Survival In Parkinson's Disease Research Articles

NfL as a biomarker for neurodegeneration and survival in Parkinson disease.

ObjectiveTo determine whether neurofilament light chain protein in CSF (cNfL), a sensitive biomarker of neuroaxonal damage, reflects disease severity or can predict survival in Parkinson disease (PD).MethodsWe investigated whether disease severity, phenotype, or survival in patients with new-onset PD correlates with cNfL concentrations around the time of diagnosis in the population-based New Parkinsonism in Umeå (NYPUM) study cohort (n = 99). A second, larger new-onset PD cohort (n = 194) was used for independent validation. Association of brain pathology with the cNfL concentration was examined with striatal dopamine transporter imaging and repeated diffusion tensor imaging at baseline and 1 and 3 years.ResultsHigher cNfL in the early phase of PD was associated with greater severity of all cardinal motor symptoms except tremor in both cohorts and with shorter survival and impaired olfaction. cNfL concentrations above the median of 903 ng/L conferred an overall 5.8 times increased hazard of death during follow-up. After adjustment for age and sex, higher cNfL correlated with striatal dopamine transporter uptake deficits and lower fractional anisotropy in diffusion tensor imaging of several axonal tracts.ConclusionscNfL shows usefulness as a biomarker of disease severity and to predict survival in PD. The present results indicate that the cNfL concentration reflects the intensity of the neurodegenerative process, which could be important in future clinical trials.Classification of evidenceThis study provides Class II evidence that in patients with PD, cNfL concentrations are associated with more severe disease and shorter survival.

Editors' note: Early predictors of mortality in parkinsonism and Parkinson disease: A population-based study

Using a long-term observational cohort based out of northern Sweden, Bäckström et al reported several independent clinical and laboratory biomarkers of survival in Parkinson disease (PD) and parkinsonism. Unsurprisingly, a shorter life expectancy was noted in older patients; patients with mild cognitive impairment, postural imbalance, or gait disorder; patients with more severe hyposmia; and patients who had progressive supranuclear palsy or multiple system atrophy rather than idiopathic PD. Of interest, an inflammatory CSF profile was also independently predictive of a shorter life expectancy (adjusted hazard ratio for death 6.31, 95% confidence interval 3.04–13.12). This is consistent with existing observational data that anti-inflammatory drugs may lower the risk of PD. Dr. Keller comments on the implications of these biomarkers for patients with early-onset PD (EOPD), suggesting that patients with EOPD may also have a shorter life expectancy compared with age-matched controls. However, only 3 of the 143 patients with PD in this study had EOPD, thereby limiting a formal subgroup analysis. Lengthier observational cohorts—with a larger number of patients with EOPD—may better elucidate the effect size of these and other survival biomarkers in patients with PD and parkinsonism. Using a long-term observational cohort based out of northern Sweden, Bäckström et al reported several independent clinical and laboratory biomarkers of survival in Parkinson disease (PD) and parkinsonism. Unsurprisingly, a shorter life expectancy was noted in older patients; patients with mild cognitive impairment, postural imbalance, or gait disorder; patients with more severe hyposmia; and patients who had progressive supranuclear palsy or multiple system atrophy rather than idiopathic PD. Of interest, an inflammatory CSF profile was also independently predictive of a shorter life expectancy (adjusted hazard ratio for death 6.31, 95% confidence interval 3.04–13.12).

Survival in Parkinson disease, the Trondheim cohort (P5.8-032)

Survival in Parkinson disease, the Trondheim cohort (P5.8-032)

Effect of extended care on cognitive function and quality of life in patients with Parkinson's disease

Objective To explore the effect of extended care on cognitive function and quality of life in patients with Parkinson's disease. Methods A total of 36 patients with Parkinson's disease who received treatment from October 2015 to April 2016 were treated as the control group, and the routine nursing intervention was given and the health guidance was given after discharge.A total of 35 patients with Parkinson's disease who received treatment from May to November 2016 were selected as the observation group.Cognitive function changes were assessed using the Montreal cognitive assessment scale (MoCA). The survival quality of patients was evaluated by Parkinson's disease survival quality questionnaire (PDQ-39). The Hamilton Depression Rating Scale (HAMD) was used to evaluate the changes of depression. Results After intervention, the observation group's attention, visual space and execution ability, language ability, orientation force, delayed recall naming ability and MoCA total score were significantly higher, and significantly higher than the control group.The differences were statistically significant (P<0.05). After treatment, the language ability, delayed recall, naming ability and MoCA score of the control group increased significantly (P<0.05). After the treatment, the two groups were significantly reduced in their daily life, cognitive ability, motor ability, interpersonal communication, physical discomfort, emotion, shame and total score (P<0.05). After treatment, the observation group was significantly lower than the control group in daily life, cognitive ability, exercise ability, interpersonal communication, physical discomfort, emotion, shame, and total score.The differences were statistically significant (P<0.05). After treatment, the HAMD scores of the two groups were significantly lower (P<0.05). After treatment, the HAMD score of the observation group was significantly lower than that of the control group.The difference was statistically significant (P<0.05). Conclusions Extended care can significantly improve the cognitive function and improve the quality of life in patients with Parkinson's disease. Key words: Extended care; Parkinson disease; Cognitive function; Quality of life

Association of Autonomic Dysfunction With Disease Progression and Survival in Parkinson Disease

Evidence suggests that development of autonomic dysfunction (AutD) may negatively affect disease course and survival in patients with synucleinopathies. However, the few available studies on Parkinson disease (PD) have conflicting results, comprise a small number of patients, have short follow-up periods, and lack pathologic confirmation of the diagnosis. To examine the association of time of onset of AutD with disease progression and survival in PD. This retrospective review of clinical data from 100 consecutive patients with an autopsy-confirmed diagnosis of PD from the archives of the Queen Square Brain Bank in London, United Kingdom, from January 1, 2006, to June 3, 2016, included patients with PD regularly seen by hospital specialists (neurologists or geriatricians) in the United Kingdom throughout their disease until death. Patients with dementia before or within 1 year after onset of motor symptoms, monogenic forms of PD, comorbidities that affect autonomic function, a coexisting neuropathologic diagnosis, or insufficient clinical information were excluded. Survival and time from diagnosis to specific disease milestones were calculated to assess disease progression. Autonomic dysfunction was defined as autonomic failure at autonomic function testing or 2 of the following symptoms: urinary symptoms, constipation, upper gastrointestinal tract dysfunction, orthostatic hypotension, sweating abnormalities, or erectile dysfunction. Multivariable Cox proportional hazards regression models on the risk of a disease milestone and death were used. A total of 100 patients (60 [60.0%] male; mean [SD] age at diagnosis, 63.9 [10.3] years; mean [SD] disease duration, 14.6 [7.7] years) were studied. Autonomic dysfunction developed in 85 patients (mean [SD] time from diagnosis, 6.7 [7.7] years) and was associated with older age at diagnosis, male sex, poor initial levodopa treatment response, and postural instability and gait difficulty motor PD subtype in linear regression analysis, but staging of α-synuclein pathologic changes was unrelated. Earlier AutD increased the risk of reaching the first milestone (hazard ratio, 0.86; 95% CI, 0.83-0.89; P < .001) and shortened survival (hazard ratio, 0.92; 95% CI, 0.88-0.96; P < .001). Older age at diagnosis and poorer levodopa treatment response were the other factors associated with shorter survival in adjusted multivariate analysis. Earlier AutD is associated with a more rapid development of disease milestones and shorter survival in patients with PD.

Dopamine transporter imaging does not predict the number of nigral neurons in Parkinson disease.

To examine possible associations between in vivo brain dopamine transporter SPECT imaging and substantia nigra pars compacta (SNc) neuronal survival in Parkinson disease (PD). Nigral neuron numbers were calculated for 18 patients (11 patients with neuropathologically confirmed PD) who had been examined with dopamine transporter (DAT) SPECT before death. Correlation analyses between SNc tyrosine hydroxylase (TH)-positive and neuromelanin-containing neuron counts and DAT striatal specific binding ratios (SBRs) were performed with semiquantitative region of interest-based and voxel-based analyses. Mean putamen SBR did not correlate with the number of substantia nigra TH-positive (r = -0.11, p = 0.66) or neuromelanin-containing (r = -0.07, p = 0.78) neurons. Correlations remained clearly nonsignificant when the time interval between SPECT and death was used as a covariate, when the voxel-based analysis was used, and when only patients with PD were included. This cohort study demonstrates that postmortem SNc neuron counts are not associated with striatal DAT binding in PD. These results fit with the theory that there is no correlation between the number of substantia nigra neurons and striatal dopamine after a certain level of damage has occurred. Striatal DAT binding in PD may reflect axonal dysfunction or DAT expression rather than the number of viable neurons.

Dementia and survival in Parkinson disease

The risk for dementia in Parkinson disease (PD) is high, with important clinical consequences for patients with PD. However, the absolute risk of dementia and how it affects survival in PD are not known. Such questions are important for patients, their families, and service providers but require long-term studies. This study is a prospective longitudinal cohort study with patients from a prevalence study of PD in Norway. Patients were reassessed 4, 8, 9, 10, 11, and 12 years after prevalence day. A dementia diagnosis according to Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, criteria was based on a semistructured caregiver interview, cognitive rating scales, and neuropsychological tests. Progression from PD to PD with dementia and death was modeled using a continuous-time three-state irreversible Markov model. A total of 233 PD patients were included, and 140 patients (60%, 95% CI 54% to 66%) had developed dementia by the end of the study period. The cumulative incidence of dementia steadily increases with age and duration of PD and, conditional on survival, increases to 80% to 90% by age 90 years. Women live with PD longer than men and spend more years with dementia. At age 70 years, a man with PD but no dementia has a life expectancy of 8 years, of which 5 years would be expected to be dementia free and 3 years would be expected to be with dementia. Dementia is a key part of survival in Parkinson disease and must be planned for in services for this condition.

Survival in Parkinson disease

To investigate predictors of survival in Parkinson disease (PD). Vital status was determined in 800 subjects enrolled in a clinical trial of deprenyl (selegiline) and tocopherol 13 years earlier. Two hundred ninety-six deaths were recorded. There was no difference in the standardized mortality ratios across gender or age group. In univariate analyses, PD-specific variables associated with mortality were increased symmetry of parkinsonism, gait dysfunction as an initial symptom, severity of parkinsonism, and rate of worsening of parkinsonism prior to study enrollment. Cumulative exposure to deprenyl was not associated with mortality. In multivariable analysis, severity of parkinsonism and rate of worsening of parkinsonism remained associated with mortality. A poorer response to levodopa was associated with increased mortality independent of disease severity or dosage of levodopa. Results were unchanged when the analysis was restricted to 747 subjects maintaining a most likely diagnosis of PD throughout 6 years of active follow-up. Parkinson disease did not affect survival differently across gender or age groups in this selected group of otherwise healthy clinical trial participants. Severity and rate of worsening of parkinsonism and response to levodopa are strongly related to survival.