Prospective memory in Parkinson’s disease: the role of the motor subtypes

Journal of Neurology - Prospective memory (PM) is defined as memory for future intentions and it is typically divided into time-based and event-based PM. Deficit of PM has been reported in patients...     

Clinical subtypes in Parkinson’s disease: the impact of MAPT haplotypes

The H1 haplotype of the MAPT gene influences the risk of PD and has been related to the development of PDD. We evaluated the influence of MAPT haplotypes on the expression of motor features in PD patients. We genotyped, for the MAPT haplotypes H1 and H2, a sample of 181 PD patients with distinct clinical subtypes: tremor dominant and non-tremor dominant (NTD). Our results indicate that the MAPT haplotypes contribute to the expression of motor features of PD. H1 homozygous PD patients are significantly more likely to present a NTD phenotype, a clinical subtype characterized by widespread pathological degeneration, than H2 carriers.     

Psychiatric symptoms screening in the early stages of Parkinson’s disease

Psychiatric complaints are common in Parkinson’s disease (PD), and have a significant influence in disease outcome and quality of life. Little attention has been paid to psychiatric symptoms at early stage disease. We aimed to screen a population of early stage PD patients for psychiatric symptoms and to study the relation with motor and cognitive function. Thirty-six early stage PD patients underwent motor [Hoehn and Yahr (HY), Unified Parkinson’s Disease Rating Scale] and cognitive [Frontal Assessment Battery, Mini-Mental State Examination (MMSE)] assessment as well as general psychiatric [Symptom Check-List 90 (SCL-90-R)] and psychosis [Brief Psychiatric Rating Scale (BPRS)] screening. Relation between psychiatric domains scores was studied with principal component analysis. Relation between psychiatric, disease related, cognitive and motor function was assessed with bivariate correlation (Pearson). SCL-90-R scores were higher for somatization (significant scores in 66.7% of patients), depression (36.1%), anxiety (27%) and obsessive—compulsive symptoms (OCS) (52.8%). Scores were highly correlated, except for psychosis and phobia. Depression and anxiety were negatively correlated to MMSE score and dopaminergic doses, respectively. BPRS scores were higher for somatic concern, depression, anxiety and hallucinations. There was segregation between depression, anxiety, hallucinations, other positive psychotic symptoms and negative psychotic symptoms. Depression was related to MMSE score. We found a high prevalence of psychiatric complaints in PD patients, mostly related to depression, anxiety, somatization and OCS. Hallucinations were also frequent, but not associated to cognitive function or dopaminergic doses, suggesting a different physiopathological background.     

Cardiac parasympathetic dysfunction in the early phase of Parkinson’s disease

Cardiac parasympathetic function is strongly affected by aging. Although sympathetic dysfunction has been well documented in Parkinson’s disease (PD), cardiac parasympathetic dysfunction has not been well studied. The objective of this study was to clarify the development of cardiac parasympathetic dysfunction in the early phase of PD and to explore the age-corrected correlation between cardiac parasympathetic dysfunction and cardiac sympathetic dysfunction. We reviewed 25 healthy controls and 56 patients with idiopathic PD of Hoehn and Yahr stages I–III. We evaluated cardiac parasympathetic function using the Valsalva ratio, the baroreflex sensitivity (BRS) and the coefficient of variation of RR intervals in the resting state (resting-CVRR) and during deep breathing (DB-CVRR). In addition, we measured cardiac ¹²³I-metaiodobenzylguanidine (MIBG) uptake to investigate the relationship between cardiac sympathetic and parasympathetic dysfunction in PD. Compared with healthy controls, patients with PD showed significantly decreased cardiac parasympathetic parameters (resting-CVRR 2.8 ± 1.3 vs. 1.7 ± 0.6%, p < 0.001; DB-CVRR 5.8 ± 2.3 vs. 3.8 ± 1.7%, p < 0.001; Valsalva ratio 1.52 ± 0.26 vs. 1.34 ± 0.17, p < 0.01; BRS 10.6 ± 9.5 vs. 5.0 ± 5.4 ms/mmHg, p < 0.01). In particular, resting-CVRR and DB-CVRR were significantly decreased in the early phase of PD. In age-corrected analyses, none of the parasympathetic indices correlated with the delayed cardiac ¹²³I-MIBG uptake. These observations indicate that cardiac parasympathetic dysfunction occurs in the early phase of PD, but not necessarily in parallel with cardiac sympathetic dysfunction.     

Striatal hand in Parkinson’s disease: the re-evaluation of an old clinical sign

Among postural abnormalities in Parkinson’s disease (PD), striatal hand (SH) is a particularly underexplored phenomenon. It leads to extreme abnormalities of hand posture, causing altered dexterity, pain and disfigurement. In our study, three blinded investigators examined several pictures of the hands of individuals with PD (N = 40) and controls (N = 15). The investigators quantified postural alterations using the Striatal Hand Score. Demographic and clinical data were also collected. As no differences were detected among investigators agreement, a final Hand Score (HS, range 0–4) was obtained for each hand. The Striatal Hand Score in both the left and right hand was significantly different in PD compared to controls (p < 0.001 for both left and right hand). Striatal hand was significantly worse on the side of PD onset, and on the side with greater PD symptomatology. The finding of a striatal hand was 100 % specific for a diagnosis of PD. Nine PD subjects were evaluated both on and off medication, and dopaminergic treatment did not significantly change the Striatal Hand Score. Our findings suggest that in patients without any explanation for hand deformities other than PD, striatal hand occurs very often, and is highly specific for the side of worst PD involvement. We recommend including an evaluation for SH as part of routine practice. This study emphasizes the importance of a careful observation of the patient in order to improve diagnostic accuracy.     

Rapid onset of efficacy of rasagiline in early Parkinson’s disease

Rasagiline is a monoamine oxidase type-B inhibitor used as monotherapy or in addition to levodopa in the treatment of Parkinson’s disease (PD). This naturalistic single-blind study was aimed at evaluating the rapidity of onset effect of rasagiline on motor symptoms in a cohort of early relatively elderly PD patients. 102 outpatients (55 males, median age 71 years) have been selected: 26 were PD therapy-naive and 76 received rasagiline as add-on therapy. The third section of the Unified Parkinson’s Disease Rating Scale (UPDRSIII) and the Hoehn–Yahr (HY) scale were assessed at baseline and after 1 and 4 weeks thereafter. The mean UPDRS III total score (?6.7 at week 1 and ?8.9 at week 4) and single items, as well as mean HY score (?0.40 at week 1 and ?0.67 at week 4), significantly decreased from baseline (p < 0.001). Improvements were significant in both therapy-naive and add-on therapy patients: the mean decreases from baseline to week 4 in UPDRSIII and HY score were ?8.8 and ?0.46, and ?9.0 and ?0.74, respectively, in the two subgroups. The mean decrease from baseline in UPDRSIII and HY score did not significantly differ in patients aged > or ≤71 years. Rasagiline had a rapid therapeutic effect from the first week of therapy, which further improved at 4 weeks. The rapid onset of action and the absence of a dose titration are important issues in the management of the PD patient.     

Mitochondria in the context of Parkinson’s disease

<正>Introduction to the disease:Parkinson’s disease(PD)is the second most common neurodegenerative disease,affecting 1–2%of the population over the age of 65.Rigidity,bradikynesia,postural instability and tremor are the principal clinical characteristics of this disease,     

Cognition and emotion in different stages and subtypes of Parkinson’s disease

This paper reviews the main neuropsychological features of movement disorders such as Parkinson’s disease (PD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), Huntington’s disease (HD), corticobasal degeneration (CBD), and diffuse Lewy body disease (DLBD). These neurodegenerative disorders all share a prominent frontal lobe-like syndrome which can be explained by damage to connections between the basal ganglia and the cortical areas involved in movement, and in behavioural and mood control. In this paper different types of cognitive and mood alteration are described in an attempt to identify additional reasons for the differential diagnosis of parkinsonism-like syndromes.

     

Transcranial sonography image characteristics in different Parkinson’s disease subtypes

Recently, Parkinson’s disease (PD) has been classified into three subtypes: postural instability gait difficulty (PIGD), tremor dominate (TD), and indeterminate PD. Transcranial sonography (TCS) is considered to be an important tool to diagnose PD. However, it is uncertain that whether there are differences in TCS image characteristics in different PD subtypes, so 373 idiopathic PD (188 PIGD, 108 TD, 77 indeterminate PD) were registered and received TCS in our investigation; also, the association between clinical characteristics and TCS results in different PD subtypes was analyzed. In accordance with several previous studies, we detected substantia nigra (SN) by TCS in 85.4% of patients with idiopathic PD; we concluded that PIGD patients had more serious disease than TD and indeterminate PD group (p < 0.05). They always had larger SN hyperechogenicity areas on TCS (p < 0.05), and we found that there was no correlation between SN hyperechogenicity and disease duration or severity (p > 0.05). Similarly, abnormal brainstem raphe signal was also more often in PIGD group than in TD and indeterminate PD group (p < 0.05), which might imply that PIGD group was vulnerable to suffer from depression in the future.     

Treatment of Parkinson’s disease in the advanced stage

Levodopa/Carbidopa, respectively, Levodopa/Benserazide is the most effective treatment for Parkinson’s disease and during the progress of the disease, patients will inevitably need to be treated with it. Nonetheless, after a certain time period most of the patients experience side effects. Mainly disturbing are motor and non-motor fluctuations and dyskinesia. Numerous options from changing the medication regimen, to continuos dopaminergic drug delivery via apomorphine or Duodopa pumps and stereotactical interventions are available. The physician’s responsibility is to choose the right therapeutic procedure for each timepoint of the patient’s disease. In this review, we provide an up to date overview of the available strategies.     

Chronic models of the preclinical and early clinical stages of Parkinson’s disease in mice

Degradation of the dopaminergic nigrostriatal system is a central process of the pathogenesis of Parkinson’s disease, which is a chronic neurodegenerative disorder. A specific feature of the disease is longterm asymptomatic progress over decades, which occurs due to the functioning of compensatory processes in the brain. Specific motor symptoms appear after substantial lesion of the nigrostriatal system and depletion of compensatory reserves. At this stage, traditional treatment of patients has low efficiency. In the present study, we developed new neurotoxic models of the maximally prolonged preclinical stage and early clinical stage of Parkinson’s disease in mice and performed a thorough evaluation of motor behavior and the morphofunctional state of the nigrostriatal system in these animals. Further comparative study of these models will help to identify: (a) specific peripheral biomarkers of each stage as a basis for the development of the early preclinical diagnostics of Parkinson’s disease; (b) the mechanisms of neuroplasticity that are responsible for asymptomatic progress of the disease; (c) molecular triggers of impaired motor behavior during the transition from the preclinical stage to the clinical stage.     

Sensitivity and specificity of cardiac metaiodobenzylguanidine scintigraphy in the early diagnosis of Parkinson’s disease

Clinical Autonomic Research - Metaiodobenylguanidine (MIBG) scintigraphy has been shown to enhance the probability of correct diagnosis in patients with parkinsonian syndromes (PS). Thus far,...     

Impairment of the supervisory attentional system in early untreated patients with Parkinson’s disease

The aim of this study was to specify the frontal type dysfunction widely reported in Parkinson’s disease (PD) early in the course of the disease and before dopaminergic therapy. Seventeen “de novo” PD patients and 17 healthy control subjects performed modified versions of the Stroop word-color test and the Brown Peterson paradigm. A dissociation between results on the two tasks was observed in PD patients. They had difficulties in inhibiting a strong habitual response and establishing a new, better adapted pattern of response; but they performed as well as controls in a dual-task paradigm requiring correct allocation of the processing resources of working memory. Early in the course of the disease, untreated PD patients suffer from dysfunction of the supervisory attentional system. However, the present findings suggest that this system is not a single unit but rather could be composed of multiple subsystems whose sensitivity depends on the origin of frontal dysfunction. Indeed, only a few of these subsystems seemed to be impaired in de novo PD patients. It can be hypothesized that those involved in the phenomena of adaptation and consolidation of currently appropriate responses depend on the dorsolateral prefrontal loop, which is affected by the dopaminergic innervation of the caudate nucleus. Received: 21 April 1998 Received in revised form: 27 January 1999 Accepted: 12 February 1999     

Dream features in the early stages of Parkinson’s Disease

Few studies have investigated the relation between dream features and cognition in Parkinson’s disease (PD), although vivid dreams, hallucinations and cognitive decline have been proposed as successive steps of a pathological continuum. Our objectives were therefore to characterize the dreams of early stage PD and to study the relation between dream characteristics, cognitive function, motor status, depression, dopaminergic treatment, and the presence of REM sleep behaviour disorder (RBD) and hallucinations. Dreams of 19 male PD patients and 21 matched control subjects were classified according to Hall and van de Castle system. h statistics was used to compare the dream content between patients and controls. We tested the relation between patients’ dreams characteristics and cognitive function (Frontal assessment battery (FAB) and Mini-Mental State Examination tests) depression (Beck depression inventory), motor function (UPDRS), dopaminergic treatment, the presence of RBD (according to clinical criteria) and hallucinations, using general linear model statistics. Patients and controls differed only on FAB scores. Relevant differences in the Hall and van de Castle scale were found between patient’s dreams and those of the control group, regarding animals, aggression/friendliness, physical aggression, befriender (higher in the patient group) and aggressor and bodily misfortunes (lower in the patient group) features. Cognitive and particularly frontal dysfunction had a significant influence on the frequency of physical aggression and animal related features, while dopaminergic doses, depressive symptoms, hallucinations and RBD did not. We found a pattern of dream alteration characterized by heightened aggressiveness and the presence of animals. These were related to more severe frontal dysfunction, which could be the origin of such changes.     

Thyroid MIBG uptake in Parkinson’s disease with diabetes mellitus

In our work, we investigated thyroid and cardiac MIBG uptake as potential differential markers. We observed reduced cardiac uptake of MIBG in PD and diabetic CAN, in agreement with the previous studies. However, there was a significant difference between the PD and diabetic cardiac autonomic neuropathy groups with respect to early and delayed thyroid MIBG uptake, in that reduced thyroid MIBG uptake was seen in PD but not in diabetic autonomic neuropathy. We therefore propose that this parameter could be a marker for identifying parkinsonism when it presents together with DM.     

Identifying subtypes of mild cognitive impairment in Parkinson’s disease using cluster analysis

Journal of Neurology - The concept of Mild Cognitive Impairment (MCI) in Parkinson’s disease (PD) has shown the potential for identifying at-risk dementia patients. Identifying subtypes of...