KeywordsParkinson’s diseaseAutoencoderDeep featuresRaw speechMLP
Article
SH-SY5Y is a cell line derived from human neuroblastoma. It is one of the most widely used in vitro models to study Parkinson’s disease. Surprisingly, it has been found that it does not develop a dopaminergic phenotype after differentiation, questioning its usefulness as a Parkinson’s model. There are other in vitro models with better dopaminergic characteristics. BE (2)-M17 is a human neuroblastoma cell line that differentiates when treated with retinoic acid. We compared the dopaminergic and serotonergic properties of both cell lines. BE (2)-M17 has higher basal levels of dopaminergic markers and acquires a serotonergic phenotype during differentiation while maintaining the dopaminergic phenotype. SH-SY5Y has higher basal levels of serotonergic markers but does not acquire a dopaminergic phenotype upon differentiation.
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Every person shows different psychological signs at the time of anger, and identification of these individual signs is crucial to understanding the problem. Anger can be perceived as a survival tool and energy source that can be wholesome or unhealthy depending on that person’s psychology. Outcomes can be unhealthy if anger continues for an extended period or if it is repressed for the time being. We experience a primary emotion before we feel anger, and that primary emotion can be a sense of fear, transgression, insolence, force, trap, or burden.
Article
Introduction Elderly individuals with neurodegenerative diseases, such as Parkinson’s disease (PD), may experience difficulties when performing functional tasks. Objective To analyze the handgrip strength, pulling force, and ground reaction forces (GRF) of individuals with and without PD when boarding a bus while performing both simple (ST) and dual tasks (DT). Method This case-control study addressed 31 individuals with PD (GPD) and 30 healthy individuals (GHI). Assessments were performed in ST and DT situations using a bus model (prototype). Handgrip strength and pulling force were measured in both upper limbs using a dynamometer, and GRF was measured using a force platform. The GPD’s and GHI’s performances were compared in both ST and DT, and the individuals were classified as fallers according to the Falls Efficacy Scale. Results In the inter-group comparison, the GPD presented significantly lower maximum force using their right hand, in handgrip strength (30.43 vs. 36.62, P = .022), and pulling force (10.77 vs 12.81, P = .037). The left hand’s pulling force proved to be the most demanding for the GPD, during ST (6.35 vs. 4.76, P = .006) and DT (6.32 vs 4.74, P = .008). The GPD also took longer to perform ST (6.14 vs. 4.67, P < .001) and DT (6.08 vs. 4.81, P = .002). Additionally, the GPD was more afraid of falling compared to the GHI (34.74 vs. 24.77, P < .001). Conclusion Boarding a bus is a complex task for individuals with PD because they present lower maximum strength in the upper limbs and more significant functional expenditure than their healthy counterparts.
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An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Chapter
Movement disorders represent a large, heterogenous group of disabling neurological conditions that recognize a variety of neurodegenerative or nondegenerative causes. They are generally divided clinically into hypokinetic movement disorders such as Parkinsonism and atypical Parkinsonism, and hyperkinetic movement disorders such as Huntington's disease and essential tremor. The etiology and progression of these disorders remain unclear, and there is a need for disease-modifying therapies. Neuroimaging techniques, including magnetic resonance imaging, positron emission tomography, and single photon computed tomography, make it possible to investigate structural, functional, and biological processes in vivo. Striving toward personalized medicine approaches, neuroimaging offers tools to aid the identification of individual disease signatures and projected clinical outcomes for targeting therapeutic intervention. Neuroimaging has multiple potential applications for clinical trials from improving study design and pathology-based phenotypic stratification and offering robust outcome measures including efficacy and safety. This chapter introduces clinical aspects of Parkinson's disease and related movement disorders, which are discussed in chapters throughout this book, and highlights the application of neuroimaging for robust measures in clinical trials.
Article
Background The association between white matter (WM) lesions and Parkinson’s disease (PD) was not fully established. We therefore applied Mendelian randomization (MR) analyses to identify the causal effect between white matter lesions and PD.Methods We performed a bidirectional two-sample Mendelian randomization (MR) study to investigate the association between three WM phenotypes—white matter hyperintensities (WMH, N = 18,381), fractional anisotropy (FA, N = 17,673), and mean diffusivity (MD, N = 17,467)—with PD (N = 482,730) using summary statistics from genome-wide association studies (GWAS). The inverse variance weighted (IVW), weighted median, MR-Egger, and MR-PRESSO methods were used to evaluate the causal estimate.ResultsSignificant evidence was suggested that higher MD was associated with a higher PD risk (OR = 1.049, 95% CI = 1.018–1.081, p = 0.022) when the outlier was removed using MR-PRESSO method. Moreover, genetically predicted PD was associated with a lower WMH load (IVW β = − 0.047, 95% CI = − 0.085 to − 0.009, p = 0.016) and a higher FA (β = 0.185, 95% CI = 0.021–0.349, p = 0.027). No evidence of pleiotropy was found using MR-Egger intercept.Conclusion Our findings provided genetic support that white matter microstructural integrity lesions might increase the risk of PD. However, genetically predicted PD was potentially associated with a lower load of white matter lesions.
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With the rapid increase in life expectancy and the proportion of the elderly population, the global prevalence of various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and Huntington's disease, is rising dramatically. The demographic trend of the aged population has attracted people's attention to the discovery and treatment of new drugs for age-related diseases. Currently, there are various drugs and treatments available for the treatment of neurodegenerative diseases, but side effects or insufficient drug efficacy have been reported. With a long history of herbs or natural compounds used in the treatment of age-related diseases, new evidence has been reported to support the pharmacological effects of Indopathy in ameliorating symptoms or interfering with the pathogenesis of neurodegenerative diseases. Many Indian medicinal plants have been used for thousands of years in Indopathy. Amongst these are plants used for the management of neurodegenerative diseases, such as Parkinson's, Alzheimer's, loss of memory, degeneration of nerves, and other neuronal disorders by Ayurvedic practitioners. Though the etiology of neurodegenerative diseases remains enigmatic, there is evidence indicating that defective energy metabolism, excitotoxicity, and oxidative damage may be crucial factors. This book summarizes the new therapeutic leads from herbal sources for various types of neurodegenerative diseases. Based on recent research, this volume makes an effort to utilize existing knowledge of some popular medicinal plants, and their biologically active components have been discussed, especially those used in Indopathy. Several promising plants such as Withania somnifera, Bacopa monnieri, Centella asiatica, and Mucuna pruriens are worth exploring for the development of neuroprotective drugs.
Article
Background Independently, veterans and individuals with Parkinson's Disease (PD) are at increased risk for suicide. To our knowledge, the risk of suicide among veterans with PD has yet to be evaluated. This study aimed to examine the associations between PD and risk of suicide, as well as suicide means among those using Veteran Health Administration (VHA) services. Methods Retrospective cohort study of individuals who used VHA services between 1/1/2001-12/31/2019. Cox proportional hazard models were used to estimate the hazard of suicide for those with PD relative to those without. A nested-case control study was carried out among the suicide decedents where logistic regression was used to assess the relationship between PD and suicide by firearms versus suicide by any other means. Results The unadjusted hazard of death by suicide for those with a PD diagnosis, relative to those without, was 1.51 (95% CI: 1.32–1.72, p < 0.0001), and was still significant after controlling for age/gender, and psychiatric/chronic physical health diagnoses (HR: 1.50; 95% CI: 1.32–1.72, p < 0.0001; HR:1.21, 95% CI:1.06–1.38, p = 0.006, respectively). Compared to the non-PD cohort, the PD group also had higher rates of mood, anxiety, and psychotic disorders. There was no significant difference between the method of suicide for those with PD versus those without PD (p = 0.60). Most suicide deaths among both cohorts were firearm-related (PD = 78.9%, No-PD = 80.3%). Conclusions PD is associated with an elevated risk for suicide. Based on the high rate of deaths by firearm, increased efforts to facilitate lethal means safety among veterans is warranted.
Article
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We investigated and characterized the prevalence of dry eye disease (DED) in Parkinson’s disease (PD). PubMed and EMBASE databases were searched for relevant studies between January 1, 1979 and March 10, 2022. Quality was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. Study-specific estimates were combined using the DerSimonian–Laird random-effects model. Prevalence of subjective DED symptoms in patients with PD and mean differences in blink rate, corneal thickness, tear film breakup time, and tear secretion volume on Schirmer test I were compared to those in controls. Of 383 studies, 13 (1519 patients with PD) and 12 were included in qualitative and quantitative syntheses, respectively. Meta-analysis revealed a 61.1% prevalence of subjective DED symptoms in PD and that, compared with controls, patients with PD had significantly lower blink rate, thinner corneal thickness, shorter tear film breakup time, and lower tear secretion volumes on Schirmer test I, without and with anesthesia.
Article
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Natural compounds with anti-aggregation capacity are increasingly recognized as viable candidates against neurodegenerative diseases. Recently, the polyphenolic fraction of propolis (PFP), a complex bee product, has been shown to inhibit amyloid aggregation of a model protein especially in the nanosheet form. Here, we examine the aggregation-modulating effects of the PFP nanosheets on α-synuclein (α-syn), an intrinsically disordered protein involved in the pathogenesis of Parkinson's disease. Based on a range of biophysical data including intrinsic and extrinsic fluorescence, circular dichroism (CD) data, and nuclear magnetic resonance spectroscopy, we propose a model for the interaction of α-syn with PFP nanosheets, where the positively charged N-terminal and the middle non-amyloid component regions of α-syn act as the main binding sites with the negatively charged PFP nanosheets. The Thioflavin T (ThT) fluorescence, Congo red absorbance, and CD data reveal a prominent dose-dependent inhibitory effect of PFP nanosheets on α-syn amyloid aggregation, and the microscopy images and MTT assay data suggest that the PFP nanosheets redirect α-syn aggregation toward nontoxic off-pathway oligomers. When preformed α-syn amyloid fibrils are present, fluorescence images show co-localization of PFP nanosheets and ThT, further confirming the binding of PFP nanosheets with α-syn amyloid fibrils. Taken together, our results demonstrate the binding and anti-aggregation activity of PFP nanosheets in a disease-related protein system and propose them as potential nature-based tools for probing and targeting pathological protein aggregates in neurodegenerative diseases.
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Background We aimed to examine whether plasma-derived phosphoglycerate mutase 5 (PGAM5) can be a biomarker for Parkinson’s disease (PD) diagnosis as well as its association with the severity of motor/non-motor manifestations of PD. Methods We enrolled 124 patients with PD (PD group) and 50 healthy controls (HC group). We measured plasma PGAM5 levels using a quantitative sandwich enzyme immunoassay. Patients with PD underwent baseline evaluations using the Unified Parkinson’s Disease Rating Scale (UPDRS), while participants in both groups were evaluated using scales for non-motor manifestations. Receiver operating characteristic curves were used to evaluate the predictive utility of plasma PAMG5 alone and combined with other factors. Results Plasma PAMG5 levels were significantly higher in the PD group; the area under the curve (AUC) of plasma PGAM5 levels alone was 0.76. The AUC values for elderly participants and patients without hypertension were 0.78 and that for was 0.79. Notably, plasma PGAM5 levels combined with plasma oligomeric α-synuclein (α-syn) and the score of the REM sleep behavior disorder questionnaire-Hong Kong (RBDQ-HK) showed AUC values of 0.80 and 0.82. Multivariable logistic analysis revealed that plasma PAMG5 levels were independently associated with PD (odds ratio,1.875 [95% confidence interval 1.206–2.916], p = 0.005) but not the severity of motor/non-motor manifestations of PD. Conclusion Plasma PGAM5 is an independent biomarker for PD, especially among elderly patients (age > 60 years) and patients without hypertension. The predictive utility of PGAM5 was improved when combined with plasma oligomeric α-syn or the RBDQ-HK score.
Chapter
An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.
Article
Full-text available
Context The cause of Parkinson disease (PD) is unknown. Genetic linkages have been identified in families with PD, but whether most PD is inherited has not been determined, Objective To assess genetic inheritance of PD by studying monozygotic (MZ) and dizygotic (DZ) twin pairs. Design Twin study comparing concordance rates of PD in MZ and DZ twin pairs. Setting and Participants A total of 19 842 white male twins enrolled in the National Academy of Sciences/National Research Council World War II Veteran Twins Registry were screened for PD and standard diagnostic criteria for PD were applied. Zygosity was determined by polymerase chain reaction or questionnaire. Main Outcome Measure Parkinson disease concordance in twin pairs, stratified by zygosity and age at diagnosis. Results Of 268 twins with suspected parkinsonism and 250 presumed unaffected twin brothers, 193 twins with PD were identified (concordance-adjusted prevalence, 8.67/1000). In 71 MZ and 90 DZ pairs with complete diagnoses, pairwise concordance was similar (0.129 overall, 0.155 MZ, 0.111 DZ; relative risk, 1.39; 95% confidence interval, 0.63-3.1). In 16 pairs with diagnosis at or before age 50 years in at least 1 twin, MZ concordance was 1.0 (4 pairs), and DZ was 0.167 (relative risk, 6.0; 95% confidence interval, 1.69-21.26). Conclusions The similarity in concordance overall indicates that genetic factors do not play a major role in causing typical PD, No genetic component is evident when the disease begins after age 50 years. However, genetic factors appear to be important when disease begins at or before age 50 years.
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Oxidant stress is associated with the generation of reactive oxygen species that are responsible for the damage of a variety of cellular components. The prevention of such biological damage can be achieved by dismutation of superoxide to H2O2 which in turn is removed by catalase and GSH peroxidase. However, redox-active iron released during the development of plasmodia in the erythrocyte can mediate the conversion of H2O2 to hydroxyl radical which is more reactive. The roles of SOD and the nitroxide SOD mimic 4-OH,2,2,6,6,tetramethyl piperidine-N-oxyl (Tempol) were examined in P. falciparum grown in vitro. Both compounds did not prevent the interference with growth inflicted by various inducers of oxidant stress. Moreover, Tempol inhibited parasite growth, in agreement with previous experiments depicting accelerated mortality in SOD overexpressing mouse model of malaria. Probably, effective defense against ROS requires balanced increments in antioxidant enzymes and is not necessarily improved by an increase in the activity of one enzyme.
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To assess and compare the prevalence of parkinsonism and Parkinson's disease in five European populations that were surveyed with similar methodology and diagnostic criteria. Joint analysis of five community surveys--Gironde (France), eight centres in Italy, Rotterdam (The Netherlands), Girona (Spain), and Pamplona (Spain)--in which subjects were screened in person for parkinsonism. Overall, these surveys comprised 14,636 participants aged 65 years or older. The overall prevalence (per 100 population), age adjusted to the 1991 European standard population, was 2.3 for parkinsonism and 1.6 for Parkinson's disease. The overall prevalence of parkinsonism for the age groups 65 to 69, 70 to 74, 75 to 79, 80 to 84, and 85 to 89 years was respectively, 0.9, 1.5, 3.7, 5.0, and 5.1. The corresponding age specific figures for Parkinson's disease were 0.6, 1.0, 2.7, 3.6, and 3.5. After adjusting for age and sex, the prevalence figures did not differ significantly across studies, except for the French study in which prevalence was lower. Prevalence was similar in men and women. Overall, 24% of the subjects with Parkinson's disease were newly detected through the surveys. Prevalence of both parkinsonism and Parkinson's disease increased with age, without significant differences between men and women. There was no convincing evidence for differences in prevalence across European countries. A substantial proportion of patients with Parkinson's disease went undetected in the general population.
Article
Data are lacking on the prognosis (institutionalization and death) of PD cases identified in population-based studies. Data from five population-based European studies were compared and pooled, Each study used comparable two-step screening methods to identify cases and performed one or more follow-up examinations of their respective participants after defined periods of time. PD was classified on the basis of questionnaire and clinical data, The studies include 16,143 participants (252 with PD), The relative risk (RR) (95% CI) of death associated with PD was 2.3 (1.8 to 3.0). The risk for death in men with PD (RR 3.1 [2.1 to 4.4]) was higher than in women with PD (RR 1.8 [1.2 to 5.1]), The rate of institutionalization varied across studies, increased with age, and was considerably higher in PD cases compared to noncases. Women with PD had a fivefold higher risk to live in a care facility than did men with PD. These data on mortality and rate of institutionalization reflect the high burden of PD in the population.
Article
Objective: To investigate whether high dietary intake of antioxidants decreases the risk of Parkinson disease (PD). Setting: The community-based Rotterdam Study, the Netherlands. Design: The cross-sectional study formed part of a large community-based study in which all participants were individually screened for parkinsonism and were administered a semiquantitative food frequency questionnaire. The study population consisted of 5342 independently living individuals without dementia between 55 and 95 years of age, including 31 participants with PD (Hoehn-Yahr stages 1-3). Results: The odds ratio for PD was 0.5 (95% confidence interval [CI], 0.2-0.9) per 10-mg daily dietary vitamin E intake, 0.6 (95% CI, 0.3-1.3) per 1-mg beta carotene intake, 0.9 (95% CI, 0.4-1.9) per 100-mg vitamin C intake, and 0.9 (95% CI, 0.7-1.2) per 10-mg flavonoids intake, all adjusted for age, sex, smoking habits, and energy intake. The association with vitamin E intake was dose dependent ( P for trend=.03). To assess whether the association was different in participants with more advanced disease, we excluded those with PD who had a Hoehn-Yahr stage of 2.5 or 3. This did not fundamentally alter the results. Conclusion: Our data suggest that a high intake of dietary vitamin E may protect against the occurrence of PD.
Article
Objective: To determine the incidence of parkinsonism and PD in the Italian elderly, and to explore the relation with age and gender. Methods: In eight Italian municipalities, a population-based, parkinsonism-free cohort was followed for an average of 3 years. At the end of the follow-up, the cohort survivors were directly contacted (screening and clinical examination). Cohort members who had died were studied using death certificates, clinical records, and information gathered from relatives and general practitioners. Parkinsonism diagnosis and subtyping were made according to specified diagnostic criteria. Results: The cohort consisted of 4,341 individuals (65 to 84 years of age): 596 died before the examination, 2,863 (76.4% of the survivors) completed the screening procedure, and 882 refused to participate. The authors found 68 incident cases of parkinsonism: 42 PD (62%), 7 drug-induced parkinsonism (10%), 8 parkinsonism in dementia (12%), 8 vascular parkinsonism (12%), and 3 parkinsonism, unspecified (5.8%). Average annual incidence rate (per 100,000 person-years) in the population aged 65 to 84 years, adjusted to the 1992 Italian population, was 529.7 (95% CI, 400.5 to 658.9) for parkinsonism, and 326.3 (95% CI, 224.1 to 427.5) for PD. Incidence rates for both parkinsonism and PD increased with age in both men and women; men had higher rates in every age group. Age-adjusted relative risk in men compared with women was 1.66 (95% CI, 1.02 to 2.70) for parkinsonism and 2.13 (95% CI, 1.11 to 4.11) for PD. Conclusions: Incidence of parkinsonism and PD increased with age, PD was the most common type of parkinsonism, and men had a risk of developing PD twice that of women.
Article
PURPOSEThe association between self-reported past food intake and Parkinson's disease (PD) was investigated in a case-control study of men and women aged 40–89 years.METHODS Newly diagnosed idiopathic PD cases were ascertained from neurologists, and from outpatient and pharmacy computerized databases, at the Group Health Cooperative (GHC) clinics in the Puget Sound region of Washington state. Control subjects were chosen from the GHC patient roster and had no reported history of diagnosed neurodegenerative disease. Dietary data were obtained from structured questionnaires.RESULTSAn increase in PD risk with increasing intake was noted for foods that contain animal fat and foods containing vitamin D. Intake of fruits, vegetables, meats, bread and cereals, or foods containing vitamins A, C, E, or iron was not significantly related to PD risk. Vitamin use, in general, was also not found to be related to PD risk, although a significant trend of increasing risk of PD was noted for intake of vitamin A supplements.CONCLUSIONS Although these data support previous findings of no association of past intake with most food groups and PD risk, they confirm an increased risk of PD associated with foods containing animal fat.
Article
Diet may play a causative role in Parkinson's disease (PD), but potential associations between diet and PD risk rarely have been assessed in prospective studies. We investigated associations between food intakes and PD risk in two large prospective cohorts in which 210 incident PD cases in men and 184 in women were documented. A positive association was found between dairy intake and PD risk in men (relative risk [RR] comparing extreme categories, 1.8; p trend = 0.004), but not in women (RR, 1.1; p trend = 0.9). No other food groups were associated with PD risk in either men or women. Further analyses among men showed significant positive associations with PD risk for intakes of several dairy foods as well as dairy calcium (RR, 1.5; p trend = 0.02), dairy vitamin D (RR, 1.6; p trend = 0.004), dairy protein (RR, 1.6; p trend = 0.01), and lactose (RR, 1.8; p trend = 0.002), but not dairy fat (RR, 1.1; p trend = 0.4). Intakes of calcium, vitamin D, and protein from other dietary or supplemental sources were not related to PD risk in men. Our results suggest that higher intake of dairy products may increase the risk of PD in men; however, this finding needs further evaluation, and the underlying active components need to be identified.
Article
Results of case-control studies and of a prospective investigation in men suggest that consumption of coffee could protect against the risk of Parkinson's disease, but the active constituent is not clear. To address the hypothesis that caffeine is protective against Parkinson's disease, we examined the relationship of coffee and caffeine consumption to the risk of this disease among participants in 2 ongoing cohorts, the Health Professionals' Follow-Up Study (HPFS) and the Nurses' Health Study (NHS). The study population comprised 47,351 men and 88,565 women who were free of Parkinson's disease, stroke, or cancer at baseline. A comprehensive life style and dietary questionnaire was completed by the participants at baseline and updated every 2–4 years. During the follow-up (10 years in men, 16 years in women), we documented a total of 288 incident cases of Parkinson's disease. Among men, after adjustment for age and smoking, the relative risk of Parkinson's disease was 0.42 (95% CI: 0.23–0.78; p for trend < 0.001) for men in the top one-fifth of caffeine intake compared to those in the bottom one-fifth. An inverse association was also observed with consumption of coffee (p for trend = 0.004), caffeine from noncoffee sources (p for trend < 0.001), and tea (p for trend = 0.02) but not decaffeinated coffee. Among women, the relationship between caffeine or coffee intake and risk of Parkinson's disease was U-shaped, with the lowest risk observed at moderate intakes (1–3 cups of coffee/day, or the third quintile of caffeine consumption). These results support a possible protective effect of moderate doses of caffeine on risk of Parkinson's disease.
Article
The prevalence of Parkinson's disease (PD) and other types of parkinsonism in three elderly populations of central Spain was investigated using a door-to-door, two-phase approach. This design called for the administration of a brief questionnaire to subjects 65 years of age or older taken from the census of one urban municipality of Greater Madrid (Margaritas, Getafe), one rural site (Arévalo County, Ávila), and one urban district of Madrid (Lista) in Spain (N = 5,278). Study neurologists extensively investigated those subjects who screened positively. The diagnoses, based on specified criteria, were reviewed to increase reliability across neurologists. We found 118 subjects with parkinsonism: 81 affected by PD (68.6%), 26 drug-induced parkinsonism (22.0%), 6 parkinsonism in dementia (5.1%), 3 vascular parkinsonism (2.5%), and 2 unspecified parkinsonism (1.7%). The prevalence was 2.2% (95% confidence interval [CI], 1.8–2.6) for all types of parkinsonism and 1.5% (95% CI, 1.2–1.8) for PD. The prevalence estimates of parkinsonism and PD increased with age, declining at 85 years and over. Age prevalence ratios were higher for men. Twenty-three subjects (28.4%) of the subjects with PD were detected through the screening and had not been diagnosed previously. Overall prevalence estimates of PD and other types of parkinsonism in central Spain rank at levels similar to those recently reported for other European and non-European elderly populations. Despite improvement in access to health services, an important proportion of PD patients may never seek neurological attention. © 2002 Movement Disorder Society
Article
An inverse association between cigarette smoking and idiopathic Parkinson's disease has been reported in several retrospective studies, but prospective evidence is available only for men. We assessed the association between the incidence of Parkinson's disease and smoking in two large prospective cohort studies comprising men and women. New cases of Parkinson's disease were identified in the Nurses' Health Study for 1976–1996, and in the Health Professionals Follow-up Study for 1986–1996. Smoking history was assessed at baseline and updated on subsequent biennial questionnaires. In women, the age-adjusted rate ratios (95% confidence intervals) for Parkinson's disease relative to never-smokers were 0.7 (0.5, 1.0) for past smokers, and 0.4 (0.2, 0.7) for current smokers. In men, the age-adjusted rate ratios for Parkinson's disease relative to never-smokers were 0.5 (0.4, 0.7) for past smokers, and 0.3 (0.1, 0.8) for current smokers. In both cohorts, the strength of the association decreased with time since quitting (among past smokers), increased with number of cigarettes per day (among current smokers), and increased with pack-years of smoking. These prospective findings confirm that an inverse association between smoking and the incidence of Parkinson's disease exists in both men and women.
Article
We investigated the association of Parkinson's disease (PD) with two estrogen receptor gene polymorphisms. In a sample of 319 unrelated PD cases and 196 control subjects including both men and women, we observed no association of PD with the estrogen receptor genotypes derived from XbaI and PvuII digests. Analyses restricted to women or to cases and controls of European origin yielded similar findings. Further analyses stratified by age at examination or by family history did not show associations. While exogenous and endogenous estrogen may modify the risk of PD in women, the two estrogen receptor gene polymorphisms considered here do not seem to contribute to PD susceptibility. © 2001 Movement Disorder Society.
Article
We studied the association of Parkinson's disease (PD) with type of menopause (natural or surgical), age at menopause, and postmenopausal estrogen replacement therapy using a case-control design. We used the medical records-linkage system of the Rochester Epidemiology Project to identify 72 women who developed PD in Olmsted County, MN, during the twenty years 1976–1995. Each incident case was matched by age (± 1 year) to a general population control subject. We collected exposure data through review of the complete medical records of cases and control subjects in the system. PD cases had undergone hysterectomy (with or without unilateral oophorectomy) significantly more often than control subjects (odds ratio [OR] = 3.36; 95% confidence interval [CI] = 1.05–10.77). In addition, PD cases had experienced early menopause (≤ 46 years) more commonly than control subjects (OR = 2.18; 95% CI = 0.88–5.39). Finally, PD cases had used estrogens orally or parenterally for at least 6 months after menopause less frequently (8%) than control subjects (14%; OR = 0.47; 95% CI = 0.12–1.85). However, the findings for early menopause and estrogen replacement therapy were not statistically significant. Despite the limited sample size of this exploratory study, we hypothesize that there is an increased risk of PD in conditions causing an early reduction in endogenous estrogen. This hypothesis needs to be confirmed in a larger study. © 2001 Movement Disorder Society.
Article
Dementia affects approximately one-third of all patients with Parkinson's disease. Currently there is no treatment to halt or reverse the disease progression. Symptomatic treatment approaches are based on substituting neurotransmitter deficits or ameliorating associated behavioral symptoms. The most prominent deficits are cholinergic, and treatment with cholinesterase inhibitors (ChE-I) has been shown to provide some benefits in cognitive and behavioral symptoms without undue worsening in motor symptoms. Based on a large, randomized, placebo controlled trial, the ChE-I rivastigmine has been approved for the treatment of dementia associated with PD.
Article
Mutations in the leucine-rich repeat kinase 2 ( LRRK2) gene have been shown to cause autosomal dominant Parkinson's disease. Few mutations in this gene have been identified. We investigated the frequency of a common heterozygous mutation, 2877510G→A, which produces a glycine to serine aminoacid substitution at codon 2019 (Gly2019Ser), in idiopathic Parkinson's disease. We assessed 482 patients with the disorder, of whom 263 had pathologically confirmed disease, by direct sequencing for mutations in exon 41 of LRRK2. The mutation was present in eight (1·6%) patients. We have shown that a common single Mendelian mutation is implicated in sporadic Parkinson's disease. We suggest that testing for this mutation will be important in the management and genetic counselling of patients with Parkinson's disease. Published online January 18, 2005 http://image.thelancet.com/extras/04let12032web.pdf
Article
Sex and ethnic differences in the frequency of Parkinson's disease have become increasingly important, because putative genetic and environmental risk factors have been identified. The authors estimated the prevalence and incidence of Parkinson's disease in a culturally diverse community in New York City over a 4-year period (January 1, 1988–December 31, 1991) using a disease registry substantiated, for older individuals, by a subsequent survey of a random sample of Medicare recipients between January 1, 1992, and December 31, 1993. The prevalence rate was 107 per 100,000 persons, and over a 3-year period the average incidence rate was 13 per 100,000 person-years. Age-adjusted prevalence rates were lower for women than for men in each ethnic group and were lower for blacks than for whites and Hispanics. Incidence rates were highest among black men, but they were otherwise comparable across the sex and ethnic groups. The estimated cumulative incidence of Parkinson's disease up to age 90 years was lower for women than for men, which could partially explain the lower prevalence rate. By ethnic group, the cumulative incidence was higher for blacks than for whites and Hispanics, but more deaths occurred among incident black cases. Discrepant prevalence and incidence rates of Parkinson's disease among blacks and women warrant further investigation. While selective mortality could partially account for this paradox, it is also possible that a delay in diagnosis due to limited access to appropriate health services among these individuals could have resulted in the observed discordant rates of disease.
Article
We investigated the prevalence of Parkinson's disease and other types of parkinsonism in a Sicilian population using a door-to-door two-phase approach. This design called for the administration of a brief screening instrument to all subjects who, on November 1, 1987, were residents of Terrasini (Palermo Province), Santa Teresa di Riva (Messina Province), and Riposto (Catania Province), Sicily (N = 24,496). Study neurologists using specified diagnostic criteria extensively investigated those subjects who screened positive. We found 63 subjects affected by Parkinson's disease, 21 with secondary parkinsonism, and seven with unspecified parkinsonism. The crude prevalence per 100,000 population was 371.5 for all types of parkinsonism and 257.2 for Parkinson's disease; for both entities, prevalence increased steeply with age and showed an inconsistent sex pattern. Our prevalence figures for Parkinson's disease are higher than those previously reported in Italy or elsewhere, which may be due, in part, to more complete case-ascertainment.
Article
A number of studies have reported lower cigarette consumption in patients with Parkinson's disease (PD) previous to onset of the disease. In an attempt to determine whether there existed a "premorbid attitude" by patients against the use of socially accepted "drugs," the premorbid tobacco, alcohol, and coffee consumption habits were compared in 128 PD patients and 256 controls. Patients and controls were selected by case control method and were recruited from the same health area and socioeconomic stratum. In males, the habits of smoking more than 10 cigarettes/day (p < 0.001) and drinking more than 50 g/day of alcohol (p < 0.001) were significantly less frequent in the PD patients than in the controls, but the differences in coffee consumption were nonsignificant. In females behavior did not differ significantly between the PD group and the controls for any of the three habits. There was no correlation between the amount of smoking and alcohol drinking and age at onset of PD or current Hoehn and Yahr's staging. Our results suggest the existence of a premorbid personality in males with PD, possibly conditioning a restrictive attitude toward the consumption of such toxic substances as tobacco and alcohol, yet a more tolerant attitude toward habits more widely accepted socially, like coffee consumption.
Article
An epidemiological study on the incidence and prevalence of Parkinson's disease (PD) was carried out in 29 provinces, cities and autonomous regions in this country in 1986. The survey was conducted in 117 areas, and 566 patients with PD were found among 3,869,162 persons examined, giving a point prevalence for men and women of 16.9/10(5) and 12.4/10(5), with the highest prevalence after the fifth decade of age. The disease was most prevalent in the southern part of China, especially in Hunan and Guangxi provinces. The incidence was 1.5/10(5)/yr in 1986. Both the prevalence and incidence of PD in China are lower than those in the white race and Japanese.
Article
Previous studies suggest that Parkinson's disease (PD) is negatively associated with early-life intake of vitamin E-rich foods and positively associated with rural experience. Using a new survey design, we attempted to confirm and extend these results. We gave a telephone questionnaire to 106 patients with PD and to their spouses as controls. It assessed premarital consumption of 31 foods of various vitamin E content, vitamin supplements, and exposure to rural living. Respondents rated food consumption with respect to what they perceived as the average for their sex and age at that time. We found female patients with PD less likely than spouses to have eaten "peanuts and peanut butter" (p less than .05), which are high in vitamin E. "Salad with dressing," also high in vitamin E, gave a similar result (p less than .05) for a male-predominant patient group. Separate comparison of male controls with female controls ruled out sex-related preferences as the explanation of our findings. Patients had more extensive rural experience and were more likely to have frequently sprayed pesticides (p less than .05) than had controls. Our results justify further investigations into early-life vitamin E intake, pesticides, and neurotoxins associated with rural life.
Article
A door-to-door survey of Parkinson's disease (PD) in Copiah County, Mississippi, using a pretested screening procedure (with a high sensitivity for detecting PD), followed by examination of all positives by a senior neurologist, revealed similar prevalence ratios for blacks and whites. The same procedure was applied in the community of Igbo-Ora, Nigeria, a black population of West Africa. To assure uniformity in the procedures and application of the diagnostic criteria, a neurologist from each survey site visited the other site. Among a black population of 3,521 over age 39 in Copiah County, there were 12 cases of PD, with an age-adjusted prevalence ratio of 341/100,000. The comparable figures for Igbo-Ora were as follows: population over age 39 = 3,412; cases of PD = 2; age-adjusted prevalence ratio = 67/100,000.
Article
A door-to-door survey was conducted in six cities of the People's Republic of China. A total of 63,195 individuals were sampled during 1983 to determine the prevalence of major neurologic disorders. The survey involved a complete census, followed by a pretested interview and brief screening examination with a high level of sensitivity for detecting individuals with frequently occurring neurologic diseases, including movement disorders. Subjects with abnormal responses or findings were examined by a neurologist. There was 100% cooperation among the study subjects. Twenty-eight individuals alive on prevalence day (Jan 1, 1983) were identified as having Parkinson's disease, yielding an age-adjusted (to the 1960 US population) prevalence ratio of 57 per 100,000 population. All subjects were older than the age of 50 years. After the fifth decade of life, the age-specific prevalence ratios increased with age.
Article
An epidemiological study of parkinsonism over a 13-year period (1967 through 1979) is presented, updating previous reports on incidence and trend in the population of Rochester, Minnesota. The overall average annual incidence of parkinsonism per 100,000 population was 20.5, adjusted to the 1970 total United States population, which is virtually unchanged from previous observations. Incidences calculated for each calendar year (1967 through 1979) revealed no remarkable change following the 1976 swine flu vaccination program. There was no sex difference and the peak incidence occurred between ages 75 and 84 years. Idiopathic Parkinson's disease was the most common variant (86%), followed by drug-induced parkinsonism (7%). There were no new cases of postencephalitic parkinsonism diagnosed during the study period. Relative frequency of other types of Parkinson's disease as identified by practicing neurologists is presented. For each case two age- and sex-matched controls were selected from the Rochester population. The survival rates in the controls were comparable to the general population of the west north central region of the United States. The mortalities in the patients were significantly higher (p = 0.001) than the controls and were unchanged from previous rates reported from the same community. In the 69 (50%) patients treated with levodopa, the mortality was comparable to that in controls. The favorable outcome in these cases is attributed to bias resulting from selection of healthier patients for treatment.
Article
Four persons developed marked parkinsonism after using an illicit drug intravenously. Analysis of the substance injected by two of these patients revealed primarily 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) with trace amounts of 1-methyl-4-phenyl-4-propionoxy-piperidine (MPPP). On the basis of the striking parkinsonian features observed in our patients, and additional pathological data from one previously reported case, it is proposed that this chemical selectively damages cells in the substantia nigra.
Article
To estimate the frequency and determine the risk factors for incident dementia in community-dwelling patients with Parkinson's disease (PD) and in control subjects. Prospective cohort study. During a 3.5-year period, 140 patients with idiopathic PD without evidence of dementia and 572 nondemented control subjects were identified in the community of Washington Heights-Inwood in New York, NY. All subjects underwent neurological and neuropsychological evaluations and follow-up examinations. Twenty-seven patients with PD (19.2%) became demented throughout 2 years, as compared with 87 (15.2%) of the control subjects. The relative risk (RR) for the development of dementia with PD was 1.7 (95% confidence interval [CI], 1.1 to 2.7) after adjusting for age, education, and gender. Predictive features of incident dementia were an extrapyramidal score greater than 25 (RR, 3.56; 95% CI, 1.4 to 8.9) and a Hamilton Depression Rating Scale score greater than 10 (RR, 3.55; 95% CI, 1.6 to 7.9). Patients with PD, especially those with severe extrapyramidal signs, have almost twice the risk for the development of dementia than do community-dwelling control subjects.
Article
We investigated the prevalence of Parkinson's disease in a representative sample of the elderly population living in the Gironde département, France. Among 3149 people over age 65, the prevalence ratio for Parkinson's disease was 1.4%, without significant difference between men and women. We found that age-specific prevalence ratios increased with age from 0.5% in the age group 65 to 69 to 6.1% in individuals over age 90. This age pattern is consistent with that found in other population-based studies. Interestingly, the slope of age-specific prevalence ratios for Parkinson's disease was similar to that previously reported for Lewy bodies. Our study showed that a high proportion (42%) of Parkinson's disease cases in elderly subjects living in institutions were undiagnosed.
Article
Using data from death certificates, we compared underlying causes of death for two populations of Michigan decedents: (1) persons 40 years of age and older for whom Parkinson's disease (PD) was listed as a contributing cause of death and who died in the years 1970 through 1989, and (2) all persons in Michigan over 40 years of age who died in 1970, 1980, or 1990. PD decedents were approximately 1.5 times more likely to die from cerebrovascular disease and three to four times more likely to die from pneumonia/influenza, but they had just 29% of the expected number of deaths due to cancer. These associations were maintained irrespective of gender or race. PD decedents had diabetes mellitus and heart diseases as frequently as decedents in the general population, but liver diseases were less frequent among PD decedents. These trends held throughout the 21-year study period. When we stratified cancers by whether they are known to be (1) highly related, (2) moderately related, or (3) weakly related or unrelated to smoking, there were still 2.5 times fewer cancers unrelated or weakly related to smoking among PD decedents than among decedents in the general population. We believe that the greater frequency of cerebrovascular disease in PD decedents may be due to a detection bias, since PD patients are more likely to be seen by neurologists, who are more apt to diagnose and document diseases of the nervous system. Pneumonia/influenza is more common among PD patients because of their relative immobility near the end of life.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
A 26-year follow-up study of 8,006 men enrolled in the Honolulu Heart Program examined the effect of cigarette smoking on the risk of developing idiopathic Parkinson's disease. Cases were identified through an ongoing search of hospital records and by the review of death certificates and medical records of local neurologists. Men who had smoked cigarettes at any time prior to study enrollment in 1965 had a reduced risk of developing idiopathic Parkinson's disease (relative risk = 0.39). Examination of smoking by pack-years revealed an apparent dose-response effect on the risk of idiopathic Parkinson's disease, but not on the age of onset. Coffee drinking was also associated with reduced risk, apparently because of its association with cigarette smoking. Although the detrimental health effects of cigarette smoking would far outweight any possible protective effect for smoking and Parkinson's disease, the association of smoking with apparent protection may contribute to understanding the underlying pathogenetic mechanisms.
Article
Oxidative stress plays an important role in the pathogenesis of Parkinson's disease (PD). In a population-based, case-control study we examined whether dietary intake of antioxidants and other oxidative compounds was associated with PD. Dietary intake was assessed by a semiquantitative food-frequency questionnaire in 110 PD case patients and 287 control subjects. A higher caloric intake was observed in patients with PD and did not vary with increasing duration of symptoms. Energy-adjusted fat intake was significantly higher among patients with PD than control subjects (p for trend = 0.007). Intake of protein (p for trend = 0.17) and carbohydrates (p for trend = 0.46) did not differ in patients and control subjects. Analyses of the primary sources of fat indicated that increasing intake of animal fats were strongly related to PD (odds ratio, 5.3; 95% confidence interval, 1.8-15.5; p for trend = 0.001). No significant differences were observed for intake of vitamins with antioxidant activity. An increase in the consumption of animal fats among patients with PD is consistent with the hypothesis that oxidative stress and lipid peroxidation are important in the pathogenesis of this disease. No effect of vitamins with antioxidant activity, either from food or supplements, was observed.
Article
A nested case-control study of 84 incident cases of patients with idiopathic Parkinson's disease (PD) detected by June 30, 1994 and 336 age-matched control subjects, compared previously-documented intake of total dietary vitamin E and of selected vitamin E-containing foods. All study subjects had been followed for 27 to 30 years after diet recording in the 8,006-man Honolulu Heart Study cohort. We determined PD outcomes by periodic cohort re-examination and neurologic testing, private physician reports, examination of O'ahu neurologists' office records, and continual death certificate and hospital discharge diagnosis surveillance. Data on vitamin E intake, obtained from three dietary data sets at the time of cohort enrollment (1965 to 1968), included a food-frequency questionnaire and a 24-hour photograph-assisted dietary recall administered by trained dietitians. Although absence of PD was significantly associated with prior consumption of legumes (adjusted OR = 0.27, 95% CI 0.09 to 0.78), a dietary variable preselected for high vitamin E content, neither food categories nor quartiles nor continuous variables of vitamin E consumption were significantly associated with PD occurrence. Though consistent with prior reports of PD protection afforded by legumes, and with speculation on the possible benefits of dietary or supplemental vitamin E in preventing PD, these preliminary data do not conclusively document a beneficial effect of dietary vitamin E on PD occurrence.
Article
Parkinson's disease (PD) shows a geographical variation. All prescriptions for anti-parkinsonian drugs were recorded for a half-year in a region with low L-dopa consumption. Hospital and outpatient records were studied and physicians were asked to supply details of PD patients in the region, with 147,777 inhabitants. The crude prevalence was 115 PD per 100,000 inhabitants, based on 170 cases. In contrast to other studies we report an age-standardized prevalence, which was 76 per 100,000, using the European Standard Population as reference. The corresponding approximate incidences were 11.0 (crude) and 7.9 (age-standardized) per 100,000 person-years. Male preponderance appeared in all age groups. Mean age at onset was 65.6 years, the highest figure reported. Variation between studies for age at onset, differences in prevalence, and male preponderance suggest environmental risk factors to be of importance for PD.
Article
We determined age-specific and age-adjusted incidence rates and mortality rates of idiopathic Parkinson's disease (PD) in a cohort of men followed for 29 years. Since enrollment in 1965, the Honolulu Heart Study has followed 8,006 American men of Japanese or Okinawan ancestry. Rescreening of the entire cohort, completed in 1994, included attempts to detect all prevalent and incident cases of PD, parkinsonism, and related conditions. PD incidence rates and age-incidence patterns were similar to rates previously published for Caucasian men in Europe and the United States, and were higher than incidence rates published for Asian men living in Asian nations. Prevalence patterns appeared to correspond more closely to patterns observed in developed nations than in Asian nations. PD was associated with markedly increased mortality that appeared to result from effects of both absolute age and disease duration. There was no firm evidence for differences in birth cohort risks of PD. These data may have implications for maturational and environmental theories of PD etiology.
Article
In a case-control study, we compared the past dietary habits of 342 Parkinson's disease (PD) patients recruited from nine German clinics with those of 342 controls from the same neighborhood or region. Data were gathered with a structured interview and a self-administered food-frequency questionnaire. Nutrient intakes were calculated from the reported food intakes through linkage with the German Federal Food Code and analyzed using multivariate conditional logistic regression to control for total energy intake, educational status, and cigarette smoking. At the macronutrient level, patients reported higher carbohydrate intake than controls after adjustment for total energy intake, smoking, and educational status (OR = 2.74, 95% confidence interval [CI]: 1.30-6.07, for the highest versus lowest quartile, p trend = 0.02). This was reflected in higher monosaccharide and disaccharide intakes at the nutrient level. There was no difference between patients and controls in protein and fat intake after adjustment for energy intake. We found an inverse association between the intakes of beta-carotene (OR = 0.67, 95% CI: 0.37-1.19, p trend = 0.06) and ascorbic acid (OR = 0.60, 95% CI: 0.33-1.09, p trend = 0.04) by patients, although only the trend for ascorbic acid intake reached statistical significance. There was no difference between groups for alpha-tocopherol intake after adjustment for energy intake. We also found that patients reported a significantly lower intake of niacin than controls (OR = 0.15, 95% CI: 0.07-0.33, p trend < 0.00005). Our results suggest that if antioxidants play a protective role in this disease, the amounts provided by diet alone are insufficient. Although the interpretation of the inverse association between niacin intake and PD is complicated by the high niacin content in coffee and alcoholic beverages, which were also inversely associated with PD in this study, the strength of this association and its biologic plausibility warrant further investigation.
Article
We assessed the prevalence of Parkinson's disease (PD) in a general elderly population in the Netherlands.The study formed part of the Rotterdam Study, a population-based door-to-door study, and included 6,969 persons 55 years of age or older living in a suburb of Rotterdam, the Netherlands. All participants were examined, and those who either had at least one possible cardinal sign of parkinsonism at the neurologic screening, reported that they had PD, or were taking antiparkinsonian drugs were invited for further evaluation. The prevalence of PD in this population was 1.4% (1.2% for men, 1.5% for women). Prevalence increased with age, and prevalence figures were 0.3% for those aged 55 to 64 years, 1.0% for those 65 to 74, 3.1% for those 75 to 84, and 4.3% for those 85 to 94. The corresponding age-specific figures for men were 0.4%, 1.2%, 2.7%, and 3.0%, and for women, 0.2%, 0.8%, 3.4%, and 4.8%. Among 95- to 99-year-old women the prevalence was 5.0%. Twelve percent of the subjects with PD were detected through the screening and had not been diagnosed previously. NEUROLOGY 1995;45: 2143-2146
Article
Levodopa therapy for Parkinson disease (PD) has improved quality of life, but mortality rates remain high. Although the presence of dementia and severity of extrapyramidal signs (EPSs) influence morbidity in PD, it is not known whether these manifestations contribute to mortality. Patients with PD were compared with nondemented and demented elderly subjects. Each underwent annual neurological and neuropsychological examinations. Dementia was diagnosed by Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised criteria, and EPSs were rated with the Unified Parkinson's Disease Rating Scale. Survival rates were compared using Kaplan-Meier analysis and Cox proportional hazards models. The risk of mortality, when compared with nondemented elderly subjects, was highest among those with both PD and dementia (rate ratio, 4.9; 95% confidence interval, 3.4-7.1), but also was elevated in patients with PD only (rate ratio, 2.7; 95% confidence interval, 1.7-4.4). Dementia in the absence of PD also was associated with an increased risk of mortality (rate ratio, 1.6; 95% confidence interval, 1.1-2.3). A high baseline total EPS score was associated with significantly earlier mortality. Compared with nondemented elderly people in the same community, patients with PD have a 2- to 5-fold increased risk of mortality. The risk is strongly related to the presence of severe EPSs, especially bradykinesia. Despite the introduction of levodopa and other advances in the treatment of PD, these factors greatly increase mortality.
Article
It has been suggested that dietary antioxidants reduce Parkinson's disease (PD) risk by neutralizing free radicals, thus preventing injury to neurons in the substantia nigra. This case-control study examined the possible role of long-term dietary antioxidant intake in PD etiology. Cases (n = 57) were males 45-79 years old with at least two cardinal signs of PD and no evidence of other forms of parkinsonism or dementia. Age-matched friend controls (n = 50) were chosen from lists provided by the cases. Usual dietary intake 20 years ago, including vitamins E and C and carotenoids, was assessed by a 102-item food frequency questionnaire. Odds ratios and 95% confidence intervals were calculated using conditional logistic regression. Antioxidant intake, adjusted for age, education, smoking, rural living, and total energy intake, was not associated with reduced PD risk. Trends toward greater PD risk were associated with higher intakes of vitamin C and carotenoids, especially xanthophylls, reflecting higher intakes by PD cases of fruit and certain vegetables. Intakes of sweet foods, including fruit, were associated with higher PD risk, suggesting that the observed trends may be due to a preference for sweet foods. This study does not provide support for a protective effect of long-term dietary antioxidant intake on PD risk.
Article
For Parkinson's disease (PD), little is known about how the choice of diagnostic criteria affects research results. Using data on PD from three community studies (from Argentina, the Netherlands, Italy), we compared the impact on prevalence of several sets of diagnostic criteria. Each set was based on cardinal signs--resting tremor, bradykinesia, rigidity, impaired postural reflexes--and required that other parkinsonism be excluded. Some sets had additional requirements related to duration of symptoms, asymmetry of signs, or response to medication. In terms of prevalence, much lower estimates were associated with the requirements of asymmetry of signs and response to medication. The assessment of these clinical features may not be practical in community studies. Impaired postural reflexes, as a cardinal sign, seemed superfluous. For community studies of PD, we recommend the following diagnostic criteria: at least two of resting tremor, bradykinesia, or rigidity, in the absence of other apparent causes of parkinsonism.
Article
To investigate whether high dietary intake of antioxidants decreases the risk of Parkinson disease (PD). The community-based Rotterdam Study, the Netherlands. The cross-sectional study formed part of a large community-based study in which all participants were individually screened for parkinsonism and were administered a semiquantitative food frequency questionnaire. The study population consisted of 5342 independently living individuals without dementia between 55 and 95 years of age, including 31 participants with PD (Hoehn-Yahr stages 1-3). The odds ratio for PD was 0.5 (95% confidence interval [CI], 0.2-0.9) per 10-mg daily dietary vitamin E intake, 0.6 (95% CI, 0.3-1.3) per 1-mg beta carotene intake, 0.9 (95% CI, 0.4-1.9) per 100-mg vitamin C intake, and 0.9 (95% CI, 0.7-1.2) per 10-mg flavonoids intake, all adjusted for age, sex, smoking habits, and energy intake. The association with vitamin E intake was dose dependent (P for trend = .03). To assess whether the association was different in participants with more advanced disease, we excluded those with PD who had a Hoehn-Yahr stage of 2.5 or 3. This did not fundamentally alter the results. Our data suggest that a high intake of dietary vitamin E may protect against the occurrence of PD.
Article
We investigated the effects of estrogen replacement therapy (ERT) on the risk of development of dementia in 87 women with Parkinson's disease without dementia (PDND), 80 women with Parkinson's disease with dementia (PDD), and 989 nondemented healthy women from the same community. ERT was protective for the development of dementia within the setting of PD (OR 0.22, 95% CI 0.05-1.0) and when PDD patients were compared with controls (OR 0.24, 95% CI 0.07-0.78), but did not affect the risk of PD. The results of the study suggest that a randomized clinical trial of ERT may be warranted.