Are patients with Parkinson's disease suicidal?

Using the National Center of Health Statistics' mortality statistics databases for 1991 through 1996 (12,430,473 deaths), we isolated 144,364 individuals 40 years of age or older with a primary diagnosis of Parkinson's disease (PD). Of these, 122 died by suicide. The rate of suicide in the general population was about 10 times higher than in patients with PD (0.8% compared with only 0.08%, respectively). These different rates of suicide cannot be attributed to differences in age, gender, race, education, or marital status. Compared with patients with suicidal PD, patients with PD who died from other causes manifested significantly lower rates of affective disorders. The referent population exhibited a higher rate of malignancy and a lower rate of depression. The findings suggest that marital status, mood disorder, and somatic comorbidity provide only a limited understanding of completed suicide.     

Alpha-synuclein is present in dental calculus but not altered in Parkinson’s disease patients in comparison to controls

Introduction

In autopsy cases staged for sporadic Parkinson’s disease (PD), the neuropathology is characterized by a preclinical phase that targets the enteric nervous system of the gastrointestinal tract (GIT). Therefore, the ENS might be a source of potential (presymptomatic) PD biomarkers.

Methods

In this clinically based study, we examined the alpha-synuclein (αSyn) concentration in an easily accessible protein storage medium of the GIT, dental calculus, in 21/50 patients with PD and 28/50 age- and gender-matched controls using ELISA.

Results

αSyn was detectable in dental calculus and the median concentration in the control patients was 8.6 pg/mg calculus (interquartile range 2.6–13.1 pg/mg). αSyn concentrations were significantly influenced by blood contamination and samples with a hemoglobin concentration of?>?4000 ng/mL were excluded. There was no significant difference of αSyn concentrations in the dental calculus of PD patients (5.76 pg/mg, interquartile range 2.91–9.74 pg/mg) compared to those in controls (p?=?0.40).

Conclusion

The total αSyn concentration in dental calculus is not a suitable biomarker for sporadic PD. Disease-related variants such as oligomeric or phosphorylated αSyn in calculus might prove to be more specific.

     

Are hospitalized Parkinson’s disease patients more likely to carry a do-not-resuscitate order?

While DNR utilization is a complex subjective phenomenon, the effect of such a decision can collectively influence attitudes of care. The role of palliative care in advanced PD has been under appreciated. We reviewed the Healthcare Cost and Utilization Project’s National Inpatient Sample (NIS) database from 2012 for all hospitalizations ⩾65 years. We identified PD by using ICD-9-CM code 332.0 and DNR status with ICD code – V49.86 entered during the same admission as a secondary diagnosis. We estimated risk of mortality by the 3 M™ All Patient Refined DRG (APR DRG) classification System and generated multivariate regression models to assess associations between DNR and PD after adjusting for confounders. Finally, we tested for interaction by risk of mortality. We analyzed 12,700,000 hospitalizations with age ⩾65 years in 2012, of which 246625 (1.94%) pts had PD. Proportion of DNR utilization was higher among PD patients vs. those without, 20895 (8.47%) vs. 723090 (5.8%) (p < 0.01). In multivariable regression analysis, PD patients were associated with higher odds of DNR utilization [Adjusted Odds ratio (aOR): 1.26, 95% CI: 1.21, 1.30, p < 0.001]. Finally, the odds of DNR utilization increased significantly with APR-DRG stage [aOR: 1 vs. 1.61 (Stage 2) vs. 2.46 (Stage 3) vs. 3.61 (Stage 4); p < 0.0001]. PD patients have higher odds of DNR utilization than the general population, which worsens with increasing objective risk of mortality. This is likely correlated with perception of end of life and importance of QOL with increasing severity of overall illness.     

Striatal β-amyloid in dementia with Lewy bodies but not Parkinson’s disease

Professor Jellinger first identified that striatal Aβ deposition at postmortem seemed to differentiate cases of dementia with Lewy bodies (DLB) from those with Parkinson’s disease dementia (PDD), a finding subsequently questioned. Our replication study in 34 prospectively studied cases assessed the ability of striatal Aβ deposition to differentiate DLB from PDD, and also assessed the relationship between striatal and cortical Aβ deposition and α-synuclein-immunoreactive pathologies, using previously published protocols. Cases with DLB had significantly shorter durations and greater dementia severities compared with cases with PDD. Striatal Aβ-immunoreactive plaques were only consistently found in cases with DLB and correlated with both the severity (positive correlation) and duration (negative correlation) of dementia. Striatal Aβ-immunoreactive plaques also positively correlated with the severity of α-synuclein-immunoreactive pathologies as well as cortical Aβ-positive plaques. Striatal Aβ deposition positively predicted dementia in Lewy body cases with high specificity and had the greatest sensitivity to differentiate DLB from PDD with 100% negative predictive value. These data suggest that striatal Aβ deposition in Lewy body diseases contributes to early dementia and in these cases may impact on the efficacy of treatments targeting the striatum.     

Duration of disease does not equally influence all aspects of quality of life in Parkinson’s disease

Health related quality of life (HRQoL) is negatively impacted in patients suffering from Parkinson’s disease (PD). For the specific components that comprise HRQoL, the relationship between clinical variables, such as disease duration, is not fully characterized. In this cross-sectional study (n = 302), self-reported HRQoL on the Parkinson’s Disease Questionnaire (PDQ-39) was evaluated as a global construct as well as individual subscale scores. HRQoL was compared in three groups: those within 5 years of diagnosis, those within 6–10 years of diagnosis, and those greater than 11 years since diagnosis. Non-parametric analyses revealed lower HRQoL with increasing disease duration when assessed as a global construct. However, when subscales were evaluated, difficulties with bodily discomfort and cognitive complaints were comparable in individuals in the 1–5 years and 6–10 year duration groups. Exploratory regression analyses suggested disease duration does explain unique variance in some subscales, even after controlling for Hoehn and Yahr stage and neuropsychiatric features. Our findings show that HRQoL domains in PD patients are affected differentially across the duration of the disease. Clinicians and researchers may need to tailor interventions intended to improve HRQoL at different domains as the disease progresses.     

When do patients with Parkinson disease disclose their diagnosis?

The authors surveyed 101 patients with Parkinson disease (PD) about their experiences disclosing the diagnosis. Ninety percent disclosed early to family; more than 25% waited at least 1 year to disclose at work. The main concerns about disclosure were fear of reflecting negatively on themselves and fear of upsetting others. Patients who delayed disclosure were more likely male, younger, and employed. There is considerable variability among patients with PD in the time to disclose their diagnosis.     

How might physical activity benefit patients with Parkinson disease?

Parkinson disease (PD) is a neurodegenerative disorder characterized by progressive motor and nonmotor impairments. These impairments incline many patients towards a sedentary lifestyle, which has many deleterious consequences. Accumulating evidence suggests that patients with PD might benefit from physical activity and exercise in a number of ways, from general improvements in health to disease-specific effects and, potentially, disease-modifying effects (suggested by animal data). Many issues remain to be addressed, including the need to perform clinical trials to demonstrate these presumed benefits of physical activity and exercise in patients with PD. These trials must also address safety issues, such as an increased risk of falls and cardiovascular complications in more-active patients. Identifying ways to induce a sustained behavioral change, using specifically tailored programs that address potential barriers such as depression, apathy and postural instability, may lead to an improved quality of life in individuals with PD.     

Are peripheral blood cells from patients with Alzheimer disease more sensitive to apoptotic stimuli?

One of the reasons for the increased susceptibility to infections in patients with Alzheimer disease may be enhanced apoptotic death of their peripheral leukocytes. If this is the case, the enhanced apoptosis may be due to components in the patients' sera or to an increased sensitivity of the cells to apoptotic stimuli. To examine this possibility, the percentage of apoptotic cells in the peripheral blood mononuclear cells (PBMC) from 12 patients with Alzheimer disease was compared with that of 12 age-matched non-demented persons and 12 middle-aged healthy control subjects. In addition, the effect of sera from subjects in the three groups on the apoptosis, interleukin (IL)-1beta, IL-2, IL-6, IL-10, and tumor necrosis factor (TNF)alpha production by peripheral blood cells from healthy control subjects was examined. It was found that the percentage of apoptotic PBMC from patients with Alzheimer disease was higher than that from the remaining two groups. However, incubation of control cells with sera from patients with Alzheimer disease and non-demented elderly persons did not affect the number of apoptotic cells. Sera from patients with Alzheimer disease and non-demented elderly subjects caused an increase in IL-2 and a decrease in IL-10 production by PBMC from middle-aged control subjects but did not affect IL-1beta, IL-6, and TNFalpha secretion, indicating alterations of the immune system related to aging.     

Are all antidepressants alike?

Antidepressants are indicated in about 40 different disorders, including mood disorders, anxiety disorders, and other disorders. We propose to call these disorders antidepressani-responsive disorders (ARDs). We describe the clinical and biological criteria that differentiate the antidepressants. Although antidepressants share the same clinical efficacy in most ARDs, the configuration of adverse drug reactions varies widely. The recent antidepressants should be preferred to the tricyclic antidepressants as first-line treatment because of their lesser risk of severe adverse drug reactions. However, several recent antidepressants have been associated with severe complications such as the serotonin syndrome and the withdrawal syndrome. Patient characteristics should be included as a criterion to predict both unwanted and favorable effects.     

Are γ-secretase inhibitors detrimental for Alzheimer's disease patients?

The recent failure of semagacestat in two large Phase III studies questions the value of γ-secretase inhibitors in treating Alzheimer's disease. Understanding the reasons of this setback may be important for the future research on effective treatments for this devastating disease.     

Upper gastrointestinal findings in Huntington’s disease: patients suffer but do not complain

We investigated, retrospectively, the prevalence of gastroesophageal inflammation in patients with Huntington’s disease (HD) during 10 years in our center. We found a high prevalence of gastritis or esophagitis even in patients without complaints, indicating that gastrointestinal disease is more common in HD than patients’ complaints. There was no correlation with motor disturbances but with the duration and severity of HD. Influences from the disease itself as well as secondary mechanisms like malnutrition, medication and general disability may contribute.