Pattern Of Parkinson's Disease Research Articles

Are Parkinson disease patients protected from some but not all cancers?

There is substantial evidence based on well designed epidemiologic studies for low cancer rates in patients with Parkinson disease (PD). This risk reduction cannot be attributed to the recognized low life-long incidence of smoking in patients with PD, as not only smoking-related cancers but also non-smoking-related ones are less common in PD. Whereas the risk for most cancers appears to be relatively low in patients with PD, breast cancer and melanomas occur more frequently in the PD population as compared with controls. The relationship between this peculiar pattern of cancer rates and PD might be related to the involvement of common genes in both diseases. Mutations in parkin gene, for example, have been reported in several types of cancer. Furthermore, genes involved in familial forms of PD appear to be abnormally expressed in cancers. Thus, parkin and PINK1 might be tumor suppressor genes, whereas DJ-1 is an oncogene. Cell survival signals may differ owing to mutated genes and represent two opposite extremes such as cell proliferation in cancer and cell death due to apoptosis in PD. Unraveling the link between PD and cancer may open a therapeutic window for both diseases.

Levodopa‐induced ocular dyskinesia in Parkinson's disease

Levodopa (LD)-induced dyskinesia (LID), one of the most common motor complications in advanced Parkinson's disease (PD), involve mostly the limbs, trunk and head, but unusual locations have been reported including respiratory muscles, the face and the eyes. The aim of this study was to further investigate the frequency and characteristics of LD-related abnormal involuntary eye movements (AIEMs) in PD. Thirty-two patients with advanced PD and various motor complications were evaluated and videotaped in an ON and OFF state. We found AIEMs in five patients (16%) which were present exclusively during the ON state and which completely disappeared when OFF. They consisted of repeated, stereotyped upward and/or sideways gaze deviation movements, sometimes phasic, brief and jerky, sometimes tonic and sustained for several seconds. The main direction of gaze deviation was toward the side more affected by parkinsonism. AIEMs typically paralleled limb and trunk LID and were modulated by the same facilitation and inhibitory maneuvers. We concluded that AIEMs are not uncommon in advanced PD and represent a particular topography of LID, hence the term 'ocular dyskinesia' to designate these AIEMs that seem to have a specific pattern in PD as compared with other forms of parkinsonism.

Age‐related accumulation of Marinesco bodies and lipofuscin in rhesus monkey midbrain dopamine neurons: Relevance to selective neuronal vulnerability

Parkinson's disease (PD) is characterized by degeneration of nigrostriatal dopamine (DA) neurons. Although aging is a primary risk factor for PD, its role in DA neuron degeneration remains unknown. Neurodegeneration in PD is not uniform throughout the ventral midbrain: the ventral tier of the substantia nigra (vtSN) is most vulnerable, whereas the dorsal tier (dtSN) and ventral tegmental area (VTA) are relatively resistant. We studied young (9-10 years old), middle-aged (14-17 years old), and old-aged (22-29 years old) rhesus monkeys to identify factors potentially underlying selective vulnerability and their association with aging. We focused on markers relevant to the ubiquitin-proteasome (UPS) and lysosome systems. Unbiased stereological counting was performed on tyrosine hydroxylase-positive (TH+) neurons and TH+ neurons containing Marinesco bodies (TH+MB) or lipofuscin (TH+lipo), markers of UPS or lysosomal activity, respectively. TH+ neuron numbers were inversely correlated with advancing age specifically in the vtSN, not the dtSN or VTA. TH intensity decreased throughout the ventral midbrain with increasing age, an effect exacerbated in the vtSN. TH+MB neurons were localized in the vulnerable vtSN of old monkeys. The number of MBs per cell increased with age, and TH intensity of TH+MB neurons decreased in middle age. Conversely, TH+lipo neurons were primarily found in the resistant dtSN and VTA. These data suggest that particular age-related changes localize to DAergic subregions relevant to degenerative patterns in PD. Furthermore, the results begin to characterize the nature of the link between aging and PD, and they support the concept that aged monkeys represent a valuable model for studying specific events preceding PD.

Vulnerability of cortical neurons to Alzheimer's and Parkinson's diseases

Alzheimer's disease (AD) and sporadic Parkinson's disease (PD) are the most frequently occurring degenerative illnesses of the human nervous system. Both involve multiple neuronal systems, but only a few types of nerve cells are prone to develop the disease-associated intraneuronal alterations. In AD affected neurons produce neurofibrillary tangles and neuropil threads, while in PD they develop Lewy bodies and Lewy neurites. In both illnesses select types of projection cells that generate long, unmyelinated or sparsely myelinated axons are particularly susceptible. This kind of selective vulnerability induces a distinctive lesional pattern which evolves slowly over time and remains remarkably consistent across cases. In the present review, lesions developing in the cerebral cortex are described against the backdrop of the internal organisation and interconnectivities linking involved cortical areas and subcortical nuclei. In AD, six and in PD, three stages can be distinguished, reflecting the predictable manner in which the proteinaceous intraneuronal inclusions spread through the cerebral cortex. In AD stages I-II and in PD stage 4, the pathological process makes inroads into the anteromedial temporal mesocortex, entorhinal allocortex, and Ammon's horn; thereafter, in AD stages III-IV and in PD stage 5, it proceeds into the adjoining high order association areas of the basal temporal neocortex. In AD stages V-VI and in PD stage 6, the damage affects additional neocortical association areas including first order association areas and eventually extends into the primary areas of the neocortex. The gradually evolving lesional pattern in AD and PD mirrors the ground plan of the cerebral cortex. The highest densities of lesions occur in the anterior mesocortical transitional zone between allo- and neocortex. From there, the involvement diminishes by degrees and extends into both the hippocampal formation and the neocortex. The severity of the neocortical lesions decreases in inverse proportion to the trajectories of increasing cortical differentiation and hierarchical refinement.

Quality of life and depression in Parkinson's disease

This paper reviews the literature on health-related quality of life (Hr-QoL) and depressive disorders, and the relationship between them, in patients with Parkinson's disease (PD). PD is associated with reduced Hr-QoL, including motor and non-motor physical consequences of the disease, emotional well-being and social functioning. While this effect is greater in advanced disease stages, there is no close relationship between disease duration and impact on quality of life, and the relationship between clinical rating scales and Hr-QoL scores is only moderate. On the other hand, presence and severity of depression in PD strongly correlates with Hr-QoL scores, and a number of studies have reported depression as the main determinant of poor HR-QoL scores. Despite being the main determinant of poor Hr-QoL and being recognized as an important problem by clinicians, until recently depression in PD has received relatively little attention in research studies. It is known that depression and anxiety occur more frequently in PD than in controls. Depression occurs in a bimodal pattern in PD, with increased rates at the onset and a later peak in advanced disease. Both anxiety and depression can also occur before the first motor symptoms of PD and predate the diagnosis of PD, indicating that these co-morbidities are manifestations of the underlying disease process of PD. Imaging studies have demonstrated abnormalities of dopaminergic, noradrenergic and serotonergic functioning with some correlation with severity of depression. The overall relationship between disease severity and rate of depression (except for off-period related depression) is poor, suggesting that nigrostriatal dysfunction alone is not sufficient to explain depressive symptoms in PD. Other factors are likely to contribute to occurrence and severity of depression in PD, either due to extrastriatal pathology or due to psychological and environmental factors leading to reactive depression. Thus, it is likely that depression in PD is multifactorial. The investigation of depression in PD is complicated by diagnostic difficulties in measuring and diagnosing depression in patients with PD due to the considerable overlap between symptoms of PD and depression. While a number of treatment approaches have been suggested, double-blind randomized controlled trials to demonstrate improvement of depression and overall Hr-QoL in PD are warranted.

Absence of the apolipoprotein E ε4 allele is associated with working memory impairment in Parkinson's disease

The apolipoprotein E (APOE) ε4 allele has been associated with an increased risk of Alzheimer's disease (AD) and weaker episodic memory among elderly. Although this APOE allele has been linked to earlier onset of Parkinson's disease (PD), an association with dementia in PD has been only inconsistently demonstrated. Given the heterogeneity of cognitive impairment patterns in PD, this study sought to determine whether an association exists between APOE genotype and specific cognitive deficits in PD. The neuropsychological test performance of 42 PD patients without an ε4 allele (PD-Non4) and of 20 with at least one ε4 allele (PD-ε4) was compared to that of 146 elderly control subjects (NC). The PD groups were comparable in overall severity of cognitive impairment and disease duration, but the PD-ε4 group was younger, had an earlier disease onset, and contained a higher proportion of persons with dementia. Both PD groups showed wide-ranging cognitive impairments relative to NC. Once age differences between groups were controlled for, the PD groups generally did not differ from each other in cognitive performance. However, only the PD-Non4 group demonstrated working memory/attention impairments (digit span, visual span, Trailmaking test) relative to the NC group. Results suggest that the APOE genotype may influence the cognitive phenotype of PD, and specifically that absence of the ε4 allele is associated with working memory impairment. Additionally, results are consistent with prior findings showing an association between the ε4 allele and earlier onset of PD and presence of dementia.

Prescribing pattern in Parkinson's disease: are cost and efficacy overriding factors?

Information on prescribing pattern of antiparkinsonian medications and factors influencing neurologists' choice of such drugs are important considerations in evaluating healthcare cost of Parkinson's disease (PD). We surveyed neurologists' perceived factors influencing their choice of drugs and actual prescribing pattern in PD. Three hundred and six patients at a tertiary hospital, diagnosed with idiopathic PD and who were dispensed antiparkinsonian drugs during a 6-month period were randomly selected. Patient demographics, type and dose of medications were analysed. A questionnaire survey evaluating the factors influencing choice of medications was administered to neurologists who practiced at the institution. The study population had a mean age of 64.4 years (SD +/- 9.9 years), and more than 80% were at Hoehn & Yahr stage 2-3. 92.3% of the study population were receiving levodopa and monotherapy, with levodopa being the most common treatment regimen. Patients who were prescribed levodopa were significantly older and at a later stage of disease compared to those without levodopa (p < 0.05). Only 26.8% of patients were prescribed dopamine agonists. In the survey, the neurologists cited severity of symptoms, and patients' intolerance of side effects, and efficacy as the most important factors influencing their choice of drugs. However, the actual prescribing pattern revealed a strong positive correlation of drug usage with cost subsidy by the institution. While factors affecting drug usage in PD are well recognised, cost and efficacy of a drug appear to be overriding practical factors in influencing usage pattern in clinical practice.

Time-course of nigrostriatal degeneration in a progressive MPTP-lesioned macaque model of Parkinson's disease.

Parkinson's disease (PD) is characterized by a progressive loss of substantia nigra pars compacta (SNc) neurons. The onset of clinical symptoms only occurs after the degeneration has exceeded a certain threshold. In most of the current 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) nonhuman primate models, nigrostriatal lesions and the onset of PD symptoms are the result of an immediate neuronal degeneration in the SNc caused by acute injection of the toxin. In order to develop a model that more closely mimics the degeneration pattern of human PD, we eventually established a protocol that produces a progressive parkinsonian state by treating monkeys repeatedly with MPTP for 15 +/- 2 d. Mean onset of parkinsonian symptoms occurred after 13.2 d of treatment. At this time, 56.8 +/- 6.3% of tyrosine hydroxylase immunoreactive neurons and 75.2 +/- 6.2% of Nissl-stained cells remained in the SNc. Striatal dopamine transporter (DAT) binding and dopamine (DA) content decreased to 19.7 +/- 4.9% and 18.2 +/- 5.6% of untreated monkeys. Parallel 123I-PEI single-photon emission computed tomography (SPECT) imaging in living animals showed a similar decrease in striatal DAT binding. In this article, we examine how this and other chronic MPTP models fit with human pathology.

Analysis of the coding and the 5' flanking regions of the alpha-synuclein gene in patients with Parkinson's disease.

Missense mutations of the alpha-synuclein gene have been reported to explain a few kindreds with autosomal dominant Parkinson's disease (PD). In order to identify mutations in our PD patients, we have screened the coding region and 5'flanking region of the gene. DNA samples from 50 patients with familial PD were screened via single-strand conformation polymorphism (SSCP) for mutations in the alpha-synuclein gene. The 5' flanking region was examined in 117 additional PD patients (27 patients with unclear family history for PD, and 90 patients without family history) and in 169 control subjects. We found one change (G199A) in exon 4 in one family with a pattern of autosomal dominant PD. However, this mutation did not result in an amino acid substitution (valine) and did not segregate completely with PD. The analysis of the 5' flanking region also showed a new polymorphism, a nucleotide insertion (- 164insA) linked to a nucleotide substitution (C-116G), in patients and in controls. The -164insA/C-116G allele was present in 52.3% of the patients and in 47.6% of the controls. We did not find significant differences regarding the allelic and genotype frequencies between PD and control groups. These results suggest that mutations in the alpha-synuclein gene are a very rare cause of familial PD and that the novel -164insA/C-116G polymorphism in the 5' flanking region does not confer susceptibility to develop PD.

A mixed D1 and D2 antagonist does not replay pattern electroretinogram alterations observed with a selective D2 antagonist in normal humans: relationship with Parkinson's disease pattern electroretinogram alterations

The human retina produces a tuned response to stimuli of increasing spatial frequency reversed at a steady state. The peak amplitude response, at medium spatial frequencies, is decreased in Parkinson's disease and in normal subjects ( n=18) treated with a D2 dopaminergic antagonist ( l-sulpiride). Here, we report that a mixed D1–D2 receptor antagonist (haloperidol) in normal subjects ( n=18) does not produce an amplitude decrease of medium spatial frequencies (SFs) responses but it decreases low-frequency response. It could argued that the increased dopamine release produced by the presynaptic D2 antagonistic action of haloperidol is subsequently counteracted at postsynaptic level by its D1 antagonistic effect, producing a net counterbalance at medium SFs. These data suggest that the two dopamine receptors may play different roles in the retinal function and in the origin of visual alterations in Parkinson's disease.

The epidemiology of Parkinson's disease in the county of Rogaland, Norway

The objective of this investigation was to clarify the epidemiology of idiopathic Parkinson's disease (PD) in the county of Rogaland, Norway. Total case ascertainment and a high diagnostic accuracy were attempted through a detailed community study and the use of a new clinical diagnostic classification. The study population comprised 220,858 inhabitants, and a total of nearly 400 patients was interviewed and examined by a neurologist. On prevalence day, January 1, 1993, 245 patients were included in the study. The diagnostic classification revealed 135 patients with clinically definite, 74 with probable, and 36 with possible PD. The crude prevalence rate was shown to be 110.9 per 100,000 inhabitants. The total age-adjusted prevalence was calculated to be 102.4 per 100,000 and to 120.9 per 100,000 men and 89.8 per 100,000 women. Among the 245 patients, 28 patients had a tremor-dominant disease, 50 patients an akinetic-dominant disease, and 167 patients a mixed clinical pattern of PD. Age-adjusted prevalence figures were slightly higher for rural compared to urban areas. About 50% of the PD patients were in need of public help, 15% had complaints about pain related to their parkinsonism, and after approximately 6 years of levodopa treatment, 20% were suffering from clinical fluctuations. The study showed that 40% of the patients had some degree of thought disorder. The prevalence figures for PD in this study are slightly lower than those reported from most previous prevalence studies with a comparable study design for case finding. This may be due to a careful diagnostic evaluation with the use of specified diagnostic criteria, excluding patients with other parkinsonian syndromes.