Depression and apathy in Parkinson’s disease

This article provides an update on depression and apathy in Parkinson’s disease (PD), both of which are common but often misunderstood. The diagnosis of depression in PD can be challenging and we still do not have solid evidence on which to base our treatment decisions. Apathy is most commonly seen in the setting of dementia or depression but emerging evidence suggests that it may be a core feature of PD. There are conflicting reports about the effects of deep brain stimulation (DBS) on mood and apathy, but studies suggest that at least some patients may develop depression and apathy after the procedure. Although we are making strides toward a better understanding of depression and apathy in PD, it is clear that more research is needed about these non-motor features.     

Depression in Parkinson’s disease

Abstract Objectives The pathophysiology of depression and anxiety in Parkinson's disease remains obscure. We aimed to compare the fractional anisotropy (FA) values of Parkinson's disease (PD) patients with and without depression to investigate the nature of depression in PD. Methods Twenty-eight patients were divided into two groups: those with depression and those without. Diagnosis of depression was made using the DSM-IV criteria. Patients in the two groups were matched for Hoehn Yahr stage. Results There were significant reductions in FA values in the bilateral frontal ROIs possibly representing anterior cingulate bundles. Conclusions The anterior cingulate bundles play an important role in depression in PD, and some aspects of depression in PD have pathological processes in common with de novo depression.     

Depression in Parkinson’s disease

Depression is common in Parkinson’s disease (PD), and its identification and treatment are critically important in disease management. Despite depression’s high prevalence and major impact on patient quality of life, questions remain regarding its epidemiology and preferred treatment. The authors of this paper summarize available information on the epidemiology of depression in PD, review treatment options, and discuss possible interactions between antidepressants and other agents. This information may help guide clinical treatment and define the need for further studies.     

Depression in Parkinson’s disease

Among the recently well appreciated non-motor symptoms in Parkinson’s disease (PD), depression plays a prominent role due to its frequency and impact on quality of life. However, depression may be confounded by motor symptoms, especially akinesia and other non-motor symptoms such as apathy, anxiety and dementia. Data on specific diagnostic tools or treatment for depressive symptoms in PD patients are still sparse. Here we summarize an expert opinion based on available data and clinical experience.

     

Caregiving and Parkinson’s disease

Abstract. Relatively little has been published in the international literature concerning the caregiving-related problems associated with Parkinsons disease. We therefore undertook two exploratory studies that have allowed us to identify the needs and specific problems perceived by such caregivers in both qualitative and quantitative terms.     

Rifampicin and Parkinson’s disease

Rifampicin is a macrocyclic antibiotic used extensively for the treatment of Mycobacterium tuberculosis and other mycobacterial infections. Recently, it was discovered that rifampicin exhibits neuroprotective effects. It has been shown to protect PC12 cells against MPP⁺-induced apoptosis and inhibit the expression of α-synuclein multimers. In in vitro studies, rifampicin pretreatment protects PC12 cells against rotenone-induced cell death. Qualitative and quantitative analyses uncover that rifampicin significantly suppresses rotenone-induced apoptosis by ameliorating mitochondrial oxidative stress. It reduces microglial inflammation and improves neuron survival. Our results indicate that rifampicin is cytoprotective under a variety of experimental conditions, and suggest that it may be useful in PD therapeutics. It is the aim of this paper to review the experimental neuroprotection data reported using rifampicin with a focus on the molecular and cellular mechanisms of cytoprotective effect in in vitro models of PD.     

Stem cells and Parkinson’s disease

Totally three articles focusing on bone marrow mesenchymal stem cells alleviating PC12 cytotoxicity induced by 6-hydroxydopamine and intracerebroventricular transplantation of non-modified/gene-modified     

Parkinson’s disease and dopaminergic neurons

Totally three articles focusing on gene therapy of Parkinson’s disease, the effect of levodopa on toxicity of dopaminergic neurons in substantia nigra and striatum, and the effect of rifampicin on reducing Parkinson’s disease-induced dopaminergic neuronal apoptosis     

Glial cells and Parkinson’s disease

Parkinson’s disease is a neurodegenerative disease characterised by a massive loss of dopaminergic neurons in the substantia nigra. Yet glial cells may also participate in the pathophysiology of the disease. Indeed, glial cells can produce trophic factors which may stimulate neuronal survival or, alternatively, they could produce toxic compounds which may be involved in neuronal degeneration. This paper reviews the potentially protective or deleterious effects of glial cells in the substantia nigra of patients with Parkinson’s disease.

     

Amyloid-β and Parkinson’s disease

Journal of Neurology - Parkinson’s disease (PD) is the second commonest neurodegenerative disorder in the world with a rising prevalence. The pathophysiology is multifactorial but aggregation...     

Gender and the Parkinson’s disease phenotype

Objectives To determine whether there are gender differences in the Parkinson’s disease (PD) phenotype using a large clinic–based cohort. Methods We examined gender differences in demographic, historical and clinical characteristics in a consecutive clinical series of 1264 individuals diagnosed with PD. Results The majority of individuals in the sample were male (67 %). Comparative analyses showed males and females were not significantly different on most demographic and historical characteristics. For both genders, the mean age and the mean age at symptomatic onset were about 70 and 63 years, respectively and, thus, disease duration was not significantly different between genders. The proportion of individuals with a positive family history of PD (15 %) was similar for both genders. A positive history of depression was significantly higher in females (35 % vs. 24 %). The UPDRS instability score was significantly worse among females, whereas the rigidity score was significantly worse for males. Females showed significantly worse ADL capacity and a more advanced H&Y stage. The proportion of individuals receiving antiparkinsonian medication (about 66 %) and time between the last dose and the clinical evaluation (about 4 hours) was similar for both genders. There was a trend for lower daily levodopa equivalence dosage and more severe dyskinesia score among females but these differences did not reach statistical significance after Bonferroni correction. Conclusions The majority of comparisons tended to highlight the commonalities in the PD phenotype between genders, particularly in reference to historical and early disease stage characteristics. However, gender may be an important factor related to the expression of PD features during the symptomatic disease course.     

Parkinson’s disease and the gastrointestinal microbiome

Journal of Neurology - Recently, there has been a surge in awareness of the gastrointestinal microbiome (GM) and its role in health and disease. Of particular note is an association between the GM...     

Astrocytes and therapeutics for Parkinson’s disease

Astrocytes play direct, active, and critical roles in mediating neuronal survival and function in various neurodegenerative disorders. This role of astrocytes is well illustrated in amyotrophic lateral sclerosis (ALS), in which the removal of glutamate from the extracellular space by astrocytes confers neuroprotection, whereas astrocytic release of soluble toxic molecules promotes neurodegeneration. In recent years, this context-dependent dual role of astrocytes has also been documented in experimental models of Parkinson’s disease. The present review addresses these studies and some potential mechanisms by which astrocytes may influence the neurodegenerative processes in Parkinson’s disease, and in particular examines how astrocytes confer neuroprotection either through the removal of toxic molecules from the extracellular space or through the release of trophic factors and antioxidant molecules. In contrast, under pathological conditions, astrocytes release proinflammatory cytokines and other toxic molecules that are detrimental to dopaminergic neurons. These emerging roles of astrocytes in the pathogenesis of Parkinson’s disease constitute an exciting development with promising novel therapeutic targets.     

Depression in Alzheimer’s disease and other dementias

Much of our current knowledge about depression in Alzheimer’s disease and other dementias is based on the 1991 National Instiute of Health Consensus Development Panel on the Diagnosis and Treatment of Depression in Late Life, and its subsequent 1997 update. However, much research has taken place since these reports. This article summarizes this research, particularly research that has taken place in the past year. Comorbid depression is common in all types of dementia. It may, however, appear to be different from classic depression. Unlike classic depression, the depression found in dementia may result from anatomic damage to the brain. This is most clearly demonstrated in vascular depression. The implications of this are many. Treatments for depression are designed for classic depression. For those with vascular depression (and other depressions associated with dementia) treatments may not be as efficacious. Newer strategies, including agents not commonly thought of as antidepressants, may be needed.     

Neurotoxicological and neuroprotective elements in Parkinson’s disease

SNpc neurons are uniquely at risk from damage by a variety of ROS, including catechol-quinones formed from autoxidation of DA; as well as Tyr O^., TyrOOH, H₂O₂, O₂^−., NO^., HONOO⁻, and HO^.. The high content of Fe²⁺ in SNPc neurons further promotes HO^. formation. Self-preservation ensures that SNpc cells are endowed with a battery of cellular antioxidants, which deactivate these cytotoxic species. Most notable are catalase, superoxide dismutase; and DT-diaphorase, which catalyzes a 2-electron reduction of catechol-quinones. Intra mitochondrial MAO can serve to protect or to damage SNpc neurons, depending on the cellular environ at any time. Newer treatment approaches towards PD include the addition of nutrients such as vitamin E and addition of antioxidant drugs that may already be in use as antiparkinsonians: deprenyl, amantadine, DA D₂ agonists, apomorphine, NMDA- and adenosine A2A-antagonists. Finally, the potential of neural transplants is explored in the proposal that Sertoli cells, or specific neural cells, or placental blood stem cells will find “routine” use instead of fetal neural cells in the treatment of last-resort for PD.     

Heart rate variability and Parkinson’s disease severity

Summary. Heart rate variability (HRV) decrease in Parkinsons disease (PD) could only be a consequence of reduce motor activity besides of being a marker of cardiovascular dysautonomia. Under continuously recorded and standardised motor activity, we studied thirty patients compared to controls in 3 PD stages: group I: less than 2 year-evolution, slight impaired without L-dopa; group II: mildly impaired with L-dopa; group III: advanced PD with motor complications. No difference was observed between group I and controls. The diurnal low frequency power (LF) and the ratio of LF/high frequency (HF) power decreased in groups II and III. The nocturnal vagal indicators: HF power and pNN50 were decreased in group III. Those parameters were correlated with Off-drug-motor handicap, suggesting an evolutive HRV decrease with disease severity but not with On-drug-motor activity. The low LF despite the higher motor activity in group III, due to dyskinesias, suggested a defective cardiovascular up-regulation.Received January 15, 2003; accepted April 9, 2003 Published online June 10, 2003