The personality associated with Parkinson’s disease

Since at least 1913 reports have suggested there are personality traits and behaviors that are found premorbidly in those who go on to develop Parkinson’s disease (PD). This premorbid personality consists of traits such as industriousness, punctuality, inflexibility, cautiousness, and lack of novelty seeking and persists after the onset of the motor illness. The existence of this personality remains controversial but is supported by case-based anecdotes, twin studies, and comparison of patients with PD with medical control patients on standardized instruments. In addition a large number of epidemiologic studies show that people who develop PD have low lifetime risks for cigarette smoking, coffee drinking, and alcohol consumption, again suggesting that there is a behavior pattern that predates PD. Despite the retrospective nature of much of these data, the use of nonstandardized instruments, and diffuse concepts of personality, the great majority of studies show striking similarity in identifying these traits. An integrating hypothesis, involving damage to dopaminergic systems, known to predate the onset of the motor illness, is discussed.     

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.     

Depression and Parkinson’s disease

Abstract.   Depression occurs in approximately 45% of all patients with Parkinsons disease (PD), reduces quality of life independent of motor symptoms and seems to be underrated and undertreated. Characteristics of symptoms differ from major depression. Because of overlapping clinical symptoms, diagnosis is based on subjectively experienced anhedonia and feeling of emptiness. Available rating scales for major depression may not be adequate to correctly measure severity of depression in PD. Anxiety and depression may manifest as first symptoms of PD many years before motor symptoms. Serotonergic, noradrenergic and dopaminergic mechanisms play key roles in the etiology of depression in PD. Tricyclic and newer, selective antidepressants including serotonin and noradrenaline reuptake inhibitors (SSRI, SNRI) appear to be effective in treating depression in PD. Selective reuptake inhibitors seem to have a favorable side effect profile. Recent controlled studies show antidepressant effects of pramipexole in bipolar II depression. New dopamine agonists pramipexole and ropinirole appear to ameliorate depressive symptoms in PD in addition to effects on motor symptoms. There is a lack of appropriate rating scales and controlled studies regarding depression in PD.     

Thought disorders among non-demented outpatients with Parkinson’s disease: prevalence and associated factors

The objectives of the study are to evaluate the prevalence and the associated factors of thought disorders in a large cross-sectional population of non-demented out patients with Parkinson’s disease (PD). Four-hundred and nineteen consecutive non-demented PD patients were studied through the DoPaMiP cross-sectional study. Demographic and clinical variables were recorded, including motor and cognitive status, dependency, depressive and anxious symptoms, dysautonomia and sleep disorders. The presence of thought disorders over the past 15 days was assessed by the Unified Parkinson’s Disease Rating Scale part I. Patients with and without thought disorders were compared using parametric tests. Logistic regression was applied to significant data. Thought disorders were present in 105 patients (25%) including vivid dreams in 83 (19.8%), benign hallucinations in 17 (4.1%), and hallucinations without insight in 5 (1.2%). No patient had delusion. Patients with thought disorders were more dependent than the others. Thought disorders were associated with longer PD duration, greater UPDRS scores and the presence of motor complications. Conversely, UPDRS tremor sub-score was lower in patients without thought disorders. Thought disorders were also associated with dysautonomia, lower MMSE score, depression and sleep disorders. Logistic regression identified PD duration, lower MMSE score, depressive and dysautonomic signs as independent risk factors. In conclusion, mild thought disorders were present in 25% of non-demented outpatients with PD, but hallucinations were present in 5% only. Thought disorders were associated with PD duration, depressive and dysautonomic symptoms and lower MMSE score.     

Occurrence of Crohn's disease with Parkinson’s disease

We retrospectively investigated the co-occurrence of Crohn's disease in a cohort of 876 patients with Parkinson’s disease, based on the observation that LRRK2 is a shared genetic risk factor. We identified 2 patients with Crohn's disease; this number was consistent with the number of cases expected in the general population.     

Balance confidence and functional mobility are independently associated with falls in people with Parkinson’s disease

The present study aimed to examine the association of falls with self-perceived balance confidence level, and balance and mobility performance in patients with Parkinson’s disease (PD). Forty-nine healthy subjects and 71 subjects with PD completed the study. Among the PD patients, 33 (46%) were fallers and 38 were non-fallers. All subjects were tested with the activities-specific balance confidence scale (ABC), one-leg-stance test (OLS), and timed-up-and-go test (TUG). Results indicated that PD fallers had significantly lower ABC scores, shorter OLS times and longer times to complete TUG than PD non-fallers (P < 0.05). Having a high ABC score (>80) was significantly associated with a lower fall risk, after adjusting for age, gender, and duration of PD, and for depression [odds ratio (OR) = 0.06, P = 0.020]. For performance-based measures of balance and mobility, a longer TUG time (≥16 s) was independently associated with increased risk of falling after controlling for relevant factors (OR = 3.86, P = 0.043); OLS time, however, was not significantly associated with falls. A lower self-perceived balance confidence level and a prolonged time to complete TUG were associated with increased risk of falling in patients with PD. Interventions to improve these modifiable risk factors could be useful in reducing future falls in the PD population and will require further study.     

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...     

Monte Carlo cross-validation analysis screens pathway cross-talk associated with Parkinson’s disease

We purposed to identify underlying functional pathway cross-talk in Parkinson’s disease (PD) through Monte Carlo cross-validation analysis. Microarray data set of E-GEOD-6613 was downloaded from ArrayExpress database. First, the identification of differentially expressed genes (DEGs) was implemented, following by extracting the potential disrupted pathway enriched by DEGs. In addition, a discriminating score (DS) was computed based on the distribution of gene expression levels by quantifying their pathway cross-talk for each pair of pathways. Furthermore, random forest (RF) classification model was utilized to identify the top ten paired pathways with high AUC between PD and healthy control samples using the tenfold cross-validation method. Finally, Monte Carlo cross-validation was repeated 50 times to explore the best pairs of pathways. After quantile normalization, a total of 9331 genes with higher than 0.25-fold quantile average across all samples were obtained. Totally, 42 DEGs and 19 differential pathways enriched from DEGs were identified. We then ranked each pathway according to their AUC values, the pair of pathways, phosphatidylcholine biosynthesis I, and PPAR signaling obtained the best AUC value of 0.942. Moreover, the paired pathways of mTOR signaling and CD28 signaling in T helper cells had higher AUC value of 0.837 in five bootstraps. Two paired pathways, including phosphatidylcholine biosynthesis I and PPAR signaling, as well as mTOR signaling and CD28 signaling in T helper cells were able to accurately classify PD and healthy control samples. Significantly, these paired pathways might be underlying biomarkers for early diagnosis and therapy of PD.