Risk of Hospitalization and Death for COVID-19 in People with Parkinson's Disease or Parkinsonism.

BACKGROUND: The risk of COVID-19 and related death in people with Parkinson's disease or parkinsonism is uncertain. The aim of the study was to assess the risk of hospitalization for COVID-19 and death in a cohort of patients with Parkinson's disease or parkinsonism compared with a control population cohort, during the epidemic bout (March-May 2020) in Bologna, northern Italy. METHODS: Participants of the ParkLink study with the clinical diagnosis of Parkinson's disease or parkinsonism and people anonymously matched (ratio 1:10) for sex, age, district, and Charlson Index were included. The hospital admission rate for COVID-19 (February 26-May 31, 2020) and the death rate for any cause were the outcomes of interest. RESULTS: The ParkLink cohort included 696 subjects with Parkinson's disease and 184 with parkinsonism, and the control cohort had 8590 subjects. The 3-month hospitalization rate for COVID-19 was 0.6% in Parkinson's disease, 3.3% in parkinsonism, and 0.7% in controls. The adjusted hazard ratio (age, sex, district, Charlson Index) was 0.8 (95% CI, 0.3-2.3, P = 0.74) in Parkinson's disease and 3.3 (1.4-7.6, P = 0.006) in parkinsonism compared with controls. Twenty-nine of the infected subjects died; 30-day fatality rate was 35.1%, without difference among the 3 groups. Six of 10 Parkinson's disease/parkinsonism patients had the infection during hospitalization or in a nursing home. CONCLUSIONS: Parkinson's disease per se probably is not a risk factor for COVID-19 hospitalization. Conversely, parkinsonism is an independent risk factor probably because of a more severe health status, entailing higher care dependence and placement in high-infection-risk accommodations. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Pretreatment of Ascorbic Acid Inhibits MPTP-Induced Astrocytic Oxidative Stress through Suppressing NF-κB Signaling.

Astrocytes are a major constituent of the central nervous system (CNS). Astrocytic oxidative stress contributes to the development of Parkinson's disease (PD). Maintaining production of antioxidant and detoxification of reactive oxygen and nitrogen species (ROS/RNS) in astrocytes is critical to prevent PD. Study has illuminated that ascorbic acid (AA) stimulates dopamine synthesis and expression of tyrosine hydroxylase in human neuroblastoma cells. However, the role and regulatory mechanisms of AA on detoxification of astrocytes are still unclear. The purpose of our study is in-depth study of the regulatory mechanism of AA on detoxification of astrocytes. We found that AA pretreatment decreased the expression of ROS and inducible nitric oxide synthase (iNOS) in MPP+-treated astrocytes. In contrast, the expression levels of antioxidative substances-including superoxide dismutase (SOD), glutathione (GSH), and glutamate-cysteine ligase modifier (GCLM) subunit-were upregulated after AA pretreatment in MPP+-treated astrocytes. However, inhibition of NF-κB prevented such AA induced increases in antioxidative substances following MPP+ treatment in astrocytes, suggesting that AA improved antioxidative function of astrocytes through inhibiting NF-κB-mediated oxidative stress. Furthermore, in vivo studies revealed that AA preadministration also suppressed NF-κB and upregulated the expression levels of antioxidative substances in the midbrain of MPTP-treated mice. Additionally, pretreatment of AA alleviated MPTP-induced PD-like pathology in mice. Taken together, our results demonstrate that preadministration of AA improves the antioxidative function of astrocytes through suppressing NF-κB signaling, following alleviated the pathogenesis of PD which induced by MPTP. Hence, our findings elucidate a novel protective mechanism of AA in astrocytes.

Cerebrospinal fluid neurofilament light and tau protein as mortality biomarkers in parkinsonism.

BACKGROUND: Mortality is increased in parkinsonian disorders, moderately in Parkinson's disease (PD) but markedly in atypical parkinsonian disorders (APD), including multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). Still, there are no reliable quantitative biomarkers for mortality. The cerebrospinal fluid (CSF) neurodegeneration biomarkers such as neurofilament light chain (NF-L), total tau (t-tau), and the tau pathology marker phosphorylated tau (p-tau) are related to mortality in other neurological disorders (eg, amyotrophic lateral sclerosis, Alzheimer's disease), but have not been investigated in this respect in parkinsonian disorders. AIMS: To investigate the CSF biomarkers' (NF-L, t-tau, and p-tau) relationship to mortality in parkinsonian disorders. METHODS: Demographic, mortality, and CSF data were collected from 68 PD and 83 APD patients. Survival analysis was conducted using Cox regression, with age at lumbar puncture, gender, diagnosis, and levels of CSF biomarkers as predictors. RESULTS: NF-L in CSF was associated with increased mortality in synucleinopathies (PD, MSA; HR 3.698 [2.196-6.228, 95% confidence interval (CI)], P < 0.001), in PSP (HR 2.767 [1.126-6.802 95% CI], P = 0.027), and in the entire cohort (HR 1.661 [1.082-2.55, 95% CI], P = 0.02). t-Tau in CSF was associated with increased mortality in PSP (HR 9.587 [1.143-80.418], P = 0.037). p-Tau in CSF was associated with decreased mortality in synucleinopathies (HR 0.196 [0.041-0.929, 95% CI], P = 0.040). Atypical parkinsonian disorders and tauopathies were associated with higher mortality (HR 8.798 [4.516-17.14, 95% CI] and HR 3.040 [1.904-4.854], respectively, P < 0.001). CONCLUSION: NF-L and tau protein in CSF might be useful for mortality prognosis in patients with parkinsonian disorders and should be investigated in larger studies.

Time Trends of the Incidence, Prevalence, and Mortality of Parkinsonism.

OBJECTIVES: We assessed trends in the incidence, prevalence, and post-diagnosis mortality of parkinsonism in Ontario, Canada over 18 years. We also explored the influence of a range of risk factors for brain health on the trend of incident parkinsonism. METHODS: We established an open cohort by linking population-based health administrative databases from 1996 to 2014 in Ontario. The study population comprised residents aged 20-100 years with an incident diagnosis of parkinsonism ascertained using a validated algorithm. We calculated age- and sex-standardized incidence, prevalence, and mortality of parkinsonism, stratified by young onset (20-39 years) and mid/late onset (≥40 years). We assessed trends in incidence using Poisson regression, mortality using negative binomial regression, and prevalence of parkinsonism and pre-existing conditions (e.g., head injury) using the Cochran-Armitage trend test. To better understand trends in the incidence of mid/late-onset parkinsonism, we adjusted for various pre-existing conditions in the Poisson regression model. RESULTS: From 1996 to 2014, we identified 73,129 incident cases of parkinsonism (source population of ∼10.5 million), of whom 56% were male, mean age at diagnosis was 72.6 years, and 99% had mid/late-onset parkinsonism. Over 18 years, the age- and sex-standardized incidence decreased by 13.0% for mid/late-onset parkinsonism but remained unchanged for young-onset parkinsonism. The age- and sex-standardized prevalence increased by 22.8%, while post-diagnosis mortality decreased by 5.5%. Adjustment for pre-existing conditions did not appreciably explain the declining incidence of mid/late-onset parkinsonism. CONCLUSION: Young-onset and mid/late-onset parkinsonism exhibited differing trends in incidence over 18 years in Ontario. Further research to identify other factors that may appreciably explain trends in incident parkinsonism is warranted.

Spinal Arteriolosclerosis Is Common in Older Adults and Associated With Parkinsonism.

BACKGROUND AND PURPOSE: There are few studies of spinal microvascular pathologies in older adults. We characterized spinal cord microvascular pathologies and examined their associations with other spinal and brain postmortem indices and parkinsonism in older adults. METHODS: We documented 3 features of microvascular pathologies in spinal cord and brain specimens from 165 deceased older participants. We also measured spinal white matter pallor. Parkinsonian signs were assessed with a modified version of the motor section of the Unified Parkinson's Disease Rating Scale. We examined the associations of spinal arteriolosclerosis with other spinal and brain postmortem indices and parkinsonism proximate to death using regression models which controlled for age and sex. RESULTS: Microinfarcts and cerebral amyloid angiopathy were not observed within the spinal cord parenchyma. Spinal arteriolosclerosis was observed at all spinal levels (C7, T7, L4, S4) examined and was more severe posteriorly than anteriorly (posterior: 4.3, SD=0.72 versus anterior: 3.9, SD=0.74; t=14.58; P<0.001). Arteriolosclerosis was more severe in the spinal cord than in the brain (cord: 4.10, SD=0.70; brain: 3.5, SD=0.98; t=10.39; P<0.001). The severity of spinal arteriolosclerosis was associated with spinal white matter pallor (r=0.47; P<0.001). Spinal arteriolosclerosis accounted for ≈3% of the variation in parkinsonism in models controlling for age, sex, brain arteriolosclerosis, and cerebrovascular disease pathologies. Further models showed that the association of spinal arteriolosclerosis and parkinsonism was not mediated via spinal white matter pallor. CONCLUSIONS: Although the regional distribution of microvascular pathologies varies within the central nervous system, spinal arteriolosclerosis is common and may contribute to the severity of spinal white matter pallor and parkinsonism in older adults.

Antipsychotics and mortality in Parkinsonism.

BACKGROUND: : The use of antipsychotic medications is associated with an increased risk of death in older adults with dementia. The risk of death in patients with preexisting parkinsonism who receive antipsychotic drugs is not known. METHODS: : Using a nested case-control design, we examined the risk of death within 30 days of newly starting antipsychotic medications among people with Parkinsonism aged 70 years and older in Ontario, Canada. Data were obtained from Ontario's healthcare administrative databases. RESULTS: : Among 5,391 individuals with parkinsonism who died during the study period (2002-2008) and a matched comparison group of 25,937 who were still alive, individuals exposed to atypical antipsychotic drugs had a higher risk of death (unadjusted odds ratio [OR] = 2.8, 95% CI: 2.1-3.8, adjusted OR: 2.0, 95% CI: 1.4-2.7). Results were similar for quetiapine use compared with no antipsychotic use (unadjusted OR: 2.5, 95% CI: 1.6-4.0, adjusted OR = 1.8, 95% CI: 1.1-3.0). Typical antipsychotics were associated with an increased odds of death compared with atypical antipsychotics (unadjusted OR = 2.4, 95% CI 1.1-5.2, adjusted OR = 2.4, 95% CI: 1.1-5.7). CONCLUSIONS: : Individuals with parkinsonism who are newly prescribed antipsychotic medications have a higher risk of death within 30 days than those who do not start these medications. Although it is not possible to establish causality, the results suggest an increased risk. It is important to be vigilant for accompanying serious medical conditions that may increase mortality in individuals requiring treatment with antipsychotics and to consider alternative approaches to treating psychosis, agitation, and aggression in this population.

Increased risk of Parkinsonism among patients with cirrhosis: a 7-year follow-up study.

BACKGROUND/AIMS: Previous studies have suggested that hepatic (toxic-metabolic) encephalopathy, the major complication of cirrhosis, is a neuropsychiatric disorder typically seen in patients with liver dysfunction after exclusion of other known brain disease. This study aims to investigate the risk for parkinsonism during a 7-year follow-up period after a diagnosis of cirrhosis. METHODS: In total, 1361 patients with cirrhosis and 6805 comparison patients without cirrhosis were included in this study. Each patient was then individually tracked for 7 years from the time of their initial diagnosis of cirrhosis to identify those who developed parkinsonism during the follow-up period. Stratified Cox proportional hazard regressions were conducted to calculate the hazard of parkinsonism for the two groups during the follow-up period, after adjusting for patient's age, monthly income, level of urbanization and geographic location. RESULTS: Of the total 8166 sampled patients, 141 (1.7%) developed parkinsonism during the follow-up period, 48 from the study group (3.5% of the patients with cirrhosis) and 93 from the comparison group (1.4% of patients in the comparison group). Stratified Cox proportional hazard regressions show that the hazard for parkinsonism for patients with cirrhosis was 2.65 times as high (95% confidence interval=1.85-3.80, P<0.001) as the patients in the comparison group over the 7-year follow-up period, after adjusting for patient's age, monthly income, level of urbanization and the geographic location of the community in which the patient resided. CONCLUSIONS: We concluded that cirrhosis significantly increased the risk of parkinsonism.

Incident mobility disability, parkinsonism, and mortality in community-dwelling older adults.

BACKGROUND: Mobility disability and parkinsonism are associated with decreased survival in older adults. This study examined the transition from no motor impairment to mobility disability and parkinsonism and their associations with death. METHODS: 867 community-dwelling older adults without mobility disability or parkinsonism at baseline were examined annually. Mobility disability was based on annual measured gait speed. Parkinsonism was based on the annual assessment of 26 items from the motor portion of the Unified Parkinson's Disease Rating Scale. A multistate Cox model simultaneously examined the incidences of mobility disability and parkinsonism and their associations with death. RESULTS: Average age at baseline was 75 years old and 318 (37%) died during 10 years of follow-up. Mobility disability was almost 2-fold more common than parkinsonism. Some participants developed mobility disability alone (42%), or parkinsonism alone (5%), while many developed both (41%). Individuals with mobility disability or parkinsonism alone had an increased risk of death, but their risk was less than the risk in individuals with both impairments. The risk of death did not depend on the order in which impairments occurred. CONCLUSION: The varied patterns of transitions from no motor impairment to motor impairment highlights the heterogeneity of late-life motor impairment and its contribution to survival. Further studies are needed to elucidate the underlying biology of these different transitions and how they might impact survival.

Association of PSP phenotypes with survival: A brain-bank study.

INTRODUCTION: The MDS-PSP criteria expand the phenotypic spectrum of PSP by adding to Richardson's syndrome (PSP-RS) other presentations such as PSP-parkinsonism (PSP-P), PSP-pure-gait-freezing (PSP-PGF), PSP-speech-language (PSP-SL), PSP-frontal (PSP-F), PSP-postural-instability (PSP-PI) and PSP-corticobasal-syndrome (PSP-CBS). Evidence about the prognostic differences between PSP phenotypes is scarce and focused on PSP-RS vs. non-PSP-RS. Using a brain-bank cohort we assessed PSP survival not only in PSP-RS vs. non-PSP-RS, but also in PSP-RS + cortical vs. subcortical phenotypes. Besides, we assessed sensitivity and specificity of the MDS-PSP criteria in of PSP and other degenerative parkinsonisms. METHODS: We retrospectively applied the MDS-PSP diagnostic criteria to 32 definite PSP cases and 30 cases with other degenerative parkinsonian syndromes (Parkinson's disease [PD; n = 11], multiple system atrophy [MSA; n = 11], corticobasal degeneration [CBD; n = 8]). We conducted survival statistics in neuropathologically confirmed PSP cases considering PSP-RS vs. non-PSP-RS and PSP-RS + PSP-cortical (PSP-F + PSP-SL + PSP-CBS) vs. PSP-subcortical (PSP-P + PSP-PGF) phenotypes. We also adjusted survival analyses for PSP tau scores. RESULTS: Diagnostic sensitivity was 100% and specificity ranged from 47% to 87% when excluding cases that met the "suggestive of PSP" definition early in their disease course but with other clinical features better matching with a non-PSP pathological diagnosis. Survival was significantly shorter in PSP-RS vs. non-PSP-RS cases, but it was more markedly shorter in PSP-RS + PSP-cortical vs. PSP-subcortical, independently of PSP tau scores, which were not associated with survival. CONCLUSIONS: PSP-subcortical phenotypes appear to have longer survival than PSP-RS and cortical phenotypes. This might be of prognostic relevance when informing patients upon clinical diagnosis.

Age of Parkinson's disease onset as a predictor for the development of dyskinesia.

The risk of developing levodopa-associated dyskinesia is known to vary inversely with the age of Parkinson's disease onset. This study quantifies dyskinesia risks for different Parkinson's onset ages in a patient population treated at the Parkinson's Disease Research, Education, and Clinical Center at the San Francisco Veterans Affairs Medical Center. Medical records were reviewed to determine age of Parkinson's onset, medication history, and dyskinesia onset. Dyskinesia risks were determined by using Kaplan-Meier analysis. Cox proportional hazard models were used to compare age groups and to perform multivariate modeling. This study included 109 patients with Parkinson's, 105 of whom had onset of symptoms after 1989. At 5 years of levodopa treatment, the dyskinesia risk for patients with onset age 40-49 was 70%, decreasing to 42% for onset ages 50-59, 33% for onset ages 60-69, and 24% for onset ages 70-79. Pairwise comparisons between the 40-49 age group and the other age groups were statistically significant in time-to-event models. After 5 years of levodopa treatment, dyskinesia risks became uniformly high regardless of age of onset. These results suggest it is appropriate to use different baseline dyskinesia risks in clinical decision-making for patients on the basis of their ages of onset. However, the most significant difference occurs between ages 40-49 and ages 50-79, and if more than 5 years of levodopa therapy are anticipated, dyskinesia risk may have less utility when deciding upon Parkinson's therapy. Drug studies for Parkinson's disease should also take age of Parkinson's onset into account when analyzing dyskinesia outcomes.

[123I]FP-CIT SPECT in Clinically Uncertain Parkinsonism Predicts Survival: A Data-Driven Analysis.

BACKGROUND: Dopamine transporter SPECT is an established method to investigate nigrostriatal integrity in case of clinically uncertain parkinsonism. OBJECTIVE: The present study explores whether a data-driven analysis of [123I]FP-CIT SPECT is able to stratify patients according to mortality after SPECT. METHODS: Patients from our clinical registry were included if they had received [123I]FP-CIT SPECT between 10/2008 and 06/2016 for diagnosis of parkinsonism and if their vital status could be determined in 07/2017. Specific binding ratios (SBR) of the whole striatum, its asymmetry (asymmetry index, AI; absolute value), and the rostrocaudal gradient of striatal binding (C/pP: caudate SBR divided by posterior putamen SBR) were used as input for hierarchical clustering of patients. We tested differences in survival between these groups (adjusted for age) with a Cox proportional hazards model. RESULTS: Data from 518 patients were analyzed. Median follow-up duration was 3.3 years [95% C.I. 3.1 to 3.7]. Three subgroups identified by hierarchical clustering were characterized by relatively low striatal SBR, high AI, and low C/pP (group 1), low striatal SBR, high AI, and high C/pP (group 2), and high striatal SBR, low AI, and low C/pP (group 3). Mortality was significantly higher in group 1 compared to each of the other two groups (p = 0.029 and p = 0.003, respectively). CONCLUSION: Data-driven analysis of [123I]FP-CIT SPECT identified a subgroup of patients with significantly increased mortality during follow-up. This suggests that [123I]-FP-CIT SPECT might not only serve as a diagnostic tool to verify nigrostriatal degeneration but also provide valuable prognostic information.

Mortality in Parkinson's disease: a 20-year follow-up study.

We determined mortality rates and predictors of survival in 238 consecutive patients with Parkinson's disease (PD) with symptom onset between 1974 and 1984. All patients were regularly followed at the Movement Disorder Clinic (Department of Neurology at the Innsbruck Medical University) until December 31, 2004, or death. As of December 31, 2004, 189 patients had died. Standardized mortality ratios (SMRs) increased over time. SMRs were 0.6 (95% CI 0.4-1.0) by 5 years, 0.9 (95% CI 0.7-1.2) by 10 years, 1.2 (95% CI 1.0-1.4) by 15 years, and 1.3 (95% CI 1.1-1.5) by 20 to 30 years. SMR for male patients was significantly increased to 1.3 (95% CI 1.1-1.6), whereas SMR increase of 1.2 (0.9-1.4) observed in female patients was not significant. Significantly increased SMRs were detected in patients with younger and older age of onset. Male gender, gait disorder, lack of tremor, and lack of asymmetry as presenting clinical features predicted poor survival in a Cox's proportional hazard analysis. This study demonstrates similar survival of patients with PD to the normal control population up to a disease duration of 10 years, followed by a modest rise of mortality with disease duration beyond 10 years compared with the general population. Under regular specialist care using all currently available therapies life expectancy in PD does not appear seriously compromised, but male gender, gait disorder, and absent rest tremor at presentation are associated with poorer long-term survival.

IL-1α and IL-6 predict vascular events or death in patients with cerebral small vessel disease-Data from the SHEF-CSVD study.

PURPOSE: The natural clinical course of cerebral small vessel disease (CSVD) was not thoroughly described. The aim of this single center cohort study was to establish biochemical predictors of vascular events and death in CSVD patients during a 24-month follow-up. PATIENTS AND METHODS: A total of 130 functionally independent patients with marked MRI features of CSVD and recent lacunar stroke (n = 52,LS), vascular Parkinsonism (n = 28,VaP) or dementia (n = 50,VaD) were prospectively recruited. Serum markers of endothelial dysfunction, inflammation and hemostasis were determined at baseline. The primary outcome was defined as occurrence of death or any vascular events during the observation. RESULTS: The mean age was 72 ± 8.1 years, and 37.6% of the patients were women. The mean follow-up time was 22.3 ± 4.3 months, and 84.6% of patients had extensive white matter lesions on baseline MRI. The overall mortality rate was 6.9%, and vascular events or death occurred in 27% of the patients. Kaplan-Meier survival curves revealed no significant differences between CSVD groups (log rank p = 0.49). Cox regression analysis revealed that IL-1α (HR 1.4; 95%CI 1.09-1.8), IL-6 (1.4;1.1-2.2), hs-CRP (1.1;1.06-1.9), homocysteine (1.4;1.1-1.8), fibrinogen (1.4;1.05-2), and d-dimer (2.7;1.6-4.5) were significantly associated with the primary outcome. IL-1α (1.3;1.07-1.8), IL-6 (1.4;1.02-2.2), d-dimer (2.8;1.6-5) and homocysteine (1.4;1.1-1.8) remained significant after adjusting for age, sex and CSVD radiological markers. CONCLUSIONS: Our study demonstrated the important prognostic role of various circulation markers of inflammation in individuals with different clinical signs and radiological markers of CSVD. The strongest association occurred between IL-1α, IL-6 and recurrent stroke, other vascular events and death.

Early predictors of mortality in parkinsonism and Parkinson disease: A population-based study.

OBJECTIVE: To examine mortality and associated risk factors, including possible effects of mild cognitive impairment, imaging, and CSF abnormalities, in a community-based population with incident parkinsonism and Parkinson disease. METHODS: One hundred eighty-two patients with new-onset, idiopathic parkinsonism were diagnosed from January 2004 through April 2009, in a catchment area of 142,000 inhabitants in Sweden. Patients were comprehensively investigated according to a multimodal research protocol and followed prospectively for up to 13.5 years. A total of 109 patients died. Mortality rates in the general Swedish population were used to calculate standardized mortality ratio and expected survival, and Cox proportional hazard models were used to investigate independent predictors of mortality. RESULTS: The standardized mortality ratio for all patients was 1.84 (95% confidence interval 1.50-2.22, p < 0.001). Patients with atypical parkinsonism (multiple system atrophy or progressive supranuclear palsy) had the highest mortality. In early Parkinson disease, a mild cognitive impairment diagnosis, freezing of gait, hyposmia, reduced dopamine transporter activity in the caudate, and elevated leukocytes in the CSF were significantly associated with shorter survival. CONCLUSION: Although patients presenting with idiopathic parkinsonism have reduced survival, the survival is highly dependent on the type and characteristics of the parkinsonian disorder. Patients with Parkinson disease presenting with normal cognitive function seem to have a largely normal life expectancy. The finding of a subtle CSF leukocytosis in patients with Parkinson disease with short survival may have clinical implications.

Parkinson Matters.

Recent epidemiological observations have drawn attention to the rapid rise in the burden caused by Parkinson's disease over the past years, emphasizing that Parkinson's disease is a matter of serious concern for our future generations. A recent report by Public Health England corroborates this message, by providing new insight on trends in deaths associated with neurological diseases in England between 2001 to 2014. The report indicates that mortality associated with Parkinson's disease and related disorders increased substantially between 2001 and 2014. This trend is partially explained by increased longevity in the population. However, it is possible that changes in exposure to risk factors, recent improvements in multidisciplinary care (leading to prolonged survival), and improved diagnostic awareness or improved registration also influenced the observed trend. Furthermore, patients with Parkinson's disease and related disorders were found to die at an advanced age, and the majority die in a care home or hospital, despite a preponderant preference for many patients and their families to spend their last days at home. To combat these concerning observations, future efforts should be focused on providing resources for vulnerable elderly Parkinson patients, avoiding unplanned hospital admissions and out-of-home deaths as much as possible. Possible solutions include a community-based network of specifically trained allied health therapists, personal case managers for Parkinson patients, dedicated Parkinson nursing homes, and improved centralised support services from university clinics to regional community hospitals aimed at facilitating optimal wide-scale care delivery.

Death certificate data and causes of death in patients with parkinsonism.

INTRODUCTION: Assessment of variables related to mortality in Parkinson disease (PD) and other parkinsonian syndromes relies, among other sources, on accurate death certificate (DC) documentation. We assessed the documentation of the degenerative disorder on DCs and evaluated comorbidities and causes of death among parkinsonian patients. METHODS: Demographic and clinical data were systematically and prospectively collected on deceased patients followed at a tertiary movement disorder clinic. DCs data included the documentation of parkinsonism, causes, and place of death. RESULTS: Among 138 cases, 84 (60.9%) male, mean age 77.9 years, mean age of onset 66.7, and mean disease duration 10.9 years. Clinical diagnoses included PD (73.9%), progressive supranuclear palsy (10.9%), multiple system atrophy (7.2%), Lewy body dementia (7.2%) and corticobasal degeneration (0.7%). Psychosis occurred in 60.1% cases, dementia in 48.5%. Most PD patients died due to heterogeneous causes before reaching advanced stages. Non-PD parkinsonian patients died earlier due to causes linked to the advanced neurodegenerative process. PD was documented in 38.4% of DCs with different forms of inconsistencies. That improved, but remained significant when it was signed by a specialist. CONCLUSIONS: More than half of PD cases died while still ambulatory and independent, after a longer disease course and due to causes commonly seen in that age group. Deaths among advanced PD patients occurred due to causes similar to what we found in non-PD cases. These findings can be useful for clinical, prognostic and counseling purposes. Underlying parkinsonian disorders are poorly documented in DCs, undermining its' use as sources of data collection.

Outcome of gastrostomy in parkinsonism: A retrospective study.

OBJECTIVE: To investigate the indications and the outcomes of gastrostomy tube insertion in patients with parkinsonian syndromes. METHODS: Consecutive patients with Parkinson's disease or atypical parkinsonism, seen in two French tertiary referral movement disorders centers, that received gastrostomy tube insertion (GTI) for feeding between 2008 and 2014 were included in this retrospective study. Data regarding clinical status, indications and outcomes were retrieved from medical files. The main outcome measure was survival duration following gastrostomy insertion according to Kaplan-Meier estimate. Cox analysis was also performed to identify factors associated with survival. Finally, we described short term and long term adverse effects occurring during the follow-up period. RESULTS: We identified 33 patients with Parkinsonism that received GTI during the study period. One patient was excluded from the analysis because of missing data. Among 32 patients, 7 (22%) had Parkinson's disease and 25 (78%) had atypical parkinsonism. The median survival following the procedure was 186 days (CI 95% [62-309]). In Cox model analysis, total dependency was the only factor negatively associated with survival (HR 0.1; 95% CI [0.02-0.4], p = 0.001). Pneumonia was the most frequent adverse event. CONCLUSION: In this sample of patients with parkinsonian syndromes, survival after GTI was short particularly in totally dependent subjects. Aspiration pneumonia was not prevented by GTI. A larger prospective study is warranted to assess the potential benefits of gastrostomy, in order to identify the most appropriate indications and timing for the procedure.

Survival and Causes of Death Among People With Clinically Diagnosed Synucleinopathies With Parkinsonism: A Population-Based Study.

Importance: To our knowledge, a comprehensive study of the survival and causes of death of persons with synucleinopathies compared with the general population has not been conducted. Understanding the long-term outcomes of these conditions may inform patients and caregivers of the expected disease duration and may help with care planning. Objective: To compare survival rates and causes of death among patients with incident, clinically diagnosed synucleinopathies and age- and sex-matched referent participants. Design, Setting, and Participants: This population-based study used the Rochester Epidemiology Project medical records-linkage system to identify all residents in Olmsted County, Minnesota, who received a diagnostic code of parkinsonism from 1991 through 2010. A movement-disorders specialist reviewed the medical records of each individual to confirm the presence of parkinsonism and determine the type of synucleinopathy. For each confirmed patient, an age- and sex-matched Olmsted County resident without parkinsonism was also identified. Main Outcomes and Measures: We determined the age- and sex-adjusted risk of death for each type of synucleinopathy, the median time from diagnosis to death, and the causes of death. Results: Of the 461 patients with synucleinopathies, 279 (60.5%) were men, and of the 452 referent participants, 272 (60.2%) were men. From 1991 through 2010, 461 individuals received a diagnosis of a synucleinopathy (309 [67%] of Parkinson disease, 81 [17.6%] of dementia with Lewy bodies, 55 [11.9%] of Parkinson disease dementia, and 16 [3.5%] of multiple system atrophy with parkinsonism). During follow-up, 68.6% (n = 316) of the patients with synucleinopathies and 48.7% (n = 220) of the referent participants died. Patients with any synucleinopathy died a median of 2 years earlier than referent participants. Patients with multiple system atrophy with parkinsonism (hazard ratio, 10.51; 95% CI, 2.92-37.82) had the highest risk of death compared with referent participants, followed by those with dementia with Lewy bodies (hazard ratio, 3.94; 95% CI, 2.61-5.94), Parkinson disease with dementia (hazard ratio, 3.86; 95% CI, 2.36-6.30), and Parkinson disease (hazard ratio, 1.75; 95% CI, 1.39-2.21). Neurodegenerative disease was the most frequent cause of death listed on the death certificate for patients, and cardiovascular disease was the most frequent cause of death among referent participants. Conclusions and Relevance: Individuals with multiple system atrophy with parkinsonism, dementia with Lewy bodies, and Parkinson disease dementia have increased mortality compared with the general population. The mortality among persons with Parkinson disease is only moderately increased compared with the general population.

Subcutaneous rotenone rat model of Parkinson's disease: Dose exploration study.

Subcutaneous administration of rotenone has recently attracted attention because of its convenience, simplicity and efficacy in replicating features of Parkinson's disease (PD) in animal models. However, the wide range of doses reported in the literature makes it difficult to evaluate the effectiveness of this technique objectively. The aim of the present study was to identify the optimum dose of subcutaneous rotenone for establishing a model of PD. We injected male Wistar rats subcutaneously with one of three doses of rotenone (1.5, 2, or 2.5mg/kg) daily for 5 weeks. Rotenone caused a dose-dependent increase in α-synuclein in the substantia nigra. Furthermore, at 2 and 2.5mg/kg, rotenone caused a significant decrease in the number of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra, and dopamine in the striatum. However, mortality at 2.5mg/kg was 46.7%, compared with just 6.7% at 2mg/kg; the high mortality observed at 2.5mg/kg would limit its application. The 2mg/kg dose showed no detrimental effect on body weight after 5 weeks of daily injections. Furthermore, rats in the 2mg/kg group showed a longer latency to descend from a horizontal bar and a grid wall, decreased rearing, and shorter latency to fall from a rotarod than rats that received vehicle or saline. Mitochondrial damage, observed by transmission electron microscopy, was also evident at this dose. Together, our data indicate that daily subcutaneous injection of 2mg/kg rotenone in rats facilitates the formation of α-synuclein and reproduces the typical features of PD, while maintaining low mortality.